Drug Evaluation Committee 2007-11 Scope of required records of deviations from the clinical trial protocol (Part 1)
Related classification: Other
First published: Jan 2008
Revised publication date: Apr 2013
Question
There is a clinical trial in which an investigational drug is taken twice a day after breakfast and dinner for one year. The sponsor asks us to submit a deviation report if the patient forgets to take the investigational drug even once.
The sponsor's view is that any matter that is not clearly declared as a deviation in the protocol should be treated as a deviation, so even one missed dose is treated as a deviation.
In the case of other clinical trials, even if it is not stated in the protocol, it is not considered a deviation if the medication adherence rate is 80% or more, etc., depending on the sponsor.
Is it really necessary to fill out a deviation report if a patient forgets to take a dose even once? I am not sure if it is really necessary, so I would appreciate it if you could tell me.
Opinion of the Pharmaceutical Manufacturers Association of Japan (PMAJ)
GCP Article 46 Guidance 2 states that "The investigator or subinvestigator must record all deviations from the study protocol, regardless of the reason. The investigator must prepare a document recording the reasons only for those deviations from the protocol that were not in accordance with the protocol in order to avoid immediate danger to the subject or for other unavoidable medical reasons, and immediately submit the document to the sponsor and the head of the site". Since forgetting to take an investigational drug is not considered to be an urgent risk avoidance, we do not think it is necessary to submit a deviation report.
However, the concept of deviation from drug compliance cannot be uniformly discussed because the impact on drug efficacy evaluation varies greatly depending on the target disease, dosage and administration, and pharmacokinetics of the drug. Therefore, the sponsor stipulates the handling of deviations from the medication compliance rate in the protocol for each clinical trial. Depending on these regulations, even a single missed dose may be treated as a deviation, and in such cases, it is necessary to record the fact of the deviation so that the fact of the deviation is known.
Therefore, if there is no prior written agreement with the sponsor, it is recommended to discuss with the sponsor whether or not to treat it as a deviation, taking the above into consideration.
Reason for revision of opinion
The referenced article has been changed in accordance with the issuance of the GCP Guidance (December 28, 2012, NHI Drugs and Food Safety Labeling Agency, No. 1228-7).