13 - C lin ic a l la b o ra to ry d a ta

1. CHOICE OF
LA B O R AT O RY
TESTS AND
METHODS

D uring the early p h a s e s of new d rug d evelopm ent, the list of

laboratory safety tests sho uld be d is c u s s e d with a toxicologist and a
clinical p harm a-colog ist in ac c o rd a n ce with p revio us d ata on the
co m p o u n d and on sim ilar products. In su b se q u e n t p h a se s, the list
of tests tak es into accou nt the results of initial tests.
It is a lso im portant to sp ecify the tim es of sa m p le collection in relation
to con-duct of the stu d y protocol, an d to d e scrib e the tech n iq u es
u se d for a s s a y s with the re ag e nt s used . In c h o o sin g m eth od s for
m e a su re m en t of lab oratory tests, the total am oun t of b lood
n e c e s s a ry and the continued u se of the techniq ue c h o s e n during
the trial m ust be taken into account. A n y c h a n g e in m ethod m ad e
during the clinical trial sh o uld b e avoid ed . If a c h a n g e d o e s occur, it
m ust be d ocu m en ted and the com patibility of results obtained
before and after the c h a n g e m ust be studied . Th is part m ust be
co vered by written instructions, esp ecially in m ulticenter stud ies
w itho uta centralized lab oratory.

O BJECTIVE

L ab oratory tests are u se d in clinical trials either to a s s e s s the

ef icacy of a m edication, or to evaluate its biological safety, or to
select sub jects (for exam p le certain sub jects w ho h ave preexisting ab norm al test d ata are exclud ed from the stud y d uring the
scree n in g p ro cess).

2. PROCESSING OF
LA B O R AT O RY
SAM P LES

in the p rotocol or in an ap p en d ix the follow ing e le m en ts are

d e scrib ed a s follow s.

2.1. Te c h n i q u e fo r c o lle c t in g s a m p l e s (4)

S h o u ld a tourniq uet be u s e d ?
W h at is the sch ed u le for sam p le collection with resp ect to
adm inistration of the stud y d ru g ?
- S h o u ld the patient b e fastin g ?
resting ? - W h at typ e of test tub e
sh ou ld be u s e d ? - W h at type of
an tico ag u lan t?
- W h at am o unt of blood shou ld be collected ?
-

In clinical research, an y error in a test m e a su re m en t or m ix-up of data

is del-eterious not only to the subject concerned , but also to future
p atients on w hom the therap y d ed u ced from the results of the trial will
be applied . If erro-n eou sly ab norm al, su ch results can c a u s e
unjustifiable restrictions in u se of the studied product, but if
erro n eo usly norm al can provide a false s e n s e of safety.

In a specific trial, the level of quality req uirem ents m ust be

p rop ortional to the im p ortance of the tests. It is very high if the m ain
endpoint is a laboratory test. To ob tain evaluab le results, in all c ase s,
one m ust be certain:

2.2. L a b e ll in g of s a m p l e s

of the right choice of laboratory tests and m etho d s for m ea su rin g

them ; of the use of a sing le techniq ue to m e a su re a given variab le
during a trial; of the p ro g ressio n cycle of laboratory sam p les;
of the routine quality control of the
m ethods; and of interpretation of results.
In this chap ter, w e h ave exclud ed the follow ing:
C o m p u te r ch e ck in g of data, and the rules on them an d on
confidentiality, d is c u s s e d in chap ter 9, the rules for archiving
co n sid ered in chap ter 16, an d that part of the report d evoted to
lab oratory safety, co ve red in chap ter 11 Statistical A n alysis and
chap ter 15 Clinical stud y Report.

Before u sin g it in a clinical trial, a test tube for sam p ling sho u ld be
labelled to limit a s far a s p o ssib le the risk of confusion. If p ossib le,
labels sh ou ld be printed ah e ad of tim e and carry the follow ing
inform ation: protocol num b er, subjects identification, specification of
the tim e (in cond uct of the study), and the date and tim e the sam p le
w a s collected. It is ad visab le to p lan to u se firm ly ad herent lab els and
indelible ink, esp ecially if s a m p le s are to b e frozen. If sub jects are
identified b y c o d e s (e.g. b y their initials or a num ber), their is a high
and se rio u s risk of a m ix-up . In s u c h ca se s, strict rules s u c h a s the
order of the subjects initials, the u se of a letter for his m iddle nam e,
the cho ice of a sing le n u m b er (for exam p le, rand om iz ation num b er
an d not C R F or hosp italisation num b er) (16) are essential. T h e s e
item s are sp ecif ed in w riting an d sh o u ld m ak e it p ossib le w ith
certainty to a s s ig n all results to the co rre sp o n d in g m edical reco rd s of
all subjects. If lab elling is not d o n e at the s a m e tim e b y the p e rso n
w ho collects the sam p le, a very strict p ro ced ure m ust be written an d
follow ed to avoid m istak e s (18).

160
161
U s e of bar co d e s greatly facilitates the p ro c e ssin g of sam p les, in
particular in a s s a y i n g m edications, with multiple, tim ed sam p les.
B ar co d e s m ak e it p o ssib le to check, at the tim e a sam p le is
collected , the co rre s p o n d en c e betw een the volunteer subject
(w earing a cod ed bracelet), the m edication ad m inistered, the test
tube, the clock tim e of the com p uter, and the chronol-o g y of events
p lanned in the protocol.
In certain c a s e s (p harm acokinetic studies), it can be useful to relabel
sam -ples in blind time (22) after collection of the sam p le. T his is not
the real tim e w h en the sam p le w a s collected w hich is indicated, but is
a rand om iz ed co d e enab ling a s s a y s to b e run w ithout b eing aw are
of the actual ord er. T h is p o s e s the problem of dilutions w hen the
m ethod of a s s a y is correct only within a narrow concentration range.
D e co d in g is only p erform ed p o st hoc, to avoid involuntary sm oo th ing
of the curve in interpreting results.
2.3. D i s p a t c h of s a m p l e s
Th e m ethod for ship p ing s a m p le s m ust be stud ied, along with the
duration for storag e and n e c e s s a ry tem p erature cond itions
(2,4,7,29), to sp ecify the p a ck ag in g m aterial for test tub es (p ack ag e
for shipp ing ) to be u se d and even o ccasio n ally to su p p ly it (in an
ad eq uate am ount). Pa c k a g in g m ust b e suited to the typ e of content
(alw ays a s s u m e d to b e infectious b e c a u s e it is im p o ssib le to prove
the contrary and to regulations p ertaining to the m ethod of transp ort
of h a z a rd o u s m aterials ( I ATA regulations:
International A ir
Tran sp o rt A sso ciatio n ) (1 1).
If centrifug ed s a m p le s are to be sh ip p e d frozen, it is n e c e s s a r y to
plan to u s e low -tem p erature co n taine rs with a sufficient q uantity of
dry ice, and p o ssib ly divided into co m p artm en ts (to avo id the risk of
b roken vials) and a control indicator to s h o w a p o ssib le b reak in
m aintaining cold tem perature. Fo r b acteriolog ical or virological
sp e c im e n s, p ac k a g in g s u c h a s that sp eci-fied b y th e .C enters for
D i s e a s e C ontrol ( C D C ) in the U S A m ight be useful: a triple screw top test tube with a b so rb en t insulation b etw een the test tu b es
(25).
T h e shipp ing c o m p a n y m ust be c h o s e n in ad vance. It is preferable
that the ship p er alw ay s be the sam e, and that he sho u ld b e
exp erien ced with this type of shipm ent.
W h e n s am p le s m ust be ship p ed a c r o s s international borders, it is
useful to enlist the a ss is t a n ce of a fonN ard ing ag ent exp erien ced in
cu st o m s hand ling p ro ce d u re s with su ch ship m ents.
Th e ship p ing certificate m ust be filled out accord ing to a predeterm ined m od el and contain at least the follow ing inform ation:
- the so u rc e of the

sa
- t
ad d
e;
- t
tem
ur
sto
of
sa
-

sp
tio
pa
pr
on
be
(b
og
sp
ns
rad
ve
sa
for
reg
ns
se
an
rec
s
co
an
air
re
ns
sh
be
ap
- t
d at
tim
de
e.

3. C ENTRALIZED LA B O R ATO RY

At the s a m e time, the a d d r e s s e e m ust be inform ed, p referably in w riting (telex or fax) of the
n um b er of s a m p le s sent, the m od e of transp ort, the tim e s a m p le s w ere sent and the sche d u led
tim e of arrival. T h e ship m ent m ust take into acco unt the duration of transp ort. It sh o uld take
place b etw een M o n d a y and W e d n e s d a y to avoid w e ek en d delivery, w here there is too great
a risk of sto rag e und er unsuitab le cond itions until the follow ing M o n -d ay. M e a s u r e s to be taken
sh ou ld also be sp ecified in the event of a d elay in delivery. T h e sh ip p ing c o m p a n y will sp ecify in
w riting the m axim um tim e for transport to the lab oratory that it can en sure.
Fo r s o m e tests, it is w ise to h ave the d isp atching laboratory keep an aliquot of each test tub e
und er g o o d sto rag e cond itions a s a b a ck u p in ca s e a prob-lem o c cu rs during transport of
sam p les.
2.4. R e c e p t i o n a n d s t o r a g e of s a m p l e s
T h e laboratory to w ho m s a m p le s are sent m ust hav e a p roced ure for their reception.
T h is co n si s ts of inspecting and counting sam p les, alon g with the filling out of a certificate
sp ecifying their cond ition, the date and tim e of arrival and cond i-tions for later storage, ad ap ted to
the p lanned a n a ly s e s (for infectious dis-e ases, sero lo g y, tum or m arkers, etc). It also m a k e s
p rovision for w hat m ust be d on e if a ship m en t of s a m p le s arrives unexp ected ly, outsid e of

162
163

norm al
w orking
hours. Lastly, it is
ad vis ab le to m ake
a blank run of the
ship p ing
cycle
before starting up a
trial requiring the
transport
of
biological sam p les.
In m ulticenter trials,
the u se of a
centralized
laboratory s e e m s
to b e a useful
solution for the
interpretation of
results (6,14,27).
Its ad v an t ag e s are:

the u se of the s a m e m ethod and the s a m e re ag e nts for a s s a y s in

all su b jects;
- the results all co m p ly with the s a m e sy st em of quality a ssu ra n ce ;
- the u se of an autom atic syste m for d ata t ran sm issio n (single
com p uter syste m ) avoid ing cop ying and d ata entry and ab le to plan
im m ediate tabula-tion of certain results (23);
- the p ossib ility of havin g a sep arate p ro g re s sio n ch an n el for
s a m p le s in clinical trials, and for identification of p erson nel involved
and the p ro ce d u re s im plem ented;
- u se of the accountability of sa m p le s to m onitor sub ject
recruitm ent; - real-tim e m onitoring of enrollm ents b y the
s p o n s o r.
-

T he re are also dificulties w hich so m e t im e s m ay be of m ajor

im portance (27):
- certain laboratory tests are reliable only if d on e rapidly, and thus
on-site (e.g. so m e hem ato log y tests), and for others, the tim es and
cond itions for sto rag e com patible with a correct result are not w ellknow n or poorly d ocu-m ented ;

O n ly two p a g e s h a ve b een converted.

P le a se g o to https://docs.zone and S i g n U p to convert all
p a ge s.