88 clinical trial volunteers died in 4 years due to direct side effects: Health ministry data
At least 1,100 people who took part in clinical trials over the past four years have died, and 88 of these deaths were caused by direct side effects of the trials, the health ministry told the Rajya Sabha last week.
But, with little transparency on how such deaths are investigated, and new rules relaxing how clinical trials are conducted in India, this data could be a poor estimate, said experts.
Clinical trials are done to test safety and effects of new drugs, dosages and ways of administration to help improve public health.
According to government data, there has been a steady rise in the number of people registering for trials in the Clinical Trials Registry of India (CTRI) — an online public record system. The health ministry said there were 859 registered trials in 2015, 873 in 2016, 2,516 in 2017 and 3,869 in 2018 (till November). While there are more volunteers, those being compensated for their participation has reduced, suggests independent information from the Central Drugs Standard Control Organisation (CDSCO) [see box]. CDSCO reported 381 deaths of volunteers in 2015, 378 in 2016, 345 in 2017 and 339 in 2018.
And, of these deaths, 18 were directly linked to trials in 2015, 27 in 2016, 30 in 2017 and 13 in 2018, CDSCO’s ethics committee said.
When it came to compensation, only in 2015 did families of all 18 participants receive compensation. The following year, 25 of 27 were compensated; it fell to 18 of 30 deaths in 2017, and to one of the 13 deaths in 2018.
Experts said ambiguity over how the compensation mechanism works could be one reason.
“It is sad that such important data is not available in the public domain but has to be accessed through a parliamentary process,” said Malini Aisola, the convener of the All India Drugs Action Network (AIDAN), an NGO.“According to law, patients or families of patients taking part in clinical trials must get a minimum compensation of Rs 8 lakh. But in the case of the only reported death of 2018, the family was given just Rs 4.87 lakh, according to the ministry’s own data,” Aisola said.
Experts said new, relaxed rules, which came into effect in February 2018, have paved the way not only for poorer regulation of how clinical trials are conducted, but also gave room for more corruption in the process. “The New Drugs and Clinical Trials Rules don’t have any specific guidelines on how volunteers are selected,” said Shelley Saha, a member of the Swasthya Adhikar Manch, an NGO that had filed a public interest litigation in the Supreme Court in 2012 over the lack of transparency in medical trials and compensation. “The only requirements seem to be that volunteers are ‘healthy’ or are ‘patients with a target disease’. There are no guidelines about selecting them, which means there are several cases of volunteers being lured from poorer, rural areas with the promise of free drugs, therapies and even jobs,” Saha said. Saha pointed out that how the Clinical Trials Registry of India’s website — where trial processes, status and results of clinical trials should be updated, has no real-time information.
“Most of the available data doesn’t reveal basic details such as sample size of the study, whether or not studies were successful, or even if the drugs have been made available to the public or stopped after the study was done,” Saha said. Further, under the new rules, clauses such as restricting one investigator to three trials, compulsory audiovisual reporting and only allowing hospitals with at least 50 beds to conduct trials have been lifted. “While this has increased the number of trials, it has also seriously hampered quality control measures,” Saha said.
In many cases, volunteers are enlisted without their consent, and with doctors not informing them of the side effects or drawing up a formal contract. One such case was that of a 63-year-old woman, whose son discovered that her doctor had started her off on trial medicines without asking her. In 2012, the son, Dattatray Taras, a Pune resident, took the help of Swasthya Adhikar Manch to file a complaint with the health ministry. Taras said a local doctor gave his mother a medicine not prescribed to her, but promised it would cure her thyroid condition. “When I checked the strip, I found a label saying it was a sample for a clinical trial,” said Taras, adding that he confronted the doctor, who told him the trial had been concluded. “I then checked Clinical Trials Registry of India website and found the trial was still going on and side effects included cramps, nausea, abdominal pain and other health complications,” Taras said. While the ministry acknowledged his complaint, there has been no progress in the case so far.
The Indian Pharmaceutical Association, which represents the clinical trials industry, maintains that number of deaths from trials is unlikely to be high, but added they were working on making clinical trials more transparent.
Dr Subhash Mandal, vice president and chairman, Regulatory Affairs Division, Indian Pharmaceutical Association, said, “Since the introduction of the New Drugs and Clinical trials Rules, 2018, in February last year, there have been several introductions and universal guidelines in terms of compensation payment and functioning of ethical committees. However, the number of deaths are unlikely to be high, we as the industry representative, are striving to bring in more transparency in clinical trials and increase quality control measures of the system.”
The government maintains that few of the deaths were directly linked to the trials. “The side effects, or Serious Adverse Events (SAEs), after clinical trials may or may not be related to the trial itself,” Ashwini Kumar Chaubey, minister of state, health and family welfare said. “SAEs, including deaths, injuries, or disabilities after clinical trials may occur due to various reasons such as existing life-threatening diseases, cancer, cardiovascular diseases or side effects of investigational products in the volunteers.” he said.