Drug Evaluation Committee 2017-44 Viewing records related to combination therapy
Related classification: Other
Initial release date: December 2017
Revised publication date: March 2021
Question
In combination chemotherapy trials, the sponsor provides the main investigational drug, and the other combination drugs are used for in-house use. The Investigator Site has been told that it would be difficult to manage the combination therapy drugs in the same way as the investigational drugs, generate data, and make the data available for public inspection because the drugs are in-house products.
The sponsor believes that it is necessary to confirm who handled the concomitant therapy drug (prescriber, deliverer, coordinator, and administrator) (monitoring is necessary from the perspective of whether the appropriate process (from prescription to administration) was followed). (We have determined that monitoring is necessary from the perspective of whether the appropriate process (prescribing to administration) is being followed). In addition, as EDC data, the prescriber is related to the prescribed amount, the deliverer to none in particular, the adjuster to the adjusted amount, and the administrator to the administered amount.
In contrast, Investigator Sites seem to be of the opinion that although EDC data is necessary, it is not necessary to specify who performed the therapy (e.g., prescriber: Dr. XX, etc.) because the concomitant therapy drugs can be handled within the scope of general practice (pharmacists and physicians who are not delegated to the clinical trial can also handle them) (and therefore, presentation as reading material is also difficult). (Therefore, it is difficult to present the data as reading material). We would appreciate it if you could provide any evidence to support the sponsor's view, such as confirmation that the appropriate process (from prescribing to administration) was followed for concomitant therapy drugs in the investigations by the authorities.
Personally, from the perspective of ALCOA, I feel that the prescriber, adjuster, and administrator who are related to the EDC data need to be checked and inspected as the person who wrote the relevant data, while the deliverer is not related to the EDC data and does not need to be checked or inspected.
JPMA's Opinion
When a drug used for adjunctive therapy is administered in accordance with the study protocol, regardless of whether it is provided by the sponsor or employed in-house, the sponsor must confirm that the drug is appropriately administered in accordance with the study protocol (see GCP Article 21, Paragraph 1, Guidance 1). .
Therefore, if the records related to the concomitant medications in question are necessary to confirm the proper clinical trial process, we believe that all such records should be made available for inspection (GCP Article 37, Paragraph 1/Section 2, Guidance 1).
Please note that the data entered in EDC does not necessarily correspond to the data required for process assurance of clinical trial implementation, and that there are data (records) that are not entered in EDC but are required to be verified for process assurance.
Supplementation
In the revised GCP Guidance (August 31, 2020), "other concomitant medications" using hospital-adopted products is described as "investigational drugs used from the Investigator Site's inventory", and the following guidance describes the contents corresponding to this opinion. Therefore, the following guidance has been added as a supplement.
- GCP Article 4.1 Guidance 5: "For investigational drugs that are not delivered by the sponsor and are used from the inventory kept by the Investigator Site, the sponsor should confirm the handling, storage, management, and prescribing procedures, etc. established by the Investigator Site."
- GCP Article 39 Guidance 4: For investigational new drugs that are not delivered by the sponsor and are used from the inventory kept by the Investigator Site, the sponsor shall follow the handling, storage, management, prescribing, etc. procedures established by the Investigator Site.
In addition, records should be prepared and maintained to show that the amount of investigational drug for use specified in the protocol has been administered to the subject and that the quantities of all investigational drugs for use have been properly controlled.