Is the use of off-label drugs under Drug Control Authority of India illegal?
Dr Sreevatsa

The MCI code of Ethics (relevant excerpt) does not cover off-label use.
7.8 A registered medical practitioner shall not contravene the provisions of the D&C Act and regulations made there under. Accordingly, 1) Prescribing steroids/psychotropic drugs when there is no absolute medical indication; 2) Selling Schedule ‘H’ & ‘L’ drugs and poisons to the public except to his patient;

In contravention of the above provisions shall constitute gross professional misconduct on the part of the physician. The responsibility arising out of off-label use in clinical practice rests with medical professionals. However, if a medical practitioner wants to conduct clinical trial on off-label use, he will have to take DCGI permission.

At one Indian site, clinical trial in unlabelled indication was a finding in CDSCO inspections. The investigator was debarred  from conducting any clinical trial for a period of six months.

How can we implement recording of consent is applicable to all clinical trials approved by the CDSCO (AV) recording for informed consent in heavy OPD of govt hospital? How will patient identity be protected being video recording? Can the monitor see the video recording?
Sucheta Pate
You need a separate place for clinical research conduct/ AV recording, where the patient’s privacy/confidentiality can be protected. The AV recording will be done by the investigator, who is aware of the patient identity. He/she is authorized to do this by DCGI order. However, this audio-video recording should be stored in a safe and secure place accessible to only the investigator and his team members who are authorized to access this audio-video recording.

The current order does not mandate any need for monitoring of AV recording  by CRA. The order mandates that AV recording should be done while adhering to principles of confidentiality.  Hence, CRA cannot view the AV recording.

Is audio-visual recording of consent applicable to all clinical trials?
Suresh Pandit
Audio-visual (AV) recording of consent is applicable to all clinical trials approved by the CDSCO.

As per the EC registration, the EC has to carry ongoing review. Is there any regulatory guidance for ongoing review?
Anand Bhatia

In 2012, the US FDA has provided guidance on Institutional Review Boards (IRB) Continuing Review after Clinical Investigation Approval. The criteria for approving research during continuing review are similar to the criteria for initial review, which focus on  assessment of risk and benefits, informed consent process, equitable selection of subjects and safeguards for the participating subjects.

The  continuing review should take place at a convened meeting of the IRB, where the IRB reviews the following information submitted by the investigator:

•    A written progress report/brief project summary that includes the following or references other documents made available to the IRB:
•    The number of subjects accrued
•    A brief summary of any amendments to the research approved by the IRB since the IRB’s initial review or the last continuing review;
•    Any new and relevant information, published or unpublished, since the last IRB review, especially information about risks associated with the research
•    A summary of any unanticipated problems.
•    A summary of any subject withdrawals from the research since the last IRB review, and the reasons for withdrawal, if known

•    A summary of any complaints about the research from subjects enrolled at the local site since the last IRB review;

•    The latest version of the protocol and sample informed consent document(s) in use at the site;

•    Any proposed modifications to the informed consent document or protocol;

•    The current Investigator’s Brochure, if any, including any modifications;

•    Any other significant information related to subject risks, such as the most recent report, if any, from data monitoring committees

•    Aggregate information about relevant regulatory actions occurring since the last review that could affect safety and risk assessments

During the continuing review and evaluating whether research continues to satisfy the criteria for IRB approval of research, IRBs should pay particular attention to the following areas: 1) Risk Assessment; 2) Adequacy of Informed Consent; 3) Local Issues, and 4) Trial Progress.

After completion of continuing review, the IRB must provide written notification informing the investigator of the IRB’s decision -  approval, suspension, or termination of approval. Any suspension or termination of IRB approval must include the reasons for the IRB’s actions and be promptly reported to the clinical investigator, institutional officials, and the FDA.

Dr Arun Bhatt is currently, president, ClinInvent, Research Pvt Ltd, 

Mumbai. Readers can send their queries at: arunbhatt@clininvent.com