Enhanced Oversight With Site Monitoring
Some enhanced oversight studies will have site monitoring. When this is the case, the clinical study will be visited by a National Center for Complementary and Integrative Health (NCCIH)-designated study monitor (contractor) as part of this program, prior to the initiation of participant enrollment and on a regular basis (at least annually) throughout the active enrollment period. NCCIH works carefully and collaboratively with the study team to determine the best approach to site monitoring, using a combination of on-site and remote monitoring to achieve the best possible outcome. Before the site initiation visit can be scheduled, all required study documents must be approved by NCCIH and your Institutional Review Board (IRB). NCCIH does not perform site monitoring on studies with a dedicated Data Coordinating Center.
Required Study Documents
Study Accrual and Retention Plan (SARP): Per the NCCIH Policy on Study Accrual and Retention for Human Subject Research, all clinical research studies funded by NCCIH are required to submit a detailed SARP prior to involving human subjects. A separate SARP must be provided for each clinical research study proposed in the funded grant. Each SARP must contain all required elements including a detailed timeline and monthly target accrual goals during the period of the award. The timeline should allow sufficient time after collection of all subject data for data cleaning, analysis, and writing prior to the end of the award period. NCCIH encourages PIs to consider accrual milestones in light of specific study context including slower recruitment during initial start-up. Accrual milestones can be customized by specific month and do not need to be linear.
As of April 1, 2022, all new and revised SARPs must be submitted using the Electronic SARP Template. The SARP will be submitted to NCCIH via the NCCIH Document Portal using the Electronic SARP Template. The corresponding PI will receive an automated email initiating completion of the Electronic SARP Template and upon successful submission. NCCIH will review the proposed benchmarks for appropriateness and compatibility with the budget and specific aims. When the NCCIH has conditionally approved the SARP, it will be routed to the Authorized Business Official for countersignature with a copy to the corresponding PI. The PI will receive a final email confirming acceptance of the NCCIH approved SARP.
Please refer to the NCCIH Policy on Study Accrual and Retention for Human Subject Research for additional information on how NCCIH might address problems with study accrual and retention during the tenure of the award. Throughout the conduct of the study, the NCCIH program director (PD) will regularly review progress to ensure that it is consistent with the accrual and retention projections outlined in the approved SARP. If study performance falls below agreed-upon benchmarks, the NCCIH PD may communicate directly with the principal investigator (PI) to further assess the specific circumstances and context.
Data and Safety Monitoring Plan (DSMP): Although a DSMP section may have been included in your grant application, NCCIH requires a detailed DSMP to be submitted for all clinical grants prior to award. The NCCIH DSMP Template is available at https://nccih.nih.gov/grants/toolbox#DSM.
Please use the NCCIH DSMP Template to generate a DSMP for your study and submit it to your PD, along with a copy of the CVs or National Institutes of Health (NIH) biosketches for all proposed study monitor(s). The DSMP must be reviewed and approved by the NCCIH PD first and then by your Institutional Review Board (IRB) prior to study initiation.
NCCIH requires independent monitoring for all funded studies involving human subjects. NCCIH typically recommends at least three independent study monitors to serve on an Independent Monitoring Committee (IMC). It is strongly recommended that one of the independent monitors be a Ph.D.-prepared biostatistician. The independent monitors must not be supported financially or supervised by the PI, and there should be no publications or collaborations between IMC members and Key Study Personnel within the last 3 years. All NIH-sponsored Phase III trials require Data and Safety Monitoring Board (DSMB) oversight. DSMB oversight should also be considered for other clinical trials with associated safety risk, including Phase I and Phase II trials. For the majority of studies that require a DSMB, NCCIH will select and appoint the board members and provide management of the DSMB.
The independent monitors meet regularly, at least annually, to review participant safety (for an interventional study) and assess study progress including participant confidentiality, recruitment and retention, and data quality and management. Annually, NCCIH will request a copy of the data report prepared for the independent monitor(s) and signed recommendation(s) for the study to continue.
Study Protocol, Informed Consent, and Case Report Forms: Please use one of the three required protocol templates in the NCCIH Clinical Research Toolbox according to the best match for the study design. The study protocol should be submitted in Microsoft Word format to streamline the protocol review process. Also, please provide a copy of the IRB-approved informed consent document and sample Case Report Forms.
Clinical Trials Registration and Reporting: Studies that meet the NIH definition of a clinical trial must register and report results at the end of the study per current NIH policy and regulatory reporting requirements (NOT-OD-16-149). NCCIH strongly encourages PIs of all NCCIH-supported clinical studies to register and report results in ClinicalTrials.gov. Please note that all entries in ClinicalTrials.gov and the NIH Human Subject System (HSS) must match.
Studies that meet the NIH definition of a clinical trial must register on ClinicalTrials.gov no later than 21 days after enrollment of the first participant. Research results must be submitted to ClinicalTrials.gov no later than 12 months following the study completion date (per the Food and Drug Administration Amendments Act and NIH policy [NOT-OD-16-149]). Failure to report results in a timely manner has legal consequences and could jeopardize grant funding and future funding to the grantee.
Please note, for studies that involve measuring expectation or the use of deception, the project description posted on ClinicalTrials.gov should not compromise the integrity of the study. In this case, it is recommended that investigators work directly with ClinicalTrials.gov staff to ensure that information is accurate and will not impair the ability to publish primary results of the trial. Investigators should contact their Authorized Business Official if there are questions about study registration and results reporting.
Ongoing Reporting Requirements
Enrollment Reports: Accrual reports will be requested by NCCIH periodically beginning 4 months from the date of the Notice of Award (NOA) to report actual enrollment compared to expected enrollment as outlined in the NCCIH-approved SARP. At times, more frequent reporting may be requested.
Independent Monitoring Reports: Please send the NCCIH PD copies of all study reports prepared for the independent monitor(s), as well as copies of signed comments and recommendations from the independent monitor(s). An automated request will be sent annually for submission of monitoring reports.
Procedures and Timeline for Study Initiation
Once the study documents are prepared, submit each document as a separate file for review by NCCIH. The first phase of NCCIH review of the required study documents typically takes 5–7 weeks. If there are additional queries, further versions of these documents will require review before they are approved. Revised documents will typically require 2 weeks for review.
After the study documents are approved by NCCIH, the NCCIH contractor will schedule the site initiation visit within 1 month. After the site initiation visit occurs, the follow-up period consists of finalization of the site visit report (2 weeks) and completion of the action item process by the study team (up to 30 days). Revised study documents are sometimes required and will be reviewed by NCCIH within 2 weeks of submission.
NCCIH will not lift human subject restrictions until all clarification issues have been addressed and the study protocol, DSMP, and SARP(s) have been approved. Please note that a restricted award prevents the grant from using funds for activities related to human participants including participant screening, enrollment, randomization, and study conduct.
REMINDER: If you are funded for an NCCIH grant, the NOA has terms and conditions that are specific to your grant. It is important to carefully review and fulfill the requirements that are outlined in your NOA.