-.

DEPARTMENT

OF HEALTH

AND HUMAN SERVICES

FOOD AND REGULATORY HEARING STEVEN FROM RECEIVING
————————————

DRUG ADMINISTWTION ON THE K. PROPOSAL M.D.
.--

TO DISQUALIFY

TEPLICX,

INVESTIGATIONAL
-—

NEW DRUGS
—~ =====-~~=====~=

— ———-——— —-—— -—-———-———_~=_—--——

REPORT
—-————-— —————————====-

OF THE

PRESIDING

OFFICER
—--— ---.=~-=~= ~-=--—-— —------- —--

------——— ——-—---—-— ———- -——

1.

INTRODUCTION

Pursuant (“C.F.R.’f)l z_ (“FDA” proposal (“Center”) investigational )

to

Title Parts

21 16

of and

the 312,

Code the on Drug

of

Federal and

Regulations Drug to and M.D. Center Administration consider Research from receiving that the

Food

conducted of the to

a h-ring Center for

12/12-13/91, Evaluation K. Teplick, The

disqualify new drugs

Steven

(C91NDS’*) .1

contended

I All references in this report are to Title 21 C.F.R., unless otherwise specified. Although many of the events cited in the charges of the NOOH took place pri~r to the revision of X investigational new drug (wIND~~) regulations on 3/19/87, the NOOH referred to the revised IND regulations. However, because the revised regulations are largely consistent with the regulations in place at the time of the events in issue (except as noted-in the” “ section) , this revision had no effect on the recommended “Analysis disposition of the charges. .Therefore, for purposes of this report, I have used and cited the current form of the regulations for analyzing the Center’s charges, unless otherwise noted.

——_

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

2

Dr.

Teplick he

should repeatedly

be

disqualified or in del-iberately a clinical ; a clinical contended regarding 312.66,

as

a clinical violated the

investigator federal using (W the ‘), More in food

because and drug

regulations new participated the with the

investigation3

investigational which he

drug, as

investigator.4 that Dr. clinical 312.62(b), Teplick

specifically, comply forth 50.27,

Center regulations

failed

to set

investigations 312.62(a),

in

ss

312.64(b), 50.25.

312.60,

and

. ——

For the

the

reasons

stated Officer

below, that Dr. new [See Center

it

is Tepli.ck

the

recommended be This disqualified document This Teplick be on this

decision from constitutes report,

of

Presiding

receiving my with report report any

investigational on the hearing. by the

drugs.

~ 16.60(e).] and record Dr. will

along this

comments the for

regarding referred matter. to

and

administrative a final

the [See

Commissioner ~ 16.95.]

determination

3 A clinical investigation which a drug is administered or more human subjects.” [s
__—_

is defined or dispensed 312.3(b).J

as to,

‘tany experiment or used involving,

in one

4 An investigator conducts a clinical direction the drug [s 312-3(b).]

is defined investigation is administered

individual who actually as “an (i.e. , under whose immediate or dispensed to a subject).”

Tn

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

3

===—.

II.

BACKGROUND

A Notice
(“IND”)S

of
w=

Claimed
ori@nalW

Investigational
~=p=sted

Exemption by of an 60 the

for

a New

Dmg

‘--

sponsor-investigator,s University of William of in one

M.D.,

Department r for

Gastroenterology, use’ J.]

emergency at Tab

subject. M.D., Drug Tab

[Center a Medical Products,s

Exhibit Officer issued in this

(f’CX”) the

Bachrach,

Center~s IND

Division on

Cardiorenal [Id. at

emergency

3/15/85.

I.]

Section 312.20 requires the sponsor intends to conduct investigational new drug that

5

a sponsor a clinical is subject

to “submit an investigation to ~ 312.2(a).~S

IND to FDA with an

if

6A initiates direction w .0.. this part sponsor. A sponsor clinical
7

as ‘tan individual who both sponsor-investigator is defined and conducts an investigation, and under whose immediate the investigational drug is administered or dispensed The requirements applicable to a sponsor-investigator under include both those applicable to an investigator and a [S 312.3(b).] is “a person investigation.” who takes responsibility [5 312.3(b).] for and initiates a

“Need for the use of investigational drug may See ~ 312.36: arise in=n emergency situation that does not allow time for the submission of an IND in accordance with ~ 312.23 or ~ 312.34. In FDA may authorize shipment of the drug for a specified such a case, use in advance of submission of an IND. A request for such transmitted to FDA by teiephone . . . .m authorization may be

-J.

This Coagulation

8

division Drug

is now Products,

called which

the is

Division directed

of Gastrointestinal by Stephen B.

Fredd,

_

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

4

Dr. letter, experience ), noted that Mr. dated

‘s

first 5/28/85, the

written in one

communication which he reported In Consumer not received [CX

to

the the

FDA was clinical the IND file

a

with

subject.

reviewing Safety the 60

(IND

Thomas Dr. letter

Hassall, . had and FDA

Officer Center’s at Tab 1.]

(ltCSOtt), standard

introductory

forms.

Dr. clinical common R. — — ‘Stern,

later protocol bile duct M.D., Drug be dated

submitted for stones, Medical Products, as the

the treatment to Officer the

necessary of file in the on both

forms, gall

including bladder [Id.] Division and

a and William of found Review

7/22/85.9 Center’s

~rdiorenal them report to

reviewed noted in

these his

documents Officer’s

acceptable, 10/11/85.

Medical

[Id.1

As

IND

sponsor to

(lssponsorn), Raymond Drug J. Lipicky,

Dr. M.D., requesting: .

wrote Acting

a

letter,

dated Division

1/28/86, of

Director,

Cardiorenal

Products,

that two colleagues become co-investigators are Steven K. Teplick, at Medical their curricula vitae enclosed

. be allowed to under my IND. These Professor of Radiology College . . . copies of and bibliographies are

.

Dr-. Fredd e was 7/22/86. was 7/22/85. [See,

9

in his [Trans. ea.,

testimony incorrectly Vol. 1 at 17.] The CX 60 at Tab F.]

stated that IND submission

the

IND date

---

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

5

[e]ach of these individuals has agreed to monitor their patients carefully, although they are not at present in a position tocarry out a controlled study comparing with They have agreed to send completed patient report forms on each patient that they treat with They are well aware of its dangers, and they will not initiate clinical studies until their protocol has been approved b their local T Institutional Review Boards. 0 Each of purchase manufactured
.

“-

these their

individuals t by the

has

agreed

to from being t

material

[CX

55

at

1-2.]

_—_

On

the

second dated

page

of

Dr. with is Dr.

‘s

letter,

a handwritten initials In 3/31/86, a record Mr. read: of Hassal a had l~The

notation, proposed telephone noted:

2/06/86,

Bachrach’s [Id.] dated

arrangement conversation

agreeable.’~ or meeting,

Dr. ‘s [sic] Jan. 28, 1986 letter requested the addition of Dr. Stephen [sic] Teplick ( Medical College) & Professor . (u. ) as investigators under Dr ‘s controlled cross-over comparison of and (protocol submitted 7/22/85). Dr. Bachrach noted on 2/6/86 that the additional investigators were ok & asked me to confirm

.

.

‘o An “Institutional Review Board~t (HIRBtt) is ‘Sany board, committee, or other group — formally designated by an institution to biomedical research involving humans as subjects, to approve —— review the initiation of and conduct periodic review of such research.~c .] The IRB used by-Dr. Teplick was the [S 50.20(i) University Committee for Human Studies. [See CX 36.] ,.. .., 4,. . . .,-, .’, : .“1 ..: ~ I .

Tn —. .— .

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

6

with the sponsor. I placed this call to notify Dr. [sic] of our acceptance of the Jan 28, 1986 proposal. [Secretary to Division of Gastroenterolo~, Department of Medicine, University of the note [Id. at 3.] investigators of this ] said she would notify (Teplick + II and make in the IND file~”

--

call

The and

record the

reflected sponsor of 3.], until

no Mr.

further Peter and to Dr.

communication A. Manilla, a

between CSO in Drug dated an

the the

agency Center’s [see stating

Division n. that
. —

Gastrointestinal sent a was INDs activities aid of a basis for the [FDA] letter ‘{currently foz being in as our

Coagulation

Products 6/14/88,

8 at the of

agency all of

performing and [was] asking

administrative for each a report IND. of Such and to at of date, E.] the a

.eview progress report

conducted evaluation

under of the

will

safety agent [CX 60

effectiveness and The provide letter

a gallstone future following:

dissolution

development.” identification

Tab the

requested

*I According to the regulations, once Dr. notified Dr. Teplick of his status as an investigator, Dr. Teplick was Irresponsible for ensuring that an investigation is conducted according to the signed investigator statement, the investigational plan, and applicable regulations; for protecting the rights safety, and welfare of subjects under the investigator’s care; and ~or the control of drugs under investigation.~t In addition, Dr. [~ 312.60.] Teplick was responsible for obtaining the informed consent of each human subject to whom the drug is administered, in accordance with J _J provisions of Part 50, except as provided in ~ 50.23. [Id.] itionai specific responsibilities are set forth in Parts 312, 50, . -A 56. [ml

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

7

supplier(s) certificates testing comparability (e.g., and further [CX55at their by

and of hospital

labeling analysis,

of

product data, any with and characteristics as IND well for

specifications additional on synthetic of as the an the

(e.g., product ..materials subjects of

stability . pharmacists); performed

information and

studies ); treatments research 4&5.]

number and

outcomes, under the

outline year.12

planned

next

Dr. 8/4/88, in of early the In with had [ listed as no

responded stating, July, patients response synthetic “Dr. 1988; that to

to

Mr.

Manilla~s and are Dr.

request,
met

in
with

a letter
me in

dated
Boston

Teplick and they Mr. both have Manilla’s

preparing . . .

detailed .ft (CX

descriptions 60 testing at Tab of “We have

treated inquiry Dr.

D“]

regarding also of Only this Dr letter. stated: material

materials, with any

difficulty ] being

destruction infusion.m

during copied at

‘s [Id.]

name”was

the

bottom

of

the

In

his

response,

however, by letter

Dr. Mr. to Manilla, Dr.

had and 8

not on

provided 12/15/88 60 at

all the Tab

~heagency C.]

information resent the

requested 6/14/88

[CX

12 Under ~ 312.33, an Annual — ==—= ‘equired to be submitted within ~versary date of the IND.

Report containing 60 days of the

this effective

information

Tn

the

Matter

Of

Steven

K.

_—.—.

Zeplick,

M.D.

-

Page

8

Dr. dated Report Case and

~ 4/20/89, to Reports stated: the

responded by IND Forms

to

che

agency’s what

second

request the The first report by

in

a

letter,

submitting file. (~tCRFs”) [See

constituted 12 at 7.]

Annual included Dr. Teplick, ..-

n.

from

subjects

treated

Dr. Teplick, at ; Medical Center, is an ixxerventional radiologist who has developed a referral practice for [common bile] duct stones. His success is less because the incidence of resistant bile duct stones is greater than with gallbladder stones. The patients received a much larger volume of tian that used for gallbladder stones in the otier two centers. The patients were generally quite ill, and treatment was nor alwavs satisfactory. Some sedation occurred. was often used to obtain partial dissolution and then followed by further lavage with My impression is that dissolution of duct stones by lavage with under circumstances where leaks into ‘de small intestine is dangerous and should be done only as a last resort. Every etfort should be made to obtain information on stone composition before dissolution, and I have advised Dr. Teplick to do this. One patient (TE-3) died after therapy, but the attending physician did not believe that played a role in the patient’s d@se. (CX 60 at at Tab the B.] end B. Dr. of Teplick’s this letter.. M.D., and stating: the details common on the name was listed In of as response the Drug that of (TE-3) the and Centerls Products, you not sent enter until you ‘tcarbon to this -

copied” report, Division a letter, more have

[Id.1 Director, Coagulation “We duct

Stephen of

Fredd,

Gastrointestinal 5/25/89, into the

dated patients reviewed

request portion

any

study notify

patient

_.—

----

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

9

that This of

it letter

is

safe

to

proceed

with placed

the

study

.

.

.

.“ on

[CX further ‘s

40

atl.]

effectively bile duct stone

a clinical onto Dr

hold13

common

subjects

entry .-protocol.

Dr. have notified of

responded Dr. duct 41 Teplick stones at 2.]

in

a .

letter . .

dated that we receive Dr. reported

6/01/89, is not

stating: to be used

“I for your that because subject’s

treatment office.” the Dr. _—___ — subject’s Teplick

until In not

permission

from explained

[CX

addition, been

death had [Id.] not

had

sooner

to for

FDA, the

considered

responsible

demise.

In

accordance of

with Dr.

~ 312.68, Teplick’s

Dr.

Fredd

requested conducted

a directed under IND

inspection in

activities

a memorandum

dated

6/23/89:

I am concerned the death [of

about the delay in reporting patient TE3], the use of company [sic] as supplier, the lack of our having the current protocol - the Teplick’s procedure with for Dr. unknown (to us) qualifications of the , the individuals administering the inade~ate informed consent form, the question of charging raised by the consent and form, and the question of what the

Section 312.42(a) defines clinical hold as ‘tan order issued to delay a proposed clinical by FDA to the sponsor [of an IND] . When a investigation or to suspend an ongoing investigation . . hold, sublects may not be given proposed study is placed on clinical The grounds for the imposition of the investigational drug . . . .“ which include safety reasons as well as deficiencies a clinical hold, are addressed at ~ 312.42(b) . in the protocol for the investigation,
#

13

-l

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

10

IRBs know of the conduct of the Dr. Teplick has used study . on 25 patients at and several had adverse reactions, mainly sedation. I cannot assess the extent of the problem with this portion of the study without your assistance in investigating all cases at the IRBs role there, and the reporting procedures in place from Dr. Teplick to Dr. I am also concerned about Dr. ‘s pr~cedures to fulfill his responsibilities as monitor in reporting the study to us, particularly adverse reactions, under 21 CFR 312.32(c)(2), 21 CFR 312.33, and 21 CFR 312.53. (CX 60 at Tab A.]

--

FDA ----

investigator,

Ms. resident

Ann

deMarco, post, with

of

the

Philadelphia an audit advice of of Dr.

District

>ntgomeryville Teplick’s Barton, Scientific her was Ray findings hand-delivered McCullough, clinical M.D.,

conducted the of the medical

trials Officer

Bette of

Lee

Medical

Center’s University

Division and by Vol 8/21/89, FDA 1 at

Investigations, in an FDA to on Form Dr.

at 483, dated in 31;

reported which

7/17/89 Arkansas Trans.

Teplick [CX

Investigator 208.]

8/28/89.

In

accordance Dr. informal by

with Teplick

~ 312.70, an

by

letter to writing. in

dated respond [CX which study,

4/12/90, to 32.] stated: but I the

the

Centar

offered at an

opportunity or in

violations Dr. Teplick III think [CX believe I 33 can at

conference letter some of the dated flaws

responded that — now that there

5/02/90, in the

he

were most

allegations

are

not

accurate.’t

,

____

“T

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

11

1“1

His

letter raised

included in the

an FDA

attachment Form 483.

which [See CX

addressed 31 & CX

the 33 at 8-

concerns 15.]

In

a

letter your

dated letter

6/22/90, of

the 2 May are

Center 1990 not not 1.] to in

responded: detail by to and the

“We

have that records our Dr. Teplick that Dr.

reviewed the

conclude study

explanations to . . the . .~l

offered FDA, [CX and 34

supported adequate The the letter FDA receiving Dr.

available concerns that Teplick — ew drugs. opportunity consent the

are at

satisfy advised

Center be

would

recommend from also

Commissioner investigational with by his an

disqualified The to letter end the [Id.

further provided

Teplick

administrative at 3.]

process

signing

a

agreement.

On

3/22/91,

Mr. Affairs,
(*fNOOH1l)

Ronald FDA, pursu~t

G.

Chesemore, issued to a Part

Associate ~’Notice 16 of

Commissioner Opportunity and for outlined

for a the

Regulatory
Hearingfs

procedures

Center’s

charges.

[NOOH,

attached,

& CX 35.]
..

On 4/08/91, this 7/10/91, Grimes-Miller, __—_ earing. matter, Dr.

Saul

H.

Krenzel,

Esq., on for

Dr.

Teplick’s “of Center, arrange calls, Dr.

attorney Teplick. Ms. a date the date Cathy for of

for On

requested Teplick Esq., Through

a hearing and were counsel contacted of
,,

behalf the to

the

a number

telephone

,,

.~.

Zn the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

12

11/04/91 requested unavailability granted held on

was an

mutually extension of a key

agreed of the

upon. hearing As and the

On

9/24/91, date, due Presiding

the to

Center the Officer, rescheduled I and

witness.

the

the

Center’s

request,

hearing

was

12/12-13/91.

I

permitted

the 2/14/92, to

hearing to submit information Both parties analysis

record allow a post I each

to

remain party to

open

until on

close the and to

of

business, transcript, any the additional hearing.

comment brief,

hearing had

summary

submit

specifically timely Administrative

requested briefs, which Record.

during I

submitted of the

considered

in

my

III.

CHARGES

The its

Center proposal

made that

the Dr. new

following Teplick drugs:

charges be

in

the

NOOH in from

support

of

disqualified

receiving

investigational

Charge A.

X:

Dr.

Teplick

violated

s

312.64(b)

by effects TE4, immediately to TE7, TE8, TE1O,

failing to the sponsor TE1l, TE15,

report alarming adverse TE19, for subjects TE3, TE21, and TE25; and

B:

__

failing to report promptly to the sponsor adverse that may reasonably be regarded as caused by, or caused by, the investigational drug for subjects TE9, TE14, TE16, TE22, TE23, and J’M.

effects probably TE13, TE6~

I

‘=—=- In

the

Matter

Of

Steven

K.

Teplick,

M.D.

-

Page

13

Charge A. B:

II: failing failing activity

Dr. to

Teplick have

violated continuing promptly IRB; promptly risk to IRB

s IRB

312.66 approval

by of in the study; ‘-

to report to the to report involving obtain

all

changes

research

c:

failing problems failing research. III: Dr.

to the IRB all human subjects; before

unanticipated and changes in

D:

to

approval

making

Charge A:

Teplick

violated

S 312.60

by in accordance with the

failing to Investigator failing IV: Dr. to

conduct the Statement; follow Teplick the

investigation and investigational s 312.62(b)

B:
-=

plan. by

Charge

violated

failing to records of investigation investigational Charge V. failing of the Charge VI: failing Charge VII: failing consent. Dr.

prepare and maintain all observations and on each individual drug. Teplick violated adequate drug. violated informed violated
i

adequate and accurate other data pertinent treated with the

to

the

~

312.62(a) records of

by the disposition

to maintain investigational Dr. to Dr. to Teplick document Teplick satisfy

~ 50.27 consent. ~ 50.25 the

by

by . of infoimed -

of

requirements

To three
.-.

support

the

charges Stephen of n. 8 at

against B.

Dr. Fredd,

Teplick, M.D., and

the current

Center Director

presented of the

witnesses: Division [see

Center’s Products
..

Gastrointestinal 3; Trans. Vol.

Coagulation 16-132];

Drug Ms. Ann

1 at

_ —

T.n the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

14

deMarco, [Trans. Officer [Trans.

FDA Vol. of Vol. the

investigator 1 at 136-242];

in

the and

Philadelphia Bette of Lee Scientific

District Barton, M.D. ,

Office Medical --

Center’s 1 at 242-322].

Division

Investigations

To two

defend witness

the on and of

charges Dr. Vice

against Teplick’s Chairman,

Dr. behalf:

Teplick, Steven of

Mr. K.

Krenzel Teplick, at

presented M.D., the 2 at

professor University 4-86

Department

Radiology
v 12

[Trans. M.D., University 1 at

Vol. Staff of 86-129],

& 130-358]; and

and Chief of Lithotripsy, 13 [Trans. at the Vol.

,

Radiologist, .-.

IV.

REGULATORY

FRAMEWORK

Section regulations

355(i)

of permitting

the

FD&C

Act

authorizes experts

FDA to

to

issue the

qualified

investigate

*2 Dr. Teplick is also currently the Director of Diagnosis and the Director of the Radiology Residency Training Program at the University of He servedas-a professor of radiology and Director of the Divi~ions of Computerized Tomography, Gastrointestinal and Interventional Radiology and Co-Director, Division of General Diagnosis at Hospital from 7/82 until 6/89. He assumed his current position at the University of on 7/1/89. [See Teplick Exhibit (“TX”) B.] Dr. ‘3-86 at. ‘~dominal imaging .ron 87-88. [See
13

-

was fellow TX H.]

a

resident in diagnostic radiology from Hospital, where he served as —— from 86-&7, and as a staff radiologist, ..

4..

— -=-=. ~n the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

15

safety

and

effectiveness use.

of Section

drugs 355(i) to

that

are provides that

intended that the public drugs. provisions use are

solely FDA may health The

for enact ‘is

investigational such regulations during may of

necessary studies include, the so of

ensure

protected regulations that and records

using among

investigational other and evaluate things, drug the approval

requiring established and

investigation that FDA may dmg to

maintained

safety of the

effectiveness section 355.

the

support

drug

under

FDA’s _—_ -.

regulations

governing new drugs consent clinical are

the set

clinical forth

evaluation in Part 312.

of Regulations boards forth in which Parts

investigational governing are 50 applicable and 56. informed

and

institutional are

review set

to

investigations

Section

312.70

of

the of

regulations investigators.

provides That

for section

the provides in

disqualification relevant part:

After evaluating all available information, including any explanation presented by the if the Commissioner determines investigator, that the investigator has repeatedly or deliberately failed to comply with the requirements of this part, Part 50 or 56, the Commissioner will notify the ~n~e~tigator and the sponsor of any investigation in which the investigator has been named as a participant that the investigator is not entitled to receive The notification will investigational drugs.

{. ,,

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

16

provide a determination. [s 312.7c)(b). ]

statement

of

basis

for

such

. —T

v.

ANALYSIS

In

preparing by the

my

report, Center in record.ls violated pursuant

I

have the

carefully NOOH*4 in As stated regulations 312.70(b), further light

reviewed of I in I receiving on that the

each

charge in Dr. 50 Dr. and

alleged the

information that 312, that

administrative repeatedly Therefore, be Each

above,

find Parts

Teplick 56. ~eplick —.. —- drugs. discussed

the to from s

recommend

disqualified charge, and

investigational charge, will be

my

findings

separately

below.

*

*

*

1’ Part 16 provides: “FDA will give to the party requesting the hearing reasonable notice of the matters to be considered at the hearing, including a comprehensive statement of the basis for the decision or action taken or proposed that is the subject of the hearing and a general summary of the information that will be presented by FDA at the hearing in support -of the decision or action.” [S 16.2Wf)-l Accordingly, any charges made outside of the NOOH, e.g., during the hearing, were not considered, because such charges would not present the clinical investigator with reasonable notice of the matters to be considered at the hearing.
——_= _-— ,earing permitted 15

I did not consider information submitted after except that information for which I specifically additional time for submission, pursuant to . . . . .

the ~ 16.80(b).

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

17

Charge A.

I:

Dr.

Teplick

violated

~ 312.64(b) effects TE4,

by: immediately to TE7, TE8, TEIOJ

failing to the sponsor TE1l, TE15,

report alarqing adverse for subjects TE3, TE19, TE21, and TE25; and by

B:

failing to report promptly to the sponsor adverse that may reasonably be regarded as caused by, or caused by, the investigational drug for subjects TE9, TE14, TE16, TE22, TE23, and JM.

effects probably TE13~ TE6,

The

Center

alleged effects

that immediately

Dr.

Teplick to the

failed sponsor effects

to for caused

report ten by, the

alarming subjects, or probably for and

adverse that caused eight he

failed by, the

to

report

adverse

investigational in violation of

drug

promptly

to

sponsor

subjects,

~ 312.64(b).

For

the

reasons

to

be

discussed by failing

below, to effects report

I

find

that

Dr.

Teplick to the TE3, to subjects

violated sponsor TE4, the TE15, TE8, sponsor

~ 312.64(b) the alarming TE21, the TE16, and

immediately by

adverse TE2S, and effects and

experienced failing to report by at

subjects promptly

by

adverse TE22,

experienced TE23.

least

TE19,

-.

Section investigator effect

312.64(b) shall that may

of

the

regulations report be to

provides the as

that sponsor caused

IC[a]n any by, adverse or probably

promptly reasonably

regarded

_—_

‘+-

In

the

Matter

Of

SteVen

K.

Teplick,

M.D.

-

Page

18

caused investigator

by,

the

~g.lb shall report

If

the the

adverse adverse

effect effect

is

alarming,

the .“17
. --

immediately

While beyond

the the

regulations above adverse is defined

do definition,

not

specifically “serious are 312.32(a)

define adverse defined. as:

“adverse experience” “Serious

effect” and adverse

“unexpected experience”

experience” in s

___ —

any experience that suggests a significant hazard, contraindication, side effect, or With respect to human clinical precaution. a serious adverse drug experience experience, includes any experience that is fatal or is permanently disabling, life-threatening, requires inpatient hospitalization, or is a congenital anomaly, cancer, or overdose

16

A “drug”

is

defined

in

relevant

part

as

follows:

(A) articles recognized in the official United States official Homeopathic Pharmacopoeia of the United Pharmacopoeia, or official National Formulary, or any supplement to any States, of them; and (B) articles intended for use in the diagnosis, or prevention of disease [in] man or cure, mitigation, treatment, other animals; and (C) articles (other than food) intended to affect the structue or any function of the body of man or other animals; and (D) articles intended for use as a component of any articles specified in clause (A), (B), or (C) . . . . [21 U.S.C. ~ 201(g)(l); see also n. 2 at 1.]

___

1’ The Center argued in its brief received February 14, that all alarming adverse effects must be reported to the 1992, sponsor regardless of whether the effects “may reasonably be regarded as caused by, or probably caused by,, the investigational Section ~ 312.64(b) distinguishes between drug.” [~ 312.64(b).] adverse effects and alarming adverse effects only in that an investigator should report all adverse effects promptly to the and alarming adverse effects should be reported sponsor, adverse effects, Thus , alarming immediately to the sponsor. still must-be reasonably or probably caused by the investigational drug.
,.
1 ,, ,,... ,. ,.. 1 4

.1,

..-

_———.

:n

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

19

.

..*

“Unexpected

adverse

experience”

is

defined

as:

any adverse experience that is not identified in nature, severity, or frequency in the current investigator brochure; or, if an investigator brochure is not required, that is not identified in nature, severity, or frequency in the risk information described in the general investigational plan or elsewhere in the current application, as amended. [S 312.32(a). ]

Dr.

Barton

testified,

as

follows:

alarming adverse events include things like death of the patient temporally related to treatment of the drug; life-threatening problems. It would also include previously unanticipated events, either in type, or in frequency . . . we would severity, expect these alarming events to be reasonably with the test article, and the associatedls test article includes not only the chemical but the delivery system . . . it does not only include the ether, it would include the tract, the catheter, the TE-tube, the balloon that occludes, et cetera. If it is part of as is defined in the the delivery system, Food, Drug, and Cosmetic Act, it is the drug Therefore, it is under the condition of use. considered a part of the investigational drug or the new drug. [Trans. Vol. 1 at 253-4.]

Also

,

according

to

Dr.

Barton,

“[aln

ala~in9

adverse

eff=t~

_—_

I* the drug experience

According to ~ 312.32(a): means that there is a may have been caused

“~ssociated with reasonable possibility by the drug.”

the

use of that the

——

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

page

20 .
,

immediately these patient events . .

we as .

expect soon

the as he

investigator can Vol. safely 1 at

to leave 248-9.]

report the

to side

the of

sponsor the

.“

[Trans.

However, guidelines “alarming system under the in

the to

Center support

did the

not

cite broad to

any

regulations of effect of

or the the I

agency phrase delivery that of

interpretation an

adverse the

effect” of

include drug. adverse when

absence regulations,

the an only the If the it

Accordingly, effect the includes

find effects

FDA’s drug

delivery with or

system following drug. of the of must

adverse

effect of the

was

observed investigational administration adverse adverse be properly an

administration adverse will not [See effect be

occurred considered

before as an

the

drug, the be

experience effects

drug. temporally

~ 312.32(a).] to the with drug that

Finally, therapy drug

all to and

related associated drug.

considered adverse effect

reasonably of the

called

The an for

subjects investigational dissolution the

entered

onto drug,

Dr. and stones.

Teplick’s

protocols

received a drug 2 at 62-3.] clinical approved

(,
[Trans. of
t

of

bile

Vol. Dr.

Regarding protocol

administration

Teplick’s

stated: Surgery is still considered to be the treatment of choice for symptomatic gallbladder stones and stones obstructing high-risk However, common bile duct. . . .:.- , . ‘. .,.. ,..:- . . . .?., . . .’ . ,-; , . .: ..’ .’!7 .: ,s. ,’ ,‘,. ,~-. ,,.>-!...,}”. . .. . .,.,
$ ! .! .,7’I . . :.. 1 ,< .fc >,’. > “:,( :. . .- .-.,. .’.8 { .’ . . . x.l, ;~. . . ... .---”. *,T ..:, ,., I ,.,. :,‘~ : ““;;.<.” , I .>!. .’ 1-... .... ..t. .,, ., ‘.\ ~., ..’ I .-..! : . ‘. .<.—,l. :.,,,.:*: ,+, -: .,,., y:>,-: (’. .. .. .. .,./’ .. -. ‘> ..*, :.,:: : ,, i !,, ,. ,..:., -’.7 /.. ‘ :’i. ,? . . ‘ ..’ .=! -’ : P. .a+~ ‘:’: ‘~”: ’... ,.., .:,,- ,*.:9 . . .. !’, ! I ... ..~..’.. l’,.. ;. ,> \ :., “- . .. . , .. . , . ,’ .’ “+:+$~”$”~.’?’” #’ .’: 1’ ..4. f.,,. ,. . y>,~ .<,/ , .

the

.,

.1.

. ,,.<
.-. T 1., .,., i“, “<”. .’ . ;%

. . .’.
: .,

/
..

.. <..: ... ’.14

.~

1 the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

21

patients or in those who refuse surgery, other modalities are offered, including endoscopic papillotomy . . . or lithotripsy and extraction percutaneously . . . or tube. In the occasional patient, all the methods may fail either because of difficulties or large stone size. alternative therapy in such patients, have either gallbladder and/or bile stones, is the infusion of gallstone for direct contact dissolution. [TX E at 3; see also CX 45 at 1.]

per

T-

.—

above technical Hence, who may duct solvents

According only after

to

the

protocol, were assessed

subjects to this be

were

“eligible for many of

to

receive

they

ineligible

other the subjects that them Cx the with 60 from at Tab in were

_—--- therapeutic —

modalities. study or had

For

reason, medical which [-;

Dr. either

Teplick’s serious

pre-existing

conditions excluded S= that

life-threatening, intervention. I problems to assess adverse have may whether effects

receiving

surgical my deliberations, medical ability and serious

u

In

considered have

subjects’ Dr. in the

pre-existing Teplick’s alarming

interfered played experienced

a role by the

subjects.

For

subject her

TE3,

the

Center for death more

alleged than an six

that

Dr.

Teplick to the

delayed sponsor effect that and

reporting that this

death

months

subject’s

was

alarming

adverse

_~

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

22

The 61

Center year old of The

presented woman who to medical renal disorder], atrial

documents died on

which 6/07/88 common

identified several bile the duct

subject hours stones. had

TE3

as

a an

following [Cx 20

infusion 5-8. of ]

dissolve record disease and

at

showed requiring congestive She

that

subject

a history [a with

end-stage

hemodialysis, heart had “) gram been from failure admitted the

hemophilia associated to the room

bleeding chronic

fibrillation. Hospital

(“ and had

emergency sepsis. bile to subject subject and infusion (ICU) bleed. of duct

on

5/25/88 tests two

with

acute

cholangitis that An she attempt record surgical of catheter to the the

negative common physically that “ and drugs, and the the

Further due the to

demonstrated large stones. The “a hospital poor

a dilated made

was

remove was

T—- tones. considered chemical 6/07/88, she was

reflected candidate, stones with

underwent On f of

dissolution following transferred and the a cardiac an

manipulation Intensive gastrointestinal she [Id. vomited, at Care

Unit

because Several and

hypotension hours expired after from

apparent infusion, arrest.

aspirated, 8.]

Dr. procedure the balloon

t on

a staff TE3, catheter

radiologist testified used to that

at he had

who had

had

performed

the placing

difficulty “When that I

administer much or confirmed duodenal

she

had

her

melanotic
_

stool, a bit of

that

pretty

probably which is

ilashed

a pancreatic

arcade

artery,

———

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

23

not

an

uncommon and prior six Dr.

thing

.

.

.

.“

[Trans. that the of

Vol

2.

at

93.]

Dr.

Teplick occurred 1/06/89, statement: to not her

agreed to the administration after physician GI --but [CX 20 bleed we?ll at 3.] the

apparent the Dr.

complication
---

The Teplick’s was

CRF,

dated

months ‘*This

event, thinks her

noted

hypotension

mainly + played

due [and] in

a significant due to

from never

our be

catheter sure what

manipulations role

demise.”

Dr. this, .—_

Teplick but this it at

testified: the had really same anything had

“I’m time

not that

saying this with to do with

I

shouldn’t I . . .“ I

have really still [Trans.

reported did don’t Vol. 2 not

happened,

believe believe at 64-6.]

to anything

do

Subject have effect, ~, death 45, of and _—_ as and the the

TE3 contributed

had

a number to neither her

of death. the

serious Death study informed of several the date

medical was an

problems unexpected of form Dr. for

that

could adverse or , Dr.

because nor an 54.] treatment date the of Dr.

protocols consent administration. hours of her [See several

Teplick

Teplick’s effect died with the within :; CRF was of TE3

listed

adverse TE3

[See after death the was at

CX--30~

cessation 6/07/88, 5.] In

1/06/89.

CX 20 hours of

3 and

summary,

death-

within

.

.

.

..

.

.—. — In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

24

both

a “serious

and

unexpected with since the reported the the

adverse

experience, drug. effect i.e., I

as

well [See of it the was that to

as n.

. 19

temporally at of 19.] this

associated Moreover, subject six proved the Therefore, Teplick was months its

investigational alarming adverse

death

not after

immediately, event occurred, Teplick of

reported Center

find

the

subcharge alarming this violated adverse

that adverse subcharge

Dr. effect

failed TE3’s the

report to the charge

immediately sponsor. that Dr.

death Center’s to

supported by failing

~ 312.64(b) effects.

report

immediately

alarming

_-

For failed the

subjects to

TE15 report

and the of

TE19, breakage

the of and

Center the that

alleged occlusive this adverse immediately 4;

that balloon

Dr.

Teplick used was the in

administration and should

effect to

alarming sponsor.

have Vol.

been 1 at

reported 159; CX 4 at

[Trans.

CX 5 at

14.]

Dr. the the

Teplick

testified of He device

that

some

of

the “

device or he broke

products upon

used contact with ones -

in with

administration product. kinds in of the that

!Idissolved testified products of ~’did that to

experimented which Vol. in I

several not had break written

determine [Trans. not to When result me, but

would 164.] subject He 1

presence the This

2 at any saw would

occurrence was [TX interesting Jat2.]

complications. put it on the

no

need break,

to

CRF.”

a balloon

#

----

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

25

.

Dr.

Teplick type.

testified [Trans.

that Vol.

he

would 163.]

change

the

balloon

and

use

another

2 at

The

dissolution the by Tab with . . [O]ne

or

“breakageCc was

of

the

balloon adverse

device event,

used as to

to evidenced

administer in [CX a report 60 at

a recognized , which he

Dr. G.]
s

had

submitted side

the

IND.

The , of

report none catheters by

stated: caused we the The be used ~

“Three the used vivo (

effects of material) its

occurred use was no — 11 with solvents.” problem dated dissolve composed destruction Tab D.] .

though the

discontinuance

significantly effect had been

destroyed observed.” cannot can In with addition, in in a

effect; concluded lumen or discussed Mr. of by

in stating

vitro,

report as

material r as [Id.] of 8/4/88, dissolution [~1 it

a double urinary, had

catheter enzyme the

other

biliary, Dr.

letter he but We have during

addressed stated: we had are no

to

Manilla, course, will

which

syringes, of of this . material

using difficulty infusion.”

it

with with [CX

catheters any 60 at

It

was

unclear of that with the ‘s

from effect “some

his

testimony on some of the

Dr. catheter broke 2 at

Teplick materials.

had

been He

aware
_—-. -— .

testified contact

of “

the

balloons Vol.

when 163.]

they He

came stated

into that

[Trans.

—-

In

the

Matter

of

SteVen

K.

Teplick,

M.D.

-

Page

26

he

had

first when

become he solid noticed . to

aware ‘*the . put . As

of

the minute

drug’s

interaction touches a little the a more system, are break ~

with

the syringe

device it’s and there’s
q

frozen then

we

became into the

sophisticated, we found out of [Id.] protocol form discuss at 1; TX did the use of that

started certain “ that

balloons that caused

material apparently was [See not

balloons them in protocol IND, the to the

made ~,

W*.

This Dr.

information Teplick. by

reflected The to the

clinical and consent did [cX 54

CX 45.]

submitted of 13.] ——=_ — discuss The

Dr. to form

however,

syringes consent

administer used [See for CX

A at not

Dr. 30.]

Teplick’s

protocol

these

issues.

Dr. block

Teplick the in Vol. to was duct . it to his device thereby

testified egress order 2 at the of to the

that

the

occlusive from the

balloon common bile

was

used or the

to gall drug. was not the

duct of

bladder [Trans. essential

reduce 161.] He

the also

systemic testified of the

absorption that drug, directly Although a

balloon in the did to

administration endoscopically Vol. Dr. In have 2 at

since into he

Europe

administered [Trans. essential, subjects. might producing

common notadminister or misuse of the

165-6.] used

consider

Teplick my opinion,

the the

device malfunction

of

the

resulted adverse

in effects.

greater

absorption

drug,

I

,,

.Fw, —

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

27
#

Dr. only at

Teplick in 163.] his the

affirmed presence The possibility

that of

the the. of

breakage investigational such or the an

of

the

balloon drug.

occurred [Trans. Vol. in Cx risk, to the as 30; 2

event consent was

was

not

discussed [-;

either Cx the 45.]

clinical Since of the the

protocol use of the

form. not without risks been CRF. result TX J

balloon introduced

and

breakage the

balloon of both of for

unknown should TE19 did on not [see have the

subject, an adverse the

occurrence event for

breakage TE15 and

reported However, in at any 2], the this the been failed [w that the while

since clinical event,
_————_ —

destruction sequelae

the

balloon two was subjects not

these

while effect

“unexpected,” did not as

“alarming.” reporting it

Therefore, to have TE19

adverse sponsor. reported mention CX 4 at the was

require an adverse CRFS had for

immediate effect, subjects

However, promptly. that 1-3 the and was

should TE15 and

The balloons 5 at unable adverse did 1-3.] to

to

dissolved TE15 that that the and the was

during TE19, breakage not

treatment. I find of

For prove effect that not all.

Center an

balloon

Q’alarming ‘$ it effect not

reported of the balloon —. indeed, was tie

immediately, an “adverse was Centergs to

prove that was at that Dr.

breakage

reported Thus,

promptly;” this subcharge

effect the failing
— —

reported charge

supported by

Teplick this adverse

violated effect.

~ 312.64(b)

report

promptly

Regarding

subject

TE4,

the

Center

alleged

that

Dr.

Teplick

failed

------- In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

28

to

report

-the

alarming

adverse administration

events of

of

severe

hyperten~ion

and

lethargy

following

Subject “malignant congestive medications disease

TE4

was

a

62

year “

old severe She

woman,

who

had heart taking

a history disease, multiple and

of and

hypertension, heart to at the failure. control time of

valvular had been

both her

her

hypertension on

cardiovascular (CX 17 at 6.]

admission

12/13/87.

A radiology pressure]
——._ —

note

on

the

hospital increased

chart during

stated: study today.” that the to

“The

BP

[blood

paradoxically so decision hospital

approximately [CX 17 at 30.] became

240/110, The

made

to

hold reported and at then 4.]

subject’s

record ‘ was] held

~tPatient No

sedated, significant effect

restarted.

on

BP.”

[Id.

Dr. this past

Teplick subject’s medical

testified blood history observed significant, [Trans. attending Need better

that pressure, of during or Vol. the

he

did

not

report in he view did

the of not of

elevation her believe was to by the the

of

because

significant that the

hypertension, the that 2 at

elevation c~.inically hypertension. Cardiology “Suggest:

‘administration contributed 181-2.]

A note admission,

day

following . . .

stated: 17 at 28.]

BP control

.“

[CX

‘—=

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

29

#

Hypertension, of 30, 45, in the

however, protocol For this

was or

not in

listed the study

as

a known consent

adverse form.

effect [See CX been prior to

& 54*] an

reason, reaction.

hypertension TE49S blood

should

have

considered was during had [See

unexpected as

pressure increased Dr. side

recorded to

220/90,

which

“paradoxically . as a

study characterized CX 17 at

[approximately] this 3.] adverse

240/110 event

Teplick effect.

I

consider range of

a

change of 90 to

in

the the

diastolic hypertensive systolic

blood range blood of 17 at the further in the an 28.] basis

pressure of 11O

from mm Hg, (220),

the in the

normal

presence occurring to be an

a high the

baseline

pressure investigational Moreover, of the

during “alarming” in blood decision 4.] was Given

administration event. pressure to that (CX formed

agent, this treating of blood

elevation physician’s [Id. at

withhold the change the an

administration subject’s Of experience,

pressure the change

“associated occurred

11 with was

administration adverse been reported

, and

that

alarming have

TE4@S to the

severe sponsor.

hypertension

should

immediately

The
.=.

Center of

alleged lethargy as

that for

Dr. TE4.

Teplick Sedation,

failed which

to

report might

the also

alarming be was

effect

characterized

“lethargy,”

“sleepiness,”

or

“narcosis,”

In ——.

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

30
.

experienced received 27-30. protocol into toxicity Dr. effects,” effects. informed received —. ‘o — — which but the ]

not

only (e.g.,

by TE8,

TE4,

but

by TE25,

many

other

subjects [See in Dr.

who CX 60 Teplickts infused , without by at

TE21,

TE15, to

TE16).

However, stated: biliary or

the

only

reference [ 4 patients ]

sedation been

l~Recently~ tract in

has at

successfully

narcosis.” to the did IND not

[CX listed state at 5.] [See other

45

at

1.]

The

protocol of was

submitted with one of systemic those in the

‘absorption that “sedation” is

[See consent

CX 54 form.

Sedation CX 30.]

not

mentioned subjects the

However, during also be

often procedures

analgesics sedation, while as an I

and or find

medications 11 could TE4 ‘s it adverse lethargy should effect.

‘:lethargy, that effect,

attributed. have been CX 17 at 3.] been

~’herefore, reported characterized

should not have [See

adverse as an

alarming

On TE4’s sedation, effect the CRF of

CRF, but severe listed

Dr. he

Teplick failed to

noted mention

the

subject’s the subject’s at of of 1-3.] the

adverse

effect adverse

alarming Specifically, four treatments. were

hypertension. “mild sedationlf sedated’f overall [Id. at

[CX for

17 three

.

treatments, [Id. as at “minor!~ 2.]

and This side

“heavily subjectfs effects.

for

one adverse

the effects

reported

3.]

F

— erefore,

I

find,

that

although

Dr.

Teplick

adequately

recorded

— ‘~--

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

31

v

TE4fs the

~tlethargy” severity of

as TE4’s

“sedation” “hypertension” with the the Center

on

the

CRF, as an

he

failed

to

record

alarming of subcharge alarming Thus, Dr. this

adverse . that adverse this violated For ‘-- these Dr.

experience reasons, Teplick effect subcharge S 312.64(b) adverse I

associated find that to

administration proved the TE4’s the charge sponsor. that

failed of severe

report hypertension the

immediately to

supported by effect. failing

Center’s to report

Teplick alarming

immediately

The ———__

Center

alleged

that atrial treatment Teplick]

“Subject fibrillation, with reported I Dr. interpreted Teplick of

TE21

experienced and in October PVCS this failed and charge to report atrial

chest

pain, balloon

PVC’s, deflation 1986. cRF.lt the the and

hypotension, during You (CX Center alarming occlusive [Dr. 35 at

occlusive and chest to

November pain mean on that the

only

2-3.] that

alleged adverse balloon

immediately fibrillation,

effects deflation

hypotension, to the sponsor.

Subject on also disease
.~=

TE21

was for

an pain

86

year to to

old a have i.e., cardiac

woman, common chronic atrial

who bile .

was duct

transferredstone. She pulmonary for [CX6at6

to was

11/18/86 noted and

due

.

on

admission

obstructive fibrillation,

cardiac

disease, several

which &4.]

she

was

receiving

medications.

-—

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

32

According dissolve right atrial monitoring Inderal Department were
Itv_tachI?

to the upper

the stones

discharge

summary: the chest be

“Attempt patient pain transferred and and .,

was would she to dose and Itsix

done

to of rapid fir :’.$ * .

3 times-but pain and and had to

complain went 12 into West .-

quadrant

fibrillation requiring IV.” of [Id.]

digitalization The Diagnostic Radiology, patient t-chycardia] 1 . No The appreciable then

high

[sic] Report (6) cc’s of PVC’S

of of the of [sic =

Request read: experienced and multifocal was

Diagnostic The

instilled.
ventricul~

runs

etat

[prematUre after be seen at

ventricular two
_ — —

contractions] of The [Id. therapy. patient’s at 8.]

then

withdrawn could

minutes time. “

effect

this
..00

cardiac

symptoms

promptly

subsided

In atrial

his

testimony, fibrillation had this he it.

Dr. as condition did not

Teplick an

stated

that experience

he

did of

not ,

report because He he found also no

adverse to

TE21 stated

prior report

her

hospitalization. because

that for

hypotension,

evidence

However, during cessation
——

the the

subject’s administration

pain of

and

cardiac and drug. dated with

arrhythmias improved Also 11/03, biliary ,

worsened following

of hospital had a

the

investigational progress notes [sic]

a Cardiology that

note the BP

in

the

commented manipulation.

subject

‘diapheresis

.-

‘a

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

33

decreased was signs reflected during

to

100 in the

systolic--now the monitoring of

increased record the same of

to the

110

.

.

.

.tc

which vital

subject’s [CX 6 at

procedure

date.
.,

14,

:;4-5

. ]

With testified ether these Vol.

respect that did not

to

the the

balloon dissolution an failed

deflation, of the effect, the

Dr. balloon

Teplick on he

previously contact replaced with any [Trans. the of

produce which

adverse during

and

devices 2 at

investigation.

232-4.]

Neither hypotension, as the known

the

clinical atrial

protocol fibrillation, effects of CRF that to

nor

the or

consent occlusive

form

listed deflation Despite medical underwent on effects,” due . ~ . ‘.” to -

balloon & CX 30.] in “poor

adverse on as removal [CX a a

[See the subject surgery, under CRF listed chest catheter

CX 45 was “ she

statement

the “reason of

condition” surgical 11/04/86. including underlying [~d. at 3.]

avoid

finally

the 5.]

stones The that

general “minor pain

anesthesia side probably

6 at

statement cardiac

“the and

was

disease

manipulation

Since

the

cardiac of

events

experienced were them both

by unexpected

TE21

during and

the life-

administration threatening,

potentially were

1 consider

alarming.

Since

they

— ‘-

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

34

associated as the discussed sponsor.

with

the

administration they should although event, promptly. Center proved effects effect the have

of

the been

investigational reported an “alarming” s deflation

agent, immediately .-adyerse .— ~~uld , I to

abovej In as been for an

addition, adverse

not

experience, also find report fibrillation deflation. that Dr. have that the

balloon’ ,, [-” that of of

reported TE21 the

1
Dr.

For

these

reasons, did not

Teplick and balloon Center’s to

alarming and Thus Teplick the the ,

adverse adverse this

hypotension occlusive the failing of

atrial

,subcharge s 312.64(b)

supported by

charge

violated alarming and

report and adverse

immediately atrial effect

adverse failing

effects to report

hypotension the

fibrillation of occlusive

promptly

balloon

deflation.

The

Center

alleged hypotension with

in

the during, You

NOOH:

“In

September, cyanotic report nails these

1987,

subject

TE25

developed treatment on the

and did not

following, alarming effects

CRF.”

[CX

35

at

3.]

Subject chronic transferred shock

TE2S

was

a

94

year

old

man disease

with

a past and

medical

history He had

of been

obstructive from obstructive

pulmonary another hospital jaundice.w

emphysema. of

with [CX

a diagnosis 14 at 3 & 11.]

“septic

and

Dr.

Teplick

admitted

that

hypotension

or

cyanotic

nail

beds

were

_—

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

35

.

not

recorded from

as the

adverse subject’s

events, heavy

because sedation

he

believed or his

these history

effects of

resulted chronic Vol.

obstructive 2 at 240; see

pulmonary also CX 14.]

disease

and

pneumonia.

[Trans.

The

hospital

report drug into the . The the

noted on

the 9/14/87: bile [sic]

administration “ duct around was was subse~ently [CX “The mild

of

the was

investigational instilled calculi breathand blood _-—._ 9/16/87, to evidence of of .

common odor or t

several noted on

biliary the patient’s due On stopped with the due to

.

[sic] pressure

procedure to

stopped 14 at 17.] was

diminishing was administered

100/50.” again: and was

study

patient The

sedation patient

hypotension from SinCe subject’s an

a blood

pressure department infusion hypotension experience therefore, adverse reported

90/50. in stable

discharged at of 18.] the was

condition.” as the “ have with been s

[Id. a result hypotension the reported

was

discontinued and sedation,

combined

adverse drug and~ CRF as was an not

“associated should effect. on his

investigational promptly TE25’s 2 & 3.] on

the

[See cRF.

312.64(b).] 14 at

hypotension

[CX

Although
__—__

the

subject

had cyanosis was

significant of the by nail the

pulmonary bed, Center no

disease

which of its

co-inmonly cyanotic

produces nail beds

doculnentation in either

produced

___ the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

36

exhibits following the bed, beds. subject

or the

testimony. infusion did to 14 at not be exhibit due

In

fact on

the 9/16/92

hospital

progress

notes stated of of the the that nail-– nail .— ~ .Y.~

specifically [thickening or ~tcyanosis” ..

l~clubbing’l hypoxemia]

thought [CX

to

58.]

The with

subject’s a notation

CRF of

recorded “heavily as an

sedation sedated” adverse

on for effect.

both

procedural but final

dates, failed page [CX 14 to noted at 2 &

9/16/87, The effects.

mention that 3“1 _————_ Therefore, promptly CRF. Teplick adverse the

hypotension subject

experienced

l~minor~l

side

as

stated

above, as an

Dr. adverse

Teplick effect the

should to the

have

reported in that the the Dr.

hypotension Thus , this

sponsor charge promptly

subcharge s of 312.64(b) hypotension

supported by for failing

Center’s to report TE25.

violated effect

subject

The

Center

charged and dislodged

that junctional during

subject

TE8 rhythm,

developed and with on the CRF, above that

chest the It and listed

pain, occlusivealleged that Dr.

atrial --that -

fibrillation, balloon only Teplick adverse .— the

treatment been noted all of

chest delayed effects

pain in to

had

reporting the sponsor.

the

alarming

-~.

In

the

Matter

Of

Steven

K.

Teplick,

M.D.

-

Page

37

TE8

was

an

83 heart

year

old failure,

woman

with

a past myocardial

medical

history

of and pain recov~red c ._ =.f.~ for the from on

congestive atrial 3/22/87” from removal another stones. cardioactive

three “who had

infarctions, sudden 12.] epigastric She had

fibrillation, [actually cholangitis, of common

developed [CX she 9 at had

3/02/87]. and bile to time of 1 because duct on

ref’used was

surgery transferred

stones, 3/05/87 to

TE8 for

hospital At the

nonsurgical she was

removal on multiple

of

the

admission

medications.

A procedural
_— —

sheet of chest

stated heaviness. . . .

that ‘7’ . ~~ which (“NTG”) to infuse

on

3/11/87, on a 1-10

the scale. with at 26

subject

had

an on

I!episode the [EKG]

QRS changes two doses An day; was on of

monitor

resolved . [Id. was

sublingular ~unsuccessfUl however, relieved 3/12/87 records MTBE study noted: ~
.——.

nitroglycerin “ the by was did attempt

& 38.] the next which “The

made

subject NTG and probably show $ that

again lidocaine. cardiac the

experienced The and not CRF

chest reported

pain,

pain ,“ The hrs halt for = “with”]

related discontinued:

to “3 forced sheet [“cum” [~d=at

was level of Another ~ some
q

1/2

of to 3/12/87 NTG

. .

. .

. .

[decreased] .“ CP [~d. [chest at

consciousness procedural relief
.mm ‘q

8.J pain]

“much

c

junctional

rhythm.

Stopped

10.]

The

Center

produced
!-.

the

subject’s

CRF,

which

had

been

signed

and

.—-

In

the

Matter

Of

SteVen

K.

Teplick,

M.D.

-

Page

38

dated the

by

Dr.

Teplick 3/17/87 subject 3/11, 3/11/87 and

on

11/24/88,

more from five the [Id.

than

18 [CX9

months at3

following & 12.] on 3/”06,

subject’s the 3/10, the stated:

discharge underwent 3/12/87,

Although 3/09, omitted The CRF

infusions Center at pain 2; -D/c . noted infra

of that Charge the

Cl?F,had , .— ~ IV.4.] and Pt

infusion. of [with c chest

“Because

probably [discontinued]. 1 remaining

cardiac

arrhythmia [Patient] [Id. at 3.]

[,]therapy was discharged

] [“cumn-

was with]

GB stone.”

Even prior

though to the

TE8

had

a

significant of cardiac infusion of

history r the

of

cardiac

disease an was product on more than was Teplick he also

administration of related her serious to the For I, the it that the infusion these

subject

experienced which

exacerbation temporally and one which occasion. .Sf report to I

abnormalities, of the to this that investigational be halted

caused

reasons, find event

adverse not only on

experience did the Dr. CRF, For

~falarming fail failed reasons, subcharge S 312.64(b) effects
__————=

therefore, adverse

to

adequately to the

report find supported by of at

immediately the the Center Center’s to the report

sponsor. its that

these Thus, this

proved charge

subcharge. Dr. the Teplick alarming TE8.

violated adverse

failing least

immediately pain for subject

chest

Regarding

subject

TE16,
.

the

Center

alleged

that

Dr.

Teplick

=~= :he Matter of Steven K. Teplick, M.D.

Page

39

effects failed lethar9Y, to ‘report sedation, promptly and the pain. subject’s adverse

of

..—
.

TE16

was

a 67 biliary

year

old tract

woman stones,

with

a Past

medical ..

‘iStory diabetes,

‘f ._ ~t. and

,

insulin-dependent recurrent two she had also [CX resection for chronic pancreatitis. undergone 2 at 7.]

myocardial

infarctions;

a pancreatic

‘tThe Regarding patient sedation, had either stone. administration to increased diagnostic of but was was .“ [CX2 the [sic] The subject~s dissolution patient of somnolence.” re~est , the arousable terminated at 14.] patient at all after and [CX report became times. 1 hour 2 at stated: increasingly The due to increasing 7.] In ??During the became and increasingly it was somnolent after medical [sic] record on June stated: 2 for the

common duct —-—_ — during — the one hour

terminated

due the

additiOn~ administration somolent administration somnolence

Regarding re~est complained Service _—_ acute 14.]

the and

subject’s report stated:

pain

after WFollowing

treatment, the abdominal perfomed. procedure? pain. The

the

diagna-stic the subject prima~ no

The of was changes lower called or chest and any an or upper

EKG showed ‘t [CX

EKG was from

2 at

change

the

previous

exam.

~.. -—

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

40

.

Dr. from the

Teplick .

responded This was

in

writing on at 5.]

that the

IsThe CRF.

patient No pain

became occurred

sedated from
. —-

reported [TXJ

infusion.”

However, 1/09/89 sedation cannot effects that the be

according (two was and

to one

the half but

subject’s years lethargy after

CRF, she and

which had

was received were

signed

on )/ This

reported, as

pain

not. adverse

regarded the

“prompt” , In was the been

notification addition, undetermined, pain, promptly since

of the and this to

the

to

sponsor. of pain to also

evidence the drug

showed was effect of

source related have

temporally pain should

subject’s reported

adverse the

sponsor.

For

the

above

reasons, to promptly in the

I

find

that its adverse Thus,

the

Center

presented that Dr. Teplick by the TE16

sufficient failed to the to

evidence report

support the

subcharge effects

experienced supported

sponsor charge

CRF. Dr.

this violated

subcharge s

Center’s

that

Teplick

312.64(b).

Regarding failed to

subject report due

TE22, promptly to the

the to

Center the

alleged sponsor effects

that that of severe

Dr.

Teplickwas pain and

-

discontinued nausea.
_—=

adverse

TE22

was

an

81

year

old
. .

woman

who

was

transferred

from

another

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

41

hospital pain, to be

with shaking a bit showed (Id.~

a two-week chills lethargic that she and . .

history fever, . .C~

of having [CX

“vomiting, been 26 at of ..

nausea, found 12.] 104°F by Her the

abdominal family

hospita-i

record to

had

a temperature

upon

admission .-

The dated pigtail

subject 3/16/89

received stated: but point [Id.

two “ thi,s the at

infusions

of was

A diagnostic attempted for severe via

report the 10

installation was only tolerated developed On the lasting no stated . [TX

catheter at and which

approximately abdominal day, TE22 and at 15

minutes pain
-

subject 22.] of experienced Dr. Teplick

nausea.t~ a second

following up nausea. that Jat5.] to

received minutes, In his

infusion which she

1 hour [Id. the

during written was not

23.]

response, related to

subject’s

nausea

the

Regarding that added: her

TE22’s pain “The was pain saris she 3/16/89 the and pain.

pain

during as was

the “+3” probably adequate anesthesia. report for only on

treatment, a scale due of

the 1 to to

CRF 4,

stated with an

recorded on 3/16

mostly

catheter [CX 26 As TE22 to both stated: dose of at 2.]

manipulations Subsequently, above, tolerate . — nausea “This the

[without] had epidural

anesthesia.” [~d. stated minutes Dr. the at that due Teplick first

3.]

noted could

diagnostic treatment In his

also 10

written

response, pain with

patient

[TE22]

experienced .

_=#==%*

111 the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

42

which

was

reported

on

the

CRF.” .

[TXJ

at

5.]

While the

the initial

CRF

for

TE22 of

did

mention was nausea.

pain, discontinued [CX 26

it

did as

not

reflect

tha-t of :.?,) .— %he the for

infusion of not the record pain

a result In fact,

severity CRF did the

and that

at

1-3.]

the

subject [Id.

had ~

experienced

nausea

infusion

on

3/16/89.

Although experiences
.-

TE22

had

a history temporally

of

pain in

and

nausea,

these with the infusion.

adverse the drug [Id. or effects, the the IND subcharge the Thus, this violated I

were severe

noted cause facts, to have that

association of though the reported proved

and at

were 12

enough Given

to

cessation even prevent been the

& 22.]

these

analgesics adverse to

anesthetics find that

were these Therefore, because effects supported

administered events I Dr. of pain the should find Teplick and

sponsor. for TE22,

Center to to the report

failed nausea

promptly

adverse subcharge

sponsor. that Dr.

Center’s

charge

Teplick

~ 312.64(b).

Regarding failed and to

subject report

TE23, that

the

center was

alleged

that due

Dr. to

Teplick extreme nausea

discontinued

decreased

blood

pressure.

:~

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

43

hypertension
q

and

diabetes, and antibiotics

as

well

as would

“pain relieve

with his

shakes pain

and . .

fever .

*9 25

Hydration at 10.]

.“

[CX

.

.-

~ .*,. -—

A radiology performed became was 18; for

note,

dated

3/15/89, 30 with the ~0

stated, minutes slight procedure In at drop at

‘C which in this

installation time blood point.” the from patient pressure. [Id. Anesthesia 138/75 to It at

approximately nauseous terminate at 6,

extremely to jd.

decided see also showed during

& 52.] pressure

addition, decreased

Record 90/60
.—.

TE23CS the

blood

infusion.

(Id.

at

23.]

In

his

written a

response, short course because

Dr. of he

Teplick which thought

stated was were

that

TE23

had by the

“received anesthesiologist

discontinued using ‘C

we

[TXJ

at

5.]

Howevert pressure termination experi.mced sponsor.

the during

subject the drug. TE23 supra.]

experienced administration As should disa-ssed have

nausea of for been

and

fluctuations res-ulting in

in the ‘“ to the

blood

of by [See

TE22, reported

the

effects

promptly

.—.

On the

CRF,

nausea-was

recorded

as

“O”

on

a

scale

of

1 to

4

[CX

-

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

44

short procedure

course was

of concerned

because about

anesthesiologist his cardiac

present status.st

during [Id. at 3.]

Therefore, that Dr. was pressure. that Dr.

I

find

that failed

for to due

TE23 report to

the

Center promptly nausea

proved to the

its

subcha~~, .— that blood charge

Teplick discontinued Thus, Teplick

sponsor decreased

extreme

and the

this violated

subcharge

supported

Center’s

~ 312.64(b).
, * * *

_—-—-

~ find surcharges. reasons, number such June

that

the

Center I

sufficiently also wish to

supported note that

the for

above a variety to One support of ‘tOn of a

However, the of its Center

presented listed TE7,

insufficient under in Charge the

evidence I. Center

surcharges was subject with low and subject TE7

example alleged:

subcharge 5, 1987, and of these

which to her

returned pressure.

hospital This subject ICU. CRF.tS

room also You

very had to at2.]”

lethargic periods report

blood

apnea

was

transferred effects

to on

the the

failed 35

alarming

adverse

[Cx

TE7

was

an

82

year

old and

woman heart

with disease.

a history She

of had

insulin-dependent been transferred to

diabetes

mellitus

--

1.1, che

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

45

.

The patient no

discharge remained

summary stable [Id.] occurred following

denied

any

adverse her the

experiences: postoperative course stated the on , TE7ts of 118/75, [Id. was was at with ..‘ts.Pme radiolc$g~ [Id. ,

throughout However,

complaints.” had

nursing return of of

notes from

apnea”

upon the the

the

subject’s

department, at 14.] Prior was

a~ministration

6/5/87. blood and 11.] as she When

to

administration to be in the her I blood the

pressure remained returned 98/48”;

recorded

range

stable to the

throughout floor,

procedure. pressure

she

recorded

“110/58 and the was

Narcan(a “became more to [Id. at

narcotic responsive the 15.] ICU

antagonist) . where . her . .“

administered [Id. at 14.] was

‘—~- ;ubject then as

She

transferred 154/60.

blood

pressure

recorded

In that from

a written she was

response, mildly She records narcotic her

Dr. sedated was

Teplick

stated: from in subject Narcan, was

“My

records

indicated

questionably awake and that alert the

questionably several hours.” [TX a rapid that a narcotic the from the the “

narcotics. The to cause rather failed the of

Jat3.] response likely agent, Center —_

showed

experienced indicating of Therefore, resulted therefore, failed to

antagonist, effects

adverse the

a result drug.

than to of been Centerts

investigational that this adverse

prove the

effect drug which,

administration should support have the

investigational Thus that , this Dr.

reported. charge

subcharge Teplick

violated

~ 312.64(b)

.~=

III

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

46

by

failing

to low

report pressure,

immediately and apnea

the for

alarming subject

adverse TE7.

effects

of

lethargy,

.--

*

*

*

.+

! .— .-— ..$

,

,

Throughout of many of

the FDA’s

hearing

Dr.

Teplick affecting This
,

testified clinical does I not

that

he

was

unaware of from

regulations new under drugs. FDA’s Teplick alarming TE21,

investigators absolve for the by him

investigational responsibility stated “—’ ceport subjects promptly TE15, above

fact

regulations. violated adverse and TE25,

find

reasons failing by report to

that

Dr. the TE8,

~ 312.64(b), effects and by by at

immediately TE3, the TE19, TE4, adverse TE16,

experienced failing least to subjects

effects TE22, and

experienced TE23.

*

*

*

Charge A.

11: failing

Dr. to

Teplick have

violated continuing

s IRB

312.66 approval

by: of the study. .

The

protocol [“CHS”],

approval the

form “IRB”

issued at Drc

by

the

Committee institution

for

Human read, as

Studies follows:

Teplick’s

This approval is given subject to the committee’s absolute right to monitor this Any failure project at any time it sees fit. to fully cooperate with this Committee on this aspect will result in the immediate

.-.

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

47

_——-_

withdrawal of approval and prompt notification to the proper agencies or authorities. You are responsible for advising the Committee for Human Studies of the date of activation. If the Committee does not hear within one year, it will be assumed that the project was not activated and approval is automatically withdrawn. If it is activated, there will be a review by the Subcommittee of the Co-tiittee for Human Studies concerning the progress and continuity of the project at least annually, but more often if the Committee so directs. Forms will be sent to you which must be immediately filled out and returned to the Subcommittee. Failure to do so will make the project ineligible for reapproval and no other projects will be considered by the CHS until compliance is complete. Also note that any radical changes once the project has begun, must be submitted in writing to the OGC [“Office of Grants and Contracts’f] and adverse reactions must be reported to the CHS . All signed consent forms must be retained and available for CHS review for a period of five years following the termination of a project. Further, a final progress report must be provided to OGC for their records. 38; CX 42 at 2; CX 43 at 2.]

.f ‘ ‘d I

-

[CX

1.

The Center alleged consent form19 to

that conform

Dr. to

Teplick failed to modify his IRBSS requirements.

his

An

internal

memorandum University,

from dated until possible

the

Office

of stated among

Grants that other of the

and the things,

Contracts IRB “tabledt~ deleted in

of

3/12/86, he had,

Dr. the __—_

Teplick’s reference

protocol to the

effectiveness

19

See

also

infra,

Charge

VII.

— -----

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

48

paragrzph [CX36 at

3 of

the

‘~Purpose

of

Research”

section

of

his

protocol.

1 & 2.]

Dr.

Teplick

submitted dated concerning 3/27/86, the at

a response which effectiveness The

to stated

the

Office that of the he

of had

Grants

,.

~d > $.* the 37 14 at

Contracts, sentence 2; see

“deleted
II

[CX

also forms, the in

CX 38

5.] from

Center, to

however, 4/10/89, the

presented all drug of will which

consent contained effective

dated statement:, your

5/19/86 “We [Cx feel 30.]

still be

that

probably

case.”

Although comply Center report thereby thus have had ,

the with records form

Center this

demonstrated requirement from IRB his IRB

that the sent on

Dr. IRB Dr. both

Teplick for

failed

to the

approval, Teplick an and

showed and approved his

that

had

annual 8/10/88,

study approval its for his on

5/6/87 8/10/89.m

continuing failed continuing to

until charge his IRB

The Teplick fact, study Dr. and

Center, did not

substantiate IRB even approval after forms this

that study.

Dr. In his

Teplick

IRB

approval his find

audited [See

examined I do not

consent that

1/23/87. supported

CX 53.] Charge

Ther&fore, 11.A.

subcharge

——_

20 clinical letter

As discussed below, the Center placed Dr. trials on clinical hold for the reasons in a letter dated 5/25/89. from Dr. Fredd,

Teplick’s expressed [Cx 40.]

in

a

4

--—- :n

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

49

2.

The his IRB

“Center alleged IRB after five approval.

that Dr. subjects,

Teplick failed as required

by

to report the terms

back to of his
. ..

The stated: Dr.

Center

presented “the protocol report before responded

a document is back to then the with

of

the

IRB with

dated the

4/09/86, condition completing

ihich .— =.!,. that five 2.] in the “Yes, [Id. at Dr.

approved Committee the to dated to you study.” Mr.

Teplick

after

patients Teplick Office we will

proceeding in and to

[CX

38

at

a memorandum Contracts, back

of be

Grants glad

4/21/86, after five

by

stating cases.”

report

3“1
.—= _-

Dr.

Teplick’s

IRB Review

reviewed of site Projects visited for

his

project, of the on

and Committee 01/23/87

the

Subcommittee for at Human 10:30

for Studies

Continuing (part 53 of this at of 2.] the

IRB) The

him the

a.m.

[ Cx Review in

minutes on Dr. he he no

Subcommittee “Six was subjects

for

Continuing were the enrolled Committee to report the

Projects study .

stated . .

02/11/87: Teplick

reminded a written patients. seen.’l

that report This

stipulated Committee due. There

that after were

was had

to seen

submit five

“is-”now-

adverse

reactions

[Id.]

From _—_

the

hospital

record, to a

it seventh the

appeared subject, IRB site

that TE9 visit.

Dr.

Teplick 11 7 at a.m. 15 and & 17;

administered 3 p.m. directly

between [CX

following

-

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

50
.

see ——

also

id. was

at

29.]

No to

documentation the IRB prior For subcharge five

of to this that

the the

initial

five of
..

subjects to the report terms

submitted additional

administration I Teplick required find that fa~leh,t~ by the

two

subjects. its IRB after

reason, Dr. as

Center back of his

substantiated to the IRB

subjects,

approval.

However, demonstrate Teplick stated ___—_ -act

as

with how

the this to have

previous subcharge continuing did knew after

subcharge, supported approval have that five

the the of

Center charge his IRB violated as still did

did that study. approval. his noted

not Dr. As The

failed suprat that his to his his as

Dr. IRB

Teplick already back 1/23/87

continuing he had patients, but

stipulation audit approve ~ 312.66 by

report IRB on

in

the to

[see

CX 53], that Dr.

continued not violate

study, alleged.

demonstrated

Teplick

Since Center’s that IRB

neither charge Dr. Teplick

of

the as

surcharges stated, s I find

under that by

Charge the failing

11.A. Center to

supported failed have to continuing

the prove -

violated his study.

312.66

approval

of

*

*

*

the ——m.F—

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

51

Charge B:

II: failing to the

Dr. to IRB.

Teplick report

violated promptly

S 312.66 all changes

by: in research activity .—

The

Center

alleged Advisory

that

Dr.

~

Teplick of the

failed University FDA had

to

report of

to

the

Human (also

Research an for and IRB) ,

Committee 1) stones to human the stones

the bile

following: duct risk suspended

that on

placed hold 2) due that of (3) infom the

the to FDA

protocol unreasonable had of FDA had

common significant

clinical subjects; study

specifically the common all that bile

p’reposed with consent

dissolution that the

duct the

and forms to

required ..—=—.. >ubjects

of

potential

a death

had

occurred.

Neither the letter in the

the

Center, Prior 5/25/89 to the

nor to

Dr. the

Teplick hearing, to Holdt’ the

addressed the Center sponsor, on the

this had Dr.

charge submitted

during a

hearing. dated

addressed “Clinical

reference study:

common

duct

portion

of

We ask that you not enter any more patients in the common duct portion of the stiudy until we have received the details on the patient (TE-3) and notify you that it is safe to proceed with the study . . . In addition we believe that you should modify your consent form for all protocols to advise potential subjects that a death has occurred . . . . (CX -_ — — 40 at 1.]

.-

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

52

The

sponsor the

responded following I

to

the

agency

in

a

letter,

dated

6/1/89,

providing

assurances: . . ‘:~,,.,

spoke to him [Dr. Teplick] on the it was his last day at yesterday, Teplick 1 have notified Dr. 80 is not to be used for the . that ~r~atment of duct stones until we receive permission from your office. I have also sent them [Dr. TepliCk other investigators] a copy of your indicating the necessity of notifying office quite promptly if there are effects. (CX 41 at 2.] and the letter, your any side

[W]hen telephone

._= —

Dr.

Teplick,

however,

had

signed

an

affidavit

on

7/31/89, who FDA

stating:

Wilson [FDA investigator On 7/27/89, Inv. obtained the affidavit] informed me that has instructed that no more patients be entered into the study that involves the dissolution of bile duct stones with I had not received AS of 7/27/89, communication from Sponsor/Investigator, “clinical regarding this He telephonically subject entry. but I cannot recall exactly when. [CX 41 at 1.]

any written , MD, hold” on told me,

In

a written

response

submitted

at

the

hearing,

Dr.

Teplick

stated: The protocol University limited to The [ IRB at [for of GB the [t’gall University “] . submitted to the IRB is specifically bladder”] calculi. of is aware

.-=>

that

the

.~. —

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

53

use of in the ductal system has been suspended. (If you wish I will have them call you) . I was not aware that the consent form required a statement that “a death occurred”. My understanding was that the cause of death was under investigation and that it had not been established that was the cause. [TX J at 11; see —— also n. 20 at 48.]

.--

Dr.

Teplick

also

provided

an

addendum:

Dr. and the IRB at were informed that could no longer be used in the common bile duet. I informed them of this personally in a meeting and should there be any question of this please contact Dr. in the department of medicine. That the FDA required all consent forms to inform subjects that a death had occurred: I had no knowledge that the FDA required this information on the consent form. Furthermore, we can only use in the gallbladder and this was a death that had nothing to do with the gallbladder. [TX V at 21.]

The that

Center Dr.

did Teplick forms In to

not

produce had received the the that interpreted information. demonstrated

any

additional notice that of in the

evidence the agency

to

demonstrate required his

consent protocol. sponsor-. . . . It

mention

occurrence wording

a death Center~s you

on

the to form option the

addition,

letter

~cwe believe --might be such

you

should that

modify Dr. [CX 40

consent had Dr. aware the

Teplick at 1.] been

not — -.:tions,

to

include however, hold”

Teplick’s of duct the portion
,

that had placed

he

had on the

“clinical

the

agency

common

—— ~ the —

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

54

of the and

the

protocol. activities to IRB. at

Since

a on

“clinical his this clinical

hold”

represented study, to ] Dr. he the was new

a change required,
----

in

research he

proceeded

convey [See

information

institution’s presentation constituted

~ 312.53(c)vii. of the new of

Teplick’s IRB

? ._ -- , )..

a meeting

institutions the required,

reasonable

notification

information.

Under

~ 312.56(d),

when agent

a sponsor an letter to notify

determines undue to safety Dr. all in the [See unaware form, been IRBs

that concern, , and it the

an which is the was

investigational addressed sponsor’s F—-- ~ho have in the

poses

agency’s

responsibility at any time of Dr. included that by Dr. the an

investigators of ] death to the

participated investigation. seemed consent had

investigation ~ 312.56(d). that and the the

discontinuance Nevertheless, should establish requirement be

Teplick in the

subject’s Center failed of this

Teplick sponsor.

dutifully

informed

For

the

above the his his

reasons, IRB study, of the and forms that did

I

find University

that

Dr. of

Teplick

adequately of the clinical to -

informed hold modify Therefore, Thus __——_ replick , this on

that

he

was

unaware that did not the to

of

a requirement had this occurred. subcharge. that all

consent I find

indicating the not by Center support failing

a death prove Center’s report

subcharge

charge promptly

Dr.

violated

~ 312.66

.

----

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

55

changes

in

research

activity

to

the

IRB.

*

*

* .. ? -. ,} . ,

Charge

11:

Dr.

Teplick

violated

~ 312.66

by:

c:

failing problems

to

report involving

promptly

risk

to

to the IRB all human subjects.

unanticipated

~ an —-_

unanticipated adverse or experi

problem .ence

involving which is not form health protocol instances intractable the at Dr.

risk,

as

explained in be the

above, study’s

is

mentioned that could

protocol threatening ~ 312.32(a). Procedures” discontinued: evidence demand physician. listed the of

informed or ] have Dr.

consent serious Teplick’s listed pain, around and at 6.] possible blood tests and

potentially [ See

life-

consequences. in where nausea no stone the “Risk

Management would be

section severe of the a leak patient, [CX 45

infusion and vomiting,

catheter, the

dissolution, of the attending form -from bruise, [CX 30 at 3.]

on

recommendation informed

Teplick’s side effects:

consent

following in the

discomfort bleeding,

venipuncture blood clot,

(excessive and

infection),

nausea

vomiting.

1.

~~There

is

no

doc~entation

that [CX 35 at

the 5.]

death

of

SUb~eCt

TE3

WaS

..—_

reported

to

the

IRB.”

_—_ —

~he

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

56

I Dr. the

interpreted Teplick IRB was the

this violated

subcharge S 312.66

to by

mean failing of with

that

the to

Center report

alleged promptly subject of an adverse was form. to circumstances under Sheet of the was death. of not [See

that to

..-

unanticipated

event associated

a death the

of

a study

that

temporally drug. represented in the at

administration death subjects consent records The described, “Survey Projects to of was that

t-h~:,,

,

investigational event and

For a risk

this to or the

reason, human

mentioned 45 at 6;

protocol 3.] subject subject’s In the The

informed presented on have the Review

CX

CX 30

Center TE3 died death

substantiate leading —. 7harge I. up to

that this

6/07/88. been annual of

[Supra.] for for which

addition,

the

Subcommittee Committee presented 44.] “toxicities section of

Continuing Studies,” to show

Human failed the

dated the

8/10/88 reporting information effects, blank.

8/10/89, TE3*s regarding

[ Cx

Although

Survey

requested side

~ idiosyncrasies, the survey had been

etc. [Id.

8**
1

$? ,

this

left

,

IIIt

In is

his true

written that I we 5.] at the

response did did No not not additional

to report

the

Center, TE3~s that

Dr. death. her

Teplick But, death as was

stated: stated due by to Dr.

previOllslyt [TXJ Teplick at

consider

information

was

produced

hearing.

~

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

57

was

at

least

temporally

related.

As

discussed to Dr.

in the Teplick Thus ,

Charge IRB” failed this

I,

SuBzQt Therefore, report supported by failing

the death
I TE3’s the to find death

should
the to

have been
proved IRB, as that to human

rePorted that required. Dr. the

Center the

--to

-s~Gharge ~ 312.66

Center’s report

charge promptly risk to

Teplick IRB all

violated unanticipated

problems

involving

subjects.

2.

“On January 23, 1987,. you reported ‘no adverse reactions had occurred. on September 26, 1986, an occlusive on August 18, 1986, a t--tube and dissolved (TEIS); on October 31, and on November 3, 1986, subject and PVCS” [CX 35 at 5.]

verbally to the IRB that ‘ Medical records show that balloon dissolved (TE19); two occlusive balloons 1986, subject TE21 had PVCS; TE21 had atrial fibrillation

I Dr.

interpreted Teplick no

this made an

subcharge oral

to

mean

that

the to

Center the in IRB,

alleged stating several to oral meeting -

that

misrepresentation had been presented had in observed, no fact minutes of that seen.” IRB had meeting

that had.

adverse Center, that

effects however, Dr. to for for no the

when

fact

The

documentation made for Projects for Dr. [CX this

demonstrate misrepresentation the

Teplick the IR13.

The

2/11/87

of -

Subcommittee acted were page, that the no

Continuing the IRB)

Review reported reactions of the

(which Teplickts 53 at 2.]

apparently study the _-—=. “There second

adverse minutes

On

stated: occurred.” did not

“Dr. [Id. list

Teplick at 3.]

reported However,

adverse of

reactions the IRB

minutes

Dr.

Teplick

.
-,

. ,.,,: i ,
.

,“. ‘“, “,...

,’I t 1.8.. , .. . . .,,. ,’

.

-

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

58

as

physically the

in

attendance Center’s

at allegation

the

meeting, remained

and

the

circumstance [Id.] .—

surrounding

unclear.

Therefore, this his

I

find that this

that Dr.

the

Center

failed made did oral not

to

suPPort

adewat.el~.~
to Center’s

.

subcharge IRB, and

Teplick then

misrepresentations support the

subcharge

charge.

3.

_—._

The Center charged that Dr. TeplickSs *’first annual report, 1986, to March 27, 1987, covering the time period from May 14, reported that nine subjects had participated in the clinical study and that there were no side effects “other than the odor on [the] breath of three subjects and one patient who of In addition, the Center became slightly sedated . . . .“ charged that the following subjects experienced adverse TE15 , reactions which were also not reported to the IRB: [CX 35 at 5 and 6.] TE19, TE21fl TE5, TE8, TE9, and TE16.

I Dr. the

interpreted Teplick IRB the

this violated

subcharge S 312.66

to by

mean failing

that

the to

Center report risk

alleged promptly to the written [CX on

that to

unanticipated The IRB’s survey, in Center survey

problems presented to

involving Dr. this by

above

listed response at Dr. 1.]

subjects. to In the this

Teplick’s subcharge. the . IRB

support received section,

42

which the

was formQs

3/27/~7,-

Teplick

reported Side (3) sedated ‘rremarks “ pts. -

llTo~icities~ the [patient] he concluded, odor of who . on became the

Idiosyncrasies, breath ——. ——slightly section of

Effects:t’ [patients], No-side

‘Other and effects,lt ‘No (1)

than pt. and

under

to

report:

complications

encountered.t’

—-

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

59

[Id.]

In Dr.

his

written

response stated: trial] of “My was

to

the first

agency annual

addressing report 8, 1987, [TX J [to after at

this the

allegation, IRB we of the ---r had used

Teplick clinical in

on

February
. . .
.

a total

6 patients

?121

6.]

In

an

earlier

version

of

his

written

response,

Dr.

Teplick

wrote:

——.

[The IRB] approved my project but never sent me any guidelines about how and when to report to them. Except, they did ask me to report after my 1st 5 patients - I did this (actually after the 1st 6 patients), and then again after the 1st 9 patients which I did I believe I reported the complications ~dor on ;c;u;ately. We did not consider the breath as a complication unless it caused sedation. We were not sure how it got to the lungs since egress into the duodenum was blocked . . . The PVC’s and chest mains were not considered to be due to .0
q

[CX

33

at

4.]

In

reviewing

the

study

records,

had

been

administered

to

6

.-

_——_

The “first annual report,” to which Dr. Teplick referred in his written response to the agency, was dated 2/09/87 and was , Chairman of the IRB. The report addressed to Dr. in a total of “We have used stated: In three of these 6 patients with common bile duct stones. One was detectable on the patient’s breath. patients the of these three patients became mildly sedated but recovered was discontinued. No other complications quickly once the [Cx 39.] were encountered.”

21

_Jn

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

60

subjects, and 11/03/86.

TE17,

TE16, [Cx

TE18,

TEIs,

TE19, the of

and

TE21, of [part

between the of the

5/20/86

1 -CX6.]

From Review

Minutes Projects

Subcommittee

for

Continuing

1~]: I - ‘~-

This site visit was held on January 23, 1987, at 10:30 A.M. Six subjects were-enrolled in this study . . . Dr. Teplick was reminded that the Committee stipulated that he was to submit a written report to Committee after he had seen five patients. This report is now due . . . . [CX 53 at 2.]

On the received -~-[CX 7 at

same

day, on

it

was

noted

that

a seventh following

subject, the site

TE9, visit.

1/23/87,

apparently

2,

5

& 15-17.]

The was

clinical not

significance in the

of protocols [See CX 30, by Dr.

on of 45

the either

breath Dr. In

of

the

subjects or the the mention

addressed Dr. consent

Teplick addition, to

sponsor, informed this clinical questions the gall

& 54.] also of his of hearing,

form [Cx had the [CX is lungs

used 30.] been

Teplick IRB approval upon

failed Dr.

experience. protocol regarding bladder. “When by the

The

TeplickJs to through Dr. Teplick
rapidly

contingent

response the

systemic 36 at 2.]

absorption At the

-

stated: excreted breath. ‘aissolve

systemically and higher consequently doses result in

absorbed, would of more

90% be than

is

detectable are used absorption to

on

the

Considerably gallstones

would

systemic

and

–4-%. —

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

61

patient doses than subjects infra testified and that at

sedation were had used been with Charges that the the smell of way of in

.

. “the

.

.

11

Dr.

Teplick who had ‘s

testified common original Vol. Dr. taken several 2 at was on to

that bile

higher duct stones, f-or 135~$; :.-’*

subjects in Dr. stones. 111.B.4. of dissipate

proposed gall

protocol 2 at

bladder 11.D.2., odor would the

[Trans. .. & IV.1.] could within Vol. be

up

by hours

clothing, following ] However, or in

administration the the nose. only room, [Id.]

[Trans. whether put one’s nose

119-20. the a

discerning be to

breath subject’s

would

right

up

Regarding adverse subjects of were adverse already

the reactions TE8,

charges

of

failing risk TE16,

to to TE19~ TE8, 1.,

report human TEz1, TEIS, ~“ should to be

the subjects the TE16,

unanticipated experienced substantive TE19, most and of issue TE21 these the by

involving TE9~ TE15@ for

effects discussed I found

subjects in Dr. Charge Teplick

For have adverse

subjects, events reportable that that several the

that in the

considered events “I

described to the of

surcharges For this events

IRB. the were

particular had and TE15, not

subcharge, been reported, risk and during in Charge I.A., TE21 to

f-ound and human either

adverse

events For or which,

unanticipated subjects balloon

involved TE19,

subjects.
- — -.

example, the occlusive as

had

the

t-tube

dissolve

infusion,

previously

discussed

was J

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

62

documented dissolution human discussed informed have catheter unreported human by subjects

by

the an

Center. unanticipated the

T-tube

or

occlusive event of [see these

balloon involving events at 6] events the Or risk was-–not hi~i:a, .could t-tube Another risk to or * to

was

adverse possibility protocol

subjects, in Dr.

because Teplick’s forms

CX 45 -.. and such

consent health

[see

CX

30

at if,

3] for

serious

consequences within of the the body

example, subject. involving and in Dr.

dissolved example was TE21, [see 3] have and

of

the

unanticipated atrial was 6] not or his fibrillation

events

PVCS

experienced

subject

which at

mentioned informed

Teplick’s forms the [see CX

protocol
.—.

CX 45 was

consent

30

at

potentially from complications t-tube or in

life-threatening of catheter Dr. either dissolution first

because of these and annual

subject

could effects. events [See

died Both

cardiac the cardiac report.

the

were CX 42

not at 1.]

addressed

Teplick’s

For that events

these Dr. to that

reasons, Teplick the Dr. IRB. did

I

find fail Thus ,

that to this

the report

Center

proved of

its these the

subcharge adverse Center’s to at report least TE15,

a number

subcharge ~ 312.66

supported by failing by

charge promptly TE16,

Teplick

violated problems

the TEX9,

unanticipated and TE21.

experienced

4.

The Center charged covering the time

that period

Teplickcs Dr. from May 6,

second 1987 to

annual May 6,

report, 1988,
.

did

In .—–.

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

63

not properly document all of the unanticipated adverse effects involving risk to human subjects observed and overstated the number of subjects treated as 14 instead of 13. Specifically the Center charged .that the following subjects experienced side effects which were not reported to the IRB: TE13, TE7, TE12, TE4, TE14, TE1O, TE3, TE2, and TEII.
._ :, = .***

..

The all In

Center of the

charged unanticipated it on the

that

Dr.

Teplick

failed effects of

to the the to

document above number

properly subjects. of adverse

adverse that and To he that support

addition,

charged study,

misreported he failed this sheet

subjects reactions presented representing ..-. — tudy .

report the

some

altogether. an IRB Dr. [Cx 43.] annual Teplick’s In Side experienced

subcharge, dated 7/14/88, report” section
reported

Center as

survey

second exhibit, etc.’~

Itannual the was

of on

his

this Effects,

‘~Toxicities,
as: ‘fNone majora

Idiosyncrasies, One 43 patient at 1.]

slight

sedation.

Infusion

stopped.ft

[ Cx

In no

a written record send of

response a second

to

the

agency, report are

Dr. (May

Teplick 1987 Only [TXJ at to 13

wrote: July

“I 1988)

have . were

annual You and

Please treated

me a copy. 3~27/87

correct.

patients

between

7/14/8~.~1

6.] .

In

contrast nine period

to

the of the

reported 13 TE7,

occurrence subjects TE12, TE4, who

of

sedation

in

only

one this and

subject, time ‘—-11)

received TE1O, involving

, during TE3, TE2, risk

(TE13,

TE14,

experienced

unanticipated

problems

to

human

‘-

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

.64

subjects

which

should

have

been

reported

to

the

IRB.

For least The

example, subjects death of

the

substantive TE3 and TE4

issues were

of

adverse addressed .. associated

effects in

for”~t Char~= +_ the event l.,

already

subject [See su~ra,

TE3

was

temporally I.A.]

with

infusion. was an

Charge event of

Death risk event or his

as to was

an-adverse human not subjects,

unanticipated the possibility protocol at 3),

involving such at an 6]

because Teplick’s [see serious [see risk, in Dr.

discussed consent

in

Dr.

[see and Subject

CX 45 &eath TE4’S were

informed be

forms a very

CX 30

would severe also and [see

obviously lethargy unanticipated

considered and hypertension events

—_

event. supra, because Teplick’s forms health and annual that to report the

Charge both

I.A.] lethargy protocol

involving addressed

hypertension CX 45 and at such 6] or

were his

not

informed could and Dr. have the

consent serious lethargy second I fail Thus , Teplick unanticipated find

[see

CX

30

at

3],

events of death in For the

consequences. hypertension report. Center a number were [See proved of

The not

events

mentioned at 1.]

Teplickls above reasons, did -

CX 43 its these the failing

subcharge adverse Center’s to by at report least

that events

Dr. to the

Teplick IRB~ Dr. the TE4.

this

subcharge s

supported 312.66 by

charge

that

violated

promptly TE3 and

problems

experienced

5.

The Center alleged covering July 14,

that 1988

Dr. Teplickls third and to June 5, 1989, reported

final the

report, project

— ---

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

65 .

“terminated the n@er [TE26]) or

“ and failed to provide any of sUbjects (GL, TE20, TE23, the side effects observed.

information TE22, JM,

regarding TJ, and .—

ES

1 Dr.

interpreted Teplick

this violated

charge

to

mean by

that failing risk

the

-. to

Center report

alleged

~~at % =.-** the

~ 312.66 involving presented period received

promptly human
report,~f

unanticipated subjects. covered report Under written, ____ and been the left the was the The

problems Center approval as

to “third

above and to on

listed final 8/10/89,

this from by the

IRB

8/10/88 IRB the

but [Cx 44 was

the

stamped section

6/05/89. ‘~terminated~t the of the

q I

labeled from the

“Changes’f name of the

word study,

and

aside

the

investigator, fo~ had

above-referenced blank. [Id.~

dates,

remainder

In

a written

response

to

the

agency,

Dr.

Teplick

stated:

I have no copy of the final report. In addition, I had no knowledge that the project was terminated. Who terminated it? . . . We received no notification from IRB The IRB survey sheet was blank because ~h~e~er terminated the project had no knowledge of the number of participants or any of the complications . . . . [TXJ at 7.]

.._..

More “tried conduct

importantly, to of . . the the .

however, delegate clinical annual

Dr. some study

Teplick of and reports the had

testified paperwork” given required the by

that required task the

he

had in the

of IRB to
,

submitting

survey

his

-~

In

the

Matter

of

Steven

K.

Teplick,

X.D.

-

Page

66

secretary. gave favor 42] in, her and all go

[Trans. my

Vol.

2 at and I

44.] said, fill . . .

Dr.

Teplick Could [the [Id.] .— a high at 48.] she

testified: you do me

“ I a

raw-data this, to his the

‘okay. this .“

through send it

and IRB secretary training.

annual

rep~rt~--CX ._ ~o Dr. =.*=4

and

According school He had

Teplick’s i.e., stated submitted responsibility. no

testimony, formal he to the medical had not

had [Id. the he

education further prepared to be his and

that

checked although at 47-8.]

reports considered

IRB, [Id.

this

Although
_—_ —

Dr. report

Teplick surveys knowledge hearing report Krenzel expert

stated [see about Dr.

that CX 42; this

he

had

signed Trans. report. that survey”) he

the Vol.

first 2 at 44.] signed [Trans. of

two 44-6.], In the Vol. a [Id. 2

annual he fact, above at 48.]

CX 43; third denied

disavowed at the

[CX had .

Teplick (i.e. ,

referenced Mr.

“annual the Dr.

entered who also confirmed TX G.]

into

record Teplick’s

a report statement.

handwriting at 51-2; TX

F;

see

The

seven during

subjects the of

referenced months these risk IRB. of

in November

the

Center’s 1988 to May

subcharge 1989.

received [See CX 23adverse have been course because of

29.] effects _reported Of

Several involving to which the

subjects to For such

experienced subjects, TE23 the

unanticipated which received should a

example, by

short

was

discontinued

anesthesiologist

,

‘~

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

67

fluctuating TE23’s event of 45 this at 6]

blood fluctuating

pressure blood risk to

and pressure human

nausea. was subjects, in Dr. an

(CX

25

at

6,

10

& 52.]

unanticipated because the

involving event or his have

adverse .— possibility $~eet Such CX an by of

was

not

discussed consent

Teplickfs [see CX 30

protocGl at as the 3].

informed had

forms

event the

could attending for this

serious

health decision

consequences, to at discontinue 6, 10 & 52.]

evidenced infusion

physician’s subject.

[See

CX 25

Regardless —— Teplick all was

of

who

prepared for

the the effects I

annual accurate

report

to

the to to

IRB, the

Dr. IRB of

responsible adverse this

reporting risk the Center the

unanticipated For

involving find that supported by failing involving

human proved this charge promptly to human

subjects. subcharge. that to the Dr.

reason, this

Thus, Teplick IRB all

subcharge ~ 312.66

Center’s to report risk

violated unanticipated

problems

subjects.

*

*

Since raised Center

I

found by the

that Center that to

Dr. in Dr. the

Teplick support Teplick IRB all

violated of Charge

several 11.C., ~ 312.66

of I by

the find

surcharges that the to

proved promptly to human

violated unanticipated

failing involving

report risk

problems

subjects.
,

— -—

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

68

*

*

*

Charge D:

II:

Dr.

Teplick obtain

violated IRB

~ 312.66 approval

by: making

.—

failing to his research.

before ..

change$,-,in, .—

1.

The Center charged that approval before using investigation his

Dr. in at

Teplick least

failed 19 ! out

to obtain in conjunction of the 26

IRB with subjects.

Although 3.] —= _and

the

informed the in use the did Center

consent of r=oval not

form as of one

used of

by the

Dr.

Teplick

[CX

30

at

discussed procedures for The

alternative the this

treatments clinical approved to addition to drug.

ductal the

stones, use of drug Vol. of 19

protocol [Cx 45.]

mention the

sub~itted received

CRFS the

subjects in 1 196-7.]

demonstrate the

that

subjects drug

investigational

[Trans.

Dr.

Teplick

admitted agent, that during was of common that delivery

to

using . [See of

in

conjunction Vol. that indicated . [Id. agents required at 2

with at

the 236-9.] used the Dr. of care -for He

investigational testified his subjects,

Trans. time

the an bile he

period approved duct used

was for

drug stones the two

dissolution Teplick differences

238-9.] because nursing required

explained in to be

mainly more

systems: during could be the

and

had

administered care and

day,

while during

minimal

nursing

administered

hours ,

when

In ___ —

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

69

nursing He testified

supervision that studies therapy. that it Dr. was he

of did of

the not the [Id.

subject himself interactions at 234.] protocol used testified approval was and, and [Id. for

was

minimal. or

[Id. know and by address

at of

236-7.] any .--

perform of He

preclinical combination he of [Id. together protocol, that could were .~ I at was unaware since 237.]

continued to

stating:,that + the ~~e

the being

needed its that from his in as I

approved he used to

indication. both modify agents the that we while we said

Teplick getting ‘t[t]here do this,

without because shouldn’t observe doing the the

IRB the was

nothing as far

protocol concerned, of

positive

negative at 238.]

effects

procedure.”

Although result of

no the

adverse sequential agent,

reactions use it was produce each of

or of

other the

side

effects drug the

occurred and use of the the as could alone. two well have

as

a

approved that

investigational products alter obscured Therefore, should consent IND have form. and the together efficacy the

possible unexpected

would of

toxicities, a result agent

as

product. the in in should

Such

evaluation this been modification

investigational the both original the have study also

investigational protocol been reported and the to

plan

documented This the change IRB.

the

sponsor

_—=~erefore-, —

I

find

that

the

Center

substantiated

this

subcharge,

‘~

In

the

Matter

of

Steven

K.

Teplick,

X-D.

-

Page

70
.

and use In his

Dr. of

Teplick in

should conjunction continuing that “any

have

amended with the

his

protocol

to

address drug,

the

investigational of the once ,\ the protocol the OGC Thus, Teplick making

addition, agreement must .“ [CX the to

IRB radical in at 2;

approval

was_based project .- h~~= of the ,

on

changes writing CX 43 that at Dr. before to 2.]

begun, IRB]

be 38;

submitted CX 42 Center’s obtain

[part this violated changes

subcharge ~ 312.66 in his

supported by failing

charge IRB approval

research.

2.
———_ —

The Center charged infusion volumes in Dr. Teplick’s

that of protocol.

Dr. in

Teplick excess

routinely employed of the 5 cc limit

specified

The after

protocol the

used placement and to

by

Dr. of

Teplick this of

stated:

“Twenty-four tube, of of the the bile The for of more the that or toxic duct will

hours continuous be

[cholecystostomy] from I to 5 cc

infusion performed
q
9-

aspiration create

uninterrupted dissolution “ same (CX 45 at is 4.]

stirring documented, Common at 5.]

gallbladder infusion stones 72 a will would “

Once stopped treated

complete
q

be be

*a* the

in “NO [~d.] of into

manner. will be

[Id.

protocol than protocol, “instillation in

continued: hours.” discussion
_——__

infusion In the the use

continued section

background of in

dogs

stated duct,

of of 10 to

the cc/hr

gallbladder, . . . . “ did

common not

duodenum

volumes

20

produce

metabolizes,

.—.

In

the

Matter

Of

SteVen

K.

Teplick,

M.D.

-

Page

71

such (Id.

as at 2.]

and

did

not

pose

an

hazard

in

the

air.

.— To support the where Center’s the For 4]; 5 at 14]; protocol example, TE9 received TE5 subcharge, limit TE16 Ms. of and 15 received cc deMarco .. 5 cc TE15 [CX 50 were 7 at cc [CX presented was given 5]; 8 n~~er,ous .— by [CX 2

examples Dr. at 20 Teplick. 5; cc

exceeded 10 TE19 cc

CX4at (CX

received

and

at

5].

Dr. vol. ——_ used [Id.

Teplick 2 at was at

admitted 306.] based on He amount in put was stone in drug [Id.] the and He the

that testified size

he

used that

more tithe

than

5 cc of ductal reason injecting it dissolve

.

[Trans. that system. that we [from that stone any that the the we

amount bile] “the we were

of by of protocol]

the

[common

134.] the

continued . . the .

explaining that was

changed volumes amount in most

specified that cases on the we

because to

seemed the have

into grossly at

the

ductal insufficient

system to at

actually He

effect the

all.t? of stone, continued address than

[Id.

135-6.] improve required

explained the for Dr. the dose contact ston-e

increase the

volume the He to less

would which by the the was stating issue, volume that either

between dissolution. revised to _—— [Id. he at had

that modifying

had of

his “20

protocol percent He the

of he

the did

gallbladder.” not the believe volume that or

137-8.] violated

later protocol

testified by

increasing

---=

In

the

Matter

of

Steven

K-

Teplick,

M~D.

-

Page

72

the did

infusion not occur

rate to

of him

the to reporrt

as this

specified to his

in IRB.

the

protocol, [Id. at

so 269-70. .—

it ]

While amount

it of

may

have

been this

necessary constituted could reason, for by of the the

for

Dr.

Teplick in

to the

inc:ea$~

athe

used, plan For submitted as IRB that submitted at 2; required approval “any in CX 43

a change have he incurred should to both

investigational to the subjects. and IRB,

which t~is it

additional have the In amended IND addition, on his has the that used protocol Center’s to obtain , IRB].” the

risks his

protocol and the

approval regulations. protocol once

sponsor

continuing agreement
_—_ —-

was the

based project of find

radical writing at that 2.]

changes to the

begun, [ Cx Center of

must 38;

be

OGC [part I

CX 42 this in

Therefore, Dr. Teplick specified supported by

proved

subcharge of Thus, the this violated making

routinely in the the

volumes approved charge IRB

excess IRB.

amounts

by that

the Dr.

subcharge ~ 312.66 changes in

Teplick before

failing

approval

research.

.* * *

Since

the

Center supported

proved the Dr.

both

of

these

surcharges 11.D., ~ 312.66 in his I

and find by

both that the to

surcharges —— — Center obtain proved IRB

Center’s Teplick

Charge violated changes

that approval

failing

before

making

research.

f

.~.

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

73

*

*

*

The of

Center the

produced

sufficient and thus, I Dr. his

evidence find that

to Dr. -.

support Teplick that 2.

the

majo~ity did .— v~olate :.*=S the IRB

surcharges, At no the reviewing any radical in writing and the I find from the

~ 312.66. provided However, annual that

hearing, of

Teplick

claimed [Trans. Vol Teplick

oversight IRB sent

work. to which

at

45-9.] its note

information

Dr. clearly

regarding
WAISO

requirements, changes to once the

stated: has of begun

the

project

must and to the For

be

submitted Contracts”]
— —...

OGC [“Office must at be 2;

Grants

adverse [CX Dr. IRB an IRB.

reactions 38; Teplick to permit CX 42

reported CX 43 at

CHS this

[part reason,

of

IRB].” that the as to the

2.]

had

received him with to meet

sufficient his to his reporting

information responsibilities requirements

investigator [-/

respect Ix”A”]

char9e

*

*

*

Charge A:

III:

. Dr.

TeplicJc

violated

S 312.60

by in accordance with the

failing to Investigator

conduct the Statement.

investigation

The
— —

Center follow Form

charged the 1572

Dr.

Teplick in Form the 1573]

with

violating

~312.60 Statement” the sponsor

by

failing [i.e. , to 8

to FDA

agreement or FDA

“Investigator to notify

prior

=—- In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

74

.

making

“changes

in

the

protocol.n

Section states: an investigation

312.60 “An is

“General investigator conducted’-:’ . . is

responsibilities responsible according investigational to for the

of-investigators” ensuring signed plan, that

investigator and applicable

statement, .. regulations

the .

The

Center had the

did

not

produce an FDA

any Form

evidence 1572. had 1572. ever

to The

demonstrate Center did that Center [CX not

that

Dr.

Teplick that Teplick a copy — _— ._

signed or an

prove Dr. presented

agency complete of Dr.

the FDA s

sponsor Form

requested the

Instead, statement.

investigator

48.]

n The FDA FORM 1572 includes clinical investigator participating Section 312.60 requires the IND . investigation is conducted according Some of the pertinent statement. proceedings are, as stated:
q

the commitments from the in a study conducted under investigator to ensure that to the signed investigator commitments to these

an the

I agree relevant, protocols protect

to

conduct the study(ies) in accordance with the current protocol(s) and will only make changes in after notifying the sponsor, except.when necessary the safety, rights, or welfare of sub]ects. personally conduct or supervise the described “

the to

©

I agree to investigation(s) I agree in the 312.64.

-

q

to report course of

to the

the sponsor investigation(s)

adverse in

experiences accordance

that with

occur

q

——-

I aqree to maintain adequate and accurate wifi ~ 312.62 and to make those records inspection in accordance with ~ 312.68. CX 48.]

records available

in for

accordance

[See

,

In ——

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

75

When or
I

Dr.

Teplick he recall [Trans. replied,

was

asked “I that 2 at don’t

whether know

he what or

had

signed

an forms

FDA are

Form . . .
or”–

1572
No,

1573, don~t

those

doing Vol.

[seeing 148-9.]

signing

FDA

Form

1572

1573].”

.. Dr. asked the Teplick Dr. purpose Dr. to Dr. testified Teplick of if dissolving ? the Teplick, consent hearing, that at Dr. 148.] form Dr. that he he had to met “use stones Dr. t wanted biliary sponsor, Dr . his in IND [for “’ for subjects. When whether information his later _——.21, protocol during Part 312 had Teplick [Id. at provided testified 26.] any written “No. When knowledge the He sent me asked who had

and the or [Id.

. ‘J

questioned of Title

Teplick had

denied ever

mentioned

pertinent

regulations.

Under

~ 312.50:

“Sponsors providing

are them

responsible with the

for information

selecting they

qualified need to of

investigators, conduct the the

investigation

properly, ensuring proper monitoring is pla-n Dr . Teplick a“tid “ ensuring with in the the IND of . that the investigation(s) investigational Although

investigation(s), in accordance

conducted protocols claixned to

general . the . .“n pertinent

contained have been

unaware

regulations

~=

Section surances the ~ the initiation

23

312.53(c) delineates sponsor must receive of clinical trials

what information from the investigator under the sponsor’s

and prior IND.

——=

II.

.ne

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

76

governing the

his

responsibilities, statement, and that of the Dr. he

and

although

he that

had he was was

not was

signed an -. .‘–

investigator

acknowledged that .’s IND

investigator was the under agency.a the

investigation

he

conducting regulated

aegis

which

by, =.**I

In that

summary, Dr.

while Teplick I that among study find he

the had

Center signed Dr.

did or

not was

present aware was, to of and be,

evidence the

to

document

“Investigator in a way that For for ,

Statement,” evidenced ‘~.xample, the and filled

that

Teplick himself Dr. enlisted forms investigator of the whether by the the on

acted an

understood things, his IRB, report that an

investigator. a protocol the Since Investigator Statement are, study

other to case

Teplick patients those

submitted in patients. the

our requires the required was

~ 312.60 Statement, effect, Statement Dr. in Teplick the

follow Investigator or not

re~irements by actually to as ~ 312.60, signed notify

in

an

Investigator I to find that changes

investigator. prior infra,

failed

sponsor addressed,

making in

protocol .

specifically

24 statement,

Teplick Although Dr. he confirmed his Mr. Krenzel: ‘What with

had intent

not to

signed an investigator act as an investigator: first ‘t experience research?

was your FDA-regulated

Dr. [Trans. VO1 2.

Teplick: at 9-10.]

“Basically,

F-=

In

the

Matter

of

SteVen

K.

Teplick,

M.D.

-

Page

77

111.B. Dr. Teplick

Thus

,

this

subcharge s 312.60

supported by with failing the

the to Investigator
..\

Center’s conduct

charge the Statement:

that

violated in

investigation

accordance

*

*

*

Charge B:

III: failing

Dr. to

Teplick follow the

violated

~ 312.60

by planx.

investigational

As an __—___ — — plan.

stated

above,

s is

312.60

requires

investigators to the in information

to

ensure

that

investigation The

conducted plan (6).] agent, clinical

according is

investigational the clinical is to acquired revise

investigational [See ~ 312.23(a)

described As new often

protocol. about or an

investigational the current

it

is

necessary Under

modify

protocol.

~ 312.30

“Protocol

Amendments”: b) Changes in a protocol. submit a protocol amendment change in a Phase I protocol (1) A sponsor describing that shall any

.——=

X The investigational plan is a requirement of the IND under ~ 312.23(a) (3) “Introductory statement and application, broad objectives “(i) . . . the general investigational plan.~t: and planned duration of the proposed clinical investigation(s) (iv) A brief description of the overall plan for ~n~e~tigating the drug product for the following year. The plan (a) the rationale for the drug or should include the following: the research study; (b) the indication(s) to be studied; (c) the general approach to be followed in evaluating the drug; (d) ‘the kinds of clinical trials to be conducted . . . ; (e) the estimated number of patients to be given the drug . . . ; (f) any risks of particular severity or seriousness anticipated . . . .“
..
I

In A=->

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

78

significantly affects the safety of subjects or any change in a Phase 2 or 3 protocol that significantly affects the safety of subjects, the scope of the investigation, or the scientific quality of the study. [5 312.30(b).] of FDA any of Therefore, protocol such the investigator in order must ‘for inform the the

---

sponsor notify

amendments

~, .— =.~”~ sponsor to

amendments.

The in

IRB the

also

required

written plan.2d

notification

of

significant

changes

investigational

1.

The Center charged by not limiting his surgical candidates

that Dr. Teplick violated subjects to individuals or who refused surgery.

his own who were

protocol Boor

_-T

The

Center for

submitted subject

a

copy

of

Dr.

Teplick’s “Patients

protocol with

which

required biliary operative Barton

selection: stones who refuse

symptomatic who 45 at are 3.] poor Dr.

stones

(gallbladder or that,

or

ductal

stones) [CX

candidates testified

surgery.” TE21:

regarding

[W]e found this patient pressuring also found next day.ss a Patient

a quotation in the records for as follows: “Surgeons are us to take her to surgery.m We the quotation, ‘tWent to surgery Neither of these would look like fiat is not an operative candidate

..

26

radical ~iting _ S.”

The lRB stated in their protocol approval form: “any changes once the project has begun, must be submitted in to the OGC and adverse reactions must be reported to the [CX 38; 42 at 2; 43 at 2; supra, Charge 11.A.]

-.
.,! .,,

.. . ...
. . ..

.
. . ‘. . .. .

.“. ”.. ,..

~~.%

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

79

We also would say for Subject TE25 ~a~t~ally, subject TE5], in the records for that subject we found quotations like, tlsurgeons very anxious tO operatec” c ‘e
q q

... . :; =..~ ‘ “f

also have for the same subject, “Patient So these are direct whisked to surgery.” quotes from the records for these two ,. subjects. [Trans. Vol. 1 at 265-6.]

As

discussed

in “Surgery

the

protocols is still gall

of

both

Dr. to stones be the

and

Dr. of

Teplick: choice the who at for common refuse 3; see

considered bladder in

treatment stones

spptomatic bile duct.

and

obstructing or . . .“ in those [TX E

However, other at 1; modalities .-

high-risk are

patients offered I=] .

surgery~ also CX 45

~.t

ch-9e

Dr.

Teplick

had

also

responded

to

the

Center’s

charge

in

writing:

Both TES and 21 were sent to us from another institution where the referring physicians did not think it was safe for them to undergo They were referred specifically for surgery. When admitted stone dissolution/efiraction. these patients were seen in to Our surgeons consultation by our surgeons. were operable candidates. felt that they Therefore, they really did not give us adequate time to treat the stones nonsurgically, but they pressured us and the referring physicians to allow them to take these patients to surgery after only a brief attempt at dissolution/extraction. [TX
—-_

.

J

at

8;

see

also

Trans.

Vol.

2 at

312.]

Dr.

Teplick

testified

that:

8!1 think

if

a boarded

physician

, . ., . .- ..,., . . . ,,

_— In ==-=

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

80

q 

‘[who] patient of these

sent is

in a good

their

[sic]

patients, candidate, ‘ I would.”

said, I would [Trans.

‘I

don’t like Vol.

think you to do

this one 313.]

surgical on him,

procedures

2 at

..

As year

previously old critically room with course a

discussed ill with

[su~ra, man who

Charge was

11.C.3.],

TE5 to septic [CX 8 of at the

was

a

77

transferred in

emergency ventilator subject’s including
___ —

ascending

cholangitis failure.” with tear a

shock 9.]

on The

a

“multiple was

system complicated artery were

series secondary

events, to an arterial [See

right

pulmonary which The to referring stated: removal If of subjectts avoid

catheter CX 8 at entitled for notes feasibility tree surgical anesthesia on continued caused
—_ _— _

placement, 9-12.] “Reason by 2/10/87 of GI

life-threatening CRF indicated, “Considered (CX 8 at by and to of The Dr. 2.]

in under too

nature. the section high The risk

surgery”: surgeons.” “[Evaluation stones

surgery on

hospital as biliary will need to

Teplick of he general an at 27.]

decompression this, of

into

tract.

unable in spite

accomplish high risk

decompression .“ 2/11/87, to by the state stones, laparotomy, duct stones, [Id. at which that

127.] was due “On

subject

received [~d.

infusion The

of notes

unsuccessful. to the life the bile

threatening patient underwent

complications

2-13-87

exploratory common

common intraoperative \

duct

exploration,
q  

removal The

of

cholangiogram

# ,. .

.—-

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

81

patient stable patient respiratory

tolerated condition. had severe failure,

the “His

procedure postoperative

well

and

was

taken was very

to

the stormy.

SICU

in The

course continued

malnutrition, acute arrest on renal 4-1-87.

septic wound .L patient

shock, infection,;,and .— expired on

acute a
=.7~J

failure, The

cardiopulmonary date.” [Id. at

that

10.]

Based arrival

on

these to The life using

discoverable md was,

records, therefore, removal Only did the shortly upon

TES

was

deemed a poor

critical surgical stones resolution was

upon

considered of the the

candidate. considered the stones

nonsurgical saving.

biliary

unsuccessful undergo the the surgical

of

subject following

manipulation. procedure of find violated otherwise the the subject’s that the his

Moreover, subject died,

operative initial assessment Thus, Teplick who I

corroborating for to by a general

unsuitability Center study have failed protocol been

anesthesia. that this Dr.

substantiate accepting

individual

would

surgical

candidate.

Regarding to either

TE21,

the

CRF

noted

“She

did

not surgeons

get

adequate were anxious the avoid The

exposure to subject, surgery] surgical

The [CX”6 “Poor M.D. at 3.] However, condition. [patient].” the

operate.” as
____

CRF described Decision [Id. at [to 2.]

follows: referring stated:

medical and pt.

of

notes

---

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

82

of the patient’s age [86 years] and condition, she was transferred here for initial attempt at dissolution of the stones percutaneously Attempt was done to dissolve the ~t~n~s 3 times but the patient would complain “ of right upper quadrant pain and chest pain and she went into rapid atrial fibrillation “and had to be transferred to 12 West for monitoring requiring digitalization and high dose of Inderal IV. This resolved but the patient was unable to tolerate medical treatment for her stones and therefore it was decided to bring the patient to the OR to treat her choledocholithiasis. ~’ [Id. went at to 4-5; surgery of see also after the su~ra, Charge I.] medical not feasible. Again, this subject (i.e.,

In view medical

-. . f, ‘-’

s ‘

only drug

conservative stones) was

treatment

dissolution
—-––=_

Therefore, subcharge subjects surgery, protocol’s subcharge

I that who

find Dr. were

that

the

Center violated poor

failed his

to

demonstrate by

its including

Teplick either

protocol candidates whom basis. charge. were

operative both on of this

or

refused by his

namely

TE5

and

TE21,

acceptable Thus, this

selection does not

criteria support the

Center’s

2.

The Center charged that Dr. Tepli.ck violated by treating TE3, TE4, TE5, TE13, and TE20 evidence of acute cholecystitis, cholangitis,

who

his own ‘pro-tocol displayed or septicemia.

The should

Center have

charged been selection

that excluded

Dr.

Teplick from the The

included protocol, Center

five based

subjects upon the that

who

protocol’s

criteria.

emphasized

the

_—_ — ‘“- In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

83

protocol stated: cholecystitis, Neither constitute that in

selection “The patient

criteria will

used show or the these of the no

by

Dr.

Teplick of

specifically acute [CX 45 at 3_.] -

evidence

cholangitis, the protocol “evidence” his opinion, tenderness, nor of some

septicemia.”n defined

Center

further Dr. would lack of

whate_w@.l,d, Teplick be stated fever, upper

conditions. “evidence” sign,” 183.] and

abdominal cystic duct.

“Murphy’s Vol. 2 at

a patent

[Trans.

For

purposes

of are

this usually

discussion, characterized fever, and for by

acute

cholecystitis by the presence counts, with

or of signs right a positive

cholangitis ___ and upper radiologic Septicemia organism symptoms, quadrant

such pain,

as

elevated in presence

leukocyte conjunction of growth biliary of

jaundice, the

examination is from diagnosed a properly

stones. a microbial

a positive blood

obtained

culture.

Dr. FDA

Teplick 483:

addressed “[TJhese

the patients

Center’s were

charge sent to

in

response treat

to these

the

Form

me to

.-.

27

Cholangitis

biliary (1990).] bladder;” necrosis, infiltration a stone disease via the

tree.”

of a bile duct or is defined as “inflammation Medical Dictionary, 25th Ed., at 294 [Stedman’s of the gall Cholecystitis is defined as “inflammation “congestion and or hemorrhagic in acute inflammation, with variable infection, ulceration, and neutrophilic of the gallbladder wall; usually due to impaction of Septicemia is a “systemic [Id.] in the cystic duct.” caused by the spread of microorganisms and their toxins [Id. at 1405.] circulating blood.”
.:.’”

i“

.“

In _#”=%

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

84

conditions they were

because treated statement who or was

the

referring

physician [CX 33 at

felt 5.]

they While clearly cholecystitis,

might Dr.

die

if

surgically.~1 may displayed septicemia. essential, been be true, evidence [Cx

Teplick’s all subjects

his

protocol of acute If the

excluded~ c!
.—

(

cholangitis, subjects amendment IRB . [See

45.]

treatment IND the or

of

the;e

deemed have 7 at

an submitted

emergency to both

a protocol and the

should n.

sponsor

3.]

According was admitted

to

the with

hospital a diagnosis [gallbladder

records of

submitted “cholecystitis” and she to was of

by

the

Center, and

TE4

“cholelithiasis” .— -common upper bile quadrant and to at 6.] of duct pain her

stones] Although

“choledocholithiasis’t a history her the or time of right was

stones]. one week

had

prior

admission, at

abdomen of

non-tender, admission [CX 17

temperature the absence antibiotics on afebrile For that at she the the the the

normal antibiotics were hospital so

? in Although 10IGF

antipyretics. for a 31 rest & 33], of an to for the the acute

instituted day during no [id.

temperature the her subject hospital was of

second and

at the

became course. produced

remained reasons,

above subject time have

definitive

evidence episode protocol. protocol.

was she been

experiencing admitted

cholecystitis Therefore,

was

would

eligible

,.

.

.

.

~_

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

85

TE13 an

had

been

admitted of his

to previously had 11-2.] records, icteric of [an] on

on

3/13/87, diagnosed evidence the

for

what

appeared lymphoma. andsu~it .— =.~’f

to

be C)n

assessment the [CX

Hodgkin’s of Center

admission angina. subject’s subject patient showed The had subject ..~. as

subject 10 at

anemia, Although the on the

lymphoxna, did not

the the the

complete becoming an

discharge 3/25/87, right

summary stating: upper

described “On 3/28/87 which duct

had

ultrasound with placed
i

quadrant bile

gallstones was

obstructing antibiotic . . . .“

common therapy [Id. pain at the or time

stone. and this

patient

prophylactically at 12.] infection of eligible for the Again,

infusions failed to with and demonstrate an acute

fever, process

commensurate administration protocol.

would

have

been,

therefore,

The

Center

alleged criteria with as described with .“ “acute

that by

Dr. including

Teplick

ignored TE3

the

protocol’s she had been had 20 and I.A.] and which at 5&

selection diagnosed been 12.] 5/25/88, cholangitis been listed As

subject and cause TE3 had to

because

cholangitis”

because her death. admitted

“cholangitis” [CX to

a contributory earlier, of 5; fever, therapy blood . . . see

been negative supra, and

oil
“acute She she had was

a diagnosis [Id. with antibiotic at

ctgram also dyspnea, for

sepsis” Charge diarrhea,

symptomatic

administered ..~ — diagnosed by

septicemia, on .. 5/27/88.

was

positive

cultures -. .

— — . In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

86

Dr.

Teplick

testified that prior Although more remained reason, or than on it TE3 to

that had her the 24

he

believed from the not she

the her

hospital acute study .

records episode [Trans-J until:, .the course. her at was the initial the of Vol.

demonstrated cholangitis 2 at 6/07/88, subject For this 61.]

recovered entry onto did

subject hours after

receive $. had defervesced, her hospital whether resolved she from

=.*”J

antibiotics was impossible had

throughout to assess

septicemia time for of the

cholangitis administration. /

been For

adequately this been reason, excluded

ineligible

protocol

and

should

have

protocol. __— —.

TE20 another to his

had

been hospital

“recently from to fever and to

treated which on he

for had

ascending been

cholangitis” 5 days to [CX afebrile performed in

at prior for 24 at on the the taken D,t’ the

discharged admitted duration. and was was “one the . bile

admission of had to and the

1/16/89. of an

He was
one-day

complaints 8“1 He

jaundice take

continued

antibiotic cholangiogram

admission same day, bile the

A transhepatic subject [Id. grew afebrile From the was at out on above 9;] noted

to

have

stone

common during subject course.

duct.” procedure

Although “heavy

cultureGroup

Enterococcus, during this his

remained [Id.]

antibiotics information,

hospital may have

subject

— ----

In

the

Matter

Of

Steven

K.

Teplick,

M.D.

-

Page

87

protocol.

.-

As

discussed

earlier, to of ascending failure history at of the from

TE5

was

a

critically hospital in assisted on septic

ill

subject 2/10/87, shock wit.~ and

-~.l, ,

transferred diagnosis multisystems 9“1 him His

another cholangitis

requiring cardiac time

ventilation. liver and [See _ dissolution be a life renal id.;

[CX failure see _ of saving since was the he

8 at made

disease, of admission.

inoperable Charges stones by the

also _ the

SuEKaf biliary procedure —_ __— ascending the

IX.C.3 by treating

& 111.B.1.] was considered physicians. on admission have been

The to

However, to excluded TE5 from

had for study .

cholangitis and should

ineligible

protocol

Thus had them

,

although of the the

the

Center

failed

to

document that of their

that would entry TE3,

TE4 have onto TE20

and

TE13

evidence from

active

acute at the

processes time of acute of

excluded the and TEs did

protocol hospital evidence at TE20 the

protocol, show and/or Although made
sil~~

records of time

subjects cholecystiti.s, their on entry

definitive septicemia TE3 and

cholangitis, onto the no protocol._ attempt have the above was

defervesced their the absence Center

antibiotics, infections antibiotics. sufficient

to

ascertain

whether in that the

active of provided

would For

recrudescence I find

_ —.

reasons,

documentation

.-

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

88

.

Ilevidencel’ ineligible

of for

acute Dr.

infectious Teplick’s

processes protocol.

which [See

rendered CX 45.]

them

As both the

discussed the agency. introduced sponsor, IRB

above, and [See the s any the IRB

changes sponsor, 312.30; evidence or the I

to

the who

protocol is

..

must to

be file

rePort$$ .— them

,t,o with

required Charge that Dr.

see to

supra, show

111.B.] Teplick the protocol violated who .

Neither notified

party the

agency find by

regarding that Dr.

modification. protocol evidence ____ --in this selection of

Therefore, criteria

Teplick subjects or . septlcemla,

his

admitting

displayed as alleged

cholecystitis, Thus Teplick plan. ,

cholangitis, this subcharge s 312.60

subcharge. that Dr.

supported by failing

the to

Center’s follow

charge the

violated

investigational

3.

The Center by treating

Teplick violated charged that Dr. ES(TE26) and GL as outpatients.

his

own

protocol

The

Center

presented Selection” [CX that of Vol. his the 2 at 45

Dr. criteria: at 3.]

Teplick’s

protocol, UNo outpatient

which studies

stated will he in the

under be was

flpatient performed.” unaware violation [Trans.

Dr.

Teplick

testified of had submitted

that das to

outpatient clinical 259-60. ]

administration protocol he

IRB.

During

the

hearing,

Dr.

Teplick

admitted

that

subject

ES(TE26) #

---

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

89

was GL,

an Dr.

outpatient. Teplick patient, this have patient

[Trans. testified: but I could done, to the

Vol. “Actually, want be it

2 at

305.] I don~t stated to be
,.

Regarding

subject

recall that short

this it’s ~~te
+—

particular possible unit, [J]ust doesn’t

to

be

admitted then

the

proc@ure
:’..W *
3

a procedure he he went

and short

admitted unit [Id.

overnight initially at 305.]

.

.

.

because mean

procedure the

wasn’t

adaitted

[to

The

Center by

referred reviewing under

to the this

Dr.,

Teplick’s made

previous in This the

admission EIR: exclusion outpatient had [CX 33 responded at 5] ; “No

to

this

charge were
.—-=.

charges protocol. ES and at 4.] was I

outpatients was

permitted followed. .’? “This “This home Although when

criteria

not

Subjects [CX is is where Dr. he 31 true

GL were Dr. my

both

participants writing: wrote: nursing

Teplick error” that was that he to

in he to a [TX J at also

and but

true~

believe

GL went available.t~ did this by the they supra, on not

back

medical Teplick

supervision claimed his

9“1
records

have

his [id.], for outpa~ien”ts 11.D. ; as

prepared the ES(TE26)

response submitted

charge Center were

discussed subjects at see the also

earlier, GL and time of at

records

demonstrated

that [See

administration. 10; CX 29 at 3.] his

Charge this

CX 23 that Dr.

Therefore, protocol drug , this to

subcharge, criteria two the

1 find
.—=

Teplick the

violated investigational Thus

selection at least

by

administering as

individuals

outpatients.

subcharge

supported

=~-

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

90

Center’s follow the

charge

that

Dr.

Teplick plan.

violated

~ 312.60

by

failing

to

investigational

.-

4.

The Center charged that infusing volumes of protocol for 23 subjects and GZ.

Dr. Teplick exceeding TE3, TE4,

violated his the 5CC limit TE5, TE7-TEX9,

proto~~,by set by his TE21-TE26,

This Charge protocol [CX

charge 11.D.2.

has

been [See the As

addressed su~ra, infusion above, than duct maximum at 4.]

in Charge

an

earlier

discussion The co has deemed clinical a maximum admitted necessary TE9 in the

for

11.D.2.] of Teplick which For he

limited at 4.]

volume Dr. 5CC,

of that to

5CC. he

45

stated

infused dissolve 200CC, [CX

volumes common 40 times 5; see

greater bile the

stones. volume

example,

received protocol.

specified

7 at

CX 45

Although the duct modify the

Dr.

Teplick

found drug

it infused

necessary into c~protocol

to subjects

increase with

the

volume bile would by

of

investigational stones, the regulations. he dose did of

common which required 111.B.]

not the [See

file

a

amendment”28 product, as Charge

investigational ~ 312.30; see

supra,

—— =.

Specifically, the IND sponsor is required tc submit the IRB changes in a protocol? which include: ~tAny increase drug dosage or duration of exposure of individual subjects drug beyond that in the current protocol, or any significant increase in the number of subjects under study.” [S312.30(b) (i).]

28

to in to the

--

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

91

No

evidence

was

produced the IND

by

either

party the

to IRF3,

suggest or the I the limit

that agency find protoco~ set .-

Dr.

Teplick regarding Center infusing protocol. that Dr.

notified the

sponsor,

protocol that of , this violated plan.

modification. Dr. Teplick the supported by

Therefore, violated ,> 5 cc the failing

that by =.**T his

the

demonstrated volumes Thus Teplick

exceeding subcharge ~ 312.60

by

Center’s to follow

charge the

investigational

,

5.

The Center charged that Dr. Teplick violated failing to perform the required cholangiograms 48 hours after stone dissolution.

his at

protocol 1, 24,

by and

The

Center the

presented following

the

protocol monitoring at

used of the

by

Dr.

Teplick,

which “Patient will after

required receive stone

subjects: [sic] and 48

follow-up dissolution the

cholangiogram . . . When tubes

1,24

hours is discretion

complete will (Steven that the be

stone removed K.

dissolution at the

established, of at the 5.] principle Dr. to Vol.

access investigator

Teplick, was had been

MD) .f~ unable to

(CX 45
locate -

Barton

testified

Center tests

documents [Trans.

demonstrate 1 at 266.]

that-these

performed.

Dr.
-

Teplick follow-up range

responded studies follow-up.

in in 24

writing: this and group 48

“It of

was

not

always

possible

to

get long

patients, cholangiograms

particularly were

hour

--

In

the

Matter

Of

Steven

K.

Teplick,

M.D.

-

Page

92

obtained also

when

possible.” “

[TX

J

at

9.]

In

a written

addendum,

he

submitted:

Concerning follow-up cholangiograms: up cholangiograms were performed when if not all, patients had possible. Most, follow-up cholangiograms at 1 + 24 hours ‘after the stones were dissolved or removed’. These would be in our x-ray files at once the biliary However, drainage catheter is removed, it is not [sic] impossible to get a follow-up cholangiogram since the cholangiogram is performed by The injecting contrast through the catheter. biliary drainage catheters were and should be removed as rapidly as possible once we felt (usually the next day). the stones are gone. the biliary The larger [sic --longer?] drainage catheter is left in the patient, the higher the incidence of complications.”
—.— -.

Follow-

-

.— _ ~:. . . -

[TX

V at

15.]

It

was

apparent

from

the

records in

that

the of testing

cholangiograms the requirements may have been

were of for the

performed current valid affected investigation, ~ 312.30; file In a

inconsistently, protocol. safety the concerns, “safety or .= “protocol neither the protocol its ~, the of Withholding but the

violation this it may subjects, quality 111.B.] to decrease

also

have the

significantly scope of the [See —. did not

scientific Charge

of However, or

the Dr.

study.” Tep~ick these

amendment” party IND

eliminate to or the I suggest

tests. Dr.

addition, notified the

produced sponsor, the

evidence IRB,

that

Teplick -. — regarding Center

agency find violated that the his

modification. subcharge that

Therefore, Dr. Teplick

demonstrated

.

— ““—” In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

93

protocol 24, and

by 48

failing hours after

to

perform stone

the

required

cholangiograms Thus , this

at subcharge .-~ 312.60

1,

dissolution. that Dr.

supported by failing

the to

Center follow

‘s the

charge

Teplick plan. -.

violated

investigational

-.. ,.

6.

The Center failing to gallbladder stated that

charged that Dr. Teplick violated his protocol perform the required ultrasound examinations and bile ducts. The consent form incorrectly the examinations were optional.

by of the

The

Center

presented of after stone

the

protocol and bile

requirement: ducts for [CX 45 to at return and but protocol, not bile would will

“Ultrasound be of The every ducts be done at 4 month to consent fGr if an any

examination –~. intervals determine form stated:

gallbladder stone

dissolution,

a period 5.]

3 years,

recurrence.” “We would of the like

informed 4 months to see

you

ultrasound stones [CX 30

study recurred. at 2 .] testing

gallbladder is optional to the

This According was

appreciated.tf the

however, an option.

ultrasound

a requirement,

Dr.

Teplick

acknowledged tests, but duct he

that thought stones.

his

protocol that [Trans. tests

required were Vol. not

these useful 320-1; to see

ultrasound detect also

common TX V at

bile 15-6.]

2 at

.#---%.

If

the

ultrasound have been

tests amended

were to

considered reflect the

unnecessary, change. As

the stated

protocol above, #

should

— ‘-

In

the

Matter

Of

SteVen

K.

Teplick,

M.D.

-

Page

94

changes IND

to

the

protocol who is-required

must

be to

reported file them In Dr.

to

the

IRB the

and agency.

to

the [See party

sponsor, see

with addition,

~ 312.30; produced sponsor, modification. subcharge perform and bile the

supra, to or

Charge suggest the

111.B.] that

neither notified

evidence the IRB

Teplick -. the the his

-..

tha.IND . 2?..$’ *
q

,

agency I find

regarding that

protocol proved by of the the failing failing gallbladder Center’s to follow its to

Therefore, that Dr. Teplick

Center protocol

violated

required Thus Teplick

ultrasound , this

examinations subcharge supported by

ducts. that Dr.

charge the
.—_

violated

~ 312.60

investigational

plan.

7.

The Center charged failing to analyze SGPT, and amylase

Teplick that Dr. bilirubin, alkaline every 24 hours.

violated his phosphatase,

protocol SGOT,

by

The

Center will

presented include bilirubin, The latter [CX 45 she at the at

the

protocol, PT, PTT,

which platelet

stated: count,

“Baseline serum SGPT,

blooa

analysis electrolytes, axnylase. 24 hours.”

CBC,

alkaline five 4.] analysis Ms. that

phosphatase, [sic] deMarco none of will testified the by the studies

SGOT, be

and every

measured that, had

during”h~ been [Trans.

investigation, performed vol.
—_

found

frequency

specified

protocol.

1 at

191-5.]

When

Dr.

Teplick

was

questioned

at

the

hearing

as

to

how

the

. — —

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

95

blood

tests

had

been

obtained,

he

stated:

No, what-I did was -this was Poorly? another one of those instances that I had For tried to delegate to other people. example, if a referring clinician called me up and said he was going to send in such-andsuch a patient for stone extrac~ion and I had an inkling that we might’ procedure, , I would ask would he please, use or have his resident draw all the himself, appropriate blood studies. sometimes I would ask, try to And then, delegate it to either -to our nurses, or call the nurses on the floor, and I failed check up on it to see whether it was actually done as it was supposed to be done. I would have had to do it myself. Otherwise, ——_ —— [Trans. Vol. 2 at 261-2.]

.-“ :, .— =.a.-

to

When reported were

questioned dates obtained,

further the he blood affirmed

regarding tests his and

the the

inconsistencies actual dates the

between tests

the

previous

statement:

listening to the reports, that they It seems, [those who drew the blood work] were always several days off from when the actual study and this is [sic] probably was performed, just simply reflects the fact that when they actually did do as I had asked them to, they didnst do it when I had asked them to do it. [Trans. Vol. 2 at 263.]

Dr.

Teplick

commented

on

the

value

of

these

tests:

___

I think sGme of the clinical studies that we way over-utilize blood I’ve done, -we get a lot of unnecessary stu[dies] my own personal blood studies . . . And it’s impression that unless there’s a clinical just having a blood study counterpart to it,

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

96

probably does these studies. [Trans. Vol. 2 at 264.]

not

contribute

significantly

to

w -.

In of

his the

written patients we did not

response did

to

the the

agency, appropriate

Dr;

Teplick blood

stat~d:=’-=’’~bme
,,

receive the

studies, on to lab stated:

but many the values.” of

it

seems the

obtain Unfortunately,

appropriate I verify no the longer

blood have

samples access of the

patients. [sic] at 9.]

patient’s [TX J

charts In his

to written

accuracy Dr.

addendum,

Teplick

——

There is no question that we were remiss in obtaining some or even the majority of the As explained previously, this blood studies. was one aspect of the study that I delegated either to the referring clinician, or to the or to our radiology nurse on the floor, nurses and I did not follow-up to see that these blood values were actually obtained.” [TXV at 16.]

As

discussed

in

the

previous the As protocol stated IRB with

subchargest should above, and the to the

if have changes IND [See party

the been to

testing amended the

was to

deemed reflect must required Charge suggest . the find be

unnecessary, the change. to them In Dr. regarding the Center

protocol who is see evidence the IRB, supra, to or I

reported to 111.B.] that file

the

sponsor, ~ 312.30;

agency. neither

addition,

produced sponsor,

Tepli.ck the

notified protocol this

the

IND

agency that

modification. subcharge that

Therefore, Dr. Teplick

proved

— --—-. In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

97

violated phosphatase, subcharge ~ 312.60

his

protocol SGOT,

by SGPT, the to

failing and Center’s

to amylase

analyze every that

bilirubin, 24 hours. Dr. Teplick plan. ~,

alkaline Thus, this

supported by failing

charge the

vi~lated ._ \. ~; =.:a ‘ ‘+

follow

investigational ~.

In

addition,

as

discussed of Dr.

in Teplick,

Charge as or the

11.C.5. principal the

,

it

was

the at

responsibility to “personally

investigator described of all test

conduct ,“ which by

supervise the

investigation(s) results, as

included the protocol.

obtaining

required

-= Therefore, surcharges find Teplick that since 2 the violated 7, Center I found and that the Center proved supported its follow its claims in 111.Ba that Dr. , I

these sufficiently by

surcharges

Charge charge the

supported failing to

~ 312.60 plan.

investigational

To

summarize, in

I

find

that

the

Center

sufficiently which

supported demonstrated —.

its that

allegations Dr. Teplick

Charges

111.A.and ~ 312.60.

111.B.,

violated

*

*

*

–~

Charae.

IV.:

TePlick violated ~ 312.62(b) by failing Dr. prepare and maintain adequate and accurate all obsemations and other data pertinent investigation on each individual treated

to records to the with the

of

.—.= — In

the Matter of Steven K. Teplick, M.D.

Page

98

--

investigational

drug.

1.

The Center accurately treatment,

charged that Dr. Teplick used~ the volue of and the side effects for

failed to report the duration of all subjects. -.

the ._ >.

“: +1”. = .- ‘ “*

I Dr. the

interpreted Teplick duration subject, and study for of ] For the

this failed of he the

charge to report

to

mean

that

the the

Center volume effects to

alleged of at for maintain pertinent

that used, least

if

accurately and the by this

treatment,

side failing

one

violated

~ 312.62(b) records Center, of

adepate the . — evidence context 111
q

accurate . this

observation did not this suua, stated:

to

The

however, it discussed [See Form 483,

present subcharge Charges I,

specific in 11, the and

subcharge; earlier the charges. FDA

example, SSi[TE19]

9/26/86 100 cc 160cc in subject and 14]

reported records

on CRF; [CX 5 at

2

MDel[TE9]

1/23/87 CRF reports hrs; records state several hours [CX 3/9,10/87 subject reported patient reported patient 10].

200cc for 1 1/2 300 cc over 7 at 2 and 15]

MC [TE8]

no volme reported in records; 3/9/87 3 hrs on CRF; 2 1/2 hrs In records 3/10/87 5 h:s on CRF; 3 1/2 hrs n [CX 9 at 2 and records.

.-

6-

[CX ——– In

31

at

7.J

his

written

response

to

the

agency,

Dr.

Teplick

stated:

!! I

.+-==. In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

99

have

records

of [TX

the J at best in

volume 10.] of own my

and In

duration his written

for

at

least of the

most

of

the he

patients.” stated: [sic] llTo charts used at 17.] and

addendum either in the

1/22/92, patient’s

the or the

knowledge, I

my

records, of

have
---

both for all

volumesjof
:1-. %=..~* *

duration

treatment

subj,,ects.””

[TX

V

The

above the

examples CRFS of to

demonstrate and the as . was of often the other

some hospital

of

the

inconsistencies regarding information to I determine have the Charge failed of in that and his Dr. the was the already “side I.], to the study. Teplick adequate to the Thus , found effects” I report find volume

between and

records This on which since in reporting ,~.,

duration

infusion. evidence In addition, remiss subjects that

important __——_ -. effectiveness that for that Dr. at the

retain of

Teplick least Center the and some

[see, Dr.

established volume the side of effects the by failing

Teplick the duration

accurately treatment, this violated records investigation drug.

used, for Center’s to and

subjects charge prepare data

subcharge

supported

~ 312c62(b) of all

maintain

observations on each individual

other treated

pertinent with the

investigational

.-=

2.

The Center charged subjects TJ, JM,

that Dr. and GM.

Teplick

failed

to

prepare

CRFS

for

_&==%

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

100

During

their

inspection were TJ, Jll unable and GL.

of

Dr. to [See

Teplick’s locate CX 28, the 27;

records, CRFS 23.] for

the the

FDA three .—

investigators subjects,

w

-.

<

=.a

Li’.
q q

In was [sic] 8

his

written for basket
q

response a retained extraction. 

to

the CBD

agency, stone On

Dr. mainly

Teplick with she received

Stated:

~t J T

treated and Of but

4/17/89 know, [TX all J

2 doses sent to in receive

(5Dr. his

CC)

As

far

as this.”

I

CRF[S] at “If 10.] TJ on

were

I

will of no

check 1/22/92,

However, did her. not Dr.

written

addendu there is

he to have case

stated: a CRF forms

reason received V at 17.]

form on all

[sic] ~ and

should GL.”

have [TX

patients

including

According been Since admitted have not trial, surgical produce — —— MTBE that been address or

to

the

hospital with

records, bile in for no

TJ, duct acute

a 64 stone. distress of the

year

old [CX when 28

woman, at she she 1.] was

had

diagnosed she was to eligible

a common and 4/12/89 for the instead the subject

afebrile on

removal protocol. had been the [Id.]

stone, hospital

would chart did than to for the fact , the need

The

whether why removal she

considered infusion, The Center

for

the

received stone. that of

rather failed

of

the

additional study. this In subject the

evidence absence did not

she further

had

been

considered anstudy

information in the

participate

.

‘—-

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

101

for

a CRF

could

not

be

assessed.

However, their 23.]

subjects respective For each and to of

JM

and

GL did [~1 subjects, to the that Teplick JM

receive char9e a CRF sponsor. CRFS had ~.II”C”5; should

which == have

was c~ . been since

not-cd

in

records. these

z~f & Cx Z.3.+

,

completed unable subjects, adequate this charge ~ prepare with the

submitted evidence that records Thus , Dr.

Therefore, been to and completed prepare the the by each failing

he for

was two

provide I find

failed GL,

and Center

maintain proved

study

for this

and

that

subcharge. that Dr.

subcharge

supported

Center’s to treated

Teplick and

violated accurate drug.

~ 312.62(b) records on

adequate

individual

investigational

3.

Teplick The Center charged that Dr. that he had University of subjects when the records available 27 individuals were treated with

reported treated to FDA

to his IRB approximately indicate that

at

the 3S only

The

Center

presented of I have have used

a

copy IRB, been

of

a

letter 7/21/89, with

Dr.

Teplick which

wrote stated: to get

to

the

University the beginning,

dated involved in

“Since . _FDA at

helping 35 .]

approval

and

approximately ~ [CX51atl

patients

-

According had treated

to

Center’s only 27

review subjects.

of

the [See

study CX 1 -

records, CX 29.]

Dr. Two

Teplick of these
.

— — =---- In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

102

subjects, study

TE9=TE14 identification

and

TE19=TE2,

had

been

assigned because CX
-.

more they had

than

one

number, times=

apparently [See _ CX 7,

received

at

two

different

18

& CX 5,

CX 21.]
.—
,.

-1”, = ..~

:

q

In the

his time

written I

response submitted of [TX of J at this

to

the letter, I did

agency, I not He [TX had have

Dr. just

Teplick moved to

stated: to my the rav~

“At

University my computer.” written

access this 17.]

data in

or his

10.]

reaffirmed V at

statement

addendum

1/22/92.

Dr.
.-.

Teplick

acknowledged was only on this an the

that approximate subjects reason, that Dr. on

the

number number. that had I

of

subjects In addition,

he

had he had in

mentioned maintained the study. the of

CRFS For

actually find that an I

participated the Center

although Teplick the how

proved number the the

subcharge subjects has that failed Dr.

reported protocol, this

inaccurate also find supports failing of data with to that

treated to Teplick adequate investigation drug.

Center charge and

establish violated and on

subcharge by

~ 312.62(b) accurate each records individual

prepare pertinent the

maintain the

to

treated

investigational

4.
-. —

The Center the subject treatment changes.

charged that had received was discontinued

the

CRF for TE8 on 3/11/87, due tG chest

did

not report and that the and

that EKG

heaviness

:—--

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

103 .

For

TE8,

the the

Center subject~ the CRF The

demonstrated s medical [CX 9 at 2]

that record failed

a discrepancy [CX to 9 at mention the 26 and

existed 38] and the

between CRF, on i.e.,

treatment argume~t in .- =.;** charge.

3/11/87. of

Center subcharge

substantially in conjunction

presented -. with

,

support [Supra,

this

a previous

Charge

I.]

In

his

initial “TE-8 were .“ in notes day in

written received due [TX an J to at

response no the 10.] of

to on

the

agency,

Dr. The

Teplick chest in the revised that received his pain and

stated: EKG changes gallbladder

3/11/87. manipulation he where this

catheter However, 1/22/92, that

substantially he stated

his

answer

addendum not

personal on the

had

reflected

subject

question:

The FDA has a copy of my personal records and The chest pain that she can verify this. developed on 3-12 is reported on the CRF form. My notes also state that on 3-12, that the gallbladder manipulations resulted in significant pain and that the pain was It was and still relieved by nitroglycerine. is my opinion that it was the gallbladder Had I manipulations that caused the main. on 3-11, I known that she had received certainly would have reported it on the CRF fem. Also noted on patient TE-8 was that she had chest pain on admission and four weeks prior to the procedure had a myocardial infarction. She has other significant cardiac disease such as atrial fibrillation and an abnormal sinus. [TX V at 18.]

-

-

,

‘—- In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

104

While based due at [See Teplick to least

I on

cannot the

ascetiain records subject’s

the submitted, chest

accuracy

of

Dr.

Teplick’s was

statements

infusion heaviness to the under to of 22 at the the 74.] and and

discontinued wh~ch-–were on III.;., adverse in he records for in 3-!l~{a8w7: Dr.

this

EKG changes ~< infusion Charge sponsor investigation In

temporally 34.] responsible that with ~ for with in his any ~

associated As discussed for in the [See

CX 9 at was

above reporting course n.

experiences accordance was responsible

occur 312.64.

addition,

maintaining 312.62 and with to s to in the

“adequate make 312.68.” monitor study those

accurate

accordance inspection ~. therefore, resolve

records [Id.] these It

available was, and to

accordance responsibility

records

discrepancies

records.

For

the

above that adverse the by

reasons, Dr.

I

find did on

that not

the report

Center TE8’s , this

proved

this infusion and

subcharge related supported S 312.62(b) data

Teplick

effects Center’s failing to 3/11/87. the

3/11/87. that Dr. and

Thus

subcharge violated the records ‘ of

charge to

Teplick maintain subject

prepare

pertinent on

investigation

for

TE8’s

treatment

5.
—._

The Center charged that the hospital records reported that TE3 over two hours and fifty minuteswhile received X42CC of over the CRF reported that the subject received 360 cc of six hours.

.~.

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

105

I Dr.

interpreted Teplick infusion

this failed amount

subcharge ‘to prepare and

to

mean

that

the

Center

alleged records
. --

that of

and

maintain for subject

accurate TE3, of

duration

as

evidenced . ~ $~u~ion with .

by in the

the the

unresolved hospital

discrepancy records noted and in his FDA

between CRF. Form of

the-record This 483 [CX IV.1. discrepancy [id. at 16].

subcharg&, 31 at 7],

along

discrepancies a the 20 at

essentially submitted CRF [CX

specific record 2] and

example that revealed

Charge this

The

Center between the

radiology

report

Dr. _—_

Teplick the He

explained subject continued records, reaffirmed [TX V at had by

in

his

written 360cc “I longer do have

response over not

that 6 hours.

his

records [TX J at

showed

received stating: I no

lo.]
with [Id.] 1/22/92.

know access his

why to

the the

discrepancy records.t~

medical He

this 18-9.]

statement

in

written

addendum

of

As

discussed and

above, accurate

Dr.

Teplick records

was in for

responsible with in was and The also to

for ~

maintaining 312.62 and with” to 21

“adequate make C.F.R. those

accordance inspection

records

available [See n. 22

accordance his resolve any

312.68.” to in the pertinent

at

74.] records

It

responsibility discrepancies _— regarding of data

monitor the study and the

these records. duration study

unresolved infusion the

discrepancy was an example of

amount in

of to evaluate

effectiveness

.

.~.

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

106

infusion. proved amount records supported s 312.62(b) its and and the by records on

For subcharge duration the CRF Center’s failing of each

the that of for

above an

reasons, unresolved infusion

I

find

that

the

Center the

discrepancy existed Thus , -. between this

regarding the_ --hospital

subject charge to

TE3. that Dr. and

subcharg% .— =.*”$ \ violated adequate and to the

Teplick maintain and data with

prepare

accurate investigation drug.

all

observations individual

pertinent the

treated

investigational

6. .~-

The Center charged adequate records study.

of

that Dr. x-rays

Teplick performed

failed to maintain on the subjects

in

his

In

a previous that

discussion, Dr. Teplick by One was

the failed the of

Center to IRB the

presented comply that with

information some his of tine

to

document modifications [Surxa, IRB the when

requested Charge the 11.A.] study risks that Teplick Grants opinion we can a such had

reviewed

protocol. by the

modifications tabled every stated: 2 hours. to

requested “Please The

initially x-rays ‘be in

address

ra-diologic

from

Committee [CX by the 36 at

recommends

exposure replied and

limited a document office 2 hours

5 x-rays.” received

m

Dr.

university?s “In ——– our

Contracts every

on is

3/27/86, not

stating: excessive. to comply 37 at 1.] with

radiograph the

However, your

reduce

radiographic the

exposure study.” [CX

wishes

without

compromising

–—- In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

107

Nevertheless, “Cholecystograms this stones radiological as of a part such of tests subcharge] are no

Dr.

Teplick~s [the will

protocol

still referred at 2-hour 45 at -\

stated: to by the Center until– the . ~; =.~** protocol records in

radiographs be performed

intervals 4.] Dr. Since Teplick’s to

longer examinations the as study, data

evident.” were Dr. pertinent

(CX included

in

Teplick to

was the

required study.

keep

Dr. limit

Teplick each

testified subject’s his “Is

during exposure

the to [Trans.

hearing five

that x-rays,

although he 267.] are had not

he

did

documented questioned: will

compliance. [sic] that to there you the have

Vol. records limited

2 at that

When obtainable to five he to that

any took IRB to or

demonstrate pursuant Yes. x-rays.’~

yourself,

exposures, replied: get the

committee’s go to the

requirements?”~ radiology department

You’d [Id.]

The rays”

parties were that for

failed taken for

to

prove any

or

disprove Dr.

that Teplick

more

than

~Cfive study IRB’s

x-

subject. his written in he As the

provided of radiologic any Dr. the

records request

documented the limitation However, compliance. for with maintaining 21 C.F.R.

acceptance number to subnit above, and and to of

-

examinations. support — responsible accordance his

failed discussed “adequate ~ 312.62

documentation Teplick records records was in

to

accurate make those

— — .-—- :n

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

108 .

available [See n. 22

for at by

inspection 74.] Dr.

in

accordance I find

with that to his

21 this produce

C.F.R.

S 312.68.1’ is and j~hi$ failed of on all each

“Therefore, Teplick’s to the

subcharge adequate Thu., Teplick

established appropriate subcharge to prepare

inability

records supported and maintain data

substantiate Center’s adequate pertinent the

compliance. -. that Dr.

charge and to the

accurate

records

observations individual

and treated

investigation drug.

with

investigational

7.

The Center charged that Dr. Teplick did not make CRF or medical record for the fourteenth subject in Dr. TeplickCs second annual report (the Center information for thirteen) .

available referred had

the to

I Dr.

interpreted Teplick

this failed and

charge to other for keep data

to

mean

that and

the

Center

alleged records

that of the for

adequate pertinent subject The its 43

accurate the

observations the unaccounted

to

investigation to in Dr.

fourteenth report. in Cx his written

referred Center

Teplick’s addressed 11.C.4. Teplick 13 that copy

second this [-; affirmed had had sent no to

annual subcharge -w in been record him by

substantially in support of Charge

presentation at

v

As s-ted
to dates the of

a~o=rDr.
agency the and that report., requested only

.

response during second the

subjects he be

treated of the the

and a

annual [TX J

report at 6.]

Center.

As

discussed

above,

Dr.

Teplick

was

responsible

for

maintaining ,

“--

In

the

Matter

of

SteVen

K.

Teplick,

M.D.

-

Page

109

‘~adequate ~ 312.62 accordance also any his

and and

accurate to make 21

records those

in

accordance available [See these n.

with for 22

21

C.F.R. in
---

records ~ 312.68.”

inspection

with

C.F.R. to in the Dr. a CRF

at 74.]_
and
.

It

was

responsibility

monitcr study

records -. Since

to +— - .. r~plye was no by

discrepancies subject, to provide Thus that and Dr. , this

records. did not record not

there this

fourteenth failing subject. charge prepare observations
..—=

Teplick or

violate for

subcharge

medical did

a non-existent the by Center’s to all on

subcharge violated adequate

support

Teplick

~ 312.62(b) anti accurate to the

failing of

maintain and other treated

records

data with

pertinent the

investigation drug.

each

individual

investigational

However,

Dr.

Teplick to both

should the

have IRB

maintained and the the

records and

of his

his inability of

correspondence to his locate generally study

sponsor, Center’s

documents poor

supported

allegation

record-keeping.

8.

The Center charged that false dates with respect values obtained.

at least to the

16 of the 26 CRFS reported SGOT and alkaline phosphatase

The

Center

presented of testimony and Charge

information 111.B.7.

related For how [Trans. the Vol. this

to

this subcharge,

subcharge the

in

its

presentation presented discovered

Center
were

explaining

date

discrepancies 198-203. ]

documented.

1 at

=~-

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

110

In

his

response the that all reported
Vol.

to

the

charge, for in

Dr.

Teplick collecting on

testified the whether

that specimens, his staff his were ]

he

had he

delegated admitted completed have [Trans. not

responsibility he of was the the lax tests. proper
x

and – st~~f k done.

checking He also

testified =. when the tests

that

may *

dates
~.,

2 at

261-3;

charge

111.B.7.

Dr.

Teplick

was records records 312.68.”

responsible in accordance available [See to monitor the this to study n.

for

maintaining with 21 C.F.R.

“adequate ~ 312.62 in was and accordance his

and and to with 21

accurate make C.F.R. _--— responsibility discrepancies the dates obtained deliberate Center’s to each report Center with those ~

for 22 these records. at

inspection 74.] records For that and Dr. It

also to

resolve reason, I

any find that false values or the failing on ‘

in proved respect for

this

subcharge the SGOT

Teplick

reported

alkaline of

phosphatase poor record-keeping supported by

subjects, false reporting. that test treated Dr.

whether

because Thus, this violated

subcharge ~ 312.62(b) for the

charge these

Teplick

values with

accurately the

investigation drug.

individual

investigational

9.

Teplick The Center charged that Dr. subject LM [TE3] which showed duct stones one year prior to the admission.

failed treatment subjectss

to

submit a CRF for for common bile May 25, 1988

The

Center

presented

no

information

to

substantiate

this

.---- m In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

111

allegation. based had on

The a May 31,

Center, 1989

however, letter to

suspected the sponsor

this

prior

treatment that this .—

stating

occurred.
-. +—
,.

:,
=.’w~~

Dr.

Teplick, to

however, the agency:

addressed

the

subcharge

in

his-written

response

This is an error. I probably confused her with one of several patients who I treated and who had recurrent common bile duct stones. On 2/6/85 LM[TE3] presented with We did a biliary drainage jaundice. procedure and found she had a large common bile duct stone which was removed surgically. We never used on her until 1988.
_——-_

[TX

J

at

10.]

In

his

addendum

of

1/22/92,

Dr.

Teplick

stated:

On 2-6-85, a patient (LM) who was subsequently known as exhibit 20(TE-3) presented to [sic] hospital with jaundice and evidence of cholangiti.s. I treated her with antibiotics and by inserting a bi.liary drainage catheter. At that time, she had one large common bile duct stone. The stone was removed surgically. There was no attempt to dissolve the stone and in 1985 we had only We did not for dissolution purposes. Consequently, start to use until 1986. no CRF form was sent or should have been sent to Dr.
q

-

.

[TX

V at

20.]

— —_

Dr.

Teplick

clearly the reason

admitted for his

that error.

the

5/31/89 Dr.

letter

existed however, #

by

describing

Teplick,

.~.

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

112

failed-to of TE3 of

document the time again, As discussed inaccurate IRB and the

accurately of her 1985

to

the

sponsor

the The quality was

actual inaccuracy of able his

treatment of his

admission. the the made poor

1989 keeping.

letter,

demonstrated previously, statements sponsor.

recordto ~j to

Center ah-out

demonstrate both the

subjec@

r’epo~~ed’

Dr.

Teplick

was records records

responsible in accordance available [See these n.

for

maintaining with 21 C.F.R.

“adequate ~ in was 312.62 accordance also any the

and and to with 21

accurate make C.F.R. for in those

for 22 at and this

inspection 74.] for case, lack subject was to to did He

~ 312.68.” monitoring

responsible discrepancies Center’s a CRF for never its a

records In Dr.

resolving however, of TE3 unable submit the not

the

study

documents. on of the Teplick one this Teplick year

subcharge suspected occurred. subcharge infusion-with admission. charge prepare data with that

focused infusion Therefore, that Dr. TE3 Thus, Dr.

Teplick’s with Center failed prior

submitting that to a

apparently support

CRF

for May the 25, Center’s i988

subject’s support by all

subcharge violated adequate

~ 312.62(b) records on of

failing-toand treated

and pertinent the

maintain to the

observations individual

investigation drug.

each

investigational

_* * *

-—= In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

113

Of

the

above that

surcharges Dr. Teplick all I to find

under violated but that

Charge

IV.,

I IV.

found 1-6

that and

the 8 and

Center that

proved of IV. by these

Charges
Charge IV.3.

surcharges,

supported did -. violate records the

the

Chat–ge —
..

Therefore, failing

Dr.

Teplick and

S 312.~~(mb) -~ +_ of all on

maintain and other treated

adequate data with

accurate to

observations each individual

pertinent the

investigation drug.

investigational

*

*

*

Charge
——

V.

Teplick violated S 312.62(a) Dr. maintain adequate records of the investigational drug.

by failing disposition

to of

the

The

regulation is of . . .

under required the .“

312.62(a) to

states: maintain

“Disposition adequate dates, records

of of and

dru~. the use by

An

investigator disposition subjects

drug,

including

quantity,

The

Center

charged

that

Dr. The

Teplick Center

failed presented

to

maintain testimony

drug on ~his’

accountability charge. Ms.

records. deMarco

testified:

. —.

No drug accountability records were available. I telephoned Dr. Teplick because, as I said, he wasn’t present and I thought And he maybe I was just overlooking them. confirmed by telephone that he had not kept He did not know drug accountability records. He didn’t know who purchased the drug. technically how it was paid for within the

.=—- In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

114

And I was not even able University. down more than one receiving record So there were no drug accountability maintained. [Trans. Vol. 1 at 205.]

to track for it. records
.—

Dr. drugs would

Teplick

testified for how order

that studies. much more pay Vol. for he

the He needed He and then

pharmacy stated and stated keep 1 J the he that

wanted the then the

control

of

the

purchased ask him to

pharmacyn tell department until it was his [of

would that

secretary Radiology] needed.
—__

would [Trans.

2 at

167-70.

Dr.

Teplick were could

claimed

that

all by

of

his

communications For evidence this of the

with reason, above [Trans. had Vol. as not

the stated

pharmacy that he

conducted not produce

telephone. written

transactions at 173.]

concerning Finally, drug Dr.

the Teplick

investigational admitted records. the source from e.q., the CX 20 of that

drug. he

vol.

2

maintained Dr. Teplick’s

accountability CRFS did note differed [See,

[Trans.

2 at

311.]

which had named in the IND.

source at 1;

the CX 55

IND at

sponsor .- . 1-2. ]

Dr.

Teplick

clearly

stated

that

he

had

not

maintained

this

type

—29

Dr.

Pharmacy.”

Teplick [Trans.

testified Vol. 2 at

that 171.]

he

dealt

with

the

“Head

of

the

— -----

ln

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

115

of Dr.

records. Teplick

[See did records

Trans. vidlate of the

vol. 312.62(a), .

2 at

311.] by failing

Therefore, to

I maintain

find

that

adequate

investigational

drug
..

..-

*

*

Charge

VI:

Dr. Teplick violated informed consent for

~ 50.27 by two subjects,

failing TJ

to document and JM.

Under may
————- these

~ 50.20: involve

“Except a human being unless informed

as

provided as a subject

in

~ 50.23, in research has the

no

investigator covered the the 50.27 informed consent form by

regulations effective legally that shall by the

the

investigator consent of

obtained or Section

legally subject’s requires consent approved legally person

subject

authorized “[e]xcept be as

representative.” provided by the by in use the ~ 56.109(c) of

,m

documented IRE3 and signed

a written or shall the be

subject A copy

subject’s given to the

authorized signing the

representative. form.c~ The IRB

also

required

documentation

~_ —

“An IRB shall require w Section 56.I09(c) states: documentation of informed consent in accordance with ~ 50.27, for some or all subjects, waive the except. that the IRB may, requirement that the subject or the subject’s legally authorized representative sign a written consent form if it finds that the research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside the research context.”

.

.

.

‘~-

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

116

31

and

maintenance

of

consent

forms

for

periodic

review.
.--

The

Center from TJ ? she did

charged TJ did did not and not not

that J14. receive have

Dr. As

Teplick discussed ; for

failed

to

obtain

info~ed . @@rge

consent YV*2.], argued Teplick Teplick was

previously this reason, I find to

[su~ra, Db. that

Teplick Dr. TJ. infusion Dr.

a CRF. ~ 50.27

Therefore, with respect

violate that after at 7.] agency, with of Dr. a

subject

admitted

JM received one Dr. dose. Teplick that consent [TXJ consent did consent not [TX

although V at 17; in see ____—also both were 12; from TXV of

discontinued CX 27 to the

Charge written from 22.] submitted that

11.C.5.; responses all subjects

stated forms at form

his

obtained at

treated no proof Also, the

However, for the review. IRB

signed Teplick

JM was any for

provide

evidence JM, in

waived with

informed

requirement

accordance

~ 56.109.

Therefore, to document JM.

I a

find signed

that

Dr. consent

Teplick form

violated (i.e.,

~ 50.27, informed

by consent)

failing for

subject

*

*

~ —-. -——

31

A1l

signed-consent for a period a project. ,

forms of (CX

must five 38;

be

retained following 2; 43 at

and 2.] the

available

for CHS review termination of -. .,.” -, . ..

years 42 at \

.

.:,

~= ~ -—— In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

117

Charge

“VII:

Dr. Teplick violated all of the requirements Center charged that adequately describe

50.25 by failing to satisfy of informed consent. The Dr. Teplickcs consent form: the purpose of the researchx :, qnd=--n

s

1.

Did

not

2.

Did not adequately discomforts to the

disclose subjects.

the

foreseeable

risks

q

3.

Did not contain an adequate explanation of whom to contact for answers to pertinent questions about the research and research subjectts rights, and whom to contact in the event of a research-related injury to the subject.

Section consent”

50.25(a) be (1) provided

requires to

that each

eight research

llbasic subject.

elements
These

of

informed include:

A statement that the study involves research, an explanation of the purposes of the research and the expected duration of the subject’s participation, a description of the procedures to be followed, and identification of any procedures which are experimental. O.,
q

(2)

A description foreseeable subject . 000
q

.

of risks .

any or

reasonably discomforts

to

the

(7)

An explanation of whom to contact for answers to pertinent questions about the research and research subjects’ rights, and whom to contact in the event of a research-related injury to the subject . . .
..m.

—. .

,

[S

50.25(a).]

-= _ _——

In

his

written

response the

to consent

the

agency, forms sent

Dr. by

Teplick Dr.

addressed My /

this

charge: “I used ,..1. . ,.. ,:’, ) “. . i ~. .. ,... . -. ...’.< - .~ .$:.-.-’” .’.- .1. .:,’.. ; .:”. .:;. 1-. .. .%:.., ~ :.. ,.:;“ ,.;;”.e ...- : ..4 ~.!’>-ll:‘+.’:’: , ; - , ,’.4’.... .>Z:< ,:: ?, ..?;. ; -@.:j :.“,..<2. /:-Y<dCz “.’ .-, ”.:---:<;! <’‘~,,j “ . (“
. ..! , .:

, ., . .$ l?, . . ,, ..”.. .’4 ..
-t ,’ ..:

. . .!. .,, .; . 7:., .,, ..:. ..-,. , .,,
.’, -,. .. , , .4-.

.’.

(“’

~~,

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

118 .

understanding deletions that affirmed was to a

is

that

each

institution form.gz ‘s IRB.”

has I

its used

own the at

additions consent

or form “-

specific by

consent

approved this I

[TXJ

12.]

He l/22/9~:

position gave

in

a written

addendum, -.

dated

=’.* . *

‘s] consent form to this [Dr. ~’s IRB. They made certain changes and I abided by the changes that they made. I assumed that the IRB was familiar with the FDA requirements for investigational informed :onsents. Consequently, I used basically Dr. ‘s consent with some modifications from our own IRB. [TX Vat22.]

.n

The his listed

Center

charged study failed

that to

the

consent the

form three

used

by Dr.

Teplick
elements

in

address the Dr. form’s

required of

above. (Charge consent:

Regarding VII.1.),

statement testified

purpose Dr.

of

the

research informed

Barton

that

Teplick’s

would not be acceptable to the Food and Drug Administration. The regulations are very specific that the purpose of the study is to determine the safety and efficacy of the That is the purpose of the study. A drug nice fringe benefit would be that it benefits the patient also, but the purpose of the study is to evaluate the new drug, evaluate
q

-.-.

Section Dr. Teplick was partly correct. ‘The IRB may require that 56.109(b) (emphasis provided) states: in addition to that specifically mentioned in information, s 50.25, be given to the subjects when in the IRB’s judgment the information would meaningfully add to the protection of the .-. Dr. Teplick was incorrect to rights and welfare of subjects.” believe that an IRB could delete or remove certain required ,. .“.. based on ,~ 50.25. ~~ ‘;.+sections .s.. Si : : ,,..-., .-> -G, + .. .-. ‘. ,T7 c’. ‘....1 ’ t. , ::;;:$::ji;:$;;.’ ‘;”’;!:.’ :-.’<::’47 ‘ .,”. .“’.’ -: ‘:!. 1:”?;:::. ;:~ :>;!”;<:::.;;”;; ; ;-:.” ., . . ~, ,
J .-<.~;.’ .~-; ‘{ ,k , -$f?t ?V’’:%+ ,,. . . ,:. P .,,. ., t$:p;:+ : -i . ;’ “-: -’ r :.->? ,’ i . ~ >’<,+:; “:.: .--: ‘1.-. %>,,7-?--;:,:2; < ,’i’,\,( ... ,,-, .< .!(}.’:.:,’ Yr. “ .: , ‘:~,.; ..--... .””...: . .’ .= . .. ‘z . .. t-”’ . “: . .. ‘-,:::;$ -~ 4;.1 !“::~’=Li~,z’3? f’ 5.+-..” !-.:J ‘ Y ~,’ +7):L ., %?*u.? : ~ K:V”’ :’.’~’ >...Y~*d!”a.a (:;---; &;f . ,.<6, . :~:; . ...*. ,-’. ‘; ‘ . .’ f “’ ; i.: ~ . ‘. , ‘“ .:.,,. “: l.i ~ ~“, .’,,!. ~-.f ,--.’< ., , . j’, +j;i-.’~~~:. i+,%&’,?+ L&:.; .. 1., ~~ ~ ““,. ,’ t.’ ‘ ::;. ~ ~A. ~ ‘ . .+4:~; ,,, ,’ ~+ ~ (.

32

‘–

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

119

its safety and efficacy. And clearly stated to the patient. purpose is to study the drug, the patient. [Trans. Vol. 1 at 270.]

that should They know not to treat

be the

The

Center of the

objected Research,” study

to

the

section that that this

of it the

the

consent failed to

form

entitled,

“Purpose inform

alleging

sufficiently was

participants Specifically,

use section

of of the

investigational.

form

stated:

_ —

to attempt to a drug called We feel that the drug w1ll probably be e~fective in your case, and, if so, our study will help establish its use as an accepted agent for dissolving biliary stones. [CX 30 at 1.]

The purpose of dissolve biliary

this study is stones using

In to

its

review the the Dr.

of

the

consent to of the the

form,

the

IRB

required

Dr. of [CX 36

Teplick the at 2.] the 37 at 2],

remove in

reference ~~Purpose Teplick

possible ResearchOO the IRB

effectiveness section. that of the as he had

Although sentence this

informed the not

deleted [CX

concerning was Charge

effectiveness removed from [See the also

sentence in

document, CX 30.]

previously

discussed

II~A.1.

.

However,

the

concept

that

infusion

was

“investigational”

was

-—=

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

120

I understand that because of the investigational nature of the treatment or procedure” there may be some unknown risks or results and that, ‘therefore, there can be no guarantee of any results or outcome of same.” [CX 30 at 1.] personal I accept the with the or procedure it is for my possible advancement of science, of humanity. [Id.]
-. .— .,

risks of this treatment full understanding that benefit, the and in the interest

Based informed
—.

on

this consent

information, form could nature adequately in

I

find have

that perhaps purpose the

while more of

Dr.

Teplick’s identified the as the

clearly the of

the

investigational form

of explained

the

research, the research

consent

purpose

investigational Center consent research. that the Dr. did form not did Thus Teplick ,

accordance its

with

~ 50.25(a). that

Therefore,

prove not this

subcharge

Dr.
the

Teplick’s
purpose Charge to satisfy of

informed
the VII.1. all of

adequately subcharge ~ 50.25

describe did by not

support

violated of informed

failing

requirements

consent.

Dr.

Barton

also the

testified foreseeable

that risks VII.2.):

the and

consent discomforts

form

inadequately to the research

described participants ..—-. ,..
.,,..

(Charge

.. . ..$

[Y]ou’11 recall from the adverse events that I’ve already listed that there were many problems that should have been reported to the patient. ‘. The patient should be aware of
f

.—--

In

the

Matter

of

SteVen

K.

Teplick,

M.D.

-

Page

121

these adverse events before consent form. And they are described here. [Trans. events

they not

sign a adequately

Vol.
which

1 at
the

270.]
consent

She form

went did

on not

to

describe

specific [Id. at

— ~,

aaverse

address. -.

27@-2.] =. .3.*

The as the

consent follows:

form

used are need

by

Dr. some

Teplick minor for

addressed discomforts

adverse associated In at as addition, times, as

effects, with

“There

venipunctures patients which

[sic]

blood

tests. and,

occasional vomiting, temporarily
.-

may can be the 3.]

experience controlled injection

nausea medically, of

well

reducing [CX 30 at

As the IND

discussed adverse

above, experiences

the

Center which

presented should agency. should have

information been reported

regarding to the

sponsor,
These consent

the

IRB,

and the
experiences Such

[See also

suwa,
have

Charges
been

I.

&

11.C.] in the

adverse form.

addressed a cardiac
~he.-. .

adverse

experiences

included

temporally-associated
conditions, subjects doses modified .—. to be of to with and severe

death,
nausea biliary particular, the for

exacerbation
‘and duct the sedation stones, consent that [Id.]

of

previous
in

observed who form required In the required should

cotion In address

higher have
the

been

complications some subjects. associated
‘ .’

product

discontinued. the

addition, placement of the

because ..-./

procedural risks --- .. ., - - ,. .. . .... , :-, ..., . < ‘ .’.-;’....’”,; & .
,,
..I--->

with

..

...

J...-

:-.
r -. . . . ,. .,,

,.

.,

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

122

cathete”r (e.g., death), these these that

to

deliver of,

the the form

investigational occlusive should Trans. the balloon, have Vol. Center

agent pain,

were

significant and of

breakage the risks reasons,

bleeding, a descriptiofi TX

consent as well. I find

provided 2 at93; demonstrated

[See that

Cat@~] For .— =.1-~ Charge vII.z.

Dr.

Teplick’s the

informed

consent ris,ks and the failing

form

did

not to charge the

adequately the that subjects. Dr.

disclose Thus , this

foreseeable subcharge

discomforts Center’s to satisfy

supported by

Teplick violated ~ 50.25 8 of informed consent.

requirements

.———_

Finally, inadequately questions and to to the

Dr.

Barton identified

addressed

the

subcharge person the to

that address

the

consent pertinent rights,

form

a contact research in
VII.3.):

about answer subject

the questions
(Charge

and the

research of

subject’s

event

a research-related

injury

[F]or the case of physical injury, and merely states, f~I should contact the investigator .ll No, we do not consider to be adequate. The regulations require the investigator be identified and the subject be informed how to contact this individual . . . At least a name and a

it that that

phone

-

-

number.
. . . .

[F]or questions about they may obtain this Grants and Contracts. is a large something.
require that the subject

rights it says that from the Office of Grants and Contracts
The regulations be informed

contact and how to contact. and a number are required.

Again,

whom to a name

-_ _—

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

123
.

[Trans.

Vol.

1 at

273.]

The the

consent IRB

form

used the

by

Dr.

Tepli.ck,

which

had

been

approved :, .— =.-*< ‘ as

by

provided

following:

1 hereby agree to permit Dr. Steven K. Teplick and such Associates and Assistants hejshe may designate (each of whom is hereafter called ‘the investigator’), to perform upon me (or upon the participant) investigational treatments or procedures
. . . .

the

[CX Q

30

at

1.] been advised that if I experience any physical injury due to this treatment or procedure, I should contact the Investigator, who is prepared to provide or obtain appropriate medical treatment . . . Further information on the foregoing as well as information regarding this research and my rights may be obtained from the Office of Grants and Contracts. I have

.—=. —

[Id.

at

1.]

Although form
as

no

specific ‘Dr. the conduct were would

telephone Teplick,~l

number as and trial, be treated or turn the

was

listed,

the

consent as well by Dr.

did

identify

~~Investigator,l~ stipulated the as be able contacts. inpatients to locate named find Dr.
as

identifying to

“Associates the clinical to

Assistants” as

Teplick all each

Because in out the

patients subject

supposed presumably of

know in

telephone Also,
——=

number

which

could was the not

Teplick.
a contact

although

a specific subject’s

individual rights,

regarding

research

consent

form

did

In ./—=..

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

124

identify could be

an

office

within

the

institution

to

which

such

concerns

directed. requiring number detail for to or

[Id.] the name

In inclusion of by the Dr.

the

absence of

of

an

IRB such

policy as the t~at K; =.*** the

statement telephone level of

information I do not

contacts, Barton

find by the

desired informed

is-’required whom to research For this

regulations answers rights

consent the I

regarding research,

contact subjects’ I for

for

questions research-related

about

and

injury. explained Thus, this

reason, contact (Charge

conclude answers VII.3.)

Teplick adequately that Dr. * to the above information. did
_—__ —

whom to subcharge

not

support

the

Center’s

charge.

Nevertheless, that the consent

the

Center form was

sufficiently incomplete, the The include risks consent new

supported because of form the it

the did

allegation not contain or been the who were
therefore,

accurate procedures appropriately nature receiving find that

information (Charge updated severity for the Center

regarding vII.2.). to of

product not

had

information of
stones.33

regarding subjects
I,

and

adverse
biliary

experiences
duct

common

demonstrated

that

Dr.

Teplick

violated

.

33

Teplick received “TO the reported treatment updated, subjects

the Center had argued that Dr. In previous charges, had not stated the correct number of subjects who had Regarding Dr. Teplickls consent form, it stated: best of our knowledge only two patients have been in the medical literature as having received this in the United States” [CX 30 at 2] and was never was aware that additional even though Dr. Teplick had received the product at his own institution.
,

In

the

Matter

of

Steven

K.

Teplick,

M.D.

-

Page

125

~ 50.25 of the

by

failing

to elements of

provide

a consent

form element

which

addressed

all

required

(specifically, consent.

s 50.25(a)(2))

informed

..-

VI.

CONCLUSION

1’
I
conclude that

Dr. problems to In the

Teplick

failed

to risk

report to

alarming subjects

and in a (Charges such to making (Charges

unanticipated
q

involving agency, he to in

human of

timely
I.A.

manner
& I.B.).

violation to IRB violation to (Charges accurate
to

~ 312.64(b) promptly prior ~ 312.66 the

addition, IRB, or

failed

report

problems changes 11.C. plan, prepare
observations

to in

the his

research Dr.

obtain . plan, in failed

approval of follow

& 11.D.). as required and maintain
and

Teplick

investigational & 111.B.); of all
on under of the

under

~ 312.60 and
pertinent the to

111.A. records
the

to

adequate
data with and

other treated

investigation drug,

each

individual

investigational maintain adequate

~ 312.62(b)

(Charge

IV.);

records

disposition
(Charge V.).

of

the
Finally,

investigational
I find that

drug, Dr.

under Teplick properly
VI.)

~ 312.62(a). failed to provide

an

adequate in

consent violation Dr. 312, I

form of Teplick

or

to

document
(Charge

informed
and 50.25 (Charge

consent,

~~ 50.27 repeatedly that

VII.).
Parts 50

Since and

violated Dr. Teplick

the should

regulations be

in

conclude

In

the

Matter

of

Steven

K.

Teplick,

M.Q.

-

Page

126

disqualified

from

receiving

investigational

drugs.

VII.

PEC o MME NDATION

.—

+—..

I

recommend

that

the

Commissioner drugs.

disqualify

Dr.

Teplick

from

receiving

investigational

JuN2h993
eddie Ann Hoffm~n, M.D.

Presiding

C)fficer

.n

==