Ask the Experts: Protections for Human Trial Participants
The FDA’s Office of Good Clinical Practice responds to inquiries on a variety of trial-related subjects, providing answers on the agency’s official regulations as well as best practices. The following is a selection of questions and answers excerpted from the CenterWatch publication GCP Questions, FDA Answers.
Question: Our study endpoint is overall survival. The team would like to collect death information for those subjects who have come off the study. Per FDA guidance, a principal investigator (PI) may access patient survival status through public channels. As a sponsor, do we need to reconsent the patients so they can authorize the PIs to provide death information to us as well as use this information for study analysis?
Answer: FDA’s regulations do not require that a subject’s request to withdraw from a study be in writing. However, the information about the subject’s withdrawal should be included in the study records (for example, annotation in the subject’s case history).
Ordinarily, once a subject indicates (orally or in writing) that he/she no longer wishes to participate in a study, then no additional data may be collected for that subject. However, there may be information or results that are received on specimens already collected (prior to withdrawal) that are received at the site after the subject’s withdrawal from the trial. Such information/results may be used. For example, FDA would expect that information about a subject’s death could be collected, even if a subject discontinued participation in a study (or was terminated from the study due to noncompliance), as follows:
Under FDA’s regulations, “human subject” means “an individual who is or becomes a participant in research, either as a recipient of the test article or as a control. A subject may be either a healthy human or a patient.” FDA has consistently interpreted its regulations as applicable only to research involving living human subjects. The information included in death records could be accessed and collected since the individuals referenced would necessarily be deceased and not “human subjects.”
Review of public vital statistics records would not constitute the collection of private information concerning a human subject. Accordingly, this collection of information would be allowed as it does not meet the definition of research involving human subjects. Reconsenting of subjects for review of vital death statistics records is not needed.
Public access to autopsy records would be determined by applicable state or local laws and regulations. There may also be applicable state or local laws related to the release of medical records of individuals who are deceased. The subject may have additional rights under state law, but that’s a question that should be posed to an attorney in the state in which you reside.
According to FDA regulations, when a subject withdraws from a study, the data collected on the subject to the point of withdrawal remains part of the study database and may not be removed.
Question: If study data with no protected health information (PHI) is entered in an electronic database, can source documentation uploaded with PHI redacted fulfill the requirement to retain “original” source documentation? Or should source documentation that includes PHI with no redaction be retained as well?
Answer: HHS’ Office of Civil Rights has jurisdiction with regard to the Health Insurance Portability and Accountability Act (HIPAA), not FDA. However, research information is viewed differently even under HIPAA. All information in study files will contain various levels of PHI, as that is defined in HIPAA, and study sites have an obligation to protect the confidentiality of all study information. However, study sponsors and regulatory authorities do have access to all information about those who are subjects in a study. Therefore, there is no need to redact any information when including pertinent information as part of a subject’s study file.
Additionally, with regard to placing study information into a subject’s electronic medical record (EMR), we actually recommend that be done. Specifically, the guidance document Investigator Responsibilities — Protecting the Rights, Safety and Welfare of Study Subjects even recommends that the clinical investigator directly inform the subjects’ personal physicians if the subjects agree.
The purpose for including study information in the EMR is to allow others who would need to treat the individual, on either a routine or emergency basis, to be aware of study treatments and/or any adverse events that were observed to better inform their diagnosis and treatment. There should be no issue of confidentiality in placing study information in the EMR since EMRs need to be maintained to at least the same level of confidentiality as study records.
Whatever you choose to do, internal SOPs should be developed to maintain consistency in operations.
Question: I was recently asked by a client if a single patient could enroll in two studies simultaneously if the drug on both studies is the same and the dosing schedule is the same. Although I feel this would be a logistical nightmare, is it actually against regulations?
Answer: We are not aware of any explicit regulatory prohibition against subjects participating in two protocols simultaneously or in the concurrent use of two investigational products. Rather, the regulatory concerns relate to whether subjects are appropriately protected (including against adverse product interactions), whether risks are minimized, whether the individual studies can yield meaningful data and whether any potential for bias is addressed.
In practice, commercial sponsors generally prohibit the concurrent enrollment of subjects in more than one study or concurrent exposure to multiple investigational agents. In fact, sponsors often require that study subjects not have participated in other clinical trials for some period prior (e.g., a 30 day “washout” period) to enrollment in their own trials and usually spell this out in the study protocol.
To read the investigator responsibilities guidance, click here: https://bit.ly/3Cdm96e.
For more information on the CenterWatch publication GCP Questions, FDA Answers, click here: https://bit.ly/3ylWOpj.