<IRB>

NOTE:

Addendum added on August 16, 2007.
ADDENDUM

.
April 16, 2007

TO:    Dr. Sally Houston, Associate Dean for Clinical Research, USF Health

Dr. Abdul Rao, Associate Vice President for Medical Affairs, USF Health

Ms. Camille McWhirter, J.D., Director, Research Compliance, USF Health

Dr. Barry Bercu, Chairperson, Medical Institutional Review Board

Ms. Patti Simmons, Director, Office of Clinical Research, TGH

Norma Epley, Assistant Director, Medical Institutional Review Board

FROM: Dr. Anthony Kirkpatrick

SUBJECT: USF Institutional Review Board

.

This is my reply to a letter to me dated February 19, 2007 from Ms. Norma Epley on behalf of the IRB at USF, received by me on March 7, 2007. Since you were copied on the letter, I am copying you on my reply. A copy of the February 19, 2007 letter is available at this site:

.

http://www.rsdfoundation.org/en/IRB_2_19_07.html

My reply is being provided on a web page with hyperlinks to facilitate access to supporting documents.

By my email correspondence dated March 14, 2007, I advised Ms. Epley,    “….it is very important that the misstatements of fact contained in your February 19, 2007 letter be addressed and corrected before the IRB proceeds any further.” Thus the purpose of the following:

CONTENTS:

I. CONCLUSIONS

II. BACKGROUND

III. SUMMARY OF FDA REGULATIONS AND POLICY

IV. VIOLATION OF FDA REGULATIONS AND POLICY BY IRB

V. THE COVER-UP
VI. ADVERSE CONSEQUENCES ON PATIENT CARE
VII. ADDENDUM

I. CONCLUSIONS

1. The Institutional Review Board (IRB) at University of South Florida (USF) is violating FDA regulations and policy by failing to carry out its obligation under the law to determine if a clinical investigation falls within the exemption set forth by the FDA from the general requirement to submit an investigational new drug application (IND).   Instead, the IRB always requires the investigator to file an IND with the FDA.

Instead of applying the FDA regulations (which establish exemption criteria) and the published FDA Guidance For Industry (which provides interpretation of the regulations) to determine if an exemption applies, the IRB always delegates that responsibility to the FDA. This is despite the fact that FDA regulations provide that the FDA will not accept an IND for an investigation that is exempt.

2. The Assistant Director of the Human Research Protection Program (Ms. Norma Epley) and the Chairman of the IRB (Dr. Barry Bercu) have conspired in a systematic cover up of the IRB’s violation of FDA regulations. This is evidenced by their falsifying the record from proceedings before the IRB at USF and their making false statements to officials at USF during an investigation of the matter.

.

3. The harm caused by the IRB’s violation of FDA regulations and policy has been devastating to RSD / CRPS patients under my care.

II. BACKGOUND

On December 19, 2005, my Application was reviewed for the first time by the IRB at USF. The Application describes a ketamine pilot study for patients with RSD / CRPS. As soon as the violation of FDA regulations by the IRB became apparent, I consulted with William G. Marshall, MD. He was responsible for facilitating the review of the ketamine pilot study. Dr. Marshall’s title at that time was:

William G. Marshall, Jr., MD, MBA

Associate Vice-President, Health Sciences Center

Associate Dean, College of Medicine

Clinical Research and Venture Development

Assistant Professor, Department of Surgery

University of South Florida

We determined that to convince the members of the IRB that they were violating FDA regulations it would be necessary to obtain an opinion from the FDA, under its letterhead, confirming the violation. Rather than confront the FDA directly with the allegation and risk damaging the reputation of USF, I decided it would be more appropriate for the International Research Foundation for RSD/CRPS, Inc. to approach the FDA. The Foundation is a non-profit organization dedicated to promoting research on RSD / CRPS worldwide.

Reference:

www.rsdfoundation.org

The Foundation, by correspondence dated September 6, 2006, sought information from the FDA with regard to published standards for IND exemption. As stated in that correspondence, the intent of the Foundation was to “help investigators and IRBs identify which studies are exempt from an IND application.”

Reference:

http://www.rsdfoundation.org/en/FDA_Correspondence_10_16_06.html#fda14

The FDA responded to the Foundation’s inquiry by email dated October 10, 2006, and advised the Foundation that, “Questions from investigators about a particular study are referred to the review division with the clinical expertise pertinent to the indication to be studied. The reviewing medical officer reviews the study and applies the criteria in the regulation.” Based upon that information, it was agreed a ketamine study in Mexico would be used as an example to demonstrate the standards for IND exemptions..

The Foundation’s simple request to the FDA resulted, wrongfully and unnecessarily, in the FDA’s Dr. Robert Rappaport issuing an unsolicited decision regarding the research in Mexico, which had been identified only as an example for the FDA to use in answering the Foundation’s question about exemption criteria. (Dr. Rappaport is Director of Division of Anesthesia, Analgesia and Rheumatology Products, FDA Center for Drug Evaluation and Research. Clinical investigators have complained to the Foundation about his lack of expertise in the area of pain management).

On November 21, 2006 the FDA advised the Foundation that Dr. Rappaport’s decision affirmed the opinion of the IRB at USF that I would need an IND to conduct my proposed studies. Any claim that the IRB reviewed my proposed study and concluded that the IND exemption criteria set forth in FDA regulations did not apply is completely without any basis in fact. On December 1, 2006 the Foundation asked the FDA to furnish the Foundation its source for this completely false, and in my opinion scandalous, assertion. The FDA has yet to disclose the source of the false information. Obviously, the source must be someone at USF who the FDA believed had the authority of the IRB to speak in its behalf.

Reference:
http://www.rsdfoundation.org/en/IRB_Documents.html#nov21
http://www.rsdfoundation.org/en/IRB_Documents.html#dec1

A review of IRB documents strongly suggests that Ms. Epley was the source of the FDA’s false information. I base this conclusion on the different versions of the action taken by the IRB on April 24, 2006, as reported by Dr. Bercu, the Chairperson of the IRB, and later by Ms. Epley in her February 19, 2007 letter. Dr. Bercu reported to me on September 13, 2006 that the IRB recommended, as a matter of IRB policy (applied to all clinical studies), that I submit an IND "or an exemption" for an IND to the FDA. Ms. Epley then reported on February 19, 2007 that a decision had been made by the IRB “requiring” an IND with no option for an exemption ever being considered by the IRB. It therefore appears that Ms. Epley unilaterally changed the decision made by the IRB, in a manner consistent with the false information given to the FDA.

The Foundation’s General Counsel responded to the FDA’s assertion:

"I would respectfully suggest to you that you make a reasonable effort to confirm “facts” you rely on before making such statements. For your information, the study Dr. Kirkpatrick submitted to his IRB is significantly different than the Mexican study. For your information, Dr. Kirkpatrick’s IRB has never rendered an opinion advising that he needs an IND to conduct his proposed studies. For your information, Dr. Kirkpatrick was advised by his IRB that it never makes a determination as to whether an IND is required for any clinical study, instead delegating that function to the FDA in every case, because “[I]t is USF policy that the FDA make the determination whether an IND. . . is required for all research which involves investigational drugs, devices, or biologics.” The Foundation’s efforts to obtain FDA guidance for all investigators is separate and apart from the research efforts of Dr. Kirkpatrick."

Reference:

http://www.rsdfoundation.org/en/IRB_Documents.html#dec1

The misrepresentations of fact of IRB records by Ms. Epley to university officials and possibly to the FDA is part of the cover-up discussed below and represents serious misconduct which should be thoroughly investigated to determine if disciplinary action is justified. In a letter dated December 21, 2006, Mr. Warren Rumble of the FDA, advised the Foundation that USF’s stated policy requiring all investigators to submit an IND is in violation of FDA regulations. Mr. Rumble wrote:

"I would like to clarify that it is the decision of an individual investigator and his/her institutional review board (IRB) whether they believe an IND is required for conducting clinical studies with a drug product lawfully marketed in the USA."

Reference:

http://www.rsdfoundation.org/en/FDA_12_21_06.html

A detailed chronology of events is published at:

http://www.rsdfoundation.org/en/FDA_Appeal.html

In his letter dated December 21, 2006, the FDA’s Mr. Rumble also confirmed that the best guidance the FDA can provide to investigators and IRBs in determining if an IND is required for any lawfully marketed drug in the USA is:

Guidance for Industry

IND Exemptions for Studies of Lawfully

Marketed Drug or Biological Products

for the Treatment of Cancer

Published By:

U.S. Department of Health and Human Services

Food and Drug Administration

Center for Drug Evaluation and Research (CDER)

Center for Biologics Evaluation and Research (CBER)

January 2004

Reference:

http://www.rsdfoundation.org/en/FDA_IND_GUIDANCE.htm

This FDA Guidance emphasizes the important role of investigators in determining whether an IND is required:

"Investigators must" apply the exemption criteria listed in 21 CFR § 312.2(b)(1)(i-v) in light of the published FDA Guidance.

Pursuant to its published Guidance, the FDA recognizes that a considerable amount of professional judgment is exercised in determining whether the planned investigation significantly increases the risk associated with the use of the drug, one criterion for an IND exemption. Accordingly, FDA maintains that, “because the assessment of risks involved in a therapeutic procedure is an everyday part of the practice of medicine, the individual investigator should usually be able to determine the applicability of the exemption.”

Although the published FDA Guidance has a provision which allows the FDA, upon request, to provide a non-binding “opinion” as to whether an IND is required, the IRB is requiring me to seek a final decision from the FDA. Moreover, any "opinion" by the FDA is based only on a “limited review”.

Reference:

http://www.rsdfoundation.org/en/FDA_IND_GUIDANCE.htm

A limited review is not the same as the review required by the IRB under the regulations. According to FDA's Mr. Rumble, even after the FDA renders an opinion:

"...... it is the decision of an individual investigator and his/her institutional review board (IRB) whether they believe an IND is required for conducting clinical studies with a drug product lawfully marketed in the USA."

Reference:

http://www.rsdfoundation.org/en/FDA_12_21_06.html

This limited review by the FDA is understandable given the financial structure within the FDA. In my email to the IRB dated December 22, 2006, I noted the apparent conflict of interest at the FDA:

"Pharmaceutical companies pay a “drug user fee” to the FDA to get drugs approved which have potential to make big $. On the other hand, the FDA receives no money to approve an Investigational New Drug Application (IND) requested by a researcher for a drug like ketamine, a drug with virtually no potential to make money for the FDA. …..     The FDA’s user fee system accounts for over half of the FDA’s funding budget related to drug studies."

Reference:

http://www.rsdfoundation.org/en/IRB_Documents.html#dec22

III. Summary of FDA Regulations and Policy:

1. Pursuant to 21 CFR 56.103(a), IRB review of clinical investigations involving human subjects is required.

2. The IRB must approve a clinical investigation if all of the criteria listed in 21 CFR 56.111 are met.

3. 21 CFR 312.2(a) requires submission of an Investigational New Drug Application (IND) to the FDA, unless all the criteria for an exemption as set forth in 21 CFR 312.2(b)(1) are met.

4. Pursuant to FDA published Guidance, the IRB is required to consult with the investigator to determine if an IND exemption is appropriate. The FDA suggests that deference be given to the investigator’s determination as to an IND exemption, since “. . .the individual investigator should usually be able to determine the applicability of the exemption.”

5. It is a violation of FDA published Guidance for persons outside the clinical care of research subjects (e.g. the IRB) to unilaterally determine if an IND is required.

6. Pursuant to 21 CFR 312.2(b)(4), the FDA will not accept an IND for an investigation that is exempt.

IV. Violation of FDA Regulations and Policy by IRB

The IRB violates FDA regulations by failing to carry out its responsibility to decide if an IND application is required, in accordance with FDA regulations and FDA published Guidance. Instead, the IRB always delegates that responsibility to the FDA.

There are email messages and observations from IRB documents that make this violation of FDA regulations and policy overwhelmingly clear.

Email message from Ms. Norma Epley to me, dated September 8, 2006:

“Dr. Kirkpatrick, it is USF policy that the FDA make the determination whether an IND, /IDE, or BBIND is required for all research which involves investigational drugs, devices, or biologics.”

Reference:

http://www.rsdfoundation.org/en/IRB_Documents.html#sep8

Prior to the ketamine study being submitted to the IRB for review, a meeting was held at Tampa General Hospital (TGH) on September 28, 2005. The following persons attended the meeting:

Barry Bercu, MD

William Marshall, MD

Norma Epley

Thomas Freeman, MD

Dennis Bandyk, MD

Anthony Kirkpatrick, MD

Email message from Ms. Epley to me, dated September 11, 2006:

“During our first meeting at TGH, I informed you that there would need to be an IND for this study or documentation from FDA that such an exemption is not required.”

Reference:

http://www.rsdfoundation.org/en/IRB_Documents.html#sep11

Ms. Epley’s email conclusively shows that the IRB required that I submit an IND, without considering whether an exemption applied, BEFORE my study was even submitted to the IRB at USF for review, in violation of FDA regulations and published FDA Guidance. My IRB application was not “reviewed” by the IRB until December 19, 2005, well after the September 28, 2005 meeting at TGH.

Reference:
http://www.rsdfoundation.org/en/FDA_IND_GUIDANCE.htm

It should be noted that neither William Marshall MD, former Associate Dean of Clinical Research for the College of Medicine, nor I recall Ms. Epley making the referenced statement at the September 28, 2005 meeting. If Ms. Epley had made the statement, I would have objected because she would have been asking me to violate FDA regulations in order to have my study approved by the IRB.

FDA regulations (21 CFR 56.108) require every IRB to establish and follow written procedures for conducting its review. No written procedure is provided anywhere within the University system stating that clinical investigators are required to have the FDA determine if an IND exemption applies. Such a procedure would, in effect, require all clinical investigators to violate FDA regulations in order to have their study approved by the IRB.

Dr. Bercu is a pediatrician and Chairman of the IRB. Dr. Bercu has ratified and supports the IRB policy articulated by Ms. Epley.

Email message from Barry Bercu MD to me, dated September 13, 2006:

“The IRB always asks the investigator to provide information to the FDA and request an IND or exemption from the FDA for off-label research use of a drug, whether it is an investigational new agent or an approved drug for an unapproved use or dose.”

Reference:

http://www.rsdfoundation.org/en/IRB_Documents.html#sep13

IRB DOCUMENTS

There are other observations contained in IRB records indicating that I was being asked by the IRB to shift its responsibility to make a decision about the IND exemption to the FDA.

During the course of review of my application by the IRB I received three letters. Two letters indicated that the IRB had not reached a final decision and stated that the IRB's decision was "deferred." These IRB letters are dated December 21, 2005 and March 28, 2006. In the March 28, 2006 letter, the IRB asks, 'Ketamine is not FDA approved for this indication, please explain why an IND has not been applied for."

Reference:

http://www.rsdfoundation.org/en/IRB_Decisions.htm

The IRB's question makes no sense unless the IRB intended to delegate the IND exemption decision to the FDA. My IRB application material (furnished to the IRB prior to the March 28, 2006 letter) provided the IRB with justification for an IND exemption under the FDA regulations and published FDA Guidance. See Section 8.2 of the Application, Sections 1.3 through 1.5 of the Research Protocol and Section 5.0 under References.

Reference:

http://www.rsdfoundation.org/en/IRB_3_11_06_application.htm

If the IRB intended to apply the FDA exemption criteria (and to consult with me pursuant to the FDA published Guidance) and then make a decision as to an IND exemption, and if the IRB had any doubts or questions about my justification for an IND exemption, one would expect the IRB to question the justification for an IND exemption as stated in the application material. Instead, the IRB gave no explanation for imposing the requirement for an IND other than "ketamine is not FDA approved for this indication." Such a statement / position by the IRB makes no sense, except to demonstrate that the IRB decided to disregard the justification offered by the Principal Investigator and delegate to the FDA the decision as to an IND exemption.

Reference:

http://www.rsdfoundation.org/en/IRB_3_11_06_application.htm

On April 25, 2006, I received a third letter from the IRB, with materially different statements than in the IRB’s previous two letters. The April 25, 2006 letter states that "Approval was withheld pending submission of the following information..."

Dr. Bercu told me that this is a form letter sent to clinical investigators when the IRB has decided that they do not need to determine the merits of the study.

Reference:

http://www.rsdfoundation.org/en/IRB_Decisions.htm

Clearly, the members of the IRB delegated the decision regarding IND exemption to the FDA.

   The IRB violated FDA regulations and published Guidance by failing to carry out its responsibility to consult with me (the Principal Investigator) regarding the IND exemption.

Section 8.2 of the IRB Application material requests that investigators justify an IND exemption for their study. This information under Section 8.2 was never questioned or challenged by the IRB Committee.

Reference:

http://www.rsdfoundation.org/en/IRB_3_11_06_application.htm#march11_App

The research protocol submitted to the IRB provides more than sufficient support for an IND exemption. For example, the research protocol references a series of ten subjects with RSD / CRPS who underwent a 5-day ketamine infusion in Germany. The results from that study were presented at an international pain meeting and published as an abstract. The clinical data was presented at 10th World Congress on Pain in 2002

Under Section 1.5 of the Application the IRB also was presented with the results from the first 30 subjects with RSD / CRPS who underwent a 5-day ketamine infusion in Germany. Some of the subjects were my patients at USF.

A careful review of IRB proceedings demonstrates that at no time did the IRB question or challenge any of the justifications submitted for an IND exemption. Nor did the IRB ever question or challenge the data offered to the IRB from the open label trials in Germany. Contrary to FDA requirements, there was no consultation whatsoever with me about the criteria for an IND exemption. This lack of consultation by the IRB with the Principal Investigator is consistent with the IRB’s decision that the IND exemption should be decided by the FDA, without my knowledge or consent. Nor did the IRB consult with the panel of three outside clinical experts who were asked by the IRB to review the study. The material sent out to these experts provided information from me on why the study should be exempt from an IND Application. All three experts approved the study without expressing any concerns about an IND requirement.

Ms. Laurie Tozier, the IRB representative assigned to my study, agrees with me. If the IRB had any concerns about an IND exemption, the IRB should have asked these clinical experts to address their concerns in regard to the IND exemption issue. The IRB did nothing.

On September 10, 2006, I advised the IRB of the following violations of FDA regulations and informed them of the adverse consequences that these violations would have on the care of my patients:

“IRBs are required to review proposed studies in consultation with the investigator to determine if the criteria for IRB approval, as set forth in 21 CFR §56.111, are met. It is our further understanding that if the 21 CFR §56.111 criteria are met, and if the investigator believes that the IND exemption applies and the IRB does not consult with or challenge the investigator on that issue pursuant to 21 CFR §312.2(b)(1)(iii), the IRB has no discretion to require an IND Application as a condition of IRB approval. Moreover, it does not seem appropriate, pursuant to FDA regulations, for the IRB at USF to require an IND Application for “all” research which involves investigational drugs. This policy at USF has the potential to make the FDA angry at the university and the investigator for not following its regulations ---- making the game of Russian roulette a more dangerous game to play with the FDA ----- leaving the lives of patients throughout the United States hanging in the balance who have no effective treatment options.”

“The IRB at USF sent our research application material for external review to three internationally recognized US experts in the field of chronic pain. The material sent out to these experts provided information from me on why the study should be exempt from an IND Application. I was told that the three experts approved the ketamine study without suggesting that an IND Application with the FDA was necessary. What was the point of sending the IRB application material out to a panel of experts if the IRB was not going to accept the unanimous opinion of experts consulted?”

Reference:

http://www.rsdfoundation.org/en/IRB_Documents.html#sep10

Only after I alleged these serious violations of FDA regulations and policies by the IRB on September 10, 2006, did Ms. Epley and Dr. Bercu present “concerns” about my justification for an IND exemption as set forth in the IRB application material. All of this back stepping, in my opinion, is consistent with and part of a concerted effort to cover up FDA violations by the IRB, and obfuscate the facts in this case.

V. The Cover-up

On January 2, 2007, I made the following request to Dr. Bercu:

“I respectfully request that you counsel Ms. Norma Epley to make a reasonable effort to confirm “facts” before disseminating information within and outside USF that is completely false, and in my opinion scandalous.”

Reference:
http://www.rsdfoundation.org/en/IRB_Documents.html#jan2
The facts presented below show that the problem with Ms. Epley has not been corrected. In fact, the problem has become much worse.

In addition, Ms. Epley and Dr. Bercu have conspired in a systematic attempt to cover up the violation of FDA regulations by falsifying the record of proceedings before the IRB at USF, and by making false statements to officials at USF during an investigation of the matter. Ms. Epley’s February 19, 2007 letter is the latest example of this misplaced effort.
¶ Ms. Epley states in her February 19, 2007 letter that there were 24 items the IRB requested that I address since 2005, and that I never addressed these items. Such a claim is blatantly false. There were13 items that remained to be addressed following the last meeting of the IRB on April 24, 2006. These items were so trivial that the IRB in fact decided that they did not need to be brought back before the IRB for final approval.
Reference
:
http://www.rsdfoundation.org/en/IRB_Documents.html#ap25

¶ In her February 19, 2007 letter, Ms. Epley criticizes my study for not having a Data and Safety Monitoring Committee. Again, such a claim is false. In fact, pursuant to Section 16.4 of the Application, the IRB had approved this Committee with the following members:

Giancarlo Barolat, MD
Director of the Barolat Institute, Denver, Colorado

Dr. Barolat was President of the International Neuromodulation Society and is on the Board of the American Neuromodulation Society and on the Editorial Board of the Journal, Neuromodulation. He is currently Director at large of the International Neuromodulation Society.
Dr. Barolat practiced at Thomas Jefferson University Hospital from 1985 to 2004 as Professor of Neurosurgery and Director of the Division of Functional Neurosurgery. Dr. Barolat has extensive experience with surgical spine procedures. As such, he has performed hundreds of complex spine operations. He has also been involved in the surgical management of intractable seizures through implantation of vagus nerve stimulator devices.
Dr. Barolat is also one of the world leaders in the area of neuro-implantable technologies for the management of pain and motor disorders. He is one of the pioneers of spinal cord stimulation for spasticity and pain management. His practice is one of the largest in the country, with national and international referrals. He has authored of over 60 medical articles and book chapters. He has lectured extensively nationally and internationally.
Timothy R. Lubenow, M.D.
Professor, Department of Anesthesiology, Rush Medical College
Medical Director, Rush Pain Center
Director, Section of Pain Management, Rush University Medical Center, Chicago, Illinois

Dr. Lubenow’s special interests include:

Complex Regional Pain Syndrome (CRPS)
Continuous Epidural Narcotic-Anesthetic Solutions for Postoperative Analgesia
Epidural infusion of Bupivacaine Clonidine Solution for the Management of CRPS
Cancer Pain
Implantable Drug Infusion Pumps
Spinal Cord Stimulation
Robert Walker, MD
Associate Professor, Department of Internal Medicine
Director of Division of Ethics and Humanities
University of South Florida, Tampa, Florida

Dr. Walker’s current duties include directing the first and third-year medical school courses in medical ethics, chairing the Ethics committee at Tampa General Hospital, staffing the ethics consultation service at Tampa General and directing a clinical team at Hospice of Hillsborough. Dr. Walker’s articles have appeared in the Journal of the American Medical Association, the Journal of General Internal Medicine, the Archives of Internal Medicine, and Academic Medicine.

Oscar A. de Leon-Casasola, MD
Chief, Pain Medicine
Department of Anesthesiology and Pain Medicine
Roswell Park Cancer Institute, Buffalo, New York
Professor of Anesthesiology, University at Buffalo
School of Medicine and Biomedical Sciences
Dr. de Leon-Casasola is licensed in New York State and is board-certified in Anesthesiology, Critical Care Medicine and Pain Medicine.
Dr. de Leon-Casasola’s research interests include advances in analgesic therapy; physiology and pharmacology of epidural opioids, perioperative surgical outcomes, thoracic and cardiac anesthesia, acute pain control and chronic cancer pain.
Dr. de Leon-Casasola has authored or co-authored 115 journal articles, abstracts and book chapters. He serves as an Associate Editor for the Latin American Journal of Pain, Argentinian Journal of Anesthesiology, The Journal of the Spanish Society of Pain, and the Clinical Journal of Pain. He also is Editor-in-Chief of Techniques in Regional Anesthesia and Pain Management.
¶ Ms. Epley has recommended that Thomas Freeman, MD, USF Department of Neurosurgery, serve on the Data and Safety Monitoring Committee. However, Ms. Epley should know that this would create a conflict of interest because Dr. Freeman was approved by the IRB as a co-investigator for the study.
¶ Ms. Epley states in her February 19, 2007 letter that the IRB made the “decision requiring" an IND. She further states that the IRB would be “derelict in its duty” not to require an IND for my study. Such claims are false, and can be seen to contradict the action actually taken by the IRB on April 24, 2006, as summarized in a letter from Dr. Bercu to me dated September 13, 2006 . In the letter, Dr. Bercu, acknowledges the IRB policy requiring all clinical investigators to apply to the FDA for an IND “or exemption”:

“The IRB always asks the investigator to provide information to the FDA and request an IND or exemption from the FDA for off-label research use of a drug, whether it is an investigational new agent or an approved drug for an unapproved use or dose. My personal experience has been that no response from the FDA within thirty days would have meant you could proceed as long you had IRB permission. As you know, the paperwork is not involved because you already have all the materials.”

“You will note item 10 from the letter to you dated April 25, 2006 that the full convened IRB recommended that you apply for an IND or an exemption from the FDA… “

Reference:
http://www.rsdfoundation.org/en/IRB_Documents.html#sep13

All references by Ms. Epley and Dr. Bercu to a “decision” or “recommendation” by the IRB are utter nonsense. There was never a decision or recommendation made by the IRB, because it had already been decided by the IRB before the IRB reviewed my study, that all clinical studies at USF require an IND or an exemption from the FDA in order to receive IRB approval.

  ¶ Ms. Epley claims in her February 19, 2007 letter that:

“…..because you are both initiating and conducting the clinical investigation ("i.e., under whom immediate direction the test article is administered or dispensed to, or used involving, a subject" [21 CFR 56.1 02(k)]), you become the "sponsor-investigator". Federal regulation 21 CFR 312.20 states "(a) A sponsor shall submit an IND to FDA if the sponsor intends to conduct a clinical investigation with an investigational new drug that is subject to Sec 312.2(a); and (b) A sponsor shall not begin a clinical investigation subject to Sec. 312.2(a) until the investigation is subject to an IND which is in effect in accordance with Sec 312.40."

Ms. Epley has chosen to ignore the express language in 21 CFR 312.20(a), which provides that it only applies to investigations subject to 21 CFR 312.2(a). When, as here, the exemptions set forth in 21 CFR 312.2(b)(1) are applicable, then the investigation is not subject to 21 CFR 312.2(a) and a sponsor is not required to submit an IND to the FDA.

¶ Ms. Epley claims in her February 19, 2007 letter that my IRB application:

“Contained no “published or abstract information on other trials using this drug in a clinical investigation, for this indication.”

“Contained no “proposed dose escalation or justification for the high dose proposed in the clinical investigation.”

Once again, Ms. Epley intentionally misstates facts with apparent ease. Either Ms. Epley has not read Sections 1.5 (PROTOCOL: German Trial) , 5.0 (PROTOCOL: References) and 8.2 (APPLICATION) of the Research Protocol and Application submitted to the IRB, or if she read it, she does not understand it.

In her February 19, 2007 letter, Ms. Epley correctly states that I did not “….. provide any published animal data to support the use of this drug in the manner proposed”. However, her criticism demonstrates how woefully deficient her understanding is of FDA’s Guidance for determining if an IND exemption applies. A lack of understanding of the published FDA Guidance on IND exemptions is a serious problem for any member of an IRB, since the primary goal of the Guidance is to minimize risk to research subjects.
According to the Guidance published by the FDA, animal studies have little importance in determining if such a clinical study is exempt from an IND. In fact, animal studies are not even mentioned in the Guidance.
Ketamine was approved by the FDA as a general anesthetic in 1970. In the proposed study, ketamine will be used at a dosage level and duration commonly employed in treating certain patient populations. Section 8.2 of the IRB Application documents that ketamine is used for general anesthesia in the ICU for periods lasting more than five days in patients with burns, asthma and head injuries. The fact that ketamine will be used in the study in the same way that it is used in the practice of medicine is an important factor in determining the IND exemption.
Ketamine will be used in a more than minimally invasive procedure. The published FDA Guidance states that risk must be balanced against many factors that serve the best interest of research subjects, including if the patient has failed all available treatment options. The research protocol states that the research subjects must have failed all reasonable treatment options. Moreover, the IRB was made well-aware through videos and patient testimonies that the clinical outcome in this patient population is sometimes lethal, i.e., suicide! Other patients suffer total incapacitation associated with severe disfigurements as the disease process spreads throughout the body. Apparently, the IRB does not appreciate the seriousness of this syndrome. The devastating consequence of total body RSD / CRPS is evident in the following video of one our fellow physicians:
Reference
http://www.rsdfoundation.org/en/Dr_Stocker_Video.htm

The FDA published Guidance recognizes that in some clinical situations it is not generally possible to have maximal efficacy in a population without inducing toxicity in some patients. For example, it is not uncommon to observe severe or even lethal side effects from cancer drugs in some patients. In general, these circumstances mean that the toxicity, even potentially lethal toxicity, of cancer drugs is described in approved labeling. Accordingly, FDA Guidance provides examples where clinical studies might produce severe side effects or even lethal side effects and yet be exempt from an IND.
Below are two examples of studies published by the FDA that, according to the FDA, are likely to be considered exempt from an IND even though the studies are more than minimally invasive. Although the examples are taken from the field of oncology, the FDA maintains that the examples are "relevant to studies of marketed drugs in other therapeutic areas."
Reference:
http://www.rsdfoundation.org/en/FDA_Correspondence_10_16_06.html#fda9

1. Phase 1 oncology trials of marketed drugs may be considered exempt if such therapy is appropriate for the patient population (i.e., if patients have residual cancer) and if there is no effective therapy (i.e., therapy producing cure or a documented increase in survival) that the patients have not yet received. It remains the investigator’s responsibility to use starting doses that appear safe based on approved labeling or detailed literature reports, use incremental changes in dose or schedule, and carefully evaluate toxicity prior to dose escalation.
2. Studies of high-dose therapy in cancer patients are likely to be considered exempt if the studies use adequately evaluated regimens that appear to have an acceptable therapeutic ratio for the population being studied. Similarly, phase 1 studies involving incremental changes from such well-described regimens are generally exempt.
Reference:
http://www.rsdfoundation.org/en/FDA_IND_GUIDANCE.htm
The FDA has repeatedly stated in its correspondence to me that this is the best Guidance the FDA can provide to investigators and IRB’s who must determine if an IND is required for any lawfully marketed drug in the USA.
Reference:
http://www.rsdfoundation.org/en/FDA_12_21_06.html
http://www.rsdfoundation.org/en/FDA_Correspondence_10_16_06.html#fda9
Contrary to FDA regulations and published Guidance, Dr. Bercu focuses almost exclusively on the risk nature of the ketamine study. Such a narrow focus on risk is contrary to published FDA regulations and policy which require consideration of many other factors that serve the best of research subjects. In his September 13, 2006, letter Dr. Bercu wrote:

“I believe you are misquoting the FDA regulations regarding an IND application. Keep in mind the high risk nature of your study.”

Reference:
http://www.rsdfoundation.org/en/IRB_Documents.html#sep13

When I met with Dr. Bercu on Jan. 2, 2007, I asked him if he read the FDA Guidance concerning the criteria for an IND exemption. He was not certain if he had. This was a shocking admission given that he is Chairman of the IRB, and given that the FDA has published this Guidance since January, 2004. I provided Dr. Bercu with a copy of the Guidance and asked that he read it and share it with the IRB Committee. Notwithstanding his commitment to "read and understand" the FDA Guidance, he is still asking me to act contrary to FDA regulations and policies.
Reference
http://www.rsdfoundation.org/en/IRB_Documents.html#jan2

In my opinion, Dr. Bercu, like Ms. Epley, is woefully deficient in understanding how to apply the FDA’s Guidance for IND exemptions.

VI. ADVERSE CONSEQUENCES ON PATIENT CARE
The harm caused by the IRB’s violation of FDA regulations has been devastating to patients with RSD / CRPS. Many of my patients have suffered needlessly. One patient almost succeeded in committing suicide due to severe depression caused by the IRB’s failure to act as required by law.

I warned the IRB on September 10, 2006, in writing, that they were violating FDA regulations and that this would lead to needless pain and suffering in my patients. In response, Dr. Bercu sent me a letter dated September 13, 2006, accusing me of “misquoting the FDA regulations regarding an IND application.”

It is clear from Ms. Epley’s February 19, 2007 letter that she and Dr. Bercu are still demanding that I obtain a decision from the FDA to determine if an IND is required for my study, and they are trying to justify the demand with misstatements of fact, misstatements of law, and by rewriting the history of my dealings with the IRB.   If it cared about the suffering of RSD / CRPS patients, the IRB could have easily contacted the FDA and learned that its policy of always requiring the FDA to decide IND exemptions is, in fact, a violation of FDA regulations.
I feel compelled to obtain justice for my patients. In light of the foregoing, it would seem appropriate to conduct a review of this entire matter by an independent panel at USF to determine if disciplinary action is justified. It seems to me that it would be useful for ALL to see that the IRB at USF is disregarding its responsibilities and its obligations under the law.

Sincerely,

Anthony F. Kirkpatrick, MD, PhD

CC: William Marshall MD, Associate Dean, USF Health
       Alan Goldman MD, Chairman, Department of Internal Medicine, USF Health

VII. ADDENDUM (August 16, 2007)

Subsequent to submitting the above Report on April 16, 2007, pursuant to the Florida Public Records Act I obtained minutes and tape recordings of the IRB meetings held on April 24, 2006 and March 26, 2007, when my study was discussed. On May 1, 2007, I sent an email to Camille McWhirter J. D. with a copy to Dennis Freeman, Dr. Allan Goldman; Dr. Abdul Rao and Dr. Sally Houston. I advised all parties:

“... you can anticipate additional allegations of misconduct on the part Ms. Norma Epley and Dr. Barry Bercu once the signal-noise ratio has been improved on the three micro cassette tapes.”

Reference:
http://www.rsdfoundation.org/en/Test_IRB.htm#May_1
Thus, the following:

CONTENTS:
I. The Coverup
II. Violation of FDA Regulations

I. The Coverup:

A transcript of the recorded IRB meeting of March 26, 2007 is available at the following site:
Reference:
http://www.rsdfoundation.org/en/IRB_Transcript_3_26_07.htm

The tape recording of the March 26, 2007 IRB meeting reveals Ms. Epley and Dr. Bercu presented incomplete, false and misleading information to the IRB members. Their misstatement of facts is inexcusable. On March 14 and March 16 2007 respectively, Ms. Epley and Dr. Bercu, were made aware of my concern about the misstatements of fact in the February 19, 2007 letter to me written by Ms. Epley on behalf of the IRB. Ms. Epley’s letter purported to justify her and Dr. Bercu’s conduct and that of the IRB with regard to their actions concerning my clinical investigation, and it was distributed to university officials and faculty. I advised Ms. Epley and Dr. Bercu that:

“… it is very important that the misstatements of fact contained in your February 19, 2007 letter be addressed and corrected before the IRB proceeds any further.”

Reference:
http://www.rsdfoundation.org/en/Test_IRB.htm#March14_K

http://www.rsdfoundation.org/en/Test_IRB.htm#March16_K
On March 15, 2007, Dr. Bercu informed me that I had until April 20, 2007 to respond to the February 19 letter, and on March 16, 2007 Dr. Bercu acknowledged,

“Tony: We look forward to your response. Barry”.

Reference:
http://www.rsdfoundation.org/en/Test_IRB.htm#March15
http://www.rsdfoundation.org/en/Addendum_1_IRB_Report.htm#March16_B
Despite Dr. Bercu and Ms. Epley having allowed me until April 20, 2007 to correct their misstatements of fact in the letter so that IRB action would not be based on erroneous information, the IRB met on March 26, 2007 and some of the same misrepresentations contained in the February 19 letter were presented to the IRB as facts by Ms. Epley and Dr. Bercu. At that IRB meeting they falsely portrayed my request for time to respond to the misstatements in the letter as a request for additional time to complete the IRB application regarding my study. In particular, they falsely stated there were 24 items which I had been requested to address, but which I had supposedly ignored. By letter dated March 27, 2007 emailed to me by Ms. Epley on March 29, 2007, Dr. Bercu advised me that at its March 26, 2007 meeting, the IRB granted me an extension until April 16, 2007 to address this allegedly missing information regarding my investigation.
Reference:
http://www.rsdfoundation.org/en/Test_IRB.htm#March27_IRB
Interestingly, the audio recording of the IRB meeting indicates it was agreed I would have until April 19, rather than until April 20 as agreed by Dr. Bercu on March 15. Thus, the new date of April 16 made it more likely that my study would be terminated before the IRB could review my response to the misstatements of fact in the February 19 letter written by Ms. Epley on behalf of the IRB.

Reference:

http://www.rsdfoundation.org/en/Test_IRB.htm#March15

On March 30, 2007 I wrote to Ms. Epley in protest, and advised her again there were misstatements of fact in her February 19, 2007 letter which I intended to correct:

“The letter from the IRB which you emailed to me on March 29, 2007 has nothing to do with the extension I requested. (Copy of your March 29 letter attached)

“I requested an extension to reply to your February 19, 2007 letter. Copied below is my March 14, 2007 email to you and Dr. Bercu, in which I state, “In my opinion, it is very important that the misstatements of fact contained in your February 19, 2007 letter be addressed and corrected before the IRB proceeds any further.”

“It troubles me that you and Dr. Bercu might allow the IRB to proceed with any decision in this matter without first allowing me to address and correct the misstatement of facts in your February 19 letter --- a letter that you wrote on the behalf of the IRB.”

Reference:

http://www.rsdfoundation.org/en/Addendum_1_IRB_Report.htm#March30

The tape recording of the March 26, 2007 IRB meeting clearly discloses that Ms. Epley and Dr. Bercu made no effort to determine the merits of the matter in a fair and objective manner.

For example:

¶ During the IRB meeting on March 26, 2007, Ms. Epley represented that there were 24 items the IRB requested that I address, and that I never addressed these items. Such a claim is blatantly false. As noted in my April 16, 2007 Report, there were13 minor items that remained to be addressed following the last meeting of the IRB on April 24, 2006. These items were so trivial that the IRB decided, pursuant to USF policy, that they did not need to be brought back before the IRB for final approval. Moreover, Ms. Epley failed to inform the IRB that my study had been approved pending the submission of these minor revisions. This decision by the IRB to approve the study pending minor revisions to be submitted to Dr. Bercu can be found in the minutes to the IRB meeting of April 24, 2006 at the following site:

Reference:

http://www.rsdfoundation.org/en/Test_IRB.htm#MINUTES_June24



¶     The false statement about 24 pending revisions generated a strong negative bias against me by the IRB members at the March 26, 2007 meeting. This fabricated, large number of pending revisions was focused upon during the 16-minute meeting as a major concern. One committee member stated that 24 pending revisions is a “new protocol altogether” and for that reason my application should be closed then and there.

Reference:

http://www.rsdfoundation.org/en/IRB_Transcript_3_26_07.htm

¶ IRB Policy 809, Paragraph 7.9.3, states that when approval is withheld pending “minor changes” to be reviewed by the IRB Chairperson:

7.9.3.1 “Such minor changes must be clearly delineated by the IRB so the investigator may simply concur with the IRB’s stipulations.

7.9.3.2 "The human research may proceed after the required changes are verified and the protocol approved by the designated reviewer."

Statements made by Ms. Epley and Dr. Bercu at the IRB meeting of March 26, 2007, confirm that of the 13 minor changes to my study recommended by the IRB, there was only one with which I did not concur. I refused to agree to “force” the FDA to determine the fate of my study.

Reference:

http://www.rsdfoundation.org/en/IRB_Transcript_3_26_07.htm

http://www.rsdfoundation.org/en/Test_IRB.htm#April24

Then as now, I will not allow the IRB to abrogate its obligation pursuant to FDA regulations to independently approve my study. Moreover, I will not allow the IRB to direct me to go to the FDA to “force” the agency to, in effect, make the final decision about approving my study. (See section below: “II: Violation of FDA Regulations”)

¶   During the IRB meeting of March 26, 2007 Ms. Epley and Dr. Bercu were asked several times why I was asking for a 30-day extension.

Reference:

http://www.rsdfoundation.org/en/IRB_Transcript_3_26_07.htm

Instead of telling the truth--that I requested the time to correct the false record created by Dr. Bercu and Ms. Epley so that the IRB could make an informed decision about my study-- Dr. Bercu and Ms. Epley concealed this information from the IRB. The February 19, 2007 letter written by Ms. Epley in behalf of the IRB, to which I wanted to respond and correct material misstatements of fact, was not even mentioned. Nor did they disclose to the IRB that I felt it to be “very important” that the misstatements of fact contained in the February 19, 2007 letter be addressed and corrected before the IRB proceeded any further.

¶      During the March 26, 2007 meeting of the IRB, Ms. Epley and Dr. Bercu proceeded to undermine my judgment and trivialize my concerns about following FDA regulations and policies. They also suggested to the IRB that I was intending to unfairly harm the IRB as well as undermine its authority.

The recording of the meeting reveals that Ms. Epley accused me of challenging the IRB’s authority. She said, “His point is that the IRB does not have the authority to make him go to the FDA and obtain an IND.” This is one of Ms. Epley’s false statements contained in her February 19, 2007 letter (which is set forth above in the April 16, 2007 Report).

At the meeting, Ms. Epley trivialized my concern about following FDA guidelines and regulations for determining IND exemptions. She gave the IRB false information about how the FDA determines an IND exemption, suggesting all that is needed is a simple phone call from the investigator to the FDA. She told the IRB, “He disagrees that an IND is needed. And all you have to do is call FDA and make that determination.”

At the March 26, 2007 meeting Dr. Bercu warned the IRB that they should give me an extension of time (to furnish the allegedly missing 24 items of information, with no mention that my request was to respond to the misstatements of fact in the February 19, 2007 letter) because, if they did not, it might give me more “potency” in my complaint against the IRB. He told the IRB that they should give me a 30-day extension because if I “fail”, I could not then say the IRB did not give me a chance, gratuitously asserting further to the IRB, “as idiotic as that may seem.”

Reference:

http://www.rsdfoundation.org/en/IRB_Transcript_3_26_07.htm

¶       Clearly reflected in the audio recording of the March 26, 2007 IRB meeting is the fact that neither Dr. Bercu nor Ms. Epley had any interest in allowing the IRB members to know of my communication with them up to that time. It is interesting to note that the “official” minutes of the meeting bear little resemblance to what is revealed in the tape recording of the meeting. Moreover, furnishing the minutes to me was delayed for over three months. One would think that this huge amount of time after the IRB meeting would have been used to make sure the minutes are accurate.

Reference:

http://www.rsdfoundation.org/en/Test_IRB.htm#June29

II. Violation of FDA Regulations

The tape recordings of the April 24, 2006 IRB meeting corroborate that at that meeting, Dr. Bercu informed me, for the first time, that I must submit an IND application to the FDA so that the FDA would decide an IND exemption, and not the IRB. He attempted to justify this demand for a decision by the FDA, instead of by the IRB:

To "force" the FDA to interpret its guidelines

To "force" the FDA to take a position

To create an "advantage" for the PI for future research

To "safeguard" the PI

Reference:

http://www.rsdfoundation.org/en/Test_IRB.htm#April24

All of these reasons given by Dr. Bercu for requiring that I submit an IND application to the FDA violate the letter and the spirit of the applicable FDA regulations.

The IRB must approve a clinical investigation if all the requirements listed in 21 CFR 56.111 of the FDA regulations are satisfied. 21 CFR 56.111(a)(1) requires that risks to subjects be minimized. 21 CFR 56.111(a)(2) requires that risks to subjects be reasonable in relation to anticipated benefits. My study meets those criteria, and on April 24, 2006 the IRB so acknowledged by granting its approval in accordance with 21 CFR 56.111, pending submission of 13 minor revisions to be submitted to Dr. Bercu, with no additional review by the IRB required, as set forth in USF policy No. 809 (IRB Review Responsibilities – Initial Review), paragraph 7.9.3.

21 CFR 312.2(a) of the FDA regulations requires an investigator to submit an IND application to the FDA, unless all the requirements for an exemption as set forth in 21 CFR 312.2(b)(1) of the FDA regulations are met, in which case no IND application is required to be submitted. 21 CFR 312.2(b)(1) identifies five requirements for an IND exemption. Requirements 1, 2, 4, and 5, relate to administrative requirements that are not applicable to my study. However, requirement 3 is applicable, and it provides that an IND exemption is appropriate if: “The investigation does not involve a route of administration or dosage level or use in a patient population or other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with the use of the drug product.”

Having already determined an acceptable and reasonable risk to subjects in the course of approving my study under 21 CFR 56.111 of the FDA regulations and USF Policy No. 809, it would have been a straightforward matter for the IRB to then consult with the investigator to determine whether an IND application should be submitted to the FDA. According to the FDA’s Office of Medical Policy, the determination of whether an IND is required for a study is made by the investigator, in accordance with FDA regulations. The FDA maintains:

"The determination of whether an IND is required for a given study is made by the investigator/sponsor, in accordance with FDA regulations."

Reference:

http://www.rsdfoundation.org/en/Test_IRB.htm#June4

At the IRB meeting on April 24, 2006, Dr. Bercu would not so much as consider my input regarding an IND, and went so far as to silence me when I attempted to bring the issue before the IRB. This is documented in the audio recording of the meeting.

Reference:

http://www.rsdfoundation.org/en/Test_IRB.htm#April24

Interestingly, my efforts to bring the IND issue before the IRB are not reflected in the “official” minutes of the meeting.

Reference:

http://www.rsdfoundation.org/en/Test_IRB.htm#MINUTES_June24

The IRB has evaluated the perceived risk to itself, and has decided its own liability exposure is minimized if the FDA is “forced” to decide an IND exemption in every case. Instead of considering the interests of the patient population that the study is designed to benefit, the IRB has focused on the interests of the IRB and USF by requiring an IND application to the FDA in every instance. Investigators need to be warned and understand that the final approval of their study will not be determined by the IRB at USF.

Reference:

http://www.rsdfoundation.org/en/Test_IRB.htm#April24

Clearly, this is not what is contemplated by FDA regulations. Dr. Bercu and the IRB may be relying on USF Policy No. 404, “Use of Investigational Drugs and Biologics”, as justification for their requirement that the FDA make the decision regarding IND exemption in every case. Paragraph 7 of USF Policy No. 404 does in fact state that the investigator in every study must request an IND from the FDA, and must further provide an IND Number or letter from FDA exempting approval. The same Policy also states in paragraph 6.4 :

"6.4 IRB Responsibilities: IRB is responsible for applying all federal regulations applicable to the use of investigational drugs and biologics, found in:

                            6.4.2    21 CFR 56 (Criteria for IRB Approval of

                            Research)

                            6.4.3    21 CFR 312 (Investigational New Drug

                           Application)"

While on the one hand the policy recognizes the legal obligation of the IRB to comply with the FDA regulations governing IRB responsibilities and IND’s, on the other hand the policy purports to opt out of regulations the IRB apparently does not like.

The IRB’s attempt to abrogate its obligation to comply with FDA regulations by adopting a “policy” is misplaced at best, unlawful at worst. Compliance with the law as embodied in the FDA regulations is mandatory, not optional at the election of the IRB. Pursuant to 21 CFR 312.2(b)(4) of the FDA regulations, the FDA will not accept an IND application for an investigation that is exempt.

On May 11, 2007 Mr. Joseph P. Griffin, on behalf of the Office of Medical Policy for the FDA, responded to questions posed by the International Research Foundation for RSD / CRPS. In his email letter, Mr. Griffin states:

“IRBs make an independent assessment of the acceptability of the risks and potential benefits of a planned clinical study to assure that human subjects are adequately protected. The issues that IRBs are required to consider are described in 21 CFR part 56 of the Code of Federal Regulations (see section 56.111--Criteria for IRB approval of research). IRBs are not specifically tasked with determining whether an IND is required for a given study. However, IRBs will often want to know whether a drug study is being done under an IND, and if not, whether there is a defensible rationale for doing the study without an IND. If an IRB is uncertain about the need for an IND, it will often direct the sponsor/investigator to ask FDA whether an IND would be needed (emphasis added).

Reference:

http://www.rsdfoundation.org/en/Test_IRB.htm#May11

By email dated June 4, 2007, Mr. Griffin added further clarification.

Reference:

http://www.rsdfoundation.org/en/Test_IRB.htm#June4

“So, the absence of any express regulatory requirement doesn’t mean the IRB or the parent institution can’t of its own initiative implement a policy/procedure that requires some confirmation about the need for an IND where the IRB has a question, either for human subject protection or general compliance purposes (emphasis added)

Mr. Griffin clearly asserts the regulatory obligation of every IRB to independently assess the risks/benefits of a planned study, as set forth in 21 CFR 56.111 of the FDA regulations. This is reflected in USF Policy No. 809. Neither the FDA regulation, nor the USF Policy, authorizes the IRB to require an IND for every clinical study, without exception.

Mr. Griffin also acknowledges that under certain circumstances, an IRB can require an IND application. My study is not a case of the IRB expressing an uncertainty about the need for an IND or having a question after thoroughly assessing it, and then directing that the FDA be queried.   Here, the IRB has adopted a policy that requires every investigator to file an IND application with the FDA, in order to “force” the FDA to make a decision, in the belief that the IRB and institution will somehow benefit as a result.

Rather than file a formal complaint with the FDA seeking FDA enforcement of its regulations, I have attempted to make Dr. Bercu and Ms. Epley aware of my concerns, in the hope that a proper resolution could be reached. It is unfortunate that they have chosen to respond to the concerns I have expressed with untruths, misstatements of fact, misstatements of law, and by attacking me personally.

By letter dated May 7, 2007, I was advised by the Vice President for Research at USF that he is forming a "team" to investigate the concerns that I have expressed in this report about the violation of FDA regulations and the systematic cover up by Ms. Epley and Dr. Bercu. I respectfully request that two of the team members with appropriate qualifications be selected from outside USF.

Reference:

http://www.rsdfoundation.org/en/Test_IRB.htm#May7

It is my hope that the IRB’s policies and operating procedures will be reviewed for both prudence and FDA compliance, so that future investigators will not be dissuaded from pursuing their research, and that the interests of the patient population for whom the research is undertaken will be primary in the decisions made by the IRB.

Sincerely,

Anthony F. Kirkpatrick, MD, PhD

CC: William Marshall MD, Associate Dean, USF Health

       Alan Goldman MD, Chairman, Department of Internal Medicine, USF Health