Our Neurosurgeon wants to participate in a surgical trial sponsored by an international not-for-profit institute. The investigators are recruited through the trial website. Trial objective is primarily to compare early vs. late interventions intra-cerebral hemorrhage. There is no financial involvement in the trial; no agreements, no indemnity and no insurance. 


The issues are:
a) Can take place without the approval of a regulatory body in India considering the trial sponsor is based outside the
country?
b) Which regulatory framework should Ethics Committee use to evaluate such studies?
c) Will CTRI registration be required and if so, is it
the investigator's responsibility?
d) Can data emanating from Indian sites (Indian patients) be shared with any regulatory approvals?
e) How about subject protection in case of injury because of delayed surgery?
Dr. Sumeet Roy

Regulatory and ethics issues:
As the study does not involve a new drug or device, it does not come under DCGI purview.
MCI Code of Ethics Regulations recommends the following:

7.22 Research: Clinical drug trials or other research involving patients or volunteers as per the guidelines of ICMR can be undertaken, provided ethical considerations are borne in mind. Violation of existing ICMR guidelines in this regard shall constitute misconduct. Consent taken from the patient for trial of drug or therapy which is not as per the guidelines shall also be construed as misconduct.

Hence the neurosurgeon should follow the ICMR guidelines. These guidelines in ethics committee section cover all types of research and classify it according to the level of risk. The decision re: level of risk is to be made by the EC and not the investigator. Pl also see section on international collaboration and epidemiology. All these point to the need for 1) EC review 2) Informed consent.

CTRI Registration
All interventional clinical trials conducted in India and involving Indian participants need to be registered. An interventional clinical trial is any research study that prospectively assigns people to one or more health-related interventions (e.g., preventive care, drugs, surgical procedures, behavioural treatments, etc.) to evaluate their effects on health-related outcomes. Thus, early and late trials, trials of marketed or non-marketed products, randomized or non-randomized trials - all should be registered.

At present, The CTRI registration is purely voluntary; however, registration is likely to have a lot of advantages both for the registrant as well as the public. Further, prior registration is now a condition of publishing clinical trial data. From 1st July 2005 the International Committee of Medical Journal Editors (ICMJE) have declared that their journals will not publish the results of any clinical trials not included on an authorized register at the trials inception.
 
Data transfer
As regards data from Indian patients going out, one needs to consider the contribution of this data and the objective of international study. If the study has a large contribution from India, there should be a legal contract with the sponsoring agency re: use of data and potential benefits - authorship, royalty etc.
 
Subject protection
Providing protection to a subject in case of an injury is responsibility of the investigator and the institute. See ICMR guidelines below:

ICMR guidelines section Compensation For Accidental Injury:
Research participants who suffer physical injury as a result of their participation are entitled to financial or other assistance to compensate them equitably for any temporary or permanent impairment or disability. In case of death, their dependents are entitled to material compensation.

Obligation of the sponsor to pay: The sponsor whether a pharmaceutical company, a government, or an institution, should agree, before the research begins, in the a priori agreement to provide compensation for any physical or psychological injury for which participants are entitled or agree to provide insurance coverage for an unforeseen injury whenever possible

Can a homoeopathic doctor, with 5 years of industry experience as a senior CRA, become sub-investigator?
Dr R Yadav

As per Indian GCP Sub-investigator and Co-investigator are synonymous.
Co-investigator: A person legally qualified to be an investigator, to whom the Investigator delegates a part of his responsibilities.

ICH GCP 1.56 Sub-investigator: Any individual member of the clinical trial team designated and supervised by the investigator at a trial site to perform critical trial-related procedures and/or to make important trial-related decisions (e.g., associates, residents, research fellows).

According to a recent US FDA guidance, during a subject's participation in a trial, the investigator (or designated sub-investigator) should ensure that reasonable medical care is provided to a subject for any adverse events, including clinically significant laboratory values, related to the trial participation.

Considering the above, a sub-investigator has to perform critical trial related procedures, make important decisions, and should be able to provide medical care for adverse events. Hence, the sub-investigator should be legally qualified to undertake these responsibilities.
Hence, a homeopathic doctor would not be able to take the role of a sub-investigator.

How does one report a pregnancy occurring during a trial? As an SAE?
Rohit Shetty

In most international trials, a pregnancy occurring during a trial is reported on a 'pregnancy report form'. In India, there is no regulatory guidance on pregnancy reporting. Hence, it needs to be reported as a serious adverse event.

A pregnancy would be reported as an SAE when there's any complication e.g. miscarriage etc, which meets one of the criteria of seriousness or if the baby is born with congenital defects. However, if a protocol defines all pregnancies to be reported as SAE, one has to follow the protocol.

Dr Arun Bhatt is currently, president, ClinInvent, Research Pvt Ltd, Mumbai.
Readers can send their queries at: arunbhatt@clininvent.com