Drug Evaluation Committee 2022-16 Use of Residual Specimens from Clinical Trials for Future Research
Related classification: Other
Date of first publication: November 2022
Question
(Background)In a clinical trial for an out-of-country company, we have been provided with an explanatory document for participation in a clinical trial, which is not described in the clinical trial protocol, stating that "residual specimens, which are the remaining blood specimens for future research, shall be stored and used for research" in the client's draft explanatory document for participation in the clinical trial. We are aware that it is not possible to conduct something that is not stated in the study protocol, but the sponsor said that it is not stated in the study protocol and has no plans to do so. Furthermore, when we informed the sponsor that we were not allowed to conduct matters not described in the study protocol, they said they would prepare a letter.
The sponsor said that they would withdraw the site from the clinical trial unless we, as a clinical trial site, approve conducting a future study that is not described in the protocol and included in the explanatory document for participation in the clinical trial.
(Questions)
(1) Is it possible to conduct a future study that is not described in the investigational protocol?
(2) Is the letter equivalent to the protocol?
(iii) Is it possible to describe in the explanatory document for participation in a clinical trial a study that is not described in the protocol?
We have been conducting clinical trials believing that the protocol is the most basic of the basics, so we feel that the very foundation of the protocol has been overturned. Please let me know.
The Pharmaceutical Manufacturers Association of Japan (PMAJ)'s opinion
With regard to the background information "to store residual specimens, which are the remainder of blood samples for future research, and to use them for research," since we do not know the details of the research, we would like to respond based on the assumption that the clinical trial is a genomic pharmacology-based trial.(1) Conducting research not described in the clinical trial protocol
The "About Clinical Trials Using Pharmacogenomics" (September 30, 2008, Pharmaceutical and Food Safety Bureau, Ministry of Health, Labour and Welfare, Notification No. 0930007), "Appendix Q&A on Conducting Clinical Trials of Pharmaceuticals Using Pharmacogenomics" and "Guidelines for the Collection of Genomic Samples and Handling of Genomic Data" (January 1, 2008, Notification No. 0930008) (January 18, 2008, Ministry of Health, Labour and Welfare, Pharmaceuticals and Food Safety Bureau, Director, Drug Evaluation and Management Division, Pharmaceuticals and Food Safety Bureau, Ministry of Health, Labour and Welfare, Notification No. 0118-1), it is recommended that, in cases where residual blood samples are stored for future research and used for research, written consent from the subject should be obtained even if the subject and timing of the research are not specifically specified at the time of conducting the trial. In such cases, it is possible to receive samples by obtaining written consent from the subject, even if the subject and the timing of the research are not specified at the time of the clinical trial.
In this case, it may or may not be stipulated in advance in the clinical trial protocol.
However, "Items to be considered when conducting clinical trials in which genomic samples are collected in drug development" (RSMP vol. 9 No. 2, 103-109, May 2019) states that "even if the specifics of the genomic analysis are not yet known, the sponsor should outline the analysis plan in the trial protocol to the extent possible Even if it is difficult to include all the details of possible future research in the protocol, it is desirable to include the outline of the analysis plan in the protocol to the extent possible.
(ii) Positioning of the letter
A4 of "Q&A on Conducting Clinical Trials of Medicinal Products Using Genomic Pharmacology" states "It is possible to prepare a plan for the study of genomic pharmacology separately from the protocol, but in such a case, it should be stated that the plan should be specified separately in the protocol, and the review by the Trial Review Committee is required as part of the protocol. However, in this case, it should be stated in the protocol that the plan is to be specified separately, and the plan must be reviewed by the investigational committee as part of the protocol. However, a letter, etc. should be prepared as necessary, and the investigator's agreement should be obtained and the investigational review committee should review the letter as with the protocol.
(iii) Inclusion of research not described in the protocol in the explanatory document for participation in a clinical trial
As mentioned earlier, when specimen residues, etc. are stored and diverted for future research, it is necessary to explain in writing to the subject in an easy-to-understand manner that analysis is planned for that purpose and the range of genes to be analyzed that are assumed at that time, and to obtain consent in writing for the implementation of genomic/genetic analysis. It is necessary to obtain consent for the genome/gene analysis in writing. Consent for genomic/genetic analysis can be obtained either in the consent for the conduct of the clinical trial or separately.
If there is a possibility that genome analysis or other research that requires consideration of personal information may be conducted, it is also necessary to take measures that do not conflict with the Personal Information Protection Law.