1. Monitoring the progress of trials and the safety of participants
2. Plans for assuring compliance with requirements regarding the reporting of adverse events (AEs)
3. Plans for assuring that any action resulting in a temporary or permanent suspension of an NCI-funded clinical trial is reported to the NCI grant program director responsible for the grant
4. Plans for assuring data accuracy and protocol compliance
1. Monitoring the progress of trials and the safety of participants.Description of these monitoring processes should include a number of elements. Who actually monitors the trials? How often are the data examined in the course of trial conduct? What do the monitors look for? What procedures are in place to insure adequate feedback of information to researchers and medical decision-makers, so that trials involving excessive risk in relation to anticipated benefits are terminated appropriately? What is the oversight or supervisory role of institutional committees, if appropriate? What procedures does the institution have for coordinating multi-center trials, if applicable?
In relation to who actually has responsibility for monitoring a trial, DSM plans should explain how the institution averts or manages any conflict of interest implicit in having a principal investigator (or a direct report of the PI) as the only monitor of trials that pose significant risk to study subjects.
2. Plans for assuring compliance with requirements regarding the reporting of adverse events (AEs). The plan should describe the processes and oversight that the institution has in place for assuring that AE reporting requirements are actually met. For multi-center trials coordinated by the institution, the plan should outline procedures by which the institution establishes a central reporting entity that collects and reports AEs to all necessary destinations, including co-investigators at participating institutions.
The requirements for proper reporting of AEs on clinical trials are complex (summarized in the Appendix). Possible destinations for AE reports include the institutional IRB, the sponsor (if an IND is involved), the FDA (for AEs from commercially available agents), and, if gene transfer is involved, the NIH Office of Biotechnology Activities (OBA). Note that current federal regulations almost always require reporting of AEs in all categories of clinical trials to the institutional IRB, in addition to what is specified in the Appendix.
Note also that there is no requirement that individual AEs be reported in real time to the NCI, unless NCI is also the IND sponsor of the study (see the Appendix). Where appropriate, investigators should summarize toxicities or adverse consequences of interventions as part of the progress reports in their non-competitive (Type 5) or competitive (Type 2) renewal applications.
3. Plans for assuring that any action resulting in a temporary or permanent suspension of an NCI-funded clinical trial is reported to the NCI grant program director responsible for the grant.These actions include, for example, any FDA actions that affect NCI-funded trials (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-053.html). It also includes actions by an IRB or by a commercial sponsor, or by the investigator him/herself, if an NCI-funded trial is involved.
4. Plans for assuring data accuracy and protocol compliance. Institutions should describe what quality-control procedures are in place for assuring data accuracy and completeness in studies funded by NCI.
If an IND is in place, quality-control procedures are generally stipulated by the IND sponsor and may be simply referenced or summarized in the DSM plan. For studies not done under an IND, the institution should describe whatever procedures are in place to assure data integrity and protocol adherence. Appropriate procedures may range, for example, from regular data verification and protocol compliance checks performed by a data manager and a principal investigator, to a formal external data-audit process by an agent external to the institution.