If there is no difference between these following two guidelines then why are these prepared separately?
Vij Chauhan
Indian GCP guidelines have been evolved with consideration of WHO, ICH, US FDA and European GCP guidelines as well as the ethical guidelines for biomedical research on human subjects issued by the Indian Council of Medical Research. ICH GCP guideline was developed with consideration of the current good clinical practices of the European Union, Japan, and the United States, as well as those of Australia, Canada, the Nordic countries and the WHO. Due to this, there are differences between ICH and Indian GCP in glossary, ethics segment, safety reporting, monitor’s responsibilities etc. Also, Indian GCP covers areas not covered by ICH GCP e.g. herbal preparations, vaccines, devices etc. Hence, both guidelines need to be followed if an international trial is being conducted in India. DCGI permission insists that the sponsor should follow Indian GCP guidelines whilst conducting the trial in India.
For phase 4 study initiated by pharma co is it necessary to provide study subjects insurance? Is it mandatory to take EC approval from all study centres for phase 4 study initiated by co (non-comparative open label study)? Is it mandatory to take DCGI approval before initiation of phase 4 study?
Dr Arindam Dey
Phase IV can cover different types of studies. (see ICMR 2006 guideline) You need to assess in which category your study falls. If it is an open label study, it will be like a phase III study. Hence, EC approval and patient insurance will be essential. If the indication is not as per DCGI approved indication, it will be necessary to take DCGI approval.
ICMR 2006 guidelines on 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 longterm 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 bioavailabilty 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 labeled 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 letrazole. Here, DCGI permission and EC approval are needed which really makes the trial a phase III study.
A homoeopathy doc holds a patent for homoeopathic medicine. He wants to run trial with same medicine at his own hospital as principal investigator and will be a self funded trial. No other centre will be involved in trial beside his own hospital. Central lab will be used for blood sample analysis; and an independent monitor will be monitoring this trial. I have following questions: Will it be OK that patent holder investigator can do the trial? Will there be any chance of bias in conduct of trial? How to prevent bias in such trials? Will data generated by this trial be accepted by GCP? Do we require DCGI approval for homoeopathy medicine?
Geeta Talele
A patent holder can conduct the trial. However, his own interest in the product can bias him to give positive results. Hence, he should organize the trial in way that his own interest in the product does not influence the documentation and measurement of efficacy / safety end points. The only way to avoid bias is by letting another investigator conduct the trial. The data will be acceptable if the trial conforms to GCP guidelines. This means that all aspects of the trials - design, conduct, monitoring, recording, analysis, reporting - meet GCP standards, As homoeopathy research comes under Dept of Ayush. You will need to check with them re: Ayush procedures for approval. DCGI approval is not required.
Can we conduct a bioavailability study (pharmacokinetics) for the drug which is not available/approved in India in healthy volunteers (10-12). The objective of the study would be just to understand or analyze the pharmacokinetic behaviour in human subjects. In such scenario only ethics committee approval is sufficient or DCGI approval is required?
Rudolph Almeida
If it is not available/approved in India, you will need a test import license from DCGI office to import the drug for pharmacokinetic study. Hence, DCGI approval of the protocol will be necessary.
Dr Arun Bhatt is currently, president, ClinInvent, Research Pvt Ltd, Mumbai.
Readers can send their queries at: arunbhatt@clininvent.com