Scientific review
Regulators
IRB
It is federally mandated that all human subject research must be reviewed by an Institutional Review Board (IRB). Each IRB must be registered and approved by the Office of Human Research Protection (OHRP) which mandates certain requirements for IRB including at least 5 qualified members of diverse backgrounds present at a meeting for quorum (IRBs generally have many more members, including specialists who can provide expertise for diverse protocols and vulnerable populations). Each IRB must have at least one lay member from the community.
IRBs are the primary regulator for research; IRBs are federally-approved and regulated. While focused on human subjects safety, IRBs also conduct scientific review to ensure that a study is sufficiently justified, that the risks of a study are minimized and do not outweigh the scientific benefits, and that methods are reasonable. IRBs essentially always have comments and require changes to studies, and try to work with investigators to make studies meet the rigorous expectations of federal regulations, ethical guidelines, and local community standards. IRBs do reject studies entirely when they do not meet standards.
The IRB requires a principal investigator (PI) be named for each study it approves. The PI is accountable for the study conduct and to make sure it follows federal regulations for human subject protection, including reporting any significant adverse events. All protocol changes must be approved by the IRB, no matter how minor. Each study approved by the IRB must provide a periodic report (usually annually) and undergo re-review and approval (in contrast RAPC only requires one-time initial approval ). IRB’s generally meet every 1-2 weeks and can process most submissions in 1-2 months.
Institutional Animal Care and Use Committee (IACUC)
Similar to IRBs, IACUC regulates pre-clinical / animal research.
NIH (or CDC, AHRQ, SAMHSA, or other funder)
Most research is reviewed and funded by the NIH, which involves an extensive review process, first by a panel of scientific peers, then by NIH staff, then by NIH regulators and those making funding decisions. All documents, including the Data Safety Monitoring Plan, must be submitted and approved. The NIH also automatically issues a “Certificate of Confidentiality” which protects study participants from research records being subpoenaed for legal proceedings. Research not funded by federal agencies undergoes a similar process of scientific review and oversight and investigators can obtain a Certificate of Confidentiality by submitting the protocol to the NIH. Prior to funding being issued, IRB approval is required. NIH or other funder review generally takes about 1 year, although multi-site studies can undergo 3-4 years of scientific review before being funded.
FDA
The process of obtaining an investigational new drug [IND] permit requires submission of a detailed protocol to the FDA, which will review, provide feedback and guidance, and approve or not approve. Investigators must submit annual reports on progress and adverse events, as well as submit serious adverse events that occur during the interim. Any changes that affect patient safety must be approved by the FDA before being implemented. The FDA has 30 days to respond to each submission and the review process generally does not exceed 2-3 months.
Data and Safety Monitoring Board (DSMB)
This is independent agency that oversees study integrity and participant safety. The DSMB reviews the study for the validity of the science to ensure that any risks posed to participants are both minimized and are “worth” the scientific knowledge gained. The primary role of the DSMB is to ensure risks and minimized and justify the scientific information to be gained. All protocol changes must be approved by the DSMB. DSMB’s meet as frequently as needed and generally process a submission in 1-2 months.
RAPC
RAPC legislation states that the committee must “review and authorize” research involving CS I/II or ANY medications used for addiction. The legislation does not clarify what those terms mean (i.e., for what purpose the RAPC is reviewing the research).
RAPC comes in late in the process, after years of scientific review by funders, IRB, DSMB, FDA, and others. While research – like legislation – is never perfect, after years of vetting it is rarely possible to make any meaningful adjustments to a research study (imagine a committee of non-experts that took every bill from the governor’s desk, spent a year looking at it, and then told the legislature they should change some things and try again - the government would not be able to function!). RAPC cannot overrule federal regulators (IRB/DSMB/FDA/DEA), so their comments are considered worthless by researchers. Unfortunately, resolving comments from RAPC requires months of letters between RAPC and investigators, resulting in no changes but further delays. RAPC, when meeting, meets every 2 months, requires submissions 2 months prior to meetings, and sends response letters to investigators 3 months after meetings; thus the absolute minimum review time is 5 months, compared to 2-4 weeks for other regulators.
Some investigators, unable to add 5 or more months to their study timeline, have submitted applications to RAPC before doing any other review (in the hopes of getting reviews done “in parallel” to save time); those are the applications that tend to have meaningful issues because they lack the refinement provided by the federally-mandated regulators.