The QI Program Handy DSMP Checklist
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Despite the requirements outlined in the Code of Federal Regulations, FDA warning letters commonly cite investigators for
failing to follow the signed investigator statement and the investigational plan. For example, investigators have been cited
for not conducting follow-up safety procedures within specified windows, failing to report adverse events to the appropriate
regulating bodies, and enrolling subjects who did not meet inclusion/exclusion criteria.11 These warning letters suggest that while the investigator may not be able to alter the provided industry developed protocol,
a less well-defined DSMP does not absolve the investigator from responsibility for ensuring subject safety and data integrity.
The general responsibilities of sponsors set forth in the federal regulations require proper monitoring of the investigation
with assurance that it is conducted in accordance with the investigational plan and protocol.3,4 Therefore, investigators who hold an Investigational New Drug Application or Investigational Device Exemption and act as
sponsors have the additional responsibility to establish monitoring procedures. 
Protocol Detective: DSMP Checklist
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GCP guidelines5 recognize that the study sponsor is responsible for adequately monitoring trials. Sponsors also should determine the appropriate
extent and nature of the monitoring based on factors such as study size, complexity, and design. The protocol should outline
plans to evaluate safety by incorporating the following measures into the protocol: safety parameters; methods and timing
for assessing, recording, and analyzing safety parameters; procedures for recording and reporting adverse events and intercurrent
illness; and the type and duration of the follow-up of subjects after adverse events. GCP guidelines also recommend a section
on data handling and record keeping in the protocol, but do not specify what this section should include.
Elements of a DSMP An adequate DSMP should address four areas: safety monitoring, data monitoring, product accountability, and privacy and confidentiality.
Each area includes a related set of elements. Table 1 illustrates these elements with examples. Safety monitoring. Safety monitoring refers to the vigilant observations required to minimize threats to the safety and welfare of research
subjects. A safety monitoring plan will be unique to each study; the monitoring activities are dictated by study-specific
risks. In determining the type and frequency of monitoring required, sites should consider factors such as the study's purpose,
design, population, procedures (including investigational products), sample size, and trial phase. Three essential elements make up a proper safety monitoring plan: important safety information, stopping rules, and adverse
event reporting. Safety monitoring itself should include collecting and subsequent monitoring of specific information/data
that would indicate a threat to a subject's health and welfare. Parameters for each safety observation should be clearly specified
in measurable terms. The frequency of safety observations should be defined for each variable and should be such that researchers
are able to identify clinical or subclinical problems at an early stage. The person(s) responsible for reviewing safety data
should be clearly identified. The FDA expects that the monitor "need not be a person qualified to diagnose and treat the disease
or other condition for which the test article is under investigation, but somewhere in the direct line of review of the study
data there should be a person so qualified."10 Stopping rules include conditions under which an individual subject's study participation will be terminated, as well as conditions
under which the entire study should be stopped or modified. The principal investigator is typically responsible for decisions
of subject termination, whereas a Data Safety Monitoring Board or safety monitor may be responsible for making recommendations
to stop and/or modify the study, depending on the phase of the investigation.
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