Table 1

Extracts from the opening paragraphs of Schedule Y in 1988 and in 2005, comparing the provisions on phase II, III and IV trials as they relate to numbers of trial subjects and centres15

Trial phase1988 Schedule Y2005 Schedule Y
Phase II‘Normally 10–12 patients should be studied at each dose level. These studies are usually limited to 3–4 centres…’‘Studies in Phase II should be conducted in a group of patients who are selected by relatively narrow criteria leading to a relatively homogeneous population. These studies should be closely monitored… If the application is for conduct of clinical trials as a part of multi-national clinical development of the drug, the number of sites and the patients as well as the justification for undertaking such trials in India shall be provided to the Licensing Authority’.
Phase III‘If the drug is already approved/marketed in other countries, phase III data should generally be obtained on at least 100 patients distributed over 3–4 centres primarily to confirm the efficacy and safety of the drug in Indian patients when used as recommended in the product monograph for the claims made. If the drug is a new drug substance discovered in India, and not marketed in any other country, phase III data should be obtained on at least 500 patients distributed over 10–15 centres’.‘(iii) For new drugs approved outside India, Phase III studies need to be carried out primarily to generate evidence of efficacy and safety of the drug in Indian patients when used as recommended in the prescribing information. Prior to conduct of Phase III studies in Indian subjects, Licensing Authority may require pharmacokinetic studies to be undertaken to verify that the data generated in Indian population is in conformity with the data already generated abroad.
(iv) If the application is for the conduct of clinical trials as a part of multi-national clinical development of the drug, the number of sites and patients as well as the justification for undertaking such trials in India should be provided to the Licensing Authority along with the application’.
Phase IV*‘In addition, data on adverse drug reactions observed during clinical use of the drug should be collected in 1000–2000 patients…’‘Post Marketing trials are studies (other than routine surveillance) performed after drug approval and related to the approved indication(s). These trials go beyond the prior demonstration of the drug’s safety, efficacy and dose definition. These trials may not be considered necessary at the time of new drug approval but may be required by the Licensing Authority for optimising the drug’s use. They may be of any type but should have valid scientific objectives. Phase IV trials include additional drug-drug interaction(s), dose-response or safety studies and trials designed to support use under the approved indication(s), for example, mortality/morbidity studies, epidemiological studies etc’.
  • *In 1988, phase IV trials were not specifically mentioned in Schedule Y: the 1988 text above is a continuation of the 1988 Schedule Y text for phase III trials.