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Most Sacred Heart of Jesus Cardiology and Valvular Institute

Nalini M. Rajamannan, MD, FACC


Visiting Scientist Mayo Clinic Telephone 920-451-4611
703 N 8th St Suite 303 Fax 920-451-4614
Sheboygan, WI

Dr. Milan Mrksich


Vice President for Research Northwestern University

May 21, 2020

Dear Dr. Mrksich, re: FWA Non-Compliance Reporting Letter to the VP

During the global pandemic of Covid-19, and the urgent need for intensive clinical trials to develop medical
therapies to slow and prevent Covid-19. I present to you evidence as an ARRA awardee who holds lifelong
responsibilities to report violations of the FWA for Northwestern. As a former investigator and an eye-
witness, I have reported these facts since I first learned that these violations were ongoing since July 2007.

I am also sending this information to the leaders of the FDA, the NIH, the United States Senate and the
House of Representatives, who have worked tirelessly to help protect the US citizens who have been injured,
and who had at the time of their surgery has no idea that they were participating in a clinical trial to test the
device for safety and efficacy.

I present to you all in this open reporting letter to the Institute Officer at Northwestern University,
new evidence of non-compliance involving countless research violations resulting in deaths, heart attacks,
and reoperations involving Northwestern University’s Federal Wide Assurance (FWA) 1549. I will also
present a chronology of my 14 year history of reporting.

I have included the federal authorities as an eye-witness to my reporting to the Institute officer today, as in
the past, Northwestern attorneys have sent cease and desist letters to stop my efforts, and also have retaliated
severely in my effort to help these patients.

The experimental research study began on March 15, 2006. I am an eye-witness and a former collaborator, as
the Valve Director for Northwestern in 2006. The study was designed to test the prototype version of the
Model 5100 and a novel experimental caliper measurement using the prototype version of the Model 1155
calipers, which required human subjects to verify the design of the ring, and the experimental protocol to
implant the ring. I was informed by the senior investigators that the patients were receiving full informed
consent for their participation to receive the experimental prototype the Model 5100, the Myxo ETlogix ring,
and the caliper measurements utilizing the Model 1155 prototypes.

I will present to you evidence that the device was investigational since March 2006 as confirmed by the
Food and Drug Administration, and that there was no informed consent as confirmed by
Northwestern University’s own IRB on July 17, 2007.
In July 2007, after a patient developed severe life threatening complications and revealed to me that she did
not sign an informed consent to participate in the study, I reported to Northwestern officials immediately the
evidence of non-compliance and removed my participation from the prospective clinical trial to test the
Myxo ETlogix Ring Model 5100 and the Model 1155 calipers.

Instead of verifying the status of the devices with the FDA, the general counsel for Northwestern, wrote the
device manufacturer who claimed the device was FDA cleared as of March 2006. Facts written in a three line
email to the attorney Ms. Julia Lynch and the Principle Investigator Dr. Patrick McCarthy.i

Recently, I learned from an FDA FOIA, that Northwestern University’s IRB was performing the annual
review of the study protocol 1532-004, to test, study and publish the data as related to the Model 5100 the
Myxo ETlogix Ring and the caliper 1155 prototype.

Instead of renewing the protocol for a retrospective chart review as indicated in the renewal application in
June 2007 for IRB 1532-004, Northwestern University’s IRB requested the proper paper work be submitted
to make the study compliant.

Ms. Osafo the coordinator for the IRB, discovered that the protocol 1532-004 was not a retrospective chart
review but a “prospective” study, in other words, a human experimental clinical trial testing the Myxo
ETlogix Model 5100 heart valve and the caliper measurements to implant the ring using Model 1155
calipers. Both versions of the prototypes were never cleared for use by the FDA as of today.

On July 17, 2007, The Principle investigator and Northwestern University Institutional Review Board
approved the termination of IRB Project Number 1532-004. The IRB Coordinator Ms. Tasha Osafo
requested the termination once the Principle investigator indicated that he would not continue the prospective
study to test the Myxo ETlogix Ring Model 5100and 1155 in patients, and he had no plans to submit the
proper paperwork to make the study compliant.ii

However, after the investigator signed the federal termination agreement, to stop the testing of the Model
5100 the Myxo ETlogix heart valve ring and the use of the calipers Model 1155, the authors on the study,
continued the study for another four months and then published the results in the Journal of Thoracic and
Cardiovascular Surgery in July 2008, without an official active IRB protocol.iii In the publication, the authors
claimed, that there was an IRB approval for the study, and that the FDA had approved the device.

Both statements are false.

In July 2008, myself and one of the human subjects enrolled without consent, informed the FDA of the
testing of the Model 5100.

The FDA Ombudsman and several other FDA officials, confirmed that they had no evidence of any
registration, nor any FDA approval for use in humans. In fact, the FDA recommended a recall of the Model
5100 and the Model 4100, which finally occurred on December 4, 2008.

Both the Model 5100, the Model 4100 heart valve rings and the calipers the model 1155, are medical devices
tested at Northwestern University, under IRB protocol 1532-004.iv
On December 4, 2008, Senator Charles Grassley launched several Senate Investigations under the Finance
Committee, and again under the Senate Judiciary Committee regarding the testing, failure to obtain informed
consent and failure to obtain an Investigational Device Exemption between 2008-2014.v

On, March 4, 2009, and again on July 16, 2009, the FDA confirmed the investigational status of the Model
5100 to the Honorable Senator Charles Grassleyvi and to the patient Ms. Antonitsa Vlahoulis.vii

Northwestern submitted several responses to the Senator’s questions, but failed to mention the fact that the
IRB protocol 1532-004 was terminated in July 2007 for non-compliance and failure to change the study from
a retrospective chart review to a prospective trial. Northwestern also failed to mention to the Senator that the
investigators continued the study without FDA and IRB approvals.

Edwards Lifesciences reported to the committee that the testing results resulted in over 122 failure modes,
which are the product defects listed for the prototype Model 5100 resulting in several major modifications
necessary to improve the Model 5100 for safety and efficacy prior to the sales on the US market.viii

I presented the July 16, 2009 FDA letter to Dr. Jay Walsh, the VP for research at the time and Institute
Officer, and to Dr. William Lowe, Dean for faculty affairs, during a meeting on the Evanston campus in
2009, and again in an email sent on August 22, 2009 at 2:22 pm.

• The evidence presented so far, confirms that at least 100 patients received an investigational Model
5100 and caliper measurements without consent. The study was published without an official active
IRB protocol.
• The Office of Research Integrity claimed that protocol 1532-003 which is an atrial fibrillation
database turned into cardiac surgical outcomes registry was the IRB approval to publish the data,
which again never provided informed consent.ix
• The FDA FOIA confirms that the outcomes protocol 1532-003 was not the approval to test the
annuloplasty rings, instead the IRB protocol 1532-004 terminated in July 2007 was the official
protocol to study the experimental Model 4100, Model 5100 and the Model 1155.
• Facts not revealed to the patients, to Senator Grassley, and to the courts in Illinois, and to the press.

In 2009, Senator Richard Lugar also wrote the FDA on behalf of the patients from Northern Indiana. In the
November 2009 letter, the FDA confirmed the fact at least 667 patients received the investigational device
the Model 5100, prior to the recall on December 4, 2008.

This fact was confirmed by Dr. Jeffrey Shuren, the head of the FDA CDRH, in a statement to the Chicago
Tribune in May 2011, that both the Model 5100 and the Model 4100 are considered investigational during
the testing.x Furthermore, the FDA confirmed that the study published in the Journal was the study the FDA
cited to confirm safety and efficacy for the FDA.xi

Never accounting for the deaths and heart attacks sustained during the experimental surgeries.

In August 2017, on behalf of the patients in the state of Wisconsin, Congressman Glenn Grothman sent two
letters to the FDA requesting a response to the evidence demonstrating the design control testing of the
device, under 21CFR820.30, including evidence of the failure to obtain informed consent, evidence of
missing adverse events including deaths, heart attacks and reoperations, and evidence of the design control
testing. The FDA then chose to not pursue reporting to the patients which was reconfirmed in a response to
the first letter to Congressman Glenn Grothman in 2017.xii
The FDA has not responded to his second letter.
• Yet, to this date the FDA has not provided a response to Congressman Grothman.

In 2017, Senator Ron Johnson also sent information to HHS, but to this date the final results of the HHS
investigation have not been revealed.

In November 2018, another patient died due to complications from the experimental surgical protocol from
the terminated IRB protocol 1532-004, as published in the Daily Northwestern.xiii

As a result of this patient’s death, in December 2018, the FDA provided a Freedom of Information from the
inspection records of Northwestern University IRB. The FOIA confirmed the following factsxiv:

• The protocol 1532-004 was terminated in July 2007 secondary to the non-compliant protocol.
• There was no informed consent for the testing of the significant risk Model 4100 and the Model
5100.
• There was no FDA documentation of the status of the device in the IRB files.
• There was no response by the office of human research protections to inform the hundreds of patients
who received the investigational devices without consent and without FDA investigational device
exemption.

In December 2018, The FDA’s biomedical research office, BIMO, met with the patients and their families
and myself regarding the injuries sustained during the testing and the patients are awaiting a response from
the FDA and Northwestern University.xv

On July 13, 2019, and December 6, 2019, Northwestern and Edwards Lifesciences attorneys claimed to the
Illinois Appellate Court and the Illinois Supreme Court (ARDC) that the Model 5100 was “FDA approved
for use in humans” based on the three line email sent from the device manufacturer sent to Northwestern
General Counsel in the Fall of 2007.xvi

Evidence so far demonstrates:


• No Active IRB protocol to test the Model 4100 and the Model 5100 during the duration of the study.
• No Investigational Device Exemption during the study which the FDA confirmed is necessary to test
the Model 5100 Myxo ETlogix Ring
• Publication of the test results of the Model 5100 Myxo ETlogix Ring without the University IRB
approval and without an IDE, and after the IRB informed the investigators not to publish the results if
they chose not to submit the paperwork to the IRB.
• Missing adverse events as reported by the student newspaper the Daily Northwestern in 2019
• 122 failure modes, i.e. .product defects, requiring major modifications of the device without
informing the patients of the potential risk imposed from the first prototype version implanted in their
hearts during the study as reported by Edwards Lifesciences to the United States Senate Finance
Committee.
• Northwestern and Edwards Lifesciences attorneys fail to report the investigational status of the
device since March 2006, to the Illinois court system.

On March 6, 2020, the FDA Ombudsman held a 30 minute conference call with Dr. Rajamannan to review
the evidence regarding the violations of the human subjects. This meeting was recorded by the FDA, myself
and reported by the reporter for KIMT in Rochester, MN.
The most recent violations of Northwestern’s Federal Wide assurance 1549:

In 2020, I have been provided with letters sent by the Northwestern’s IRB’s to one of the human subjects
illegally enrolled in the protocol 1532-004:

Ms. Heather Gipson, in 2011 confirmed that the patient was enrolled against his wishes and his data was
included in the study.xvii

Ms. Natalia Henry, in 2018, confirmed that Northwestern “had thoroughly reviewed the matter in
2011….and considered the matter closed.”xviii

Therefore, acknowledging that the human subject was enrolled in the study without consent, and that his data
was included in the study.

The patient has requested that Northwestern retract his data from the publication in 2008, however, he
received the attached letter from the chairman of the IRB claiming, the matter was closed.xix

Later that year, the patient discovered for the first time evidence of the severe injury he sustained during the
experimental heart surgery, which we all know now that he never signed any form of consent.

Natalia Henry’s letter closing the investigation, and not allowing the human subject to present the new
information of the injury is another example of the IRB’s non-compliance and unwillingness to protect these
human subjects.

The patient’s injury not revealed to him during his index hospitalization by the surgeon who is responsible to
report the injury, also not revealed to him in 2011 by Ms. Heather Gipson the chairman of Northwestern
University’s IRB in 2011, and again not revealed to him by Ms. Natalia Henry in April 2018.

Northwestern University has failed to inform the patients of the testing of an investigational significant risk
heart device the Model 4100 and the Model 5100.

Northwestern University has failed to retract the study without an IRB, and without an FDA IDE.

Northwestern University has failed to provide the lifelong protections from the unauthorized prospective
testing of the Model 5100, Myxo ETlogix Ring, confirmed investigational as of March 2006.

Northwestern University’s IRB chairman has stopped any future investigation of the unauthorized testing of
the investigational Myxo ETlogix Device, placing the human subjects at lifetime risk without the lifelong
support of the office of human subject research subjects, under 45CFR46 and 21CFR820.30 and 21CFR50.

During the Covid-19 pandemic, the human subjects are currently participating in the ongoing clinical trials
which include Northwestern University. The Adaptive COVID-19 ACTT trial (NCT04280708) patients
enrolled at Northwestern are at risk due to the ongoing non-compliance of the Federal Wide Assurance 1549,
since March 2006.

As the newly appointed Vice President for Research, I present to you this evidence as a former co-
investigator, ARRA/NIH awardee, VA physician at Northwestern University, who holds life-long reporting
responsibilities, until these patients are provided with the proper health care for the unauthorized
experimental surgeries, under the IRB protocol 1532-004.

A protocol which was terminated on July 17, 2007, by Northwestern University’s own IRB.

It is clear that the repeated missteps by Northwestern University office of human subject research, and the
non-compliant Federal Wide Assurance 1549, in responding to the unauthorized testing of heart rings
without FDA oversight and without patient consent, is costly for the patients from the device testing and now
for the patients who are enrolled in the ACTT Trial, and all of the other protocols which fall under
Northwestern University Federal Wide Assurance.
As the result of the non-compliance, the COVID-19 clinical trials will now be under critical review with the
knowledge that Northwestern University has a 14 year history with firm evidence of failure to inform
patients of the human experimentation, failure to help the patients who sustained injuries, the failure to apply
for an FDA IDE, the failure to report the recall and the ongoing failure by the current chairman of the IRB to
keep the investigation of the experimental studies ongoing as required under the HHS and global laws which
protect human subjects dating back to the Nuremberg Code.
I have requested meetings with the Northwestern University leaders for years, but these requests have been
rejected.

I have upheld my federal responsibility to continue to help these patients. As the Institute Officer and Vice
President for Research your response should be immediate with no further delays as human lives are at stake.

Respectfully,

Nalini M. Rajamannan, MD

cc:

Honorable Senator Charles Grassley


President Pro Tempore
Senate Finance Committee, Senator Charles Grassley

Honorable Congressman Glenn Grothman

Honorable Senator Ron Johnson


Chairman Senate Committee on Homeland Security

Dr. Janet Woodcock


Director of Drug Evaluation and Research
Food and Drug Administration
Dr. Barbara Mulach
Director of Scientific Coordination and Program Operations
National Institute of Health

i
https://www.scribd.com/document/442173743/ORIRajamannanResponse-080918
ii
https://www.scribd.com/document/440983779/R-CHI-Northwestern-IRB-Exh-15-Dtd-8-8-08-Redacted
iii
https://www.scribd.com/document/394411803/Paper-Ring-Highlighted-Problems-Model-
5100?secret_password=pX8iBU8RDj3Lr2WmLsRw
iv
https://www.scribd.com/document/371299198/FDA-Recall-Documents-2-Heart-Valves-2-
2?secret_password=nvwfkIdwnMmOHle506tN
v
https://www.finance.senate.gov/ranking-members-news/grassley-seeks-answers-about-the-use-of-a-heart-device-in-clinical-
research
https://www.grassley.senate.gov/news/news-releases/grassley-seeks-documents-northwestern-university-heart-valve-device
https://www.grassley.senate.gov/news/news-releases/continues-press-northwestern-university-heart-valve-disclosures
vi
https://www.scribd.com/document/440983640/FDA-Response-to-Senator-Grassley-2009
viiviivii
https://www.scribd.com/document/442174497/FDA-Letter-7-16-09-Vlahoulis
viii
https://www.scribd.com/document/399069069/Final-FDA-MEETING-JMJ
ix
https://www.scribd.com/document/442173743/ORIRajamannanResponse-080918
x
https://www.chicagotribune.com/lifestyles/health/ct-met-medical-devices-patients-20110522-story.html
xi
https://www.scribd.com/document/442037095/Lugar-FDA
xii
https://www.scribd.com/document/442173802/FDA-July-2017
xiii
https://dailynorthwestern.com/2019/05/23/top-stories/years-after-surgery-documents-renew-patients-malpractice-claims-
northwestern-memorial-doctor/
xiv
https://www.scribd.com/document/365868212/NW-IRB-Resp-Ltr-June-2011?secret_password=gsKbPTv07dTUCjEhvASA
xv
https://www.scribd.com/document/399069069/Final-FDA-MEETING-JMJ
xvi
https://www.scribd.com/document/442173743/ORIRajamannanResponse-080918
xvii
https://www.scribd.com/document/365868212/NW-IRB-Resp-Ltr-June-2011?secret_password=gsKbPTv07dTUCjEhvASA
xviii
https://www.scribd.com/document/462451667/2018-04-04-NW-IRB-Response-Ltr
xix
https://www.scribd.com/document/365868212/NW-IRB-Resp-Ltr-June-2011?secret_password=gsKbPTv07dTUCjEhvASA