Drug Evaluation Committee 2007-34 Re-enrollment of subjects who dropped out during the observation period
Related classification: Other
First published: August 2008
Revised publication date: March 2012
Question
I would like to know about "Re-assignment of subjects who dropped out during the observation period after re-consent.
Is it possible to re-consent after a certain period of time and reincorporate into the observation period a case that was not enrolled or assigned due to selection/exclusion criteria in the observation period?
If a patient's condition at the time of entry into the observation period is considered to have been accidentally met the criteria due to special circumstances such as tests, we believe that there is no problem in obtaining re-consent and starting the clinical trial from scratch. Since the patient was excluded from the observation period prior to the administration of the investigational drug, we believe that there is no bias against the evaluation of the efficacy and safety of the investigational drug.
Opinion of the Pharmaceutical Manufacturers Association of Japan (PMAJ)
If there is no provision in the protocol for subjects who violate the selection/exclusion criteria during the observation period after consent to participate in the clinical trial, they would normally be treated as dropout cases.
Guidance 1 of Article 44, Paragraph 1 of the GCP states, "In selecting subjects, the investigator shall, from the viewpoint of protecting human rights and based on the selection and exclusion criteria specified in the protocol, take into consideration the subject's health condition, symptoms, age, gender, ability to consent, dependency on the investigator, and participation in other clinical trials, etc., and shall select subjects who have not participated in other clinical trials. The regulations stipulate that "the appropriateness of requesting a subject to participate in a clinical trial shall be carefully considered, taking into account the subject's health condition, symptoms, age, sex, ability to consent, dependency on the investigator, etc., and whether or not the subject is participating in other clinical trials. The appropriateness of treating a subject who has dropped out of a clinical trial due to the circumstances described in your question as a subject for the same clinical trial again must be carefully judged from a medical perspective. In particular, if the subject can be considered to benefit sufficiently from other treatment methods, further consideration is needed for re-inclusion. In addition, since there is a possibility of giving the impression that the subject is being coerced into participating in a clinical trial, careful judgment must be made from an ethical standpoint as well.
In your question, you mention the aspect of bias in the evaluation of the efficacy and safety of the investigational drug, but in this case, the most important thing to consider is the interests of the subjects and the ethical aspects of the decision. We recommend that the sponsor make a final decision on whether or not to allow the subject to participate in the clinical trial again, after careful discussions with the medical experts and the investigators.
Reason for revision of opinion
In accordance with the revision (October 24, 2011) of the "Implementation of Standards for Conducting Clinical Studies on Drugs," the commentary of GCP Article 44, Paragraph 1, Operational Notification 1 has been changed.