Subject: Appeal of decision by Dr. Robert Rappaport
Dear Dr. Galson:
The International Research Foundation for RSD / CRPS respectfully requests that the FDA reconsider and withdraw a decision made by Dr. Robert Rappaport on October 20, 2006. It is our understanding you are Dr. Rappaport’s supervisor, and as such, you are authorized to consider this appeal. If we are incorrect in our understanding, please forward this correspondence to the correct person and notify us immediately.
On September 6, 2006 the Foundation wrote to Ms. Leah Ripper at the FDA, and requested that the FDA provide the Foundation with “the citations of authority containing the standards that your office relies upon in determining if a study submitted to your office is exempt from an IND application.” As stated in the Foundation’s correspondence to Ms. Ripper, we are preparing a report intended to help investigators and IRBs identify which studies may be exempt from an IND application, thus saving the investigators from submitting unnecessary IND applications and thereby saving the FDA unnecessary review and paper work.
"We are writing a report which will be published on the Foundation’s web site:
The intent of the report is to clarify the FDA policy that will help investigators and IRBs identify which studies are exempt from an IND application, thus saving the investigators from submitting unnecessary IND applications."
By email dated October 10, 2006, Ms. Ripper responded and advised the Foundation:
"At this time, we do not have any written guidance on standards or criteria for exempting an investigational study from the requirements for an IND other than what is found in our implementing regulations at 21 CFR 312.2(b). 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. Depending on the situation, the decision may be verbal based on a telephone conversation with the investigator or may be in writing in response to submission of a written summary of the proposed protocol or the protocol itself."
Based upon the statements in her email, the Foundation suggested to Ms. Ripper that the FDA demonstrate its decision making process by using, as an example, a research protocol for a study currently taking place in Mexico with regard to RSD/CRPS. The Foundation provided this protocol to Ms. Ripper by email on October 13, 2006, in which the undersigned stated, “In writing this protocol pursuant to 21 CFR §312.2(b)(1)(iii) of FDA regulations, I used the published FDA criteria that were attached to my email to you dated October 10.” It is important to note that by email dated September 8, Ms. Ripper advised the Foundation that the authors of these criteria “are our subject matter experts on IND exemption policy.” The clear intent was that the example Mexican protocol would be reviewed pursuant to these criteria, or not at all. The matter was referred by the FDA to Dr. Rappaport for a decision.
On October 16, 2006, Dr. Rappaport requested that a telephone conference be held the following day with Dr. Anthony Kirkpatrick, Chairman of the Foundation’s Scientific Advisory Committee. Dr. Kirkpatrick advised Dr. Rappaport at the outset of their telephone conference on October 17 that the primary purpose of the Foundation contacting the FDA was to address complaints received by the Foundation about how his division at the FDA reviews requests for IND exemptions, as set forth in the Foundation’s letter to the FDA dated September 6, 2006. Dr. Rappaport said he was not interested in hearing about the complaints. He said that the complaints should be made to Warren Rumble, the Ombudsman for the FDA, even though this approach to resolving complaints is not consistent with the published policy of the Office of the Ombudsman.
During that telephone conference on October 17, Dr. Rappaport asked if the purpose of the telephone conversation was to obtain a decision about a protocol being used in Mexico. Dr. Kirkpatrick emphatically said that this was not the case. He further stated that if Dr. Rappaport did not agree with the objective criteria for an IND exemption that are promulgated by the FDA’s Office of Medical Policy, the Foundation did not want him to make a decision about the example Mexican research protocol. Dr. Rappaport stated that the FDA intended the published criteria to apply only to cancer drugs, and that he had no intention of applying the published criteria in rendering a decision on the example protocol. At that point, it should have been clear to Dr. Rappaport that no decision about the example Mexican research protocol was being sought.
Dr. Rappaport became noticeably upset during the October 17 telephone conference when Dr. Kirkpatrick stated that his understanding of the published FDA criteria
[i.e., that the criteria are applicable to all drugs]contradicted Dr. Rappaport’s understanding, [i.e. that the criteria are intended exclusively for cancer drugs.] Dr. Kirkpatrick suggested to Dr. Rappaport that it appeared to the Foundation that the reason the Office of Medical Policy promulgates standards and criteria for IND exemptions is to avoid arbitrary and capricious decisions by the FDA on the IND exemption issue. Dr. Rappaport responded by admonishing Dr. Kirkpatrick for being "unprofessional" in making such a suggestion.
The Foundation’s position can be verified by reference to the Foundation’s October 16 (prior to the October 17 telephone conference) email message to the FDA Office of Regulatory Affairs (with a copy to Dr. Rappaport, which he acknowledged receiving on October 16). It was that email message that triggered Dr. Rappaport’s request for a telephone conference the following day. In the email, Dr. Kirkpatrick wrote that he expected Dr. Rappaport to “adopt” the criteria promulgated by the Office of Medical Policy in deciding if an IND exemption would be granted for the example Mexican protocol. He further stated in the email message that if Dr. Rappaport adopted the guidance promulgated by the FDA, it would permit his division “to process IND exemptions in a more fair and efficient manner.”
On October 20, 2006, the Foundation received a letter signed by Dr. Rappaport stating:
“Based on the information provided, we have concluded that the study you have proposed does not meet all of the requirements for exemption from the IND regulations and, therefore, an IND will be required to conduct your investigation.”
The decision by Dr. Rappaport appears to be based solely upon a retaliatory motive, since all communication between the Foundation and the FDA prior to his decision reflects that no decision could have or should have been made with regard to the example Mexican protocol. His conduct is tantamount to an attack on RSD/CRPS patients with intractable pain who have no reasonable treatment options available.
It is our understanding that retaliation is regarded as a very serious violation of the FDA rules of employee conduct, and it will not be tolerated:
Dr. Rappaport’s decision is also incongruent with an email message of October 16, 2006, where Parinda Jani, Chief of Projects and Management, states, on his behalf, that the example Mexican research protocol contains insufficient detail “to render a written opinion on the IND exemption issue.”
In rendering a decision which was not requested, and which was based on incomplete information, Dr. Rappaport has, perhaps inadvertently, confirmed the complaints received by our Foundation. Dr. Rappaport refused to consider the published FDA standards for IND exemption promulgated by the Office of Medical Policy in connection with cancer studies, even though the FDA considers that “guidance” to be the current and most useful information available from the FDA on this issue when deciding an IND exemption in areas other than cancer. Dr. Rappaport insisted that the IND guidance promulgated by the Office of Medical Policy should be applied only to cancer drugs. This directly contradicts the position of the FDA’s Office of Medical Policy:
“The analyses and examples in that guidance concerning whether risk is significantly increased provide some insight into how FDA thinks about this issue generally and thus may be relevant to studies of marketed drugs in other therapeutic areas. At present, this guidance is likely the most useful information available from FDA on this issue.”
For reasons known only by Dr. Rappaport, he made the decision that the example Mexican research protocol will require an IND, despite being specifically told a decision was not being sought, and despite his not having all the information that would be necessary to make an informed decision.
In light of the above, it is clear that Dr. Rappaport’s decision about the Mexican research protocol is improper and has no credible basis. His tone and offensive comments during his October 17 telephone conference with Dr. Kirkpatrick strongly suggest a retaliatory motive in rendering this unsolicited decision, rather than an objective assessment based on FDA policy. It is respectfully requested that you recognize the impropriety of Dr. Rappaport’s decision and withdraw it immediately.
We trust that you will respond to this appeal in a timely and effective manner.
International Research Foundation for RSD/CRPS
Anthony F. Kirkpatrick, MD, PhD
Chairman, Scientific Advisory Committee
Timothy Lubenow, MD
Jerry H. Trachtman, ESQ
[Editor’s Note: As soon as Dr. Galson’s decision is received it will be published by the Foundation.]
Andrew von Eschenbach, MD
Fax 301 443-3100
Robert Temple, MD
Director, Office of Medical Policy
Fax 301 796-9840
Ombudsman, Center for Drug Evaluation and Research
Fax: 301 827-4312
Sent by email and fax to the FDA on November 20, 2006