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 920-451-4611
Sheboygan, WI
www.SacredCardiology.com

November 7, 2022

President Michael Schill

2-130, Rebecca Crown Center
633 Clark Street
Evanston, IL 60208

Dear President Schill:

As the newly minted President for Northwestern University, I am reporting to you the
ongoing federal violations of Northwestern University’s Federal Wide Assurance 00001549,
since at least March 2006. I am a former Associate Professor at Northwestern University, and
Valve Director for the Bluhm Cardiovascular Institute. I am also an eye-witness as a former
collaborator to the clinical trial testing Dr. Patrick McCarthy’s invention the model 5100. I
understand from the work at your previous institutions, as the Dean of the Law School at the
University of Chicago and President of the University of Oregon, that your leadership
commanded transparency in the governing of these institutions. My role as a former
investigator on a federal clinical trial led by Dr. Patrick McCarthy and Dr. Robert Bonow,
discovered that the senior physicians failed to apply for the federal authorizations required
prior to the testing of significant risk annuloplasty ring in a safe and legal manner in patients.
The patients, as well as my reporting. are protected under Northwestern University’s Federal
Wide Assurance 00001549. It is my responsibility to continue to report the federal violations
until the patients are informed, the ongoing harm is resolved, and Northwestern University’s
federal wide assurance is placed in federal compliance. According to the public FDA
database, there are a large number of injuries and deaths related to the Myxo ETlogix as
listed in the graph below, from 2006 to 2022.
President Schill, I am certified in the training of the IRB federal laws which protect human
subjects in the United States since 1989. I have held many IRB protocols at the Mayo Clinic
and Northwestern University from 1996 to the present. I am an expert in Valvular Heart
disease. My research training began in 1987 at the Mayo Clinic, as funded by several NIH
training grants. I was recruited in 2000, to start a basic science research laboratory to test the
mechanisms of Valvular Heart disease at Northwestern. I received many grants during my
role as a basic scientist, and echo lab director for the VA Hospital Lake Side. As an NIH
ARRA Obama investigator, and the recipient of a non-Retaliation Title IX statement from
Northwestern University, I have lifelong federal responsibilities to report these violations to
Northwestern University. The General Counsel for Northwestern University continue to
violate the non-retaliation Title IX statement from July 2007, by making defamatory
statements regarding my credibility, instead of addressing the risk and harm to research
patients.

My reporting of Federal Research harm to you President Schill, under the FWA requires a
five day response time, which is November 11, 2022.

https://irb.northwestern.edu/submitting-to-the-irb/reportable-new-information.html

In 2006, I was promoted to the role as Valve Director, and I was in the operating room on
several occasions reviewing Dr. McCarthy’s experimental surgeries, before I learned the
truth that Dr. McCarthy was not providing informed consent for the patients in May 2007.
My role as a research collaborator, was to see the patients pre-operatively and review their
echocardiogram results before and after surgery. I removed my participation in May 2007,
once the first patient suffered a serious adverse event. By her own discovery, that the device
was not listed in the Edwards Lifesciences brochure, she confirmed that Dr. McCarthy did
not inform her that he was enrolling her in a prospective clinical trial to test the McCarthy
Myxo ring and his experimental sizing protocol. Furthermore, in 2008, the FDA first learned
of the testing and eventual marketing and sales of the device, across the state lines.
I have several lines of evidence regarding the FDA’s federal determinations the testing and
sales of the Model 5100, annuloplasty ring and investigational protocol to size the Edwards
Lifesciences annuloplasty rings. Northwestern’s letters since 2007, addresses the three line
email, which the general counsel and Dr. McCarthy received in August and September 2007,
claiming the device was internally approved for use in humans by the company. A statement
which is incorrect according to the evidence submitted to the Senate Finance committee and
also the FDA’s statements to Senator Grassley and President Obama. Instead of immediately
contacting the patients that the Myxo ring is classified investigational, Northwestern
continued to allow the surgeon to test his experimental protocol. (ORIResponse Appendix 1)

To reiterate, Northwestern University’s IRB played a critical role in the experimental

research testing of the Model 5100, the Model 4100 and the sizing protocol. The IRB
protocol l532-003 is the minimal risk database, which collected patients’ medical history, but
never disclosing the fact that they were being enrolled prospectively for a first in human use
clinical trial to test the inventions which were undergoing testing at Northwestern University
as funded by Edwards Lifesciences. In 2008, the prototypes were also undergoing
bioengineering testing at Edwards Lifesciences in house bioengineering plant. This is a
violation of Northwestern University’s FWA 00001549. (FDA FOIA Documents)

As discovered during the Senate Judiciary investigation, the University issued a HIPAA
waiver in June 2006, to waive the patients’ rights to know that their data was being used for
future publications. The Waiver is one of two University’s IRB protocols to test the
surgeon’s devices, 1532-003 a minimal risk database, and 1532-004, which specifically
outlines the Myxo protocol and sizing experiment. The second protocol 004, was approved
under an expedited HIPAA waiver granted in June 2006. The IRB coordinator, Eileen Yates
did not question Dr. McCarthy regarding the status of the Model 4100 and 5100 protocols
outlined in the submission. (FDA FOIA Documents) (Senate Responses Appendix_2-3)

In May 2007, as revealed pursuant to an FDA’s FOIA 2018-9249, the principal investigator
applied for a renewal of the IRB protocol 1532-004, but this time, his application was denied
immediately as submitted.

The University’s IRB coordinator, Tasha Osafo, requested paperwork to be submitted to

comply with the federal laws for a “prospective study.” Instead of submitting the
paperwork to place the study in compliance, the investigator terminated the protocol,
agreeing to not perform future studies, no future data analysis, and no future publications.
Instead of terminating the protocol as agreed upon on July 17, 2007, the investigator
continued the study protocol until November 2007, and published the scientific paper in
July 2008. FDA FOIA Documents: R_CHI Ex 14, 15
Furthermore, the scientific results were published also in an AATS abstract, formerly
including my name, before the AATS removed my name due to Dr. McCarthy’s ethics
violations, as confirmed with Michael Chin in 2021. Dr. McCarthy published a second
scientific publication of the surgical results in patients as of July 2008.

https://www.jtcvs.org/article/S0022-5223(08)00278-X/fulltext

What is of great concern, is that the surgeon continued to test the protocol 1532-004, from
2006-2020, again using a tissue collection minimal risk database, STU000012288, with a
waiver as cited in his two 2020 publications. Never providing informed consent as required
under Northwestern University’s FWA 00001549.

https://pubmed.ncbi.nlm.nih.gov/33168163/

Despite the fact that the FDA concluded after inspecting the University’s IRB in August 8,
2008, that patient notification was warranted, the protocol continued without informed
consent and patients were not informed.

The hospital sent a letter to the patients in January 2009, as required by the FDA Compliance
officer Kezr. However, the letter Northwestern’s CEO sent to patients does not mention that
the device was investigational at the time of the first in human study, and that the results
were paid for by Edwards Lifesciences to garner Market share of their device portfolio.
Furthermore, Northwestern’s CEO failed to include in the January 2009 letter, that the device
was removed from the US market for misbranding violations on December 4, 2008. The
FDA required Edwards Lifesciences to recall the Model 4100 and 5100, for failure to alert
the FDA of the testing of the prototype under design control federal laws 21CFR820, and
sales of the device on the US market across state lines without registering the device in the
FDA’s listing database. ( See Dean Harrison letter: Appendix 4)

The notification required is for all of the patients who underwent the terminated
experimental prospective “Myxo protocol 1532-004,” from 2006-2020. The number of
patients is a total of 1000+ to date.

There are many patients who have a Pre-Clinical Prototype implanted, and the modified
version of the Myxo ETlogix ring and who underwent the experimental sizing protocol, and
who have no idea the device was placed in their hearts, using an experimental sizing method
performed by the inventor Dr. Patrick McCarthy, according to the November 26, 2008 FDA
letter, all of these patients are required to be informed. (FDA determination letter:
Appendix_5)

The design history of the device, includes three different versions of the Model 5100 and I
refer herein to them as (i) the pre-clinical prototype version of the Myxo ETlogix funded by
Edwards and tested at Northwestern, in humans from February 2006 through November 2006
(“Pre-Clinical Prototype”); (ii) the Myxo ETlogix, is a substantially modified design of the
Pre-Clinical Prototype based on the November 2006 Failure testing results which uncovered
122 failure modes in the prototypes already placed in patients; and (iii) the dETlogix (the
Myxo ETlogix with modified IFUs) sold by Edwards after receiving FDA clearance until the
company pulled the DETLogix off the US market, sometime after 2016. The fourth ring, the
IMR ring Model 4100 was also tested under Northwestern University’s FWA, but I do not
have the federal evidence surrounding the testing of the Model 4100, except for the recall
documents.(Recall documents_Appendix_6)

The published data for the IMR ring:

https://pubmed.ncbi.nlm.nih.gov/16820643/

The clarifying chronology that I set forth in this letter is based on information provided
primarily from the Senate Documents, FDA FOIA 2018-9429, and the Circuit Court case in
Cook County.1

A central element in presenting this further information to you is my ongoing federal

responsibility to report to Northwestern University, the facts that neither Edwards
Lifesciences, the sponsor and manufacturer, nor Dr. McCarthy, the principal investigator,
obtained an Investigational Device Exemption (“IDE”) for the Pre-Clinical Prototype. An
IDE is a federal requirement, which notifies the FDA of the first in human clinical trial
testing of a device which is a major modification of the predicate device. Furthermore, I am
an eye-witness to the dataset, which indicates experiments which Dr. McCarthy performed to
test in patients the Pre-Clinical Prototype in at least 59+ patients apparently did not obtain the

1
I have developed this chronology of events from various documents attached as Appendices to this letter and also from the sworn
testimony of Dr. McCarthy in a Cook County, Illinois civil suit filed by a patient in whom a Pre-Clinical Prototype was implanted
informed consent of those patients. I am also concerned that Medicaid and Medicare
reimbursement for implantation of the Pre-Clinical Prototype and the Myxo ETlogix may not
have been appropriate.

The chronology as outlined in the Senate and FDA FOIA Evidence:

On October 13, 2005 during a dinner meeting at Tommy Bahama Restaurant, Edwards
engineers provided several options to Dr. McCarthy for the design of his invention the model
5100 annuloplasty ring prototype. The summary of the meeting and the decision making
process to choose which prototype would best represent the model 5100, is described in the
Design Input Memo dated November 11, 2005 (Appendix A). Dr. McCarthy tested the
prototype ring design during the dinner meeting by placing a suture through the ring during
the meeting. Dr. McCarthy also tested the caliper design, Model 1155, to perform the novel
sizing algorithm. The algorithm is part of the Northwestern University IRB protocol 1532-
004, which was terminated on July 17, 2007 by IRB Coordinator Osafo for non-compliance.
(FDA FOIA 2018-9249, r_CHI Ex 14) Edwards Lifesciences bioengineers and Dr.
McCarthy, agreed Dr. McCarthy would be the first to implant the Pre-Clinical Prototype in
ten patients’ hearts. If those procedures were successful, they would consider release of the
Pre-Clinical Device to additional surgeons for additional implants.

On February 27, 2006, Edwards filed a first internal justification to file (“First JTF”)
outlining the modifications made to a predicate device, the Geoform Annuloplasty Ring,
which resulted in the Pre-Clinical Prototype (also referred to as the McCarthy Type II
Annuloplasty Ring, Mitral Model 5100) (Appendix B).

Dr. McCarthy conducted the limited release testing of the Pre-Clinical Prototype as a first in
human clinical trial, from February to May 2006. (AATS Abstract, May 2007) Dr. McCarthy
then reported the results of that testing to Edwards and then approved the release of the Pre-
Clinical Prototype to four additional surgeons. From May to November 8, 2006, Dr.
McCarthy and the four additional surgeons implanted the Pre-Clinical Prototype in a total of
59+ human patients and provided input to Edwards which resulted in the further safety
modification of the Pre-Clinical Prototype. The further modifications also incorporated
information from implanting physician/surgeon surveys and Edwards’ internal
bioengineering tests. The first and second limited release implantation and testing of the Pre-
Clinical Prototype in human subjects occurred without FDA premarket notification and no
clearance nor an IDE and without informed patient consent.2

2
Northwestern University and hospital confirmed to the Senate Judiciary Committee, that patients at Northwestern Memorial
Hospital where Dr. McCarthy implanted the Pre-Clinical Prototype consented only to be listed in the IRB outcomes registry. Dr.
McCarthy did not inform Northwestern’s IRB or the patients that he was testing a Pre-Clinical Prototype. He and the sponsor
Edwards Lifesciences, never applied for an IDE. The IRB first learned that in July 2007, after a patient who had the Pre-Clinical
Based on the foregoing testing of the Pre-Clinical Prototype 122 possible failure modes were
identified in a failure mode effect analysis (FMEA) dated November 2, 2006 (Appendix C).
As a result, five major modifications were made to the Pre-Clinical Prototype resulting in the
clinical version of the device, the Myxo ETlogix, including a marker to designate the front
from the back of the ring, to ensure safety during the implantation of the ring. Previously, the
surgeons have to guess which direction the device went into the heart. The Myxo ETlogix
was the production version to be sold commercially in the United States without further
anticipated modification, without FDA registration, without an FDA submission for a PMA,
nor an official FDA 510(k) clearance, as confirmed by the FDA Congressional to Senator
Grassley and President Obama.

On November 20, 2006 Edwards filed a second internal justification to file (“Second JTF”)
(Appendix D). First sales of the Myxo ETlogix in the United States were initiated sometime
after the Society of Thoracic Surgeons meeting in January 2007.

Results of the combined testing of the Pre-Clinical Prototype and the Myxo ETlogix were
published in the Journal of Thoracic and Cardiovascular Surgery in July 2008 (Appendix E).
The reported results spanned the time period from March 2006 through November 2007.
However, the publications indicate that the reported results were “cherry-picked” from the
totality of the data, as discussed below.

In August 2008, the FDA contacted Edwards regarding the marketing of the Myxo ETlogix
without FDA pre-market clearance. By letter dated August 15, 2008 Edwards reported to the
FDA that it believed it did not need to submit a new premarket notification (510(k)), as
Edwards believed that the Myxo ETlogix was similar to predicate devices sold and approved
by the FDA via a 510(k), namely the Geoform and the Physio rings. (Please review the
attached August 15, 2008 letter, Appendix_7)

In response to the testing and sales of the Myxo ETlogix without FDA registration or
approval, representatives of FDA and Edwards met on October 14, 2008 during which FDA
confirmed that there was a need for clinical testing of the Myxo ETlogix in human patients,
confirmation of the “major modifications made to the Myxo ETlogix ring” including shape,
biomaterials and indications for use (Appendix F). The FDA commented during the meeting
that Edwards could only use human patients with myxomatous disease to test the device as
there was, at that time, no animal model equivalent to validate the Myxo ETlogix prior to
premarket notification. The FDA confirmed that the company cannot internally approve the

Prototype implanted needed her device replaced. The patient informed me that she had not consented to be implanted with an
experimental device. I promptly reported this to the General Counsel, medical school deans of Northwestern University,
Northwestern Memorial Faculty Foundation and Northwestern Memorial Hospital.
device as it was not a minor modification, but a major modification to the predicate device
(Appendix F).

During the October 14 meeting the FDA also confirmed that the validation of the Myxo
ETlogix was necessary prior to FDA clearance as the Myxo ETlogix had significant changes
to the design, changes to biomaterials in addition to changes to the surgical technique used to
implant the valve in the heart, which were different from the predicate devices. The FDA
confirmed that these test results were necessary to approve the third generation of the device
on April 10, 2009. The third generation of the device was the dETlogix, with modified
indications for use and a modified name to rectify the misbranding of the Myxo ETlogix
(Warning Letter - Appendix G). The Myxo ETlogix ring never received FDA approval for
myxomatous disease and as of today, would require an IDE as disclosed to Senator Charles
Grassley, President Barack Obama, and one patient Antonitsa Vlahoulis. ( IDE letters dated
3-4-3009 and 7-16-2009, Appendix 8_9)

As of today, the issue for Northwestern University is the ongoing harm as listed in the public
FDA Database, MAUDE, referenced earlier in this letter. Edwards’ 2008 submission to the
FDA disclosed an adverse event rate of only approximately three percent. Dr. McCarthy
testified in the aforementioned Cook County civil suit (FN1) that he performed
approximately 59 initial implants between March and November 2006 and published the
majority of the results in scientific abstracts and publications. His testimony confirmed that
at least one patient sustained a heart attack during the placement of the Pre-Clinical
Prototype. However, this heart attack and other adverse events, including a second heart
attack, several re-operations and two deaths, were not included in the published manuscript
nor the information considered by the FDA during its 2008 compliance review or in making
its decision to clear the dETlogix for marketing. It is now known that the adverse event rate
was closer to at least 50 percent, not the previously-represented three percent. Dr. McCarthy
confirmed during his Cook County testimony that he removed five patients’ test results from
the data released for publication in Journal of Thoracic and Cardiovascular Surgery in July
2008 and from the information Edwards submitted to the FDA in 2008 (Transcript of
Testimony - Appendix H).

I believe that if FDA had known the true adverse event rate of 50%, and if Edwards and Dr.
McCarthy had not withheld key information about patient deaths and heart attacks, FDA
would have required an immediate IDE for the Model 5100, and further clinical testing
instead of clearing the dETlogix for marketing based on the missing adverse events.

Based on data published in July 2008, missing from the publication are at least two deaths,
two heart attacks and several reoperations. Both patients Maureen Obermeier and Dr. Albert
Edwards were never informed of their adverse events, by Dr. McCarthy for over 5 and 9
years respectively. Northwestern University IRB confirmed to Dr. Edwards, 5 years later that
he was never given informed consent. (See 2011 IRB letter to Al Edwards_Appendix_9)
Over 15 years, I have reported to Northwestern University and never intended to harm the
University or its reputation. As a matter of fact, quite the opposite. However, after many
attempts to communicate with the University about these problems, I received a handful of
responses, none of which indicate that this problem would be addressed. I also provided the
IDE letter to the VP for research Dr. Walsh twice in 2009, once during an in person meeting
at the Crown Center and the second time via email. No response from the leaders at
Northwestern University to stop the study, retract the paper and inform the patients.

Furthermore, as I know it is my obligation to protect the patients, I have attempted to reach

out to different media outlets over the years. There inquiries to the University resulted in
negative and retaliatory statements about me defaming my character. I would like to meet
with you, so that you can hear my plans for a successful resolution to this ongoing problem
which has placed numerous human research subjects at risk and Northwestern University’s
IRB in violation of the FWA 00001549.

Therefore, I pose the following additional questions to Northwestern University’s President

Schill and the University’s Board of Trustees, who I have been in contact with since 2009,
requesting a meeting to help the patients and to protect Northwestern University’s FWA:

1) Kindly indicate whether Northwestern University will evaluate the missing adverse
event data from the published study in the Journal of Thoracic and Cardiovascular
Surgery in July 2008, and the ongoing use of a waiver until 2020, once the Protocol
waiver 1532-004 was terminated by the IRB, and inform all 1000+ patients of the
testing of the Myxo protocol as determined by the FDA dating back to November 26,
2008 to protect these patients’ rights under the FWA 00001549?

2) President Schill will you meet with me, during the 5 day response time to the ongoing
federal violations, now that you have received this letter as of November 7, 2022,
under the five day response FWA requirement?

3) President Schill will you allow Dr. McCarthy to continue to experiment on patients
under Northwestern University’s FWA 00001549, without informed consent as
outlined in this letter and also by the Daily Northwestern in 2019?

Sincerely,
Nalini M. Rajamannan, MD,
Most Sacred Heart of Jesus Cardiology and Valvular Institute
Cardiologist and Heart Valve expert
(312) 498-9496

Attachments: Appendices Numerical, Appendices Alphabetical, FDA FOIA 2019_9249

Separate email: IRB Protocol 1532-003 and Protocol 1532-004, CV, and non-retaliation
evidence