Routine Plus Oversight Level
Clinical studies funded by the National Center for Complementary and Integrative Health (NCCIH) that propose enhanced data collection or analytic designs will be reviewed by an NCCIH biostatistician as a Routine Plus oversight study. This statistical review will examine proposed study aims, data collection methodology, power calculations, and the overall statistical analysis plan to enhance success in study implementation. All questions raised during the statistical review must be satisfactorily addressed prior to award.
Clinical activity cannot begin until these documents have been reviewed and approved by NCCIH.
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. A SARP must contain all the required elements outlined in the NCCIH Study Accrual and Retention Plan Template including a detailed timeline and graph depicting 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. The SARP must be approved by NCCIH and then submitted by your Authorized Business Official before a Notice of Award (NOA) will be issued. 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 will 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 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 copies 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 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. For small studies with simple study designs, with agreement of the NCCIH PD, a single independent monitor may serve in this capacity.
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.
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 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. NCCIH will not issue an award until all clarification issues have been addressed, and the DSMP and SARP(s) have been approved. The first phase of NCCIH review of the required study documents typically takes 2–4 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. Generally, NCCIH provides review of required study documents prior to the NOA.
In some cases, NCCIH may issue a restricted NOA until the required study documents are submitted and approved by NCCIH. 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 the NOA.