Dr.P.M.Bhargava, former Director of the Centre for Cellular and Molecular Biology (CCMB), who raised the issue of using patients from India and other Third World countries as guinea pigs by Novo Nordisk, told Pharmabiz that he was surprised to read the clarification issued by Dr Reddy's Laboratories. It was not in their interest to issue the statement. He said. "I am very proud of Dr Reddy's Lab and I find it was totally unnecessary to issue a statement like that. After all, the expose of the clinical trial of the drug was not directed against the company," he said.

However, he said the clarification issued by Dr Reddy's was full of inconsistencies and contradictions. According to Dr Reddy's statement, Novo Nordisk conducted long- term toxicology studies quite apart from the regulatory toxicology studies that were required prior to the commencement of trials on humans. It was in these long- term toxicology studies several rats were observed to have developed urinary bladder tumours. Dr Bhargava says if at all Novo Nordisk wanted to conduct long- term toxicology studies there must have been a reason for it. And if there was a reason, clinical trials should not have been commenced. If all the regulatory requirements were satisfied, then why this study at all, asks Dr. Bhargava.

Dr Bhargava also debunks Dr Reddy's statement that " it is a known fact that the development of such tumours in rats is species- specific and does not have any implications for humans. He said, " As far as I know tumours caused by chemicals are generally not species- specific. Since there is no evidence, we cannot conclude that it is species- specific. But tumours caused by virus are species- specific. For example, Rous Sarcoma virus is specific for chicken."

As far as chemicals are concerned there would be some reaction initially, but the tumour would appear several years later. A chemical itself may not be carcinogenic but one of its metabolics, which is formed during the detoxification process, could be carcinogenic.

Dr Bhargava who also sat on several committees to decide on the protocols on the clinical trials, was surprised how the Drug Controller General of India had permitted the Phase 3 human trials without completing the mandatory Phase 2 animal trials. The different phases of clinical trials cannot overlap. One cannot go into the subsequent phase without completing the earlier phase, he said. The regulations in India stipulate that carcinogenicity study on animals must be completed prior to the launching of trials on human beings.

Novo Nordisk had earlier stated that it had conducted clinical trials on 2,500 people in 32 countries, to which Dr Bhargava said, "We would like to know which are these 32 countries. We also want to know how many patients from each country have been administered the drug. If it turns out that 95% patients are from the developing countries, and a few from the developed countries, then we have a problem."

He said the regulatory system in many of the developing countries were not stringent and therefore, there was every reason to suspect that the patients from the poor countries were used as guinea pigs.

According to Dr Reddy's statement all the patients were asked to reassess their continued participation in clinical trials and all of them signed a new Patient Informed Consent Form, which included the information about the tumours found in rats.

Dr Bhargava says in the developing countries one can make the poor patients sign on anything. We do not know what they were told. An illiterate person would not know what it is all about.

What Novo Nordisk is going to do with the patients after suspending the clinical trials? Medical ethics demand that if any adverse reaction is found and the trial has to be discontinued, then the company will take care of all the expenses involved in taking care of the adverse reaction or compensate the patients suitably for the delay in starting another treatment. That means it is the responsibility of the company conducting the trials to offer enough money to take care of the adverse reaction and pay for starting a fresh treatment. Is this ruling a part of the Consent Form, asks Dr Bhargava.