- Posted October 9, 2013 by
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NORTHWESTERN UNIVERSITY RESPONSE TO THE HONORABLE SENATOR GRASSLEY CONTRADICTS THE OFFICE OF RESEARCH INTEGRITY STATEMENT TO THE PATIENT
In December 2009- The Wall Street Journal, Mundy and Favole wrote a story about the Myxo device, entitled:
Doctors' Spat Exposes FDA Loophole
The story published the ongoing investigation by the Senate Finance Committee of the University, the FDA and the Company.
They published and vetted the office of research integrity statements sent to the patient.
They also published the letter sent by the Honorable Senator Grassley to Northwestern University:
December 3, 2008
Henry S. Bienen, PhD President
Northwestern University 633 Clark Street
Evanston, IL 60208
Dean M. Harrison
President and Chief Executive Officer Northwestern Memorial Healthcare 251 East Huron Street
Chicago, IL 60611
Dear Dr. Bienen and Mr. Harrison:
The United States Senate Committee on Finance (Committee) has jurisdiction over the Medicare and Medicaid programs. As a senior member of the United States Senate and as Ranking Member of the Committee, I have a special responsibility to the more than 80 million Americans who receive health care coverage under those programs to ensure that taxpayer and beneficiary dollars are appropriately spent on safe and effective drugs and devices.
I recently received troubling allegations that the Myxo ETlogix 5100 Ring (Myxo Ring), an annuloplasty ring used in heart valve repair, has not been approved and/or cleared for marketing by the Food and Drug Administration (FDA). At the same time it appears that the Myxo Ring has been, and perhaps continues to be, implanted in patients by Dr. Patrick McCarthy, a cardiothoracic surgeon at Northwestern Memorial Hospital. Furthermore, I was informed that the device is being implanted without an Investigational Device Exemption (IDE), which would allow the device to be used in a clinical study to collect data in support of an application to the FDA for approval. It is my further understanding that Dr. McCarthy invented this device, which is manufactured by Edwards Lifesciences (Edwards), and receives royalty payments from Edwards.
These allegations were brought to my attention by Dr. Nalini Rajamannan, Associate Professor and Valve Director of the Bluhm Cardiovascular Institute at Northwestern University’s (Northwestern/University) Feinberg School of Medicine. In addition, Antonitsa Vlahoulis, one of the patients who received the Myxo Ring during her operation in April 2006, expressed concern to my Committee staff that this device had not been approved and/or cleared by the FDA when it was implanted in her without her informed consent.
Dr. Rajamannan and Ms. Vlahoulis also told my Committee staff that they have both brought their concerns to Northwestern. According to a letter that the University sent to Ms. Vlahoulis, dated September 18, 2008, Northwestern’s Office for Research Integrity completed its own investigation of the allegations and concluded that the implantation of the device was “not research and did not require IRB approval.” The letter also stated that Edwards confirmed in an email to Northwestern that the device was commercially available.
I am also aware of the fact that Edwards Lifesciences wrote in an email to Dr. McCarthy that “According to the FDA guidance document dated January 10, 1997…model 5100 is a minor modification of model 4200, GeoForm Annuloplasty Ring, cleared under K032250. The applicable 510(k) number for model 5100 is K032250.” I cannot judge whether or not the Myxo Ring required FDA approval or clearance; however, Dr. Rajamannan told Committee staff that, in her opinion, the Myxo Ring is not a minor modification because, among other things, the shape of the ring is triangular whereas other annuloplasty rings are oblong. She also told my staff that after bringing this matter to Northwestern’s attention, the University began to take action against her.
My Committee staff’s own search for the Myxo Ring on FDA’s website did not produce any information regarding the Myxo Ring other than 8 adverse event reports that were submitted to FDA’s Manufacturer and User Device Experience Database (MAUDE).
In investigating these allegations, I would appreciate Northwestern’s response to the following questions and requests for information. Please repeat the enumerated question and follow with the appropriate response.
1) Please provide the Committee with a copy of the report, memorandum, or any other documentation of the internal investigation completed by Northwestern’s Office for Research Integrity.
2) Please provide a copy of all internal communications and correspondence regarding the Myxo Ring and the use of the device as part of an outcomes study. This request covers the period of January 2006 through the date of this letter.
3) Please provide a copy of all communications and correspondence with Edwards Lifesciences and FDA regarding the Myxo Ring. This request covers the period of January 2006 through the date of this letter.
4) What information regarding the Myxo Ring was provided to the Institutional Review Board during its review of the protocol and consent form for the
outcomes study entitled, “Early and Late Outcomes Following Surgical Intervention for Atrial Fibrillation Database”?
5) According to a July 24, 2008 letter to Dr. Rajamannan from Northwestern Medical Faculty Foundation, Inc., pursuant to the Foundation’s request, Dr. Rajamannan “agreed not to provide clinical care at Northwestern Medical Faculty Foundation and Northwestern Memorial Hospital.”
a. Please explain why this request was made of Dr. Rajamannan.
b. Did the University and/or Northwestern Memorial Hospital have concerns regarding her clinical performance?
c. Prior to bringing her concerns regarding implantation of the Myxo Ring to the attention of the University, did Dr. Rajamannan receive any poor job performance evaluations? Has the University taken any disciplinary actions against Dr. Rajamannan in the past?
d. Please provide the Committee with a copy of Dr. Rajamannan’s personnel records. Dr. Rajamannan provided a signed authorization on October 28, 2008, for the release of her personal information.
6) Please provide a copy of any forms filed with the University and Northwestern Memorial Hospital detailing Dr. Patrick McCarthy’s outside income and conflicts of interest from January 2004 through June 2008.
7) Because reporting practices vary widely from one institution to another, I would appreciate you also placing this income into a chart, detailing compensation from device companies to Dr. McCarthy. This request covers the period of January 2004 through June 2008. For each payment to Dr. McCarthy from a company, please provide the following information:
a. Name of company;
b. Date of payment;
c. Payment description (CME, honorarium, research support, royalties, etc.); and
d. Amount of payment.
In cooperating with the Committee’s review, no documents, records, data or information related to these matters shall be destroyed, modified, removed or otherwise made inaccessible to the Committee.
I look forward to hearing from you by no later than January 5, 2009. Sincerely,
Charles E. Grassley Ranking Member
"Morgan, Lewis & Bockius LLP 1111 Pennsylvania Avenue, NW Washington, DC 20004
Tel: 202. 739.3000
COUNSELORS AT LAW
Barbara Van Gelder
November 4, 2009
VIA E-MAIL AND FIRST CLASS MAIL
The Honorable Charles E. Grassley United States Senate
135 Hart Senate Building
Washington, D.C. 20510-6200 Attn: Mr. Brian Downey
Re: Letter of September 30, 2009 to Northwestern University Dear Senator Grassley:
On behalf of Northwestern University ("Northwestern" or "the University"), undersigned counsel is responding to your letter of September 30, 2009 to Dr. Henry S. Bienen, former President of Northwestern University. The University responds as follows:
Request 1: Did Dr. McCarthy, Northwestern and/or the Hospital request confirmation from the company that the Myxo ETlogix 5100 Ring was cleared by the FDA before Dr. McCarthy first implanted the device? If so, on what date was the request(s) made, by whom, to whom at Edwards, and on what date was the assurance(s) received?
Response 1: Northwestern is not involved in clinical activities as described above and; therefore, does not have any documents responsive to this request.
Request 2: Please provide the Committee with a copy of emails, letters, memoranda, or any other documentation of Edwards' assurance to Dr. McCarthy, Northwestern, and the Hospital that the Myxo ETlogix 5100 Ring was cleared by the FDA prior to use in the cardiac surgery outcomes registry. This request covers the period of August 1, 2005 through April 30, 2006.
Response 2: To clarify, the Myxo ETlogix 5100 Ring was not "use[d] in the cardiac surgery outcomes registry." The registry was not aimed at a particular device; rather it was a registry of subjects with cardiovascular disease requiring surgical intervention. In any event, Northwestern has previously provided the Committee with all responsive emails, letters, memoranda or any
The Honorable Charles E. Grassley November 4, 2009
COUNSELORS AT LAW
other documentation on January 5, 2009 and January 16, 2009, see generally NWU00002, NWU00003, NWU00008, NWU00009, NWU00012, and NWU00013.
Request 3: Ifwritten assurance or confirmation was not requested and/or provided, please explain why not and on what basis Dr. McCarthy, the Hospital and/or Northwestern determined that the device had been cleared for use.
Response 3: See response 2.
Request 4: The Hospital stated, "At no time did any surgeon at the Hospital believe themselves to be implanting an investigational or experimental device." Other than Dr. McCarthy, how many other surgeons at the Hospital implanted the device during the period March I , 2006 and August 30, 2007? Did any of these surgeons inquire about the approval status of the device before they first used the device? Ifnot, on what basis did they determine that they were implanting a cleared device?
Response 4: The University does not have any information that is responsive to this question.
Request 5: What policies and protocols do Northwestern and the Hospital have in place to ensure that the appropriate assurances are obtained regarding the status of a device before it is first used by a faculty member and/or Hospital physician?
Response 5: When a researcher submits a proposal to conduct a study on a medical device, Northwestern University's Office for the Protection of Research Subject (OPRS) requires that Section 19 of the "New Project Submission Form" (see the attached screen shots from Section 19 at NWU000289-293) be completed. Section 19 requires researchers to provide information on
all medical devices to be used in proposed studies, including:
• if it is an FDA-approved device being used for an approved use, the device name and brochure;
• if it is an FDA-approved device being used for an unapproved use, the device name, IDE number and brochure; and
• if it is a non-FDA-approved device, the device name, IDE number and brochure.
If the proposed research study will use an FDA-approved device for an unapproved use, or a
non-FDA-approved device, there are additional questions regarding whether the device is exempt from FDA IDE requirements, a non-significant risk device or significant risk device, and the justifications for those determinations. OPRS presents the information provided by the
researcher to the IRB, which must determine that the infonnation provided is satisfactory before approving the research study.
OPRS publishes the Human Subject Protection Policy Manual ("HSPPM"), available at http://www.research.northwestem.edu/oprs/irb/policies/ documents/Northwestem.HSP P .Policy.v
The Honorable Charles E. Grassley November 4, 2009
COUNSELOILS AT LAii'
5.0 May3.l.2007.pdf, (NWUOOOI81-288) which sets forth information on the University's policy relating to human subject research. Section X.M. of the HSPPM provides specific guidance regarding research on investigational medical devices and compliance with IDE regulations (NWU000268-270).
Request 6: What policies and protocols do Northwestern and the Hospital have in place to respond to instances where the university and/or the hospital realize after the fact that a device being used in the hospital for treatment or research has not been appropriately cleared by the FDA? How many times has such an occurrence taken place in the last 5 years? What measures were taken by Northwestern and/or the Hospital to address the matter? Were the patients subsequently informed or re-consented? Ifnot, why not?
Response 6: When the IRB becomes aware that a previously approved research study may be using an unapproved device, OPRS will immediately notify the OPRS Director and an IRB Chair or the Chair for Administrative Review. One of the Chairs will make a determination as to whether the alleged practices appear to have caused injury or any other unanticipated problems involving risks to subjects or others. The IRB Chair may suspend the study procedures or place
a "partial clinical hold" on some aspect of the study (e.g. the enrollment of new subjects, or one arm of a clinical study), taking into consideration the welfare of currently enrolled subjects pending further investigation and review of the allegation. (See HSPPM Section XI at Bates Number NWU000185-188.)
An audit of the study will be performed to confirm or refute the allegation. Once the audit has been completed, the findings will then be reviewed by a convened IRB panel and/or subsequent IRB Chairs meetings. The IRB Panel will then determine the next steps to be taken and who, both internally and externally, needs to be notified. Depending on the findings, further action will be taken per the HSPPM. OPRS staff has no record of such an occurrence in the past five years.
If you or your staff has additional questions or concerns regarding this matter, please do not hesitate to contact me."