In Part One of this post, I discussed the decision tree used by NIH to determine if a study meets their 2014 clinical trial definition. Here, I will cover the implications of having a study be classified a clinical trial based on NIH’s criteria.

I’ll draw on information I learned from two presentations at PRIM&R’s 2017 SBER Conference (SBER17) and 2017 AER Conference (AER17). The first, a session at AER17 titled “SBER in the Era of the Revised Common Rule: An Overview of the Most Relevant Regulatory Changes” given by Yvonne Lau, MBBS, MBHL, PhD (Director, Division of Education and Development, Office for Human Research Protections). The second, a session at SBER17 titled “Clinical Trials in the SBER Context” by Melissa W. Riddle, PhD (Chief, Behavioral and Social Sciences Research Branch, National Institute of Dental and Craniofacial Research) and Cindy S. Shindledecker, CIP (Director, Health Sciences and Behavioral Sciences Institutional Review Board, University of Michigan). (Dr. Riddle was absent, but her colleague Wendy Webber, ND, PhD, MPH, Acting Deputy Director, National Center for Complementary and Integrative Health, was able to do an impromptu presentation on behalf of NIH.)

To be considered a clinical trial by the NIH, an NIH-funded study must meet four criteria: 1) The study must involve human subjects; 2) the human subjects must be prospectively assigned to an intervention; 3) the study must be designed to evaluate the effect of the intervention; and 4) the effects of the intervention must pertain to health-related outcomes, which can be evaluated by either biomedical or behavioral measures.

Per Riddle and Shindledecker, if a study is determined to be a clinical trial, the following requirements will apply:

• Good Clinical Practice (GCP) training will be required of all study personnel.
• Use of a Single IRB for multisite clinical trials.
  This requirement, which went into effect January 25, 2018, only applies to studies where the same (non-exempt) protocol is being administered at each participating site. If a clinical trial involves more than one site, but each site is performing a unique function in the study, then a Single IRB is not required. (Sites with disparate functions may still opt to defer to a Single IRB, but it is not mandatory). If the same protocol is being implemented across multiple sites, NIH requires that the Single IRB be designated at the time that the grant proposal is submitted.
• Registration on ClinicalTrials.gov.
  In an effort to promote transparency, NIH requires researchers to register their study on ClinicalTrials.gov within 21 days (exact number of days may vary by NIH center) of enrolling their first human subject. Researchers must also disclose the ClinicalTrials.gov registration information in the consent documents so potential participants are aware of the public study registry. This requirement will be study-specific, not grant-specific, so studies funded by the same grant must each be registered individually.
• Reporting on ClinicalTrials.gov.
  To further encourage transparency, NIH requires researchers to report their aggregated study results on ClinicalTrials.gov within 12 months of completing data collection on the primary endpoint. (Riddle and Shindledecker did not say specifically, but I assume information about when and where the study data will be publicly posted should also be included in the consent document).

Clarification: The above are NIH requirements only; these requirements apply only when a study is funded by the NIH and determined to fit their definition of a clinical trial.

Significantly, if these requirements are not met, the institution will lose its NIH funding. This penalty is not limited to the noncompliant study. Rather, the punishment for noncompliance on one study is that every NIH-funded study in the institution’s portfolio will lose its funding. (I am not sure if the institution will also lose future NIH-funding opportunities, or if there is a corrections process.) 

Due to the stringent requirements for studies that are determined to meet the NIH definition of clinical trial, and the institution-wide consequences if the requirements are not met, I offer two recommendations:

First, institutions need to establish monitoring and education programs so that principal investigators are aware of the implications of a clinical trial designation and so institutions can ensure that all deadlines are met.

Second, IRBs should be very discerning when deciding if a study is a clinical trial under the NIH definition to ensure they apply the policies associated with the study’s funding and limit the pool of studies that will require this additional oversight.

Meanwhile, the presentation by Lau delved into requirements for studies that meet the Common Rule’s definition of clinical trial: “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 the interventions on biomedical or behavioral health-related outcomes.” The Common Rule includes one requirement for federally funded clinical trials, so defined:

• Posting Consent Forms. Researchers must post one IRB-approved consent form used to enroll participants on a publicly available federal website to be designated. (This could end up being ClinicalTrials.gov, but another site may be chosen.) The consent document must be posted after recruitment closes (no later than 60 days after the last study visit). The federal department or agency may permit or require redactions. (Though not stated, I assume the fact that the consent form must be posted publicly should be indicated in the consent form).

Correction: This post initially incorrectly stated that the definition of “clinical trial” is only tied to studies with NIH funding; however, NIH and the Common Rule have different definitions of a clinical trial. The post also tied the 5th requirement, posting consent forms, to NIH-funded studies only; however, this requirement applies specifically to studies that meet the Common Rule’s definition of a clinical trial, not only to NIH-funded studies.

Sarah Luery is an IRB Administrator at the University of Southern California and a member of the 2017 SBER and AER Conference Blog Squad.

Members of PRIM&R’s Blog Squad and other guest contributors are valued members of our community willing to share their insights. The views expressed in their posts do not necessarily reflect those of PRIM&R or its employees.

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