Queries on GCP

Dr Arun D Bhatt, well known pharmacologist from Mumbai, answers your questions on Good Clinical Practices. Send in your questions at: arun_dbhatt@hotmail.com. All queries should ideally reach him by the 15th of each month.

How do we record the consent if the patient or his legal representative is unable to read and write?

Dr Sunder , Chennai

In such a case, the consent process must be performed in presence of an impartial witness. The investigator, or a person designated by the investigator should read and explain the written informed consent and other information - patient information sheet. If the patient or his legally acceptable representative gives oral consent, the impartial witness is requested to sign and personally date the consent. The relevant guideline from ICH-GCP is cited below:

ICH GCP 4.8.9: ‘‘If a subject is unable to read or if a legally acceptable representative is unable to read, an impartial witness should be present during the entire informed consent discussion. After the written informed consent form and any other written information to be provided to subjects, is read and explained to the subject or the subject’s legally acceptable representative, and after the subject or the subject’s legally acceptable representative has orally consented to the subject’s participation in the trial and, if capable of doing so, has signed and personally dated the informed consent form, the witness should sign and personally date the consent form. By signing the consent form, the witness attests that the information in the consent form and any other written information was accurately explained to, and apparently understood by, the subject or the subject’s legally acceptable representative, and that informed consent was freely given by the subject or the subject’s legally acceptable representative.

What is the role of Independent Data-Monitoring Committee (IDMC) in a trial?

Dr Kavita Singh, Hyderabad

As per the ICH-GCP guidelines, the definition of Independent Data-Monitoring Committee (IDMC) (Data and Safety Monitoring Board, Monitoring Committee, Data Monitoring Committee) is as follows: An independent data-monitoring committee that may be established by the sponsor to assess at intervals the progress of a clinical trial, the safety data, and the critical efficacy endpoints, and to recommend to the sponsor whether to continue, modify or stop a trial. US FDA has developed ‘‘Guidance for Clinical Trial Sponsors On the Establishment and Operation of Clinical Trial Data Monitoring Committees’’.

The increasing use of IDMCs in industry-sponsored trials is due to several factors, including:

• the growing number of industry-sponsored trials with mortality or major morbidity endpoints;
• the increasing collaboration between industry and government in sponsoring major clinical trials, resulting in industry trials performed under the policies of government funding agencies, which often require IDMCs;
• heightened awareness within the scientific community of problems in clinical trial conduct and analysis that might lead to inaccurate and/ or biased results, especially when early termination for efficacy is a possibility, and demand for approaches to protect against such problems.

All clinical trials do not require monitoring by a formal committee external to the trial organizers and investigators. IDMCs have generally been established for large, randomized multi-site studies that evaluate interventions intended to prolong life or reduce risk of a major adverse health outcome such as a cardiovascular event or recurrence of cancer.

Because monitoring of accumulating results is almost always essential in such trials, IDMCs should be established for controlled trials with mortality or major morbidity as a primary or secondary endpoint.

They may also be helpful in settings where trial participants may be at elevated risk of such outcomes even if the study intervention addresses lesser outcomes such as relief of symptoms.

Although IDMCs may prove valuable in other settings as well, an IDMC is not needed or advised for every clinical study.