Trial Errors

In March 2010, Ajay Naik’s day-old son, Yathartha, was due to get vaccinated at Chacha Nehru Bal Chikitsalaya in Indore. However, instead of the conventional polio and BCG shots, Naik’s son is alleged to have been inoculated with vaccines undergoing clinical trials. Naik, a daily-wage labourer, says that his wife had been asked to sign some papers without any explanation, and that he was not aware of what was going on.

Soon, white spots began appearing all over the infant’s body. The parents believe they were caused by the experimental vaccine. “No parent would allow a clinical trial on their newborn, not for all the money in the world,” declares Naik.

Eventually, the boy, who is now three, recovered. However, the family did not receive any compensation and had to bear the financial burden of his treatment.

Dr Hemant Jain conducted the trial on Naik’s son. According to a June 2011 report on clinical trials by Madhya Pradesh’s Economic Offences Wing, he conducted many such trials between 2006 and 2010, and received Rs 1.7 crore for his trouble. When Business Line contacted Jain, he said Naik’s claims were a hoax, but declined to elaborate.

Three years ago, a similar story played out in the national capital, but with a tragic ending. Manoj Vasisht was admitted to a hospital in West Delhi with a severe case of jaundice. His wife, Veena, says that the doctors took the family’s consent to try out a new treatment. “Would you argue with the doctor if he asks you to sign something claiming it would benefit your husband,” she asks. The treatment did not work and her husband died. Business Line was unable to ascertain if the drugs were administered as a last, life-saving attempt or as an experiment.

“They are rich people. He is gone, I have to feed a family,” says Veena, adding that she does not wish to fight for compensation, as it is beyond her means. The widow, who is in her mid-30s, works as a housemaid to make ends meet.

The death of Veena’s husband is not an isolated case. An affidavit filed by the Central Government before the court contains some damning numbers. It states that 2,644 people died during trials of 475 drugs between 2005 and 2012 “…of which 80 deaths were found to be attributable to the clinical trials”. It goes on to add: “Around 11,972 serious adverse events (excluding death) were reported during the period from January 1, 2005 to June 30, 2012, out of which 506 events were found to be related to clinical trials.”

Activists claim that the number of lives lost is far higher. They allege that pharmaceutical firms have been carrying out large-scale drug trials across the country, using Indians as guinea pigs, often with fatal consequences for the patient.

Indeed, the report by Madhya Pradesh’s Economic Offences Wing states that six doctors in Indore alone had unethically recruited about 3,307 patients for trials between 2006 and 2010. Of these, at least 81 people suffered “serious adverse events/deaths”, including 18 children. None of these deaths were disclosed by the Ethics Committee. No autopsy was conducted on any of the victims. And none of the victims received any compensation.

High Stakes

Drug trials are, or until recently were, a booming business, particularly for contract research organisations (CRO), hospitals, and apparently, some doctors. CROs conduct research on behalf of drug developing companies.

At stake is a business that research firm Frost and Sullivan estimates to be worth about $500 million currently. By 2016, that number is slated to cross $1 billion.

Over 100 companies conduct clinical trials in India, including top multinationals such as Pfizer and GlaxoSmithKline, Indian companies such as Dr Reddy’s and Lupin, as well as CROs such as Quintiles and Clinigene. In all, the industry employs about 15,000 people.

While it is accused of cutting corners, the clinical research community says that unethical practices are not the norm.

“The majority of adverse events in clinical trials are manifestations of the disease the patient is suffering from. Some may be totally unrelated or due to concomitant illnesses,” says Dr Shoibal Mukherjee, Clinical Pharmacologist and Head, Asia Medical Sciences Group, Quintiles.

A growing number of people believe otherwise. Astha (name changed on request), a paediatrician in a Government hospital in Delhi, is one of them. “I have seen senior doctors ask seriously ill patients to register the names of their children for new medicines,” she says. “The patients are mostly illiterate; they don’t know what they are signing. All that is required is a thumb impression or signature on the consent form. How difficult is it to get that from a patient who has implicit trust in you?”

It may not be fair to tar the entire industry with the same brush. A clinical research professional says that drug developers will not knowingly spend vast amounts of money on a molecule or drug that will cause harm and has little chance of success. Apart from the reputation loss, it is financially unviable.

Clinical trials are governed by regulations in the Drugs and Cosmetics Act. These regulations are considered soft since they are not binding.

As allegations of malpractices piled up, a PIL was filed against such trials in the Supreme Court. The Court has ruled that no new clinical trials would be allowed till a mechanism is in place to monitor them and safeguard lives. Stung into action, the Centre said it would not allow clinical trials for 162 drugs permitted by it earlier.

Things have come full circle for the industry.

Early days

Clinical trials took on real potential in India after it joined the World Trade Organization (WTO) in 1995. Suddenly, the country, which had until then charted its own course on patents, held strong possibilities as a destination for drug trials; WTO signatories have to protect product patents.

In addition, India had a huge, medically under-served population, as well as competent and cheap medical and research staff. The clincher, of course, was the promise of conducting trials at a lower cost — at less than half the amount spent in developed countries. Estimates suggest that in the US, clinical trials for one drug can cost $300-600 million.

However, it was only after India became fully compliant with the product patent regime, in 2005, that the industry really took off.

That year, another important amendment was made to the Drugs and Cosmetics Act. After completion of Phase I (see: How it happens ) of a drug at a foreign site, companies could submit the data to the Drug Controller General of India (DCGI), the drug regulator. The DCGI could give permission either for a repeat of the Phase I trials in India or commencement of Phase II trials in conjunction with the same trials at other sites. The data generated could then be used by the companies in their patent applications abroad.

These changes made India an attractive destination for clinical research.

However, there were infirmities in the law. Activists say it lacked the bite to protect patients against exploitation and ensure adequate compensation.

Moreover, the Central Drugs Standards Control Organisation (CDSCO), which oversees clinical research and is headed by the DCGI, was unable to deal with the sudden rise in such studies, says Amit Sengupta, Associate Coordinator, People’s Health Movement. CDSCO is responsible not only for permitting and monitoring clinical trials, but also for drug safety and approving manufacture/import of new medicines, among other things.

The regulator is itself short of manpower, making proper monitoring of drug trials difficult.

“The current manpower of six Deputy Drugs Controllers (DCs) and 18 Assistant Drugs Controllers (ADCs), assisted by 75 drug inspectors and 55 technical data associates on contractual basis is far short of the actual manpower requirement proposed by the Hathi Committee in 1975 and the Mashelkar Committee in 2003,” says a report by the Ranjit Roy Chaudhary Expert Committee, set up to formulate policy and guidelines for approval of new drugs, clinical trials and banning of drugs.

“There is a requirement to strengthen manpower. The Government is seriously looking at giving (the body) autonomy,” says G.N. Singh, who heads the DCGI.

Uninformed Consent

Most of the concerns around drug trials revolve around two issues: informed consent and compensation for trial participants who fall ill, are injured or die during trials.

Poor, uneducated patients are said to be the first choice for companies looking to recruit a vast number of patients for trials.

One doctor Business Line spoke to says that since these patients are unaware they are being put on trials, they do not speak out if something untoward happens.

Nitin (name changed), an endocrinologist at a private hospital in Delhi, who was earlier with a Government hospital, says that “free medicines” are a bait used by some doctors. The doctors, he adds, are paid by clinical research organisations to recruit patients and conduct trials.

Asked about consent, Nitin says: “Doctors will tell them that these are new medicines that are not yet available in the market. Almost like it is a privilege. Are they told about all the side-effects? Not necessarily.”

CROs and drug-makers, however, claim that such practices are infrequent.

Time for Transparency

All drug trials are supposed to be supervised by Ethics Committees. Until recently, these committees were not only responsible for monitoring clinical trials but also required to investigate deaths and decide the quantum of any compensation.

Dr Anand Rai, a public health activist who was among those who petitioned the Supreme Court against drug trials, has raised questions about the manner in which these committees function and points at conflicts of interest. The Ethics Committees are set up by the sponsors of clinical trials themselves. Often the principal investigator (the doctor conducting the trial) is part of the committee.

Amulya Nidhi, a health activist with the Swasthya Adhikar Manch and fellow petitioner, concurs with Rai. “The doctors who conduct trials frequently sit on the ethical committees,” he says.

“Everything depends on the honesty of the investigators and the Ethics Committees overseeing the trials,” says Rai. He says that Government data on deaths and injuries during clinical trials is grossly inadequate (just 80 deaths recorded between 2005 and 2012). The DCGI’s office, he adds, does not have its own data. It relies on data compiled by investigators and ethics committees. “The actual figures are much higher.”

The rules have now been changed. The Ethics Committee, investigators and sponsors have to file separate reports on deaths during a trial to a DCGI panel, which will then investigate the same.

Nidhi and Rai want advocates to be present when patients sign consent forms to ensure they understand the content, context and risks of the drug trial. They also want patients being put through trials to be given life-long medical care.

“When all the players in the industry get so many benefits, why are the poorest the only ones that lose, asks Rai.

aesha.datta@thehindu.co.in