October 28th 2011
Coalition against BAYER Dangers (Germany)

Open letter to BAYER:

Trial-related deaths in India

Bayer AG
CEO Marijn Dekkers
51368 Leverkusen

Dear Mr Dekkers,

according to figures given by the Indian Ministry of Health, 668 Indians died during pharmaceutical trials over the last year. In previous years the figures were 288 in 2008 and 637 in 2009. A major part of the trials was conducted on behalf of international companies.

In respect of those figures, 138 of the test persons who died during a period of four years were participating in clinical trials conducted by BAYER. At least four test subjects have died during the last year of tests for the anti-thrombosis drug Xarelto (active ingredient: Rivaroxaban).

What is the reason for those deaths? We request that you disclose all relevant data concerning the clinical trials that BAYER has conducted in India over the last five years.

Please answer the following questions for each study.
=> Which drug was used? In which amount was it administered?
=> Who was commissioned to conduct the trial? Where were the tests conducted?
=> How many test subjects took the drug over which period of time?
=> Which side effects occurred with which frequency? How many deaths occurred?
=> What compensation was paid to next of kin and aggrieved parties?
=> Why does BAYER conduct so many studies in India?
=> Which precautionary measures are taken to avoid further problems?

We look forward to your swift reply.

Kind regards,

Philipp Mimkes
Jan Pehrke
Coalition against BAYER Dangers

14 November 2011; The Independent: How drugs companies exploit Indian 'guinea pigs'

=> The clinical trial scenario in India

October 11, 2011, Pharma Biz

Experts find gross discrimination in paying compensation to trial victims by MNCs

Even as the number of deaths of patients participating in clinical trials are steadily increasing over the years in consonance with the increase in the number of clinical trials by MNCs in the country, experts say there is gross discrimination in payment of compensation to the victims by multinational pharma companies.

According to data made available by the experts, the number of deaths of patients participating in clinical trials have increased as is the number of clinical trials by MNCs involving new drugs in the country. While 137 deaths were registered in the year 2007, the number rose to 288 in 2008, 637 in 2009 and 668 during 2010.

Meanwhile, experts are of the view that these figures are understated because many deaths are not reported to the Drugs Controller General of India (DCGI) by treating them as 'routine deaths not related to clinical trials'. Ironically, the investigators, who are on the payroll of drug companies that sponsor and fund the trials, are the ones who decide the causes of the deaths.

Regretting that the trial victims are well compensated abroad while they are humiliated at home by the MNCs, well-known health expert and Editor of the medical journal MIMS Dr CM Gulhati said that case histories show that there are double standards employed by drug companies in different countries in paying compensation to trial victims.

He said that till the end of 2009, there was not even one case of compensation to patients who died during clinical trials even though it is mandatory in the country. Lately, a total of 10 companies submitted a list of just 22 patients to whose families compensation was paid. In the case of Bayer, only five out of 138 deaths and in the case of sanofi aventis, only three out of 152 patients who died were offered compensation.

A glance at the amounts shows that an arbitrary sum of Rs.1,50,000 was paid to each of the eight victims by five different companies (Merck, Wyeth, Amgen, Sanofi and Pfizer). Bayer paid Rs.2,50,000 each in five cases while Eli Lilly paid Rs.2,00,000 to two families each and Rs.1,00,800 to one family. The average of all payments comes to a measly Rs.2,38,000 (or US$ 5,000) per dead participant.

In comparison, Dr Gulhati said, on August 11 this year, Pfizer started handing over US$ 1,75,000 (Rs.84 lacs) to each victim of its Trovan (trovafloxacin) trial on children in Kano, Nigeria. In addition it agreed to pay US$ 10 million (Rs.48 crore) to the state government of Kano towards legal expenses incurred in long drawn litigation on behalf of its citizens.

In Germany, the erstwhile Hoechst (now part of sanofi aventis) paid more than 60,000 Euros (Rs.40 lacs) to the family of a woman who died during trial of an antidepressant agent nomifensine (Alival) later withdrawn on safety concerns. The company's top executive in the United States was slapped a fine of US$ 300,000 (Rs.1.44 crore) for concealing the drug's adverse effects.

In the United States, US$ 3.8 million (Rs.18 crore) was paid to poor women with high risk pregnancies who did not suffer any physical harm but asserted that that they were not informed that administered drugs were "experimental" and the consent form was far "above their reading level" and therefore invalid. Ramesh Shankar, Mumbai

Trial-related deaths: Health ministry plans to finalize Schedule Y1

INDIA: Since the topic concerning mortalities related to clinical trials in India is being addressed by the National Human Rights Commission (NHRC), the drug control authorities want to make an official announcement regarding the proposed Schedule Y1 for efficient and timely streamlining of the sector.
The draft notification was issued in January 2011. In view of the recent controversies regarding the number of clinical trial-related deaths, the Health Ministry now wants to finalize the Schedule Y1 document by incorporating suitable recommendations from stakeholders.
In the interim, sources confirm that the NHRC has served notices to the Drugs Controller General of India (DCGI) office and the Indian Council of Medical Research (ICMR), and are in the process of filing detailed reports to the human rights body.
Official versions of the incidents declare that, “The death of a subject enrolled in the clinical trials may occur during the trial due to various reasons. These could be disease related deaths like cancer or other serious diseases, administration to critical and terminally ill patients, side-effects or other unrelated causes. Such deaths are investigated for causal relationship to the study trial.”
The year 2010 witnessed as many as 22 cases of trial-related deaths. In April, the DCGI sent a directive to sponsors/clinical research organizations (CROs) involved in the clinical trials of 2010 to compensate the families and dependents of the deceased. Sources confirmed that the Ethics Committees were also asked to look into the above death cases and suggest compensatory payment.
Sources reveal, “It is proposed to further strengthen the regulations relating to clinical trials by making specific provisions under the Drugs and Cosmetics Rules for providing financial compensation to trial subjects in case of trial related injury or death. The responsibilities of Ethics Committee, Sponsor & Investigator are also proposed to be enhanced to ensure that financial compensation as well as medical care are provided to trial subjects who suffer trial related injuries or deaths. The format for obtaining informed consent of trial subjects is also proposed to be amended to include the details of address, occupation, annual income of the subject so as to have information regarding socio-economic status of trial subjects.”
The list generated by the authorities feature 161 clinical trial related deaths between January and June this year. The death figures for 2010 and 2009 are 668 and 637, respectively.
The 161 trial related deaths were reported by 35 sponsors/CROs including Amgen, Bayer, Bharat Serums, Boehringer Ingelheim, Catayst, CD Pharma, Dr Reddy’s, Excel Life Science, Frensenius Kabi, GSK, Icon, Inc GVK Bio, Invida, J & J, Jubilant Clinsys, Lambda Therapeutic, LG Life Sciences, Manipal Acunova, Max Neeman, Merck Specialties, MSD, NIMR of New Delhi, Novartis, Parexel, Pfier, Piramal Life Sciences, PPD, Quintiles, Sanofi Aventis, SIRO Clinpharma Pvt Ltd, Spectrum, Sristek of Hyderabad, St. John National Academy of Health Sciences, Sun Pharma and the George Institute. As per the official list with health ministry, 44 companies reported 668 cases in 2010, while 50 companies were involved in such cases during 2009.

The compensation provided for 22-trial related deaths is a follows:
Sr. No Sponsor/CRO’s Investigational Product (IP) Compensation
1 Merck Safinamide Rs. 1,50,000/-
2 Wyeth Temsirolimus Rs. 1,50,000/-
3 Quintiles MLN0002/Placebo Rs. 3,00,000/-
4 Quintiles BI 1744/Trial Procedure Rs. 3,00,000/-
5 Lilly H3E-MC-JMHR Rs. 1,08,000/-
6 Lilly H3E-EW-S124 Rs. 2,00,000/-
7 Lilly Pemetrexed Rs. 2,00,000/-
8 Bayer Rivaroxaban/ Placebo/Warfarin Rs. 2,50,000/-
9 Bayer Rivaroxaban Rs. 2,50,000/-
10 Bayer Clexane/Placebo Rs. 2,50,000/-
11 Bayer Rivaroxaban Rs. 2,50,000/-
12 Bayer Rivaroxaban Rs. 2,50,000/-
13 Amgen AMG-706 Rs. 1,50,000/-
14 Amgen AMG-479/AMG102 Rs. 1,50,000/-
15 Bristol Myers Brivanibalaninate/ Sorafenib Rs. 2,50,000/-
16 Sanofi Aventis Blind Rs. 1,50,000/-
17 Sanofi Blind Rs. 1,50,000/-
18 Sanofi Blind Rs. 2,00,000/-
19 PPD XL-184/Placebo Rs. 10,00,000/-
20 Pfizer Sitaxsentan/Placebo Rs. 1,50,000/-
21 Pfizer Sitaxentan/Placebo/Sildenafil Rs. 2,25,000/-
22 Pfizer Axitinib Rs. 1,50,000/-

May 5, 2011, Business Standard (India)

Pharma majors under fire over trial compensation

A Union health ministry probe has revealed that pharmaceutical majors conducting clinical trials in India have not given compensation to majority of the volunteers who died during the trials. Of the 671 deaths that were reported in 2010, the ministry has evidence of just three cases of compensation.

The ministry has asked 44 pharmaceutical companies, including global drug majors such as Eli Lilly, Novartis, Pfizer, Bayer, Merck, Johnson & Johnson and Sanofi Aventis, to explain why they have not given the compensation, which is mandatory under the current drug laws.

A Novartis spokesperson said the clinical trial investigator (who conducted the trial for Novartis) had asserted the deaths were not because of the study medication but due to progression of underlying disease (which won’t necessitate compensation). Similar arguments were made by most pharmaceutical firms that figured in the list. The data compiled by the ministry show there were 152 deaths reported during Sanofi Aventis’ clinical trials, while in the case of Bayer, the number stood at 138.
The probe, carried out by the ministry under the instructions of a parliamentary panel — Committee on Government Assurances headed by Bharatiya Janata Party MP Maneka Gandhi — also revealed that 88 per cent of the deaths pertained to diseases of cancer and cardiovascular and cerebrovascular disorders.
In a submission to the committee, ministry officials said that except in 26 cases, all other deaths seemed to have occurred due to the advanced stage of illness the clinical trial volunteers were in.
Eli Lilly, Amgen, Bayer, Bristol Squib Myers, Boehringer, Quintiles, Sanofi Aventis and Pfizer are among the companies whose clinical trials figure in this list of 26 cases.
The argument, however, has not gone well with the committee. “Of the 671 deaths they (ministry) have mentioned, 26 are directly related to the administration of the experimental medicine. But they are not sure about the other cases as they use terms like ‘could be’ and ‘may be’, instead of outright rejection. They need to be more specific,” said Maneka Gandhi.
Gandhi said the committee was compelled to seek such information as the ministry did not have any records on the number of deaths and the socio-economic status of the clinical trial subjects who died.
According to Gandhi, the increasing number of clinical trial deaths — 137 deaths registered in 2007, 288 in 2008 and 637 in 2009 — is turning regulatory monitoring increasingly important.
The number of clinical trials going on in India is not more than 1,500, a meagre number as compared to over 100,000 trials that are happening across the world.
The number of trials happening in the US in a year is about 52,000. However, there is no country-specific data on the number of deaths in such trials.
“I am almost sure that other countries do not have this data. This is because there is no centralised body that collects this type of data in those ministries. Clinical trials in those countries (mainly developed) are a more decentralised affair with regulation at regional/local level being sufficient to ensure protection of subjects in such trials,” a World Health Organization (WHO) official said.
Experts, however, feel that identificaiton of actual clinical trial victims and compensating them is a universal practice and needs to be followed in India as well.
“There cannot be a comparison based on deaths as deaths during clinical trials can happen due to various reasons. But what excuse can one give when it comes to compensation? While every clinical trial volunteer is entitled to compensation in case of a severe adverse reaction, is it the same here? In India, it is zero,” said C M Gulhati, a Delhi-based medical expert.
McKinsey estimates that the clinical trials industry in India will touch Rs 5,000 crore by 2011. Joe C Mathew / New Delhi

December 07, 2010, Business Standard

R&D firms should compensate clinical trial injuries: DCGI

Contract research organisations (CROs) undertaking clinical trials of drugs on behalf of their multinational pharmaceutical clients will not be able to pass on the blame of trial-related injuries to their foreign sponsors in future.
The Drugs Controller General of India (DCGI), the apex drug regulator, has included a new clause in the trial approval letters, making these firms also accountable for any possible adverse event. Till now, it was the sponsor’s responsibility to pay compensation to the clinical trial subjects.
The development is part of a series of measures undertaken by DCGI to strengthen regulatory monitoring of clinical trials in the country.
According to sources, DCGI now insists that the clinical trial applicant takes care of all trial-related injuries and medical treatments as a prerequisite to receive an approval letter.
The drug regulator also plans to insert further instructions which mandate an undertaking from the sponsor company that the medicine — once developed using the Indian trial data — will have to be marketed in the country for the approved trial indications.
The freedom to add more conditions in the approval letter allows the regulator to tighten the scope of its power beyond what has been implicitly stated under current drug laws.
A senior health ministry official said the Central Drugs Authority Bill, pending with Parliament, would improve clinical trial regulations in the country.
During April 2009-March 2010, DCGI granted 237 permissions for global clinical trials in the country.
Pharma majors such as GlaxoSmithKline, Johnson & Johnson, Sanofi Aventis , MSD, Eli Lilly, Novartis, Bristol Myers Sqibb, Bayer Healthcare, Astra Zeneca and Pfizer and CROs like Quintiles, ICON, GVK BIO Siro Clinpharm, Parexel, PRA International PPD, Covance, Omnicare and Kendle are among the leading international clinical trial applicants in India.
Regulation of clinical trials becomes important as cases of deaths among patient groups undergoing drug under trials are not uncommon.
According to official records, 462 deaths of clinical trial subjects were reported during the year (till June 2010). The number of deaths were 637 in 2009, 288 in 2008 and 132 in 2007.
Since such deaths could be related to diseases like cancer or administration to critical or terminally ill patients or side effects of unrelated cause, strict regulatory vigil is essential. Joe C Mathew / New Delhi