Indian patients lose out to clinical trial rulebook

Aspirin is one of world’s most popped pills, the answer to maladies ranging from simple aches and pains or even a mild fever.

Aspirin is one of world’s most popped pills and is the answer to maladies ranging from simple aches and pains to even a mild fever.

However, this drug may soon be prescribed for a far more severe condition if initial observational studies are validated. Cancer Research UK is funding a 12-year global trial to study the effects of aspirin in cancer patients. Initial results show that aspirin has tumor-reducing properties.

The agency approached Mumbai’s Tata Memorial Hospital in 2013 to enrol Indian patients in the study. The 10,000 patients, almost Rs 100 crore-study was supposed to incur Rs 15 crore in its Indian leg.  All that the trial subjects have to do is to take aspirin for five years after treatment with cancer therapies.

However, it’s possible the tests may not be conducted because of regulatory issues relating to clinical trials

“It is a new cancer drug for the DCGI and will need to be cleared by the regulator. Basically, the study is a non-starter,” says Dr C S Pramesh, an oncologist with Tata Memorial Centre in Mumbai.

“Think of the cost of aspirin, think of what potential it has to transform lives even if there is a 5% improvement in survival rates,” said Pramesh. “The cost of aspirin is peanuts and we would have the ability to improve outcomes in survival in large number of cancers immensely.”

In January 2012, Swasthya Adhikar Manch filed a public interest litigation (PIL) in the Supreme Court alleging illegal conduct of clinical trials in the country and sought the creation of an expert committee for overlooking the process.

The NGO cited government data saying that from January 2005 to December 2013, there were 17,778 cases of adverse events from clinical trials including 3458 deaths. “These are the numbers reported by the companies and investigators,” Nidhi adds. “The actual ones may be far more.” Of the above numbers, 89 deaths and 506 serious adverse events have been stated to be related to clinical trials, according to documents. Two cases amongst the 89 deaths have been paid compensation till May 2014.

Since then, the apex court has passed three major orders on the conduct of clinical trials. The DCGI also amended regulations significantly, but the changes have irked industry and academia.

One amendment made is that any health issue that arises during a clinical trial must be compensated by the company regardless of whether it is connected to the drug. Amulya Nidhi, co-convenor of NGO Swasthya Adhikar Manch points out it is difficult to connect a health problem to the clinical trial as the very nature of the product is experimental.

Suneela Thatte, president of Indian Society of Clinical Research (ISCR), said that if the compensation rules are so open that when “anything and everything” that happens to a patient becomes a responsibility of the sponsor, “it instantly kills academic research, because no academician can afford to do research in such kind of setting.”

“Suppose I get on for a skin infection on a clinical trial for a skin ointment and I suffer a heart attack, the cost of treating it along with the bypass needs to be borne by the investigator,”  said Pramesh.

Nidhi brushes aside this contention saying that it is difficult to connect a health problem to the clinical trial as the very nature of the product is experimental.

Other issues which are proving difficult to deal with include the mandatory audio-visual consent from trial subjects–which investigators say is difficult to obtain if the disease involved is a societal stigma. Besides, capping the number of trials per investigator to three ,which will result in cherry-picking of trials which have the maximum grant, could also be an issue as could the uncertain timelines of regulatory approval which deters companies from committing funds.

Despite the change in rules, the case has been languishing in the apex court for more than two years now and the uncertainty in laying down final rules, controversial or not, is resulting in Indians losing out on potentially life-saving therapies.

In 2009, London-based drugmaker AstraZeneca Plc conducted pan-Asia trials of its experimental cancer drug, gefitinib. The drug did not show the expected results in the previous trials, according to Pramesh. In the Asia leg of trial, however, a genetic deviation made all the difference.

“Dramatic complete and partial remissions (Lazarus responses) have been documented in patients with lung adenocarinoma having multiple brain, lung and bone metastases (secondary cancerous growths) on gefitinib, including one such report in an 84-year-old female,” a excerpt from the Journal of Cancer Research and Therapeutics, dated September 2010, said.

“It was found to be a really good drug which has now completely changed the way we look at lung cancer,” said Pramesh. “So the first-line treatment for lung cancer is now this drug which we would have lost, had it been researched in today’s environment.”

“An absolutely promising drug, something which would have been a boon for a lot of our patients finally at the end of their options could have been completely unavailable because we lack the trials to support it,” he adds.

Another example cited over the past year is French drug major Sanofi’s experimental dengue vaccine which had studies in almost every Asian country, except India, due to the current regulatory environment. India records nearly 60 lakh of diagnosed dengue cases every year, according to a study conducted by US-based Brandeis University.

Today, India hosts less than 1.5% of global clinical trials, according to ISCR. So of out of 1,80,649 studies conducted in 178 countries, 2,563 studies reach Indian shores. The National Institute of Health, an agency of the U.S. Department of Health & Human Services, has pulled out 40 clinical trials from India, according to Pramesh.

“The crux of the litigation was improving the existing rules and regulations and enforcing them well. Clearly there has been a sea change in the rules and regulations since the Supreme Court’s first intervention,” Sameer Sah, principal associate of law firm Khaitan & Co, said.

He said that as a lot of operational aspects are still being finalised, there may still be room for improvement.

“While it is difficult to predict the path ahead, it is less likely that the Supreme Court will pass a lot of major orders leading to further regulatory changes,” Sah added. “One would expect some orders in cases where compensation was not given in the past but for future matters, unless some major defect is pointed out in the regulations, I don’t really think the Apex Court is going to be making far reaching pronouncements.”

The next hearing for the PIL is scheduled in early-2015.

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