Even as the multinational drug major GlaxoSmithKline (GSK) has started patient enrolment in TIDE trial on the controversial diabetes drug rosiglitazone (Avandia) at 10 sites in India, experts in the field have questioned the propriety of conducting such a trial which, they fear, will put hundreds of ill-informed patients at risk of morbidity and mortality in the country.
Avandia became a controversial drug when the medical experts raised concern that the drug could expose diabetes patients to an increased risk of heart failure and possible death.
According to reports, Drugs Controller General of India (DCGI) Dr Surinder Singh has already given permission to the GSK to conduct Thiazolidinedione Intervention in vitamin D Evaluation (TIDE) trial on rosiglitazone (Avandia) at 10 sites in India including St Johns Medical College, Bangalore. Sources said that the patient enrolment for the trial at St. Johns Medical College has already begun. Other trial sites in India are Mumbai, Nasik, Pune, Cochin (two), Kottayam, Trichy, Vijayawada and Karnal.
It is part of an international clinical trial, at the behest of US FDA, to examine the cardiovascular effects of treating diabetes patients with one of two drugs β rosiglitazone and pioglitazone.
Experts argue that since 2007 huge amount of data has been generated worldwide which conclusively proves that rosiglitazone is inferior to pioglitazone in its cardiovascular safety profile thus making the trial virtually meaningless.
They are of the view that several clinical trials have already confirmed that rosiglitazone increases the risk of heart attacks, whereas pioglitazone is at best neutral or perhaps somewhat protective. Not a single study has suggested that pioglitazone might carry more risk. Most physicians in US have already switched from rosiglitazone to pioglitazone with four times as many prescriptions written for pioglitazone than for rosiglitazone in 2008.
In 2008, based on unfavourable data on rosiglitazone, both the American and the European Diabetes Associations advised that 'given that other options are now recommended, the consensus group members unanimously advised against using rosiglitazone'.
βIt is most unethical and inhuman to administer a drug that is already known to be inferior to the comparator molecule. Furthermore, patients in India are being denied the ability to make an informed decision because the trial consent form does not present a true and accurate portrayal of the existing safety data on rosiglitazone. Otherwise why would a fully informed patient willingly participate in a trial involving a drug that has little role in the treatment of diabetes?β, questions Dr CM Gulhati, a medical expert and editor, Monthly Index of Medical Specialities (MIMS), a medical journal.
No wonder it is very difficult to enroll subjects in such a trial in western countries. Therefore, belatedly sites in India and other developing countries such as Chile, Mexico, Colombia and Pakistan have been added to increase enrolment to meet regulatory requirement in the United States.
There is no justification to conduct the trial on Indian subjects by making them guinea pigs, Dr Gulhati said and added that a subsidiary purpose, to test if vitamin D supplementation has any role on death and cancer given along with the two drugs, is totally irrelevant to India with so much sunshine-supplied vitamin D.