Monitoring of Phase I and II NIH Sponsored Clinical Studies

In accordance with the attached National Institutes of Health (NIH) notice (Tab 1), beginning October 1, 2000 clinical investigators are required to submit, along with their grant application or protocol, monitoring plans for Phase I and Phase II clinical studies. The attached NIH Notice is intended to assure that Clinical Investigators comply with the requirement to adequately monitor phase I and II clinical investigations. An adequate level of monitoring is commensurate with the nature of risks / size and complexity of the clinical trial. Although in many cases the NIH funding Institutes/Centers (NCI, OBA, NIAD etc.), determine the NIH monitoring methodology, the attached guidance requires that the investigator make written assurance that ALL regulatory bodies (NIH, Food & Drug Administration (FDA) and Institutional Review Board (IRB)) are adequately apprised of Adverse Event (AE) monitoring, reporting, and analysis.

At a minimum investigators must submit a written description of AE reporting mechanisms to the NIH, which include methods for reporting AE’s to FDA, the relevant IRB and Data Safety Monitoring Board (if applicable). The written description should be included as part of the clinical protocol. In studies involving potentially high risk or special populations, investigators must consider additional monitoring safeguards.

1. NIH/FDA/IRB/ Reporting Requirements:
   1. NIH Reporting Requirements:
      1. NIH reporting requirements may range from individual adverse event reports to summary reports. If you have questions, contact the specific NIH funding Institute and Center (IC) for their guidance on the AE reporting mechanism. Additionally, the IC will be copied on each AE report sent to the FDA.
      2. The reporting requirement, as approved by the IC, is in addition to the annual progress reports to the NIH for Type 5 awards (non-competing awards).

         In addition to any written description of the NIH supported monitoring plan, the following references may be cited as part of the overall plan, as appropriate:

   2. FDA Reporting Requirements (Drugs):
      1. For studies involving investigational drugs, reference 21 CFR 312.32 (Tab 2).
      2. For studies involving marketed drug products, reference 21 CFR 314.80 (Tab 3).
      3. For studies involving Licensed Biological Products, reference the Guideline "Postmarketing Adverse Experience Reporting for Human Drug and Licensed Biological Products: Clarification on What to Report" (Tab 4).
   3. FDA Reporting Requirements (Devices):
      1. For studies involving investigational devices, reference 21 CFR 812.150 (a) 1 (Tab 5).
      2. For studies involving marketed devices, reference 21 CFR 803 (Tab 6).
   4. IRB Reporting Requirements, Drugs and Devices:
      1. Research Subjects Review Board (RSRB): reference RSRB Policy Letter of 9/29/00 (Tab 7).
   5. Industry Sponsor Reporting:

      In addition to the above, if the investigation is partially sponsored by a pharmaceutical or medical device manufacturer, investigators may also be required to submit reports to the sponsoring company. A written description of sponsor reporting should also be included in the monitoring plan of the grant application or clinical protocol.

2. Methods for Submission of Monitoring Plans:
   1. If you are submitting a clinical protocol as part of the grant application, you should include a specific section of the protocol that addresses, and makes reference to, the applicable AE monitoring/reporting plan(s). An example of a protocol specific monitoring/AE Reporting plan is contained in Tab 8.
   2. If your protocol is not fully developed at the time of grant submission, you should prepare a summary statement and include copies or references to the applicable regulations/procedures defined above as part of the grant application.