Print edition : December 16, 2005

AN innocuous statement published in a few newspapers in July should have caused a sensation in India and abroad. But it did not.

It was issued by Dr. M. Krishnan Nair, the former Director of the Regional Cancer Centre, Thiruvananthapuram, to announce that a scientific paper titled `Five year survival results of a single group study of intralesional tetra-O-methyl nordihydroguiaretic acid in oral squamous cell carcinoma (M4N study)" has been awarded the `Best Clinical Award' in the 10th International Congress on Oral Cancer held in the Island of Crete in Greece and the authors have been awarded a cash prize of 1000 euros.

"In this particular study the authors were able to obtain the best relapse-free survival at five years compared to all historic data on this cancer that too with a short exposure to M4N. The Food and Drug Administration of USA has approved this drug for clinical use," the note sent to newsrooms on July 7 said.

It ended cryptically, explaining the significance of the award: "It may be noted that a great hue and cry was raised by two doctors in Regional Cancer Centre along with a few members of the lay public in the media in Kerala about the use of this drug."

Dr. Krishnan Nair seemed to imply that a follow-up study of the patients involved in the controversial Hopkins-RCC drug trial was conducted and it proved the critics of the trial wrong by demonstrating that the series of three to five injections of M4N (originally also G4N) into the tumours of the 18 (originally 27) patients had demonstrated "the best relapse-free survival (of the patients) at five years compared to all historic data on this cancer - that too with a short exposure to M4N".

The statement said the paper was presented at the Greece conference by Dr. Manoj Pandey, who along with Dr. Krishnan Nair and Dr. Radhakrishna Pillai of the RCC, and Prof R.C. Huang of Johns Hopkins University, had conducted the controversial drug trials in 1999-2000. It claimed the new study as the joint work of four authors, Dr. Pandey, Dr. Krishnan Nair, Huang and, surprisingly, Dr. B. Rajan, who succeeded Krishnan Nair as the Director of the RCC.

The paper made no mention that the original study had 27 (not 18) patients, at least some of whom were also administered the water-soluble and potentially more dangerous experimental chemical, G4N, either separately or along with M4N. Given below are responses to Dr. Krishnan Nair's statement and some other questions posed by Frontline to a cross-section of people involved both in India and abroad with the controversy - and therein lies a tale:

Dr. Krishnan Nair: "Dr. Manoj Pandey sent me the paper he presented at the conference and I merely forwarded it to the media."

Ru Chih C. Huang: "The data speak for themselves. It is very heartening to know that this study supports my original discovery and development of a potential breakthrough in oncology, and that there appears to be a longer-term benefit for patients worldwide, particularly for patients in India since the oral cancer incidence is very high in your country."

Jennifer C. Stern, clinical research manager, Erimos Pharmaceuticals (to an unrelated question on the company's obligation to the 27 RCC patients): "Erimos was not involved with the clinical study in India, although we are very interested in the continuing positive outcome of the study conducted there. Although we have no obligation to the patients in the study, the high survival rate in the study encourages us to progress the development of EM-1421 [M4N] speedily but safely."

Dennis O'Shea, spokesperson, Johns Hopkins University: "Professor Huang did not participate [in this study]. Her name is on the paper as a result of her initial involvement in the study back in 1999-2000. [Technically, I am told, this paper would be considered a product of that study rather than a follow-up study, since the patients were only followed-up in the course of their regular medical treatment and no additional experimental intervention occurred.]... Since Prof. Huang did not participate, there was no need for Johns Hopkins review or IRB approval... No, we are not aware [where this follow-up study had taken place or whether it had subsequently obtained IRB approval in India]."

Dr. V.N. Bhattathiri, formerly Associate Professor of Radiotherapy at the RCC, whose initial revelations from within the RCC made the Hopkins-RCC trial an international focus of attention: "It is an unbelievable claim. If it had to be real then the conclusion should rather have been that some patients survived beyond five years in spite of the injected chemicals."

Dr. V.P. Gangadharan, the other whistleblower at the RCC: "Many such awards are often sponsored by pharmaceutical companies. The results seem to be a manipulation of facts rather than based on facts. Quite a few of the patients died long ago."

Dr B. Rajan: "I was not involved in any such study. I had no role in the original study either. To my knowledge no follow-up study has taken place at the RCC. But I don't know if Dr. Pandey or the others subsequently monitored the patients. It may be a result of routine follow-up of the patients. I have no idea why my name is mentioned as one of the authors."

Dr. C.R. Soman, chairman of the Thiruvananthapuram-based activist organisation Health Action by People: "When the trial is being condemned all over the world they are claiming that they continued the study. The chances are it is mere fiction. Someone has manufactured this data, because, as we know it, most of the patients did not turn up for follow-up treatment. Gift authorship is as unethical as concocting and tutoring data. The RCC Director has to do some explaining, he being mentioned as a senior author in the paper. He has to call for the entire set of case sheets and disclose how many times the patients came for follow-up in the past five years. To claim that the condition of patients improved due to the experimental `drug' is a lie."

Dr. Krishnan Nair, in a subsequent conversation with Frontline: "I want to clarify that the paper is not based on any follow-up study. The study was stopped abruptly after the Government of India ordered its suspension [for six months] in 2001. The paper is based on the results obtained till then."

Dr. Manoj Pandey was on long leave. There was no response from him to an e-mail.

There are reports that in March 2005 a similar paper [but without the name of Dr. Rajan as one of the authors] was presented at the Annual Meeting of the Society of Surgical Oncology held in Atlanta, U.S.

One question had no immediate answer: Who would benefit from creative, positive data on survival of patients from a condemned clinical trial in India?

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