Poor healthcare for its millions makes India a favourite hunting ground for global pharma giants seeking living human bodies to try out their untested drugs. Is there an ethical way out?
Nimisha Jaiswal Delhi

Despite their own woeful lack of access to the most elementary in healthcare, Indians provide the global multibillion pharmaceutical industry with its most preferred 'human labs' for carrying out drug trials. Such tests are necessary to establish the efficacy and possible side-effects of new medicines before they can become part of the pharmacopoeia. Obviously the person whose body is made the site of such pharmaceutical experiments has to bear the drug's unexplored consequences.

So how did India come forward on the world stage as a favourite host for these trials? The answers are not hard to come by, and are not only about 'value-neutral' requirements of the scientific method - for instance, the need to test a drug on a different gene pool, so that it does not cater solely to patients in the West. Indeed, the sheer low cost - a drug trial is 60-80 per cent cheaper in India than in other countries - seems to be a major factor. 

Moreover, poor access to healthcare makes millions of Indian citizens extremely attractive to companies seeking 'medically naive' patients, in whom the lack of any prior treatment makes it easier to isolate the effects of the trial drug. India also provides the largest 'disease pool', comprising every variety of every conceivable disease. 

Ethical concerns surrounding drug trials include the question of 'informed participation'. An informed participant understands the consent form and the implications of participation, the experimental nature and stage of licensure of the drug, the alternative treatments available, and the fact that participation is a matter entirely of choice. In India, however, it is a sense of desperation from the lack of affordable healthcare that often drives the impoverished participants of drug trials, for whom any 'treatment' is often seen as better than no treatment. 

Illiteracy ensures that in the face of complicated consent forms, which may abide by the letter of the law but are difficult for a patient to comprehend, most end up being a lot less questioning than their counterparts abroad, and easier to convince. "Poor and illiterate patients can be easily recruited, and they may not even know they are participating in clinical trials. For example, a trial called TIDE (on Rosiglitazone) was moved to India when patients in the US refused to participate," says Dr Chandra M Gulhati, Editor, Monthly Index of Medical Specialties.

However, this does not mean there are no rules and guidelines in India concerning the ethics of drug trials and the rights of participants. There is Schedule Y of the Drugs and Cosmetics Act, 1940 (DCA), and a 100-page Indian Council of Medical Research (ICMR) document titled 'Ethical guidelines for bio-medical research on human participants' elucidates the rules and protocols regarding trials. Also, the recent setting-up of the Clinical Trials Registry-India (CTRI), which makes the registry of every drug trial mandatory, is being applauded as a significant step forward even by critics of the existing regulations. This is expected to improve accountability and access to information.

Although rules and regulations exist, questions have always been raised about how seriously they are adhered to. The 'HPV Demonstration' projects in Andhra Pradesh and Gujarat, conducted by PATH, a US-based NGO, in collaboration with ICMR and the state governments, have brought to light significant flaws in the system. Using GlaxoSmithKline's Cervarix vaccine and Merck's Gardasil vaccine, these projects were termed 'post-licensure observation studies', and thereby kept out of the purview of trial regulations by law, despite clearly being Phase 4 trials - the final phase of a clinical drug trial, post-licensure. 

SAMA, a resource group on women and health, questioned the project on multiple grounds, especially the rationale behind choosing only the remotest districts. There were alarming reports that the Integrated Tribal Development Authority (ITDA) allowed wardens and headmistresses to give consent on behalf of children studying in its schools in adivasi areas, instead of the parents. The consent forms lacked adequate information, with little detail on the side-effects and the alternatives available. The absolute lack of transparency and the vague nature of nomenclature was questioned through several Right to Information (RTI) applications, and in various memorandums and public meetings, but the Drug Controller General of India (DCGI) simply hid behind Section 81D of the RTI Act, citing 'classified information as trade secrets'.

Anjali, a member of SAMA, points out the lack of infrastructure for cervical cancer screening or follow-up in our public health system. The two vaccines do not, in fact, cover cent per cent of the cervical cancer strains, and their long-term efficacy remains unproven, she adds. The girls participating in the projects, however, were given an illusion of complete safety from cervical cancer.  

Insisting that the picture is not all that starkly dark, Mahesh Gupta (name changed to protect anonymity), a senior surgeon who has conducted a drug trial in NCR, refers to the extensively detailed information brochure that the pharmaceutical company had provided him, mentioning all the known side-effects and the requirements of the trial. Even the consent form that was shown to this reporter provided great detail in simple English and Hindi. The optional nature of participation and the provision that the participant could opt out of the trial at any point were clearly stated right at the beginning and repeated further down the form, which also listed the possible side-effects and alternative treatment options. The participants could also consult the doctors and other staff at the trial site.

However, a trial cannot be validated simply on the basis of a well-written consent form. "In the end, what remains most important is good faith," avers Gupta, speaking about the common instance of his patients asking for his opinion regarding the trial. While Gupta makes it clear to them that his job is only to provide all the necessary information and the final decision must be their own, not every doctor necessarily does so. There is no mechanism in place for recording consent meetings, nor is there any way to assure that patients read the consent forms thoroughly.

"Truly, money is the most important factor", agrees Gupta, stating that extraordinary amounts of funds are invested by pharmaceutical companies even in the preliminary trial phases. 

As post-trial follow-up is not mandatory, sponsors are not required to continue providing patients a drug found to be useful (but unaffordable), or to deal with withdrawal symptoms and delayed adverse effects on their general health. "One of the basic principles of the Helsinki Declaration (widely regarded as the cornerstone document of human research ethics) is that the interests of subjects must not be subjugated to those of the society at large," stresses Dr Gulhati. "If long-term follow-up does not take place, the very purpose of clinical trials is lost because monitoring of adverse effects is one of their basic functions." However, what is best for the patients, and for the test, is often a casualty to the kind of big money involved.

So must drug trials be stopped? "We do not oppose all drug trials, but we must prioritise on the kind of clinical trials that are carried out," says Anjali. While lifestyle diseases have a myriad trials to their name, not much is being done to address rampant communicable diseases like tuberculosis, kala-azar and malaria that kill Indians in huge numbers every year. There is, therefore, a need to give top priority to improving India's public health system before it can cope with drug trials and enable them to be conducted ethically. According to Dr Gulhati, the government should demand a "global fund to develop new remedies", so that patent-free drugs can be developed and produced cheaply, and made universally available. 

"Above all," says Anjali, "while using marginalised populations, your ethics need to be extra stringent so they are not marginalised further." It is only when mechanisms are in place to ensure that trials are handled ethically, and participants are not merely used as guinea pigs, that clinical trials would help provide better healthcare not only to future beneficiaries, but to the participants as well.

This story is from the print issue of Hardnews: JUNE 2011