safety and ethics review
Regulators
IRB
Protection of human subjects (both safety and ethical treatment) is the main role of the IRB and the most important regulatory element of research. IRBs review all elements of a study, including rationale, protocol, consent forms, procedures, and all other documents that a participant is exposed to. For example, all recruitment materials must be IRB approved. Documents that are IRB-approved are dated and stamped, and cannot be changed without IRB approval (even if you are just changing a date or correcting spelling of a word); all research staff must have human subjects training which is renewed every 2-3 years; any change in staffing must be reported to and approved by the IRB. Basically, a study cannot deviate at all from what is IRB-approved without modifying the IRB application and getting re-approved.
IRBs consist of experts in the field, experts in ethics, experts on particular vulnerable populations (e.g., prisons, pregnant women, veterans, children), and community representatives (required on all IRBs). Studies must obtain “initial” IRB approval in order to get funded; this ensures that the basic concept of the study is likely to be able to proceed. Following funding, investigators will iron out details in the protocol, refine measures, design recruitment materials, etc., and then submit a “major modification” including all these changes for review. Reviews can take from a few weeks to (if very complicated and requiring a lot of back-and-forth between the committee and the research team) a few months. Investigators must submit for annual approval (“continuing review”) of all studies. Investigators must also submit details of any protocol violations or serious adverse events, generally within 5 days of occurrence. IRBs are quite strict on how the deal with violations of protocol, particularly if the violation COULD have resulted in any risk to the patient. For example, the UCSF IRB committee Dr. Coffin sits on terminated a study because the investigators re-labeled a mis-labeled medication bottle, rather than discarding the bottle.
IACUC
While regulating animal research rather than humans, IACUC has defined standards for animal safety and ethics, and carries the same authority as an IRB does for human research.
FDA
Potential benefits must outweigh risks and adverse events must be reported annually, with more frequent reporting for serious events.
DSMB
The mission of the DSMB is to ensure that the risks posed to study participants are minimized and are worth the potential benefits. For example, if a study can’t enroll enough participants to be able to detect a benefit of the medication, the DSMB will shut down the study.
RAPC
RAPC lacks appropriate diversity (e.g., community representation, vulnerable population expertise) on the committee, lacks an ethical framework from which to review studies, lacks capacity to monitor studies as they progress, and lacks the vast resources necessary to do anything in a timely manner.
RAPC has specific consent language which it says must be used in consent forms; however this language conflicts with language required by the University of California and most other IRBs. Each time RAPC responds to a protocol stating that consent language must be changed, investigators reach out to their IRB, which tells them that the language cannot be changed. The investigator then sends a letter to the RAPC explaining that the IRB – which is the federally-mandated regulator and has the final say on any research proposal – will not allow RAPC language in the consent. Because no study can deviate from IRB determinations, the RAPC cannot enforce changes, and these dialogues just result in further delay before a study can begin.