The monitoring entity should be described in the Data Monitoring Plan submitted with the New Protocol Application. The monitoring entity is an identified individual or group assigned to conduct interim monitoring of accumulated data from research activities to assure the continuing safety of research participants, relevance of the study question, appropriateness of the study, and integrity of the accumulating data. Membership should include expertise in the relevant field of study, statistics and research design. The monitoring entity might be the Project Director (or PI), a Data Monitoring Board, or an equivalent body such as an industry-sponsored Data Monitoring Committee (DMC), a NIH sponsored cooperative group, a coordinating or statistical center, a monitoring committee formed by a sponsor other than NIH, or a Medical Monitor (an individual rather than a DMC). Depending on the needs of the study the monitoring can be any of the following:
Investigator
The principal investigator could perform this function. This type of plan is appropriate when the study involves a small number of subjects; the study is conducted only at one site; and the range of possible study events that could have an important impact on the risks and benefits of research participants is narrow. In such cases, continuous monitoring of events by the investigator, and prompt reporting of toxicity to the IRB and, when applicable, the FDA, the NIH, or others, may be adequate.
Monitor/Monitoring Group
A qualified and objective individual or group not directly involved with the design and conduct of the study (e.g., safety officer, designated Medical Monitor or Monitoring Group) could perform this function. These individuals may or may not be employees of MHC or its subsidiary hospitals or the study sponsor. However, conflict of interest is an important consideration when employees of the study sponsor have the primary responsibility for monitoring data from the standpoint of scientific integrity and participant safety.
This type of plan is often appropriate to monitor data and safety for research studies that involve:
- endpoints that are not serious irreversible events;
- an intervention (for example, to relieve symptoms) that is not high risk and the effects of which would not generally be so compelling as to ethically warrant early termination for effectiveness;
- short term treatments where effects are evaluated over periods of a few days to a few months; and
- a smaller number of subjects where the study is completed quickly and the risk can be adequately assessed through simple comparisons.
In these studies, valuable secondary objectives such as characterization of the effect (i.e., magnitude, duration, time to response), assessment of the effect in population subsets, comparison of several doses/or comparison of the new product to an active control can be ethically pursued even when the conclusion regarding the primary efficacy outcome is clear. Early termination for effectiveness is rarely appropriate in such studies. First, the study may be essentially completed by the time any interim analysis to evaluate effectiveness could be undertaken. Second, the effectiveness of an intervention, for example, to relieve symptoms, would not generally be so compelling as to override the need to collect the full amount of safety data, or to collect other information of interest and importance that characterizes the effect.
Data and Safety Monitoring Board (DSMB)/Data Monitoring Committee (DMC)
An independent Data and Safety Monitoring Board (DSMB)/Data Monitoring Committee (DMC) external to the trial organizers and investigators could perform this function. A DSMB/DMC is a formal committee that is established specifically to monitor data throughout the life of a study to determine if it is appropriate, from both the scientific and ethical standpoint, to continue the study as planned.
In general, an independent DSMB/DMC is the most appropriate way to monitor data and safety for studies that involve:
- Large numbers of subjects where risk may better be assessed through statistical comparisons of treatment groups;
- Blinded study treatment groups where the validity and integrity of the study may be adversely affected by having an individual or group associated with the design and conduct of the study break the blind;
- Multiple clinical sites where there is a need for investigators to submit reports of adverse events to a central reporting entity, such as a coordinating center or statistical center, responsible for preparing timely summary reports of adverse events for distribution among the clinical sites, and to the IRBs;
- High risk interventions where death or severe disability is a major risk of research participation; and/or
- Controlled trials with mortality or major morbidity as a primary or secondary endpoint where increased morbidity or mortality may better be assessed through statistical comparisons of morbidity or mortality among treatment groups.
DSMBs/DMCs are typically made up of individuals who have expertise in the field, experience in the conduct of clinical trials, and/or statistical knowledge, and who do not have any serious conflicts of interest, such as financial interests that could be substantially affected by the outcome of the trial, strong views on the relative merits of the interventions under study, or relationship with the sponsor or those in trial leadership positions that could be considered reasonably likely to affect their objectivity.
DSMBs/DMCs meet at least annually or more often depending on the nature of the trial being monitored. DSMBs/DMCs can monitor the timeliness of accrual, the quality of data collection and management, and the accumulating outcomes to assure the safety of participants and the scientific integrity of the study.
Regardless of data and safety monitoring plans by the sponsor or others, the principal investigator is ultimately responsible for protecting the rights, safety, and welfare of subjects under his/her care and for ensuring that the study is conducted at his/her investigative site in accordance with the IRB-approved protocol, and applicable regulations and requirements of the IRB.