Drug Evaluation Committee 2008-14 Implementation of Pharmacogenomics in Clinical Trials
Related classification: Clinical Trial Review Committee
First published: Jan. 2009
Revised publication date: Mar. 2021
Question
We are an SMO with affiliated medical institutions. We provide secretariat services for the Clinical Trial Review Committee as a support service for the medical institutions. For the past two years, we often review clinical trial protocols that include blood sampling for genetic analysis, which is not used in the application for approval. However, the investigational review committee sometimes loses a lot of time when blood samples for genetic analysis, which are not used in the application and for which the type of gene to be analyzed is not known, are included in the protocol.
The specimen collection stipulated in the protocol is reviewed on the assumption that the results of the analysis will be used for the application, but it seems strange that the collection of specimens that will not be used for the application and may or may not be analyzed at any time are listed in the protocol and submitted to the clinical trial review committee. Is it not?
GCP is a ministerial ordinance that applies to clinical trials conducted for the purpose of application for approval, reexamination, and reevaluation, so I think it would be strange to stipulate in the clinical trial protocol the collection of specimens that will not be used for those purposes.
The sponsor is told that there is no censure from the authorities at the time of notification of the clinical trial, but I wonder if they did not say, "Actually, we do not know when we may analyze the samples, but we have included the collection of blood samples for genetic analysis in this protocol.
The sponsor says that this is common in many clinical trial protocols of foreign-affiliated companies and that it is a method that is standardized worldwide. The positioning of clinical trials may differ between Japan and other countries (ICH-GCP does not have the same provisions on clinical trials as Japan).
Opinion of the Pharmaceutical Manufacturers Association of Japan (PMAJ)
GCP is a ministerial ordinance that applies to clinical trials conducted for the purpose of application for approval, reexamination, and reevaluation, and we think it is not appropriate not to stipulate this in the clinical trial protocol on the grounds that the specimens are collected to obtain data not used for such applications. Since the protocol covers and describes the procedures and actions to be taken in the clinical trial, we believe that the protocol should also describe the invasion of subjects for other purposes, i.e., blood sampling, not only for the purpose of application.
In the development of new drugs, pharmacogenomics research on the relationship between individual differences in response to drugs and genetic polymorphisms has been actively pursued worldwide, as it is expected to provide useful clinical findings such as improved efficacy and avoidance of serious side effects. In clinical trials involving genomic and genetic analysis, it is essential to consider the well-being of the subjects. Furthermore, since the study may involve the genetic information of not only individual patients but also their blood relatives, it must be carefully conducted based on an ethical and scientific study plan.
There are various types of clinical trials in which this genomic and genetic analysis is conducted. For example, "a clinical trial in which the target genes for investigation and the timing of implementation have already been identified at the clinical trial planning stage," "a clinical trial in which genomic biomarkers related to the drug response (efficacy or safety) may be investigated, but the target genes have not been identified at the clinical trial planning stage, or the timing of implementation has not been determined, A clinical trial whose timing has not yet been determined.
It is considered appropriate to review the appropriateness of conducting a comprehensive clinical trial including pharmacogenomics study from scientific, ethical, legal, and social perspectives at a clinical trial review committee for a clinical trial that has such a purpose. For your reference, the "Result of the Public Comment on the Review of the Ethical Guidelines for Human Genome/Genetic Analysis Research" (December 2004, Ministry of Education, Culture, Sports, Science and Technology, Ministry of Health, Labour and Welfare, and Ministry of Economy, Trade and Industry) states that "With regard to the way the investigational committee should be, etc. you mentioned, the current Pharmaceutical Affairs Law (... omitted...) In light of the purpose of the provisions of the current Pharmaceutical Affairs Law (...abbreviated...), we believe it is necessary to establish an organization, operation, and system in which all matters related to clinical trials at a facility are properly deliberated and investigated in order to protect subjects in clinical trials (ethics) and ensure the quality of data (science). This is the opinion of the Japanese Ministry of Health, Labour and Welfare.
As you may already know, the Drug Evaluation Committee of the Japan Pharmaceutical Manufacturers Association (JPMA) has published "Considerations for Conducting Clinical Trials Involving Genomic Data in Drug Development" on its website for your reference.
In addition, according to a notice issued on August 31, 2020 by the Director of the Drug Evaluation and Control Division, Pharmaceuticals and Consumer Health Bureau, Ministry of Health, Labour and Welfare (Pharmaceutical Affairs Bureau, No. 0831-10) regarding notification of clinical trials, it is required to notify whether a clinical trial that includes genomic testing, etc. is applicable or not. In addition, the example of the list for submitting information to the authorities attached to the "Notice on the Provision of Information to Administrative Organs for the Preparation of Guidelines for the Use of Pharmacogenomics in Clinical Trials of Pharmaceuticals (NHI Drug Evaluation and Review No. 0318001)," issued on March 18, 2005, includes an application to indicate whether banking is conducted in the clinical trial or not. The example of the list for submitting information to the authorities attached to the "Provision of Information to Administrative Agencies Concerning the Preparation of Guidelines for the Preparation of
Reason for revision of opinion
Revision of "Handling of Notification of a Clinical Trial Plan for a Drug by a Person Who Wants to Request a Clinical Trial" (Pharmaceutical and Food Safety Bureau of Japan, No. 0831-10) issued on August 31, 2020, and change of the title of the website for reference.