Effective January 25, 2018, the National Institutes of Health (NIH) is introducing a number of significant changes intended to “enhance the accountability and transparency of clinical research.” The forthcoming changes are detailed below.
Forms-E Application Package and New PHS Human Subjects and Clinical Trial Information Form
The PHS Human Subject and Clinical Trial Information form consolidates, into a single location, information that is currently scattered across a number of forms.
Four Key Questions:
Does the study involve human participants?
Are the participants prospectively assigned to an intervention?
Is the study designed to evaluate the effect of the intervention on the participants?
Is the effect that will be evaluated a health-related biomedical or behavioral outcome?
It requests a great deal more information than is currently required.
Most importantly, the form poses four key questions that determine whether the proposed research involving human subjects is a clinical trial (see broader definition of clinical trial below).
If the answer to all four questions is "yes," then a clinical trial is being proposed. The expertise of the Principal Investigator (PI) or other key personnel will likely be needed to complete certain protocol-related data fields of the form (e.g., masking, statistical design, and power, etc.).
The PI and Research Administrator should partner early in the process to complete the form when proposing a clinical trial.
When will FORMS-E Application Packages be Available?
You may be seeing them now. NIH started posting updated Funding Opportunity Announcements (FOAs) around October 25, 2017. The U-M eResearch Proposal Management System (eRPM) will introduce support for the FORMS-E application package near the end of November 2017.
Excellent Resources to Learn More About the New Application Package
NIH announced Forms-E changes in April 2017. (See NOT-OD-17-062.)
A research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include a placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.
NIH adopted a new definition of clinical trials in 2014 (see NOT-OD-15-015) as part of its effort to improve transparency in the human subject research it funds. It defines a clinical trial as: “a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include a placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.” Note that the definition of clinical trials includes health-related behavioral outcomes.It's helpful to review the four questions that will appear on the PHS Human Subjects and Clinical Trial Information form and can be previewed in this online decision tree.
NIH is now putting this new, more expansive definition into practice.
When Will this Happen?
Beginning with proposals submitted on or after January 25, 2018, new and existing requirements for Principal Investigators (PIs) proposing to conduct a clinical trial will go into effect.
What are the Requirements for Conducting a Clinical Trial?
Complete Good Clinical Practice Training. NIH expects all NIH-funded clinical investigators and clinical trial staff who are involved in the design, conduct, oversight, or management of clinical trials to be trained in Good Clinical Practice (GCP).
Only Use a Clinical Trial-Specific FOA Proposals involving clinical trials must be submitted to an FOA or Request For Proposals that explicitly states it will accept clinical trials. After January 25, 2018, NIH will no longer accept clinical trial applications through existing parent announcements.You must use a clinical trial-specific FOA.
Use a Single IRB for Multi-Site Clinical ResearchAll sites participating in multi-site clinical research studies will use a single Institutional Review Board (sIRB) to conduct the ethical review required for the protection of human subjects. See below for more information.
Beginning January 25, 2018, all NIH-funded multi-site studies involving non-exempt human subjects research will be required to utilize a single IRB-of-Record (sIRB) for the review of human subject protections. Use of a sIRB avoids duplicative review by multiple institutional review boards. The NIH policy applies to:
IH-sponsored multi-site studies, where the same protocol is used at multiple sites;
Only the IRB review functions will be handled centrally. Related local functions (e.g., ancillary committee review, training fulfillment verification) remain the responsibility of the individual participating institutions. The conduct and reporting of the research remain the study team's responsibility. See Study Team Process on the Research Compliance Website for more information on ceding review to a non-U-M IRB acting as an sIRB.
U-M recommends the use of an external IRB (either an accredited commercial or other academic IRB) for multi-site studies.
How Do I Budget for an sIRB?
To comply with the NIH sIRB policy, U-M plans to cede IRB oversight to an external IRB when a U-M PI is the awardee of a multi-site grant. The associated costs of may be direct charged to your grant if funded. Before you begin an application for funding of a multi-site study, contact the applicable U-M IRB to discuss sIRB options and costs.
If U-M serves as the sIRB of record, there is no cost, currently, but you will need prior approval from the applicable U-M IRB if you wish to have U-M take on this responsibility.
Stay tuned (or sign up) for RAPid announcements (sign up here) that will provide more information and, later in November, a glimpse of what the forms will look like in eResearch. * If an award involves both domestic and foreign sites, the domestic sites would be expected to use a single IRB and the foreign sites could use their own IRBs or Ethics Boards. See NIH for specific details.