Drug regulator seeks inquiry into Bhopal clinical trial
FAISAL ZAIDI
The trial on victims of the gas tragedy was conducted in 2006 by Bhopal hospital for Theravance drug
India’s drug regulator has ordered an inquiry into one of the clinical trials that were conducted at Bhopal Memorial Hospital and Research Centre (BMHRC) during which three subjects died.
The Drug Controller General of India issued an order on Tuesday to the Bangalore office of Quintiles Transnational Corp., the world’s largest pharmaceutical services company, to audit the human clinical trial. The sponsor of this trial was US-based, Nasdaq-listed innovator firm Theravance Inc. The trial was for its drug Vibativ (generic name telavancin).
“We will audit the data available with the company following the completion of the trial,” said a health ministry official who did not want to be identified. “Clinical trial audits were supposed to begin in September but following the news of the trials at BMHRC, we have (advanced) them. The audit will start next week.”
As per documents available with Mint, at least seven different human clinical trials were conducted at BMHRC and at least 10 deaths occurred during these trials.
The regulator’s move comes after television news channels reported that BMHRC had conducted human clinical trials on victims of the Bhopal gas tragedy between 2004 and 2008. The trials were abruptly stopped soon after the death of 49 babies at the All India Institute of Medical Sciences, New Delhi, during clinical trials was reported. The story was first reported in June by NewsX.
Experts are raising questions over ethical issues, including whether informed consent was taken from the subjects, and why a hospital entrusted with the responsibility of treating victims of the gas tragedy and conducting research into preparations for similar emergencies was carrying out such trials. Its website says the institute was started as per the directive of the Supreme Court to provide advanced tertiary level super-specialty care to the victims of the Bhopal gas tragedy as well as to extend its services to the public at large.
Moreover, four of the seven trials were conducted as phase 2 or 3 clinical studies, many years before the drugs were approved for marketing in Europe and the US.
The Indian Council of Medical Research, Council for International Organizations of Medical Sciences and the World Health Organization have codes of conduct for drug trials. “Guidelines require that people with reduced autonomy should not be subjected to trials. Bhopal gas victims have zero autonomy since they are totally dependent on treatment provided by the BMHRC,” said C.M. Gulhati, editor of medical journal Monthly Index of Medical Specialities.
The telavancin trial that will now come under the drug regulator’s scanner received approval in April 2006 for testing the drug for hospital-acquired pneumonia (HAP). As of now, the drug is approved for marketing in the US only for one indication—skin infections. This approval was received in September 2009. In November, the US Food and Drug Administration (FDA) had asked for additional data to approve the drug for HAP. However, in January this year, this additional data was also deemed “incomplete” by FDA.
Theravance and its contract clinical research organization (CRO) Quintiles completed the trial in India in June 2007 after having screened eight subjects for the trial, while only four completed the trial. During the one-year period of the trial, three deaths occurred.
Calls and emails to Theravance remained unanswered.
“The case of telavancin is even more irrational. Merely four subjects completed the trial. Data on a such a minuscule (number) is worthless because it can neither give credible information either on efficacy or safety. As per well-accepted rules of medical statistics, for determining even a huge 10% side effect one would need at least 100 subjects. For determining 1% side effect, the requirement will be about 1,000 subjects,” said Gulhati.
Documents available with Mint also reveal that the research organization had taken approval in August 2008 to conduct the trial for platelet inhibitor drug prasugrel (marketed as Effient in the US and Prasita in India) but the principal investigator Skand Kumar Trivedi later withdrew from the study and hence the trial at the site was never initiated.
However, a former BMHRC doctor Mint spoke with insisted the trial was conducted at BMHRC. “It was called the Plato trial and was conducted at the hospital. And in all these seven trials, victims of the gas tragedy were also used as subjects,” said the doctor. He requested anonymity. The doctor added that he had been involved in some of these clinical trials. He was with the hospital between 2003 and 2008.
A search of the Indian clinical trial registry as well as the US registry did not throw up Bhopal as one of the sites for the trial.
Principal investigator Trivedi denied having conducted the trial. “The prasugrel trial was not conducted here,” he said, refusing to give more information because the matter is “subjudice and the Madhya Pradesh government is conducting an inquiry”.
A member of the ethics committee at the hospital and the hospital spokesperson also declined to comment, citing similar reasons.
When the Bangalore office of Quintiles was contacted for comment, Mint was directed to its US headquarters. An email to the US office sent on Tuesday remained unanswered.
“The most unethical part of these trials was that informed consent was not taken. The enquiry commission put out a notice asking people to come forward and report to them if they had not given informed consent. About six-seven people did come forward but there will be more. If the subject has not given informed consent, he may not even be aware that he was part of a clinical trial,” said the same doctor.
India’s drug regulator has ordered an inquiry into one of the clinical trials that were conducted at Bhopal Memorial Hospital and Research Centre (BMHRC) during which three subjects died.
The Drug Controller General of India issued an order on Tuesday to the Bangalore office of Quintiles Transnational Corp., the world’s largest pharmaceutical services company, to audit the human clinical trial. The sponsor of this trial was US-based, Nasdaq-listed innovator firm Theravance Inc. The trial was for its drug Vibativ (generic name telavancin).
“We will audit the data available with the company following the completion of the trial,” said a health ministry official who did not want to be identified. “Clinical trial audits were supposed to begin in September but following the news of the trials at BMHRC, we have (advanced) them. The audit will start next week.”
As per documents available with Mint, at least seven different human clinical trials were conducted at BMHRC and at least 10 deaths occurred during these trials.
The regulator’s move comes after television news channels reported that BMHRC had conducted human clinical trials on victims of the Bhopal gas tragedy between 2004 and 2008. The trials were abruptly stopped soon after the death of 49 babies at the All India Institute of Medical Sciences, New Delhi, during clinical trials was reported. The story was first reported in June by NewsX.
Experts are raising questions over ethical issues, including whether informed consent was taken from the subjects, and why a hospital entrusted with the responsibility of treating victims of the gas tragedy and conducting research into preparations for similar emergencies was carrying out such trials. Its website says the institute was started as per the directive of the Supreme Court to provide advanced tertiary level super-specialty care to the victims of the Bhopal gas tragedy as well as to extend its services to the public at large.
Moreover, four of the seven trials were conducted as phase 2 or 3 clinical studies, many years before the drugs were approved for marketing in Europe and the US.
The Indian Council of Medical Research, Council for International Organizations of Medical Sciences and the World Health Organization have codes of conduct for drug trials. “Guidelines require that people with reduced autonomy should not be subjected to trials. Bhopal gas victims have zero autonomy since they are totally dependent on treatment provided by the BMHRC,” said C.M. Gulhati, editor of medical journal Monthly Index of Medical Specialities.
The telavancin trial that will now come under the drug regulator’s scanner received approval in April 2006 for testing the drug for hospital-acquired pneumonia (HAP). As of now, the drug is approved for marketing in the US only for one indication—skin infections. This approval was received in September 2009. In November, the US Food and Drug Administration (FDA) had asked for additional data to approve the drug for HAP. However, in January this year, this additional data was also deemed “incomplete” by FDA.
Theravance and its contract clinical research organization (CRO) Quintiles completed the trial in India in June 2007 after having screened eight subjects for the trial, while only four completed the trial. During the one-year period of the trial, three deaths occurred.
Calls and emails to Theravance remained unanswered.
“The case of telavancin is even more irrational. Merely four subjects completed the trial. Data on a such a minuscule (number) is worthless because it can neither give credible information either on efficacy or safety. As per well-accepted rules of medical statistics, for determining even a huge 10% side effect one would need at least 100 subjects. For determining 1% side effect, the requirement will be about 1,000 subjects,” said Gulhati.
Documents available with Mint also reveal that the research organization had taken approval in August 2008 to conduct the trial for platelet inhibitor drug prasugrel (marketed as Effient in the US and Prasita in India) but the principal investigator Skand Kumar Trivedi later withdrew from the study and hence the trial at the site was never initiated.
However, a former BMHRC doctor Mint spoke with insisted the trial was conducted at BMHRC. “It was called the Plato trial and was conducted at the hospital. And in all these seven trials, victims of the gas tragedy were also used as subjects,” said the doctor. He requested anonymity. The doctor added that he had been involved in some of these clinical trials. He was with the hospital between 2003 and 2008.
A search of the Indian clinical trial registry as well as the US registry did not throw up Bhopal as one of the sites for the trial.
Principal investigator Trivedi denied having conducted the trial. “The prasugrel trial was not conducted here,” he said, refusing to give more information because the matter is “subjudice and the Madhya Pradesh government is conducting an inquiry”.
A member of the ethics committee at the hospital and the hospital spokesperson also declined to comment, citing similar reasons.
When the Bangalore office of Quintiles was contacted for comment, Mint was directed to its US headquarters. An email to the US office sent on Tuesday remained unanswered.
“The most unethical part of these trials was that informed consent was not taken. The enquiry commission put out a notice asking people to come forward and report to them if they had not given informed consent. About six-seven people did come forward but there will be more. If the subject has not given informed consent, he may not even be aware that he was part of a clinical trial,” said the same doctor.
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