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 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

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
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 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
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.
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 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 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 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 indicating that this
problem would be addressed. 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