We want to conduct a PMS study for an approved device in India. Is it necessary to take an EC approval before conducting such a study?
Bhavik Shah
Please see ICMR guideline recommendations on objectives of phase IV study and need for EC/DCGI approval.

Phase IV - The phase IV studies should have valid scientific objectives. After approval of the drug for marketing, phase IV studies or post marketing surveillance is undertaken to obtain additional information about the risks and benefits resulting from long term usage of drug. It is an important aspect of drug trial on the long term effects of the drugs and the adverse reactions induced by drugs, if any, should be brought to the notice of the Ethics Committee. There is a need to correlate the adverse events reported during phase IV trials with the toxicity data generated in animals, to draw markers for future warnings of potential adverse events likely to occur with other drugs. These trials may not be necessary for approval of new drug for marketing but may be required by the Licensing Authority for optimizing its use. These studies also include those on specific pharmacologic effect, drug-drug interaction(s), dose-response studies, trials designed to support use under approved indication(s) e.g. mortality/morbidity studies, clinical trials in a patient population not adequately studied in the pre-marketing phase, e.g., children; and epidemiological studies etc. Bioequivalence and bioavailability study also falls under this category.

In addition there are phase IV studies that are designed to evaluate the marketed drug in specifically designed studies, which have inclusion/exclusion criteria, objectives and end points. The drug is used for the labelled indication in these studies. Therefore Licensing Authority permission is not needed. However, EC permission is needed.

A third type of post-marketing study involves evaluation of the drug for a new indication of a marketed drug, e.g. studies with letrozole. Here, DCGI permission and EC approval are needed which really makes the trial a phase III study.

Can we enrol an illiterate subject in a non-therapeutic trial?
Darshana Patel
For non-therapeutic trials, see below ICH GCP recommendations for use of LAR.

4.8.12 When a clinical trial (therapeutic or non-therapeutic) includes subjects who can only be enrolled in the trial with the consent of the subject's legally acceptable representative (e.g., minors, or patients with severe dementia), the subject should be informed about the trial to the extent compatible with the subject's understanding and, if capable, the subject should sign and personally date the written informed consent.

4.8.14 Non-therapeutic trials may be conducted in subjects with consent of a legally acceptable representative provided the following conditions are fulfilled:

●The objectives of the trial cannot be met by means of a trial in subjects who can give informed consent personally. The foreseeable risks to the subjects are low.
●The negative impact on the subject's well-being is minimized and low.
●The trial is not prohibited by law.
●The approval/favourable opinion of the IRB/IEC is expressly sought on the inclusion of such subjects, and the written approval/ favourable opinion covers this aspect.

Such trials, unless an exception is justified, should be conducted in patients having a disease or condition for which the investigational product is intended.

Subjects in these trials should be particularly closely monitored and should be withdrawn if they appear to be unduly distressed.

Does the EC in India need regulatory approval letter before they approve?
Divya Ganapathy
As per Schedule Y, clinical trial on a new drug shall be initiated only after the permission has been granted by DCGI office and the approval obtained from the respective ethics committee(s). You need to inform the DCGI office about the EC approval before initiation of trial. Similarly, you also need to give a copy of DCGI approval to EC before the trial initiation.

Is it mandatory that the investigational products (for BA/BE studies) should be stored in humidity chambers (controlled humidity and temperature)? If so, which guideline specifies that?
Rendeep Rajendran
The US FDA recommends that the drug should be kept in storage conditions consistent with product label. If you check the product label, most would contain storage requirements which specify temperature and the need to protect the tablets from moisture.

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