NIMH Recruitment of Participants in Clinical Research Policy

Purpose/Background

The mission of NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery, and cure. Effective clinical research relies on the ability of researchers to meet recruitment goals. Recruitment goals should include consideration, as appropriate, for inclusion of women, members of racial and ethnic minority groups, and populations across the lifespan, in accordance with NIH policies.

In 2005, via NOT-MH-05-013 , NIMH instituted the Policy for the Recruitment of Participants in Clinical Research to monitor the recruitment of participants in NIMH-sponsored clinical research studies that expect to enroll 150 or more participants in a single study. For the purposes of this policy, a participant is a research subject who will contribute to the primary analyses (e.g., in the case of a randomized clinical trial, this number typically reflects the number of participants who are randomized and contribute to intention-to-treat analyses and does NOT include screened or consented participants who fail to meet full inclusion criteria or are otherwise not randomized). In 2016, via NOT-MH-16-013 , NIMH expanded this policy to apply to all NIMH extramural-funded clinical research studies proposing to enroll 150 or more participants per study, and all clinical trials, regardless of size, to enable staff to more effectively monitor the recruitment of participants in NIMH-sponsored clinical trials  and other clinical research  studies. The NIMH strives for effective and efficient recruitment of participants into NIMH-supported clinical research studies, and this policy specifies the approach for monitoring recruitment of participants in NIMH-funded clinical research.

Policy

The current NIMH recruitment policy, described in NOT-MH-19-027  Oversight and Monitoring of Clinical Research funded by the NIMH, reiterates the required monitoring of the recruitment of participants in NIMH-sponsored clinical research studies that expect to enroll 150 or more participants per study, and all clinical trials, regardless of size. NIMH will ensure that Principal Investigators (PIs) establish realistic recruitment milestones from the outset of a clinical research project and that progress is monitored throughout the course of the research.

This policy also applies to clinical studies submitted through collaborative funding opportunity announcements (e.g., PAR-19-297 and its reissuances) only if the planned combined enrollment across all sites is 150 or more, or the study is a clinical trial of any size.

For individual research grant/contract/cooperative agreement awards that consist of multiple studies that do not involve pooled analysis across studies (i.e., the studies are independent and independently analyzed), the policy applies only to those independent studies that enroll 150 or more participants and clinical trials of any size.

Definitions

• Clinical Research : (1) Patient-oriented research. Research conducted with human subjects (or on material of human origin such as tissues, specimens and cognitive phenomena) for which an investigator (or colleague) directly interacts with human subjects. Excluded from this definition are in vitro studies that utilize human tissues that cannot be linked to a living individual. Patient-oriented research includes: (a) mechanism of human disease, (b) therapeutic interventions, (c) clinical trials, or (d) development of new technologies. (2) Epidemiologic and behavioral studies. (3) Outcomes research and health services research. Note: Studies falling under Exemption 4  for human subject research are not considered clinical research by this definition.
• Clinical Trial : A research study¹ in which one or more human subjects² are prospectively assigned³ to one or more interventions⁴ (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.⁵

Responsibilities

• Principal Investigator(s) (PI),determines the preliminary recruitment milestones for the recruitment phase of the study, ensures recruitment plans for appropriate representation of women, minorities and participants across the lifespan in accordance with the approved application and NIH policies, submits triennial interim recruitment reports into the NIMH Recruitment Milestone Reporting System (RMR), and upon request, provides additional information via the Authorized Organization Representative (AOR) to NIMH officials regarding recruitment remediation efforts. In addition to the triennial interim recruitment reports in RMR, the PI is responsible for electronically reporting and updating their data on participants and clinical trials in the NIH Human Subjects System (HSS) , and for those studies required to register at ClinicalTrials.gov , ensure that NIMH-approved modifications to trial protocols are reported accordingly.
• NIMH Program Officials (POs) review the proposed recruitment milestones for appropriateness and feasibility, and request any additional information needed from the PI/AOR prior to award. The PO, together with Grants Management (GM)/Contracts Management (CM) staff, will discuss and determine the terms and conditions of the award and inform the PI/AOR. In coordination with GM/CM staff, the PO will monitor recruitment and determine whether the recruitment goals are being met in accordance with the terms and conditions in the Notice of Award. If changes to the recruitment targets are needed, the PI will enter revised targets in RMR and the PO will evaluate and approve or disapprove the revised targets.  
• NIMH Grants Management Specialists (GMSs) and/or Contract Management Specialists (CMSs) ensure that NIMH actions comply with federal regulations and NIH policy. They receive documents for inclusion in the official grant or contract files and specify the appropriate terms and conditions for the award notice. Awards will not be issued without proper documentation, including:
  • Pre-determined recruitment milestones that are expected to be met.
  • Recruitment targets for inclusion based on gender, race, ethnicity, and lifespan, as described in NIH policies (see links below).
  • Any other identified requirements for completion of the approved research project.
• Clinical Trials Operations Branch (CTOB) staff members consult with the PO, GMS, and PI/AOR in cases where recruitment deficiencies are identified or changes in recruitment numbers raise concerns, to determine appropriate action.

Procedure

Cumulative recruitment milestones must be established in RMR, by the PI, for all NIMH extramural-funded clinical research studies proposing to enroll 150 or more participants per study, and all clinical trials, regardless of size. When developing milestones for recruitment, consideration must be given, as appropriate and in accordance with NIH policies, to recruitment of women, members of racial and ethnic minority groups, and participants of all ages. In addition, consideration must be given to the timing of milestones to ensure that recruitment will take into consideration the necessary study start-up time and end with enough time remaining within the proposed project period to allow for necessary follow-up and analysis. The identified milestones, or targets, are to be cumulative in nature to eventually meet the total sample of the proposed study. The planned start and end dates for recruitment and cumulative recruitment targets are entered into the NIMH Recruitment Milestone Reporting (RMR) system at http://wwwapps.nimh.nih.gov/rmr/. PIs can log in to this site using their eRA commons username and password. A user’s manual is available by selecting “Help” at the bottom of any screen.

• After the recruitment start date, and in accordance with the terms and conditions of the award, the PI submits triennial interim reports on actual recruitment progress in RMR on April 1, Aug 1 and Dec 1.
• At any time during the project period, if modification of the total number of participants is needed based on scientific results or other unexpected events, the PI, via email from the AOR, notifies the assigned PO and GMS/CMS (and other relevant regulatory bodies, as appropriate) and proposes an adjusted target number of participants. The requested changes will be evaluated, approved or disapproved by the PO and GMS/CMS staff.
• If changes to the total number of participants are approved by the PO and GMS/CMS, in accordance with the terms and conditions of the award, the PI submits modified recruitment targets via RMR for approval by the PO and continues to provide NIMH with cumulative actual recruitment updates triennially via RMR. Also, the PI, with approval by the AOR, is responsible for electronically reporting and updating their data on participants and clinical trials in the NIH HSS . For clinical trials, NIMH-approved (and other relevant regulatory bodies, as appropriate) modifications to trial protocols must be submitted to ClinicalTrials.gov .
• If changes to the interim (but not total) recruitment targets are needed, the PI must provide an explanation for the changes via email to the PO and enter adjusted interim target numbers in RMR for PO approval.
• At each instance that actual recruitment numbers for cumulative recruitment or minority inclusion fall below 85% of RMR target, the PO is automatically alerted by the RMR system to review the recruitment report, and, as necessary, to follow-up with the PI to discuss recruitment challenges and efforts to improve recruitment. At the PO’s discretion, a recruitment remediation plan and monthly reporting may be implemented as described in greater detail in bullet below.
• Once a PO requests recruitment remediation in the RMR system, the system sends an email to the PO and PI with a copy to the NIMH team (GMS/CMS, GMO and CTOB staff) requesting (1) a memo with (a) information about recruitment delays, including previous and ongoing barriers to participant recruitment and (b) a proposed plan to remediate recruitment shortfalls, including a clear description of how challenges have been addressed and how remaining issues will be resolved to ensure recruitment goals are reached with available time and resources, and (2) monthly recruitment targets (entered in RMR). Once the PO and NIMH team have reviewed the memo and the monthly targets, the finalized memo must be submitted via email from the AOR to the NIMH team and the PO will approve the monthly milestone targets in RMR. Once a remediation plan is in place, RMR will require monthly reporting until the NIMH team considers the remediation plan was a success. Otherwise, monthly reporting will continue until the end of the grant period. If recruitment does not show adequate improvement, the NIMH team will determine viable options depending on the severity and duration of the recruitment shortfalls. If the deficiencies persist, the NIMH team will take further action, in accordance with Public Health Service policy, which could include orderly phaseout, suspension, termination, or withholding of support.⁶

Resources

• ClinicalTrials.gov 
• NIMH Recruitment Milestone Reporting System
• Frequently Asked Questions about Recruitment Milestone Reporting (RMR)
• Points to Consider about Recruitment and Retention While Preparing a Clinical Research Study
• NIH Policy and Guidelines on the Inclusion of Women and Minorities as Subjects in Clinical Research 
• NIH Policy and Guidelines on Inclusion Across the Lifespan in Research Involving Human Subjects 
• NIH Human Subjects System 
• NIH Grant Policy Statement (2018) 
• Federal Acquisitions Regulations 

¹ See Common Rule definition of research at 45 CFR 46.102 (l) .

² See Common Rule definition of human subject at 45 CFR 46.102 (e)(1) .

³ The term “prospectively assigned” refers to a pre-defined process (e.g., randomization) specified in an approved protocol that stipulates the assignment of research subjects (individually or in clusters) to one or more arms (e.g., intervention, placebo, or other control) of a clinical trial.

⁴ An 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. Examples include: drugs/small molecules/compounds; biologics; devices; procedures (e.g., surgical techniques); delivery systems (e.g., telemedicine, face-to-face interviews); strategies to change health-related behavior (e.g., diet, cognitive therapy, exercise, development of new habits); treatment strategies; prevention strategies; and, diagnostic strategies.

⁵ 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. Examples include: positive or negative changes to physiological or biological parameters (e.g., improvement of lung capacity, gene expression); positive or negative changes to psychological or neurodevelopmental parameters (e.g., mood management intervention for smokers; reading comprehension and /or information retention); positive or negative changes to disease processes; positive or negative changes to health-related behaviors; and, positive or negative changes to quality of life.

⁶ See NIH Grants Policy Statement 8.5.2 at https://grants.nih.gov/grants/policy/nihgps/nihgps.pdf  and Federal Acquisition Regulations Part 49 at https://www.acquisition.gov/far/part-49?searchTerms=Federal%20Acquisition%20Regulations%20Part%2049 .