The National Institutes of Health (NIH) now includes research on behavioral outcomes in its definition of a clinical trial. They also require the use of a single IRB (sIRB) for multi-site studies. Review this question tree to determine whether your research qualifies as a clinical trial.
In addition to the definition update and changes to human subjects protections review, NIH is also requiring additional training in the form of Good Clinical Practice and an expectation that all trials will be registered with the U.S. National Library of Medicine through ClinicalTrials.gov.
NIH Definition of Clinical Trials
NIH 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 placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.”
Prospectively assigned refers to a predefined process specified in an approved protocol that stipulates assignment to one or more arms of a clinical trial.
Intervention is defined as a manipulation of the subject or subject’s environment for the purpose of modifying one or more health-related biomedical or behavioral processes and/or endpoints.
Health-related biomedical or behavioral outcome is defined as the pre-specified goal(s) or condition(s) that reflect the effect of one or more interventions on human subjects’ biomedical or behavioral status or quality of life.
Studies that propose to conduct a clinical trial at the time of the application submission must include with the application:
Protection of Human Subjects section that describes all of the human subjects components of the study
Data and Safety Monitoring Plan (DSMP), which may involve the creation of a Data and Safety Monitoring Board (DSMB) for multi-site clinical trials involving interventions that entail potential risk to the participants, and generally for NIH-Defined Phase III clinical trials
Inclusion of Women and Minorities
PHS Inclusion Enrollment Report(s)
Inclusion of Children
NIH is launching a series of initiatives to enhance the accountability and transparency of clinical research. These initiatives target key points along the entire clinical trial lifecycle, from concept to results reporting. The Research Methods Resources website provides investigators with important research methods resources to help them satisfy these new requirements.
Single IRB (sIRB) Requirement
NIH requires a single IRB review for multi-site or cooperative studies. All domestic sites participating in multi-site studies involving non-exempt human subjects research funded by NIH must use a single Institutional Review Board (sIRB). The goal of this policy is to enhance and streamline the IRB review process for multi-site research without compromising ethical principles and protections for human research participants.
NIH defines a multi-site study as one that uses the same protocol to conduct human subjects research at more than one site. So the same protocol is being conducted at multiple locations. A site is considered to be conducting human subjects research if it is “engaged” in the research.
There are some exceptions to this, but in general, an institution is engaged in research when:
It is the grantee institution, directly receiving an award from NIH, even if all of the human subjects activities are being carried out at other sites.
Its employees or agents interact or intervene with human subjects by manipulating their environment or by performing invasive or noninvasive procedures.
Its employees or agents obtain informed consent from human subjects
Its employees or agents receive identifiable private information or identifiable biological specimens.
At this time, RIT is unable to act as the relying IRB for multi-site research review requiring an sIRB; please contact firstname.lastname@example.org if you will be engaging in research that requires sIRB review.
Good Clinical Practice Training
NIH requires all staff and investigators involved in the conduct, oversight, and management of NIH-funded clinical trials to be trained in Good Clinical Practices (GCP). GCP training is available through RIT’s CITI program.
Register with ClinicalTrials.gov
NIH-funded clinical trials must register with the U.S. National Library of Medicine through ClinicalTrials.gov. ClinicalTrials.gov is a database of privately and publicly funded clinical studies conducted around the world.
To ensure compliance with the NIH policy, RIT requires that:
Clinical trials are registered at ClinicalTrials.gov at the time of IRB review.
Results information from clinical trials is submitted to ClinicalTrials.gov not later than one year after the trial’s primary completion date (i.e., the date of final data collection for the primary outcome measure).
Consent forms include the following text: “A description of this clinical trial will be available on http://www.ClinicalTrials.gov as required by U.S. Law. This Web site will not include information that can identify you. At most, the Web site will include a summary of the results. You can search this Web site at any time.”
NIH funding proposals are required to include a plan outlining how applicants will comply with the policy. We recommend that the following text be used to describe the plan: “In compliance with NIH policy, this clinical trial will be registered with ClinicalTrials.gov. Registration will occur at the time of IRB review and results information will be submitted not later than one year after the trial's primary completion date. Additionally, the relevant informed consent documents will include a specific statement relating to posting of the clinical trial information at ClinicalTrials.gov.”
Pre-Award and Post-Award Processes
NIH outlines the pre-award and post-award process to illustrate what gets considered during peer review, requirements for information submitted just-in-time for award, and monitoring requirements post award.