Single IRB requirement intended to streamline multi-site clinical research

NIH national institutes of health logo single IRBBeginning September, 2017, the National Institutes of Health (NIH) will require that a single IRB (sIRB) of record be used in the ethical review for all NIH-funded non-exempt, multi-site human subjects research protocols in the United States (NOT-OD-16-094). The sIRB policy applies to all multi-site human subjects research regardless of the NIH funding mechanism (e.g., SBIR/STTR awards, grants, cooperative agreements, contracts or other mechanisms such as Cooperative Research and Development Agreements (CRADAs), and Interagency Agreements (IAA)).

The goal of this policy is to enhance and streamline the IRB review process, in the context of multi-site research, so that research can proceed as effectively and expeditiously as possible. In addition to streamlining some aspects of IRB reviews, the new sIRB policy presents an opportunity to harmonize the standards used in clinical research in the United States and streamline future administrative responsibilities.

The sIRB policy takes effect on September 25, 2017. This date is four months later than the effective date that appears in the sIRB policy document. NIH extended the effective date to allow additional time for successful implementation.

Finally, beginning in January 2020, the revised Common Rule will expand the studies to which this requirement will apply. The revised rule will require single IRB review for all multi-site studies conducted in the United States, rather than having each site’s IRB bear regulatory responsibilities. This had been a controversial provision of the NPRM, but became less so following the issuance of the NIH policy for research it funds.

Resources and guidance are available on the NIH Office of Science Policy website (http://osp.od.nih.gov/office-clinical-research-and-bioethics-policy/clinical-research-policy/models-irb-review). But for now, the question remains on whether the requirement for sIRB review will be equally protective of subject interests and actually demonstrate to be more effectual.

Pearl IRB will keep you updated on future developments impacting clinical research through our blog. For immediate updates, follow us on Twitter or send your inquiries to our experts directly.

Common Rule changes will impact informed consent, IRBs, and more

HHS changes Common RuleOn January 18th, the US Department of Health and Human Services (HHS) and 15 other federal departments and agencies issued a final rule to revise the federal Policy for the Protection of Human Subjects. The Policy for the Protection of Human subjects, aka the Common Rule, outlines all federal regulations concerning clinical research involving human subjects. The final rule contains significant departures from the Notice of Proposed Rulemaking, issued in September of 2015, as a result of public feedback and concerns to the original notice of changes. The final revisions to the Common Rule can be found here, but continue reading for a condensed summary of the critical changes.

Regarding informed consent:

  • A requirement for simplifying research consent forms. Study consent forms must concisely state a study’s scope, risks, and benefits so that individuals can make informed decisions regarding participation.
  • Consent forms for certain federally funded clinical trials must be posted on a public website.

Regarding IRBs:

  • The Final Rule includes new requirements to use a single IRB for multi-institutional research studies. However, there is flexibility in allowing large groups of studies to be removed from this requirement. Researchers will have the option of relying on broad consent obtained for future research as an alternative to seeking IRB approval to waive the consent requirement (e.g. for studies on stored identifiable data or biospecimens). Researchers will not be required to obtain consent for studies on de-identified, stored data, or biospecimens. The provision that would have required researchers to obtain consent before using a study participant’s de-identified blood and tissue samples for secondary research was removed from the NPRM.

Regarding risk-based monitoring:

  • There are new exempt categories of research based on the level of risk they pose to participants. For example, there is a new exemption for secondary research involving identifiable private information if the research is regulated by, and participants protected under, HIPAA.
  • Removal of the requirement to conduct continuing review of ongoing research studies in certain instances where such review does little to protect subjects (e.g. low risk studies).

These changes are set to take place in January of 2018 with the exception of the single IRB review requirement (slated for January of 2020). The political landscape remains uncertain with the possibility that Congress may overturn these and other regulations recently initiated by the previous administration. We at Pearl IRB recommend that you familiarize yourself with the full list of regulations and begin preparations for the new Common Rule. Our team of experts can help facilitate this process and meet the needs of your current and upcoming clinical trials.

Phase I study death in France prompts EMA updated guidelines on FIH trials

In January of 2016, a Phase I drug trial in France, conducted by the French contract research organization Biotrial, left one volunteer dead and five others hospitalized: four with permanent neurological damage. The drug, named BIA 10-2474, is under development, by the Portugal-based pharmaceutical company Bial, for pain relief. This is a therapeutic area where non-addictive drugs are in great need. BIA 10-2474 differs from other medications in this class as it is an inhibitor of fatty acid amide hydrolase (FAAH). This is in contrast to oxycodone (which works on opioid receptors) or naproxen (inhibitor of cyclooxygenase enzymes).  How and why this catastrophe happened has been a focus of significant speculation in the medical and scientific communities. But crucial details, such as in vitro and animal studies, are lacking. At the time of the incident, PubMed listed no publications of any type from Bial on this class of drugs.

Following the Biotrial incident, the EMA updated its guidelines on first-in-human (FIH) clinical trials. Following its review of FIH trials in late May, EMA released a draft concept paper for public consultation through 30 September 2016. EMA states the concept paper will be a foundation for a draft revision to its current guidelines, which it expects to release in late 2016. According to EMA, FIH trials have changed considerably since the last guidance was published in 2007, and current trials often involve more elements, such as multiple ascending doses (MAD), food interactions, and several subject groups. The EMA says it plans to extend its FIH trial guidance to cover issues such as early phase clinical trial design, integration of non-clinical pharmacology and toxicology data, definition of stopping criteria, and the rolling review of emerging human data during the study.

Most testing for the US drug industry’s late-stage human trials is now done at sites outside the country where results often can be obtained cheaper, faster, and with less red tape. A study by Glickman et al (N Engl J Med. 2009 Feb 19;360(8):816-23) reviewed over 300 published Phase 3 trials and found that almost a third of those led by US pharmaceutical companies were being conducted entirely outside the country. The researchers found, at the same time, that the number of FDA-regulated investigators running trials abroad increased by 15% each year, while the number of US-based investigators declined 5.5% annually.

The bureaucracy associated with gaining FDA approval has been in the headlines numerous times over the years. The FDA process was recently questioned following meningitis outbreaks at Princeton University and the University of California, Santa Barbara in 2015. These outbreaks were unique because the meningitis vaccines required by schools didn’t protect against the particular meningitis strain that was determined to be the cause of the outbreak. However, a vaccine for the serogroup B strain, named Bexsero, was approved in 2012 by the European Medicines Agency (EMA) for use in the EU.  The vaccine had also been previously approved for use in Australia and Canada. Within nine months, FDA permitted students on affected campuses to use the vaccine. FDA has not yet approved a design for Novartis’ Phase III trials. Completion of these trials, in addition to the submission of a new drug application to FDA, will take years to complete and cost millions of dollars.

Why doesn’t FDA just approve a product already approved for use in the EU? Do the EMA and FDA have significantly different approval standards? It has been suggested that competition between regulatory authorities could cause a “race to the bottom” as agencies cut regulations to be competitive and draw the most applications.

FDA is in the process of collecting and reviewing safety information pertinent to FAAH inhibitors under investigation in the US. In the meantime, additional FAAH inhibitors are also under development, including Janssen/Johnson & Johnson’s JNJ-42165279 for social anxiety disorder and Pfizer’s PF-04457845 for osteoarthritis pain. Therefore, updates to the regulations are timely and necessary. And, sponsors must carefully weigh the benefits (both to the sponsor and the study subject) of performing FIH trials in the EU, US or elsewhere.

Share your thoughts with us on EU vs. FDA FIH regulatory hurdles at Pearl IRB.

NPRM released outlines changes to Common Rule

A Notice of Proposed Rulemaking (NPRM) released 8 Sep 2015 outlines revisions to the Common Rule (45 CFR 46 subpart A) meant to modernize, strengthen, and make it more effective.

The most significant changes to the Common Rule proposed in the NPRM are as follows:

  1. Improve informed consent by increasing transparency and by imposing stricter new requirements regarding the information that must be given to prospective subjects, and the manner in which it is given to them.
  2. Generally require broad informed consent for the use of stored biospecimens in secondary research, even if the investigator is not being given information that would enable him or her to identify whose biospecimen it is.
  3. Exclude from coverage under the Common Rule certain categories of activities that should be deemed not to be research, are inherently low risk, or where protections similar to those usually provided by IRB review are separately mandated.
  4. A new process would allow studies to be determined to be exempt without requiring any administrative or IRB review. Certain exempt and all non-exempt research would be required to provide privacy safeguards for biospecimens and identifiable private information.
  5. Change the conditions and requirements for waiver or alteration of consent such that waiver of consent for research involving biospecimens (regardless of identifiability) will occur only in very rare circumstances.
  6. Mandate that U.S. institutions engaged in cooperative research rely on a single IRB for that portion of the research that takes place within the United States, with certain exceptions and holding unaffiliated IRBs directly responsible for compliance with the Common Rule.
  7. Eliminate the continuing review requirement for studies that undergo expedited review and for studies that have completed study interventions and are merely analyzing data or involve only observational follow-up in conjunction with standard clinical care.
  8. Extend the scope of the policy to cover all clinical trials, regardless of funding source, conducted at a U.S. institution that receives federal funding for non-exempt human subjects research.

Comments on the NPRM must be received by OHRP no later than December 7, 2015. Please click here to read the NPRM in its entirety.