The Parliamentary Standing Panel attached to the Health Ministry has dug out many flaws in the conduct of phase III clinical trials and criticised the Health Ministry for misleading the committee on the information.
“The very purpose of phase III trials is to determine any ethnic/racial differences in the safety, efficacy and metabolism of drugs. Hence to serve any useful purpose, patients of different ethnicities living in India should be enrolled. For example, the results of a trial conducted only on Indo-Aryans may not be applicable to Mongoloids or Dravidians due to genetic differences,’’ the report of the panel said.
“In response to a question as to how various ethnic groups are being enrolled in phase III clinical trials, the Committee was informed that “most trials were taking place in cosmopolitan towns. It is understood that cosmopolitan cities have a heterogeneous population comprising various ethnic groups. Otherwise there is no proactive, specific procedure to test new drugs on different ethnic groups,’’ it said.
However, a scrutiny of randomly selected clinical trial sites shows that the Ministry’s submission is incorrect and the basic purpose of phase III trials, even when conducted, is not being served, as per the report.
“A trial (rifaximin) took place at Kota, Jaipur and Mumbai. Kota and Jaipur can hardly be classified cosmopolitan in demography. Another trial (doxofylline) took place just in Hyderabad and Aurangabad. Aurangabad certainly is not a cosmopolitan city. Sites of another trial (ramosetran) were limited to Betul, Indore and Bhopal (all in Madhya Pradesh) and Vadodara (Gujarat). None of them is a cosmopolitan town. Trial on FDC of etodolac with paracetamol was conducted just in Maharashtra (Nagpur, Pune and Mumbai). Trials on another FDC of aceclofenac with drotaverine were conducted only in Maharashtra (Aurangabad, Pune and Mumbai). In the case of FDC of diclofenac with serratiopeptidase (India being the sole country in the world to have approved such a combination),’’ the report said.
On the other hand an analysis of 164 randomly selected sites of pre-approval drug trials shows that only one site was located in Guwahati, where one can find adequate number of patients of Mongoloid origin since many of them also come from other North East states for treatment, it said.
“It is obvious that DCGI clears sites of pre-approval trials without application of mind to ensure that major ethnic groups are enrolled in trials to have any meaningful data. Thus such trials do not produce any useful data and merely serve to complete the formality of documentation. The Committee recommends that while approving phase III clinical trials, the DCGI should ensure that subject to availability of facilities, such trials are spread across the country so as to cover patients from major ethnic backgrounds and ensure a truly representative sample. Besides, trials should be conducted in well equipped medical colleges and large hospitals with round the clock emergency services to handle unexpected serious side effects and with expertise in research and not in private clinics given the presence of well equipped medical colleges and hospitals in most parts of the country in present times,’’ the report said.