Drug Evaluation Committee 2022-16 Use of Residual Specimens from Clinical Trials for Future Research
Related Category: Other
Initial Publication Date: November 2022
Question
(Background)In a clinical trial conducted by a foreign company, the sponsor provided a draft of the informed consent document for trial participation that included a provision regarding “the storage and use of residual blood samples—remaining from blood samples collected for future research—which is not specified in the clinical trial protocol.”We understand that we cannot proceed with activities not specified in the clinical trial protocol; however, the sponsor stated that they would not include this in the protocol and had no plans to do so. Furthermore, when we informed the sponsor that conducting activities not specified in the protocol is not permitted, they indicated they would draft a letter.
The sponsor has stated that, as the Investigator Site, we are authorized to conduct future research not specified in the clinical trial protocol, but that unless such research is included in the informed consent document for trial participants, the Site’s participation in the trial will be withdrawn.
(Question)
① Is it possible to conduct future research not specified in the clinical trial protocol?
② Does the letter carry the same weight as the clinical trial protocol?
③ Is it possible to include research not described in the clinical trial protocol in the informed consent document for trial participants?
I have always believed that the clinical trial protocol is the absolute foundation of clinical trials, so I feel as though this is overturning that very foundation. Please advise.
JPMA Opinion
Regarding the statement in the background information, “Storing residual blood samples—which are leftover from future research—and using them for research,” since the details of the research are unknown, we will base our response on the premise of a clinical trial utilizing genomic pharmacology.① Conducting Research Not Specified in the Clinical Trial Protocol
“Regarding Clinical Trials Utilizing Genomic Pharmacology” (Notification No. 0930007 dated September 30, Heisei 20, issued by the Director of the Evaluation and Control Division, Pharmaceutical and Food Safety Bureau, Ministry of Health, Labor and Welfare),“Attachment: Q&A on the Conduct of Clinical Trials of Medicinal Products Utilizing Genomic Pharmacology” and “Guidelines on the Collection of Genomic Samples and the Handling of Genomic Data” (Notification No. 0118-1, January 18, Heisei 30, from the Director-General of the Pharmaceutical andLiving and Health Bureau, Director of the Pharmaceutical Review and Management Division), in cases where residual blood samples are stored for future research and used in such research, it is possible to receive sample donations by obtaining written consent from the subjects, even if the specific subjects or timing of the research are not specified at the time the clinical trial is conducted.
In such cases, this may or may not be specified in advance in the clinical trial protocol.
However, as stated in “Matters to Be Considered When Conducting Clinical Trials Involving the Collection of Genomic Samples for Drug Development” (RSMP vol. 9, No. 2, 103–109, May 2019) state that “even if the specifics of the genomic analysis have not yet been determined, the sponsor should include an outline of the analysis plan in the clinical trial protocol to the extent possible.” Therefore, while it may be difficult to include all future research possibilities in the clinical trial protocol, it is considered desirable to include them to the extent possible.
② Regarding the Status of the Letter
Question A4 of the “Q&A on the Conduct of Clinical Trials for Drugs Utilizing Genomic Pharmacology” states: “It is possible to prepare a plan regarding genomic pharmacology studies separately from the clinical trial protocol; however, in such cases, the protocol must state that the plan is defined separately, andand that plan must also be reviewed by the Institutional Review Board (IRB) as part of the clinical trial protocol.” Therefore, while we do not believe it is strictly necessary to state in the clinical trial protocol that the research is planned, we believe that, if necessary, a letter or similar document should be prepared, and—after obtaining the principal investigator’s consent in the same manner as for the clinical trial protocol—it should be reviewed by the IRB.
③ Regarding the inclusion of research not described in the clinical trial protocol in the informed consent document
As noted above, when preserving and repurposing specimen residues for future research, it is necessary to provide participants with a clear written explanation—including the planned analysis for that purpose and the scope of genes to be analyzed as anticipated at that time—and to obtain written consent for the performance of genomic and genetic analysis.Consent for the performance of genomic and genetic analysis may be obtained either as part of the consent for the clinical trial or separately.
Furthermore, if there is a possibility of conducting research involving genomic analysis or similar studies that require consideration of personal information, it is considered necessary to take measures that do not violate the Act on the Protection of Personal Information.