What is “Single IRB”? What is the SMART IRB (Streamlined, Multisite, Accelerated Resources for Trials IRB) reliance system and how does it facilitate the process?
Well, what’s more efficient for a clinical trial testing a drug at 50 different sites? Having 50 different institutional review boards (IRBs) review and approve the study documents? Each approving different inclusion and exclusion criteria and human subject protections at their site? Or having all 50 institutions agree to rely on one IRB that has been designated to review the multi-site study?
And, let there be no mistake: streamlining the ethical and regulatory review process for participating sites ensures the scientific validity of the study as well. If one IRB requires the exclusion of subjects with neutrophils less than 1200 and others do not, data will be skewed.
Inconsistent approaches to IRB review introduce burdens and inefficiencies for sponsors, investigators, collaborating institutions, and IRBs. As such, single IRB (sIRB) reviews are required for all non-exempt multi-site studies supported by the Nation Institutes of Health (NIH) and Department of Health and Human Services (HHS).
The SMART IRB initiative was led by Harvard Catalyst and the National Center for Advancing Translational Sciences (NCATS). SMART IRB received NCATS federal funding to harmonize and streamline the sIRB process by promoting the alignment of policies and processes and the adoption of common forms, practices, and workflows to be used among study teams and participating qualified and vetted IRBs, thereby ensuring a high level of protection for research participants and reducing administrative burden. In short, SMART IRB established a simplified process for getting reliance agreements for sIRB review in place.
On April 14, 2025, NIH sent Harvard University a Stop Work Order for the SMART IRB federal funding contract. The order did not include a reason or explanation. Harvard University was told to cease all work on the SMART IRB federal contract immediately. While Harvard has been trying to reinstate the work order, to date, they have not been successful. The SMART IRB Agreement, however, remains operative.
The SMART IRB Agreement is an independent legal agreement between SMART IRB Participating Institutions; as such, SMART IRB Agreement V3.0 remains available for use by current signatory institutions (e.g., Pearl IRB), and the existing arrangements under the prior Legacy Agreements remain valid. But, NIH manages SMART IRB website content and new guidance and resources will not be published.
As of the posting of this blog, SMART IRB website content is current and factual, harmonization and guidance documentation remain, and organizations may use the website to initiate new agreements and sign on to V3.0.
However, instances of “here today, gone tomorrow” are not outside the realm of possibility. Prior to April 18, Covid.gov was a tool to connect people to information about Covid vaccines, testing, treatment, and long Covid. The website also formerly helped people find healthcare: for example, pharmacies and community health centers that offered Covid tests. Now, Covid.gov has been updated to promote a debated and unproven notion suggesting that, before infecting humans, Covid originated in a research laboratory in Wuhan, China.
While organizations may use the SMART IRB website to initiate new agreements, Pearl IRB suggests that institutions NOT use the ONLINE joinder system. Harvard personnel manning the help desk are working on a volunteer basis now – they are not being paid. If issues arise executing an online agreement, SMART IRB volunteers will not be available, or slow, to assist.
If you would like to join SMART IRB V3.0 and the highly qualified group of institutions and individuals protecting humans involved in clinical research DO SO NOW while the website is intact. Do not put it off. The team at Harvard is working to process submissions as they come in and the more voices calling for the use of this important tool, the better.
If you have any questions about your reliance agreement or the single IRB process, please contact Pearl IRB.
Although the SMART IRB initiative is not about Harvard, the stop work order was.
If you would like to discuss your concerns about the SMART IRB reliance program, please contact HHS leadership and your elected representatives.