Why clinical trials evoke suspicion

It is not difficult to see why drug trials on mentally ill patients or the use of cervical-cancer vaccines on tribal girls evokes strong reactions. This is precisely the picture that healthcare workers warn us about, a potentially exploitative situation for vulnerable and marginal people.

But a Government panel investigating the cervical-cancer vaccine trial on tribal girls in Andhra Pradesh and Gujarat had given it an “all clear”. The tribal girls were part of a larger trial that included urban and rural girls, we were told. The niggling questions, though, remain. Was consent taken from the girls, or was it a guardian or a caretaker who gave permission for the girls to participate in the trial?

FUZZY RULES

Question marks arise over the trial of dapoxetine (to treat premature ejaculation) on mentally ill patients. In a written reply to Parliament, Union Health Minister Ghulam Nabi Azad said that psychiatrists at Indore’s Mahatma Gandhi Medical College had enrolled subjects “as per inclusion and exclusion criteria of approved protocol” and the patients were mentally sound.

The Drugs and Cosmetics Act and Rules do not prohibit clinical trials on mentally ill patients, but informed consent needs to be obtained from a legally acceptable representative of the patient, he added.

The classic sitting-on-the-fence reply does not call right from wrong. Why were mentally ill patients part of the study, and not those with all faculties intact? Was it part of a larger study? Or, since psychiatrists prescribe the particular drug, did they naturally enrol people who come to a psychiatrist? In which case, the patient may not be “mentally ill” as commonly understood (meaning not in control of their mental faculties)?

This is the fate of clinical trials in the country. Despite clarifications from the Government, there remains that disconcerting feeling. As a result, discussions on clinical trials in the country do not get too far, without the word “guinea pig” cropping up close on its heels.

An opaque shroud overhangs clinical trials. And though trials are registered in the country, the information tap runs dry in the case of an adverse event linked to the trial, directly or otherwise.

The clinical trial industry, though, loves to shoot the messenger, blaming the media for reporting incidents that go awry. But the media is the least of its worries. Good science and medicine are being sacrificed at the altar of mistrust, because the industry and the Government’s regulatory framework are not transparent. To put the confidence back into the system, both sides need to work harder to protect the patient or volunteer participating in the trial, at all costs. Clinical trials involve testing of medicines or medical devices on human volunteers in various stages to check the safety and efficacy of the medicine before it is sold in the market. Countries participate in trials to tailor medicines to local needs, to bring in new and critical drugs, and to give local doctors exposure to global practices.

But health-workers observe that clinical trials done locally for foreign companies do not benefit local people. The local researcher merely carries out instructions from the foreign company, and the intellectual property and data remain with the company after the trial.

A clear regulatory framework is needed to ensure clean science, benefits to the local people, and protection and compensation of the patient/volunteer in the trial, since they are not paid. In fact, a regulatory authority is needed to watch over clinical trials, publicise good trials and investigate and nail the bad ones.

But the Government’s track record here is not satisfactory. A Bill to protect human volunteers in a drug trial — the Biomedical Research on Human Participants (Promotion and Regulation) Bill — is pending for close to eight years. It has seen several draft versions, at least four health ministers and the bureaucrats who have worked on it are now retired!

Rules need to be outlined with clarity, and they should not be compromised depending on who does the trial — a profit or not-for profit organisation, a private or government institution, observes Dr Mohan Das Mallath, with Tata Memorial Cancer Hospital.

Globally, too, drug trials operate in an atmosphere of heightened sensitivity. Prior to exposing humans to new drugs, medicines are tested on animals — rats, monkeys, dogs and so on, to test for toxicity. This practice, too, is under severe scrutiny with progressive groups urging international law-makers, the industry and universities to base their science on modern, alternative and humane technologies rather than use animals. This being the levels of ethical behaviour demanded of the industry, there is a compelling need for great levels of transparency and accountability.

COMPENSATION ISSUES

Confidence further slips between the cracks, when there is an adverse event or death linked to a trial. The familiar cloud of opacity descends. Was the death caused by the medicine trial, the illness or an accident not related to the trial? Could the death have occurred even if the patient was not on the drug? For instance, patients in advanced stages of cancer participate in a trial because no other medicine may help. So death here may not be linked to the trial.

Of the 1,144 deaths during clinical trials in 2010 and 2011, a large number was attributed by Government to cancer and other terminal illnesses, besides adverse events linked to trials, say media reports.

And when it comes to compensation, there is a tendency to remain tight-fisted, when in fact, trial sponsors should loosen their purse strings and compensate more than promised. A little goodwill goes a long way in bridging the gap of mistrust. Yet while such a demand can be made of wealthy sponsors or drug companies, it could inhibit research by smaller academic institutions. And here, the Government needs to outline methods to support academic researchers, while protecting the patient in the trial. Complicated compensation formulas, currently being discussed, will not help. Credible science and medicine can only be developed on ethical practices, for man or animal.

Projected to touch $1.5 billion by 2010, clinical trials now struggle at $400 million. The prevailing uncertainty has caused India to lose out to destinations such as South Korea, Malaysia and China. Drug trials in India, at 500 in 2010, have almost halved in 2011. Fewer trials are cleared today, despite the regulator’s office being better equipped, observes Dr Arun Bhatt with ClinInvent, pointing to eroding confidence at several levels.

Accrediting doctors, medical institutions and ethical committees involved in clinical trials can put trust back in trials. And a clear policy for the industry, with a non-negotiable stance on patient safety, will help the country shed its fear of becoming a “guinea pig” in research.

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