In May 2007, the U.S. Food and Drug Administration (FDA) released a draft of its Guidance for Industry: Protecting the Rights, Safety and Welfare of Study Subjects—Supervisory Responsibilities of Investigators (the guidance). The guidance does not confer any rights on subjects, or bind the FDA or the public to new regulations. Instead, the guidance seeks to help investigators meet the FDA’s expectations with respect to protecting human subjects and ensuring the integrity of the data from clinical investigators. The guidance pulls together investigator obligations currently listed in the Form 1572 or Investigator Agreement (as applicable), and 21 CFR Parts 812, 312, 50 and 56. The guidance focuses on "general responsibilities that are applicable to clinical trials of drugs, biologics and medical devices."
The following are among the main themes addressed in the guidance.
The guidance reaffirms that investigators must abide by the commitments articulated in Form FDA-1572, known as the Statement of the Investigator. The FDA proposes no changes to Form FDA-1572.
Supervision of Clinical Trials
Although investigators are expected to delegate some of the duties associated with clinical research, the guidance stresses that investigators must supervise all tasks that are delegated and maintain a list of those tasks. This list should document the trainings and qualifications of the delegate relevant to the applicable task and the dates of the delegate’s involvement in the study. Investigators are responsible for any regulatory violations associated with inadequate supervision. According to the guidance, investigators should not delegate tasks associated with clinical trials unless:
- The person to whom the task is delegated is qualified (including licensure requirements, if applicable) to perform the task.
- The person to whom the task is delegated is adequately trained.
- The investigator has a "detailed plan" for supervising and overseeing the conduct of the clinical trial, the elements of which are set forth in the guidance.
- The investigator oversees third parties that might be involved with the clinical trial (e.g., SMO employees, lab employees). The guidance provides an exception for device studies in which a technician employed by the sponsor has more specialized expertise than the investigator to handle a device (e.g., programming an investigational pacemaker). In such circumstances, the technical work should be delegated to the sponsor’s technician. Provided that this delegation is described in the protocol, the sponsor—as opposed to the investigator—would be responsible for overseeing the technician.
The guidance provides an illustrative list of examples of inappropriate delegation, for example, delegates obtaining informed consent who "lack medical training" or familiarity with the test article, or screening evaluations conducted by delegates without medical training. In addition, the guidance provides a detailed list of factors that tend to undermine an investigator’s ability to provide adequate supervision (e.g., overburdened study staff, conducting research at multiple sites). Finally, the guidance sets forth general parameters for investigators to oversee and/or review procedures and data conducted by non-study team members (like the pathology department) or by off-site third parties. Overall, the guidance seems intended to raise the bar on the level of investigator attention to, involvement in and scrutiny of clinical research.
Protecting Human Subjects
Investigators have been, and remain, responsible for protecting the rights, safety and welfare of subjects under their care in a clinical trial. This includes:
- Providing adequate medical care to subjects who suffer from adverse events, including significant laboratory values, associated with the clinical trial: If the subject has a primary care physician, the investigator should coordinate with such physician to accommodate the subject’s medical needs. Such care and attention should extend beyond the identified end of the clinical study, if applicable.
- Being readily available to subjects during the conduct of the trial at their site: The investigator need not be physically present, but should be in reasonably close proximity and accessible by phone or other electronic communication. Subjects should know how to reach the investigator. If the investigator cannot be available to subjects during a portion of the clinical trial, the investigator should make arrangements to have a specific qualified physician available to treat subjects who might need medical treatment, and this delegation should be documented in Form 1572.
- Complying with the protocol in order to avoid unnecessary risks to the subjects.
- Remaining involved in securing appropriate medical care for subjects who experience adverse events or are otherwise injured as a result of their participation in the study even if the follow-up extends beyond the life of the study.
In general, the guidance does not depart significantly with the FDA’s previous position on the extent to which investigators are responsible for protecting the welfare of subjects who are enrolled in clinical trials.