Letter to FDA on IRBs

March 10, 1998

Michele Russell-Einhorn
Director of Regulatory Affairs
Office for Protection from Research Risks
National Institute of Health
6100 Executive Blvd., Suite 3B01
Rockville, MD 20892-7507

RE: Protection of Human Subjects: Suggested Revisions to the Institutional Review Board (IRB) Expedited Review List. Fed. Reg. eg 60607, November 10, 1997.

Dear Ms. Einhorn:

The American College of Nuclear Physicians and the Society of Nuclear Medicine would like to thank you for allowing us this opportunity to comment. Together, our organizations represent 12,000 physicians, professors, technologists, radiopharmacists, and scientists in the field of nuclear medicine. We consider the republication of the list that identifies research on human subjects that may be reviewed by the Institutional Review Board (IRB) and the expedited review process a very important issue.

Nuclear medicine has one of the best safety records in the medical field. However, despite the low levels of risk involved in radiopharmaceuticals and its consistent safety record, it is excluded from the expedited review category, thus significantly slowing the time available to get a project through the IRB process.

It is with this in mind that the ACNP and SNM would like to offer the following comments:

• Current IRB regulations prevent expedited review from occurring whenever ionizing radiation is employed in a project.
• There is no threshold amount of radiation that triggers IRB review.
• There is no differentiation based on whether the radiation studies are the primary reason for the project or simply document the project's results.
• There is no reason to believe that ionizing radiation in normal diagnostic quantities presents any unusual risk to the patient that should preclude expedited review.
• Researchers employing ionizing radiation in any quantity, currently face additional delays above those imposed on other low-risk procedures.
• It is appropriate that when the radiopharmaceutical is the subject of investigation (IND drugs) or the procedure is investigational, then full IRB reviews should occur.

It is our opinion that 1.) in cases where the radiation study involves FDA approved radiopharmaceuticals and no investigational drugs are required for the radiation studies, there should be no prohibition on expedited review, and 2.) in the case of radiation-based projects there should be a dosimetric threshold limit above which an IRB review is required. Radiopharmaceutical studies performed in the usual clinical manner, or as a method of documentation of the outcome of other interventions in the protocol, should be eligible for expedited review.

Furthermore, we suggest that the following section as proposed below should be changed.

"6. Collection of data through use of the following procedures:

1. Noninvasive procedures routinely employed in clinical practice and not involving exposure to electromagnetic radiation outside the visible range (i.e., not involving x-rays, Micorwaves, etc.)
2. Physical sensors that are applied either to the surface of the body or at a distance and do not involve input of significant amounts of energy into the subject or an invasion of the subject's privacy.
3. Weighing, testing sensory acuity, electrocardiography, electroencephalography, thermography, detection of naturally occurring radioactivity, electroretinography, echography, sonography, ultrasound, magnetic resonance imaging (MRI), diagnostic infrared imaging, doppler blood flow, and echocardiography.
4. Moderate exercise, muscular strength testing, body composition assessment, and flexibility testing involving healthy subjects."

Many routinely performed diagnostic procedures involving exposure to ionizing radiation do not impose greater than a minimal risk. Expedited review of research studies involving the use of such diagnostic procedures should be permitted based on certain radiation exposure. Moreover, subcategory a, as proposed, does not make sense since MRI and diagnostic infrared imaging, which are later recognized as expeditable subcategories, involves exposure to electromagnetic radiation outside the visible range.

It is therefore our suggestion that this category should be divided into two categories and changed to the following:

• Collection of data through use of the following procedures performed in accordance with standard clinical practice:

1. Diagnostic imaging procedures that do not involve the input of significant amounts of energy, to include:

1. Diagnostic procedures (e.g., X-rays, CT scans, nuclear medicine procedures) involving exposure to ionizing radiation provided that (1) the radiation dose from any single procedure does not exceed the 3 Rems effective dose equivalent (EDE); 3 Rads to the active blood-forming organs, lens of eye, or gonads; or 5 Rads to any other organ; (2) the total radiation dose (i.e., from all such procedures performed for research) does not exceed, within 1 year, 5 Rems effective dose equivalent (EDE), 5 Rads to the active-blood-forming organs, lens of eye, or gonads; or 15 Rads to any other organ; and (3) and any agent to be used for image enhancement, if applicable, is approved by the Food and Drug Administration and does not, in itself, pose greater than minimal risk.

Precedence for the minimum risk status of the radiation exposure limits cited above can be found in the FDA regulations, 21 CFR Part 361, "Prescription Drugs for Human Use Generally Recognized as Safe and Effective and not Misbranded: Drugs Used in Research", S. 361.1, Radioactive Drugs for Research Use."

Again, we appreciate this opportunity to express our views on this subject. We hope that our opinions will be given every consideration in this review process, and should you have any questions or wish to discuss our position in further detail, please contact David Nichols, Director of Government Relations, at 703-708-9773.

Sincerely,