By Panduka Karunanayake -
In the recent past, the government has been working on promoting the conduct of global clinical trials in Sri Lanka. In 2010, Treasury Secretary Dr P.B. Jayasundara, addressing the corporate sector at a breakfast meeting, revealed that it hoped to create a clinical trials “industry” to earn US$ 1 billion annually (Ceylon Daily News, Business Section, 9 July 2010) – only global clinical trials ‘imported’ to Sri Lanka, not locally initiated ones, could possibly achieve this. A national steering committee comprising economic, legal, academic and medical experts was convened by him to draft legislation and create regulatory and administrative frameworks for this. Several articles commenting on this have appeared in Sinhala and English newspapers.
The Clinical Trials Act is now ready. But it is not quite clear whether the government will go ahead with it as it is, or whether it will incorporate this in a broader legislation that will cover pharmaceutical products generally.
Global clinical trials
Clinical trials are human experiments conducted on patients or healthy volunteers (who were earlier called ‘study subjects’ and are now called ‘participants’); they seek to determine the safety and efficacy (or otherwise) of pharmaceutical products in specific diseases. They became common in the 1990s, initially as experiments in academic medical centers of industrialized countries. However, they have now lost much of their academic poise and objectivity, and are used to generate the data necessary for pharmaceutical companies to obtain marketing licenses for their products from regulatory authorities, such as the US Food and Drug Administration (FDA). They are now commonly conducted by contract research organizations (CROs), using patients from underdeveloped countries.
Clinical trials have thus gone ‘global,’ because CROs find it easier to conduct them in underdeveloped countries, as this is cheaper or has less ethical encumbrances or legal risks.
CROs are, however, only interested in those countries that provide the necessary regulatory, administrative and political backing that ensure data quality, financial accountability and some social legitimation. Hence, the government’s keenness on the framework.
In fact, even at present a few global clinical trials do take place here, through some local CROs and academics in ‘public-private partnerships.’ The framework is designed to accelerate and expand this and reach out to ‘industrial’ proportions.
Once ready, the framework would make it easier for a foreign pharmaceutical company (known as the sponsor) to outsource one of its clinical trials to a local CRO. The CRO will obtain prior approval for the research protocol designed by the sponsor, and obtain the services of local doctors to carry it out. The doctors will help the CRO to find patients, conduct the trial over a few months and collect the data on safety and efficacy. This data will then be ‘exported’ to the sponsor, who will then obtain its marketing license (provided the product proves to be safe and efficacious), and proceed to sell it in global markets at global prices.
The main beneficiaries of this process are pharmaceutical companies (sponsors), local CROs and doctors. Local hospitals will receive some funds and technology transfer. The Treasury Secretary believes that the process will add US$ 1 billion annually to the national coffers, although how is not clear. (India, which has over 150 FDA-registered CROs conducting over 750 clinical trials, managed to earn US$ 0.2 billion in 2009.)
The participants are given the experimental product or placebo for a few months, and are thereafter left with the legacy of their disease and the effects of the experiment. They cannot seriously be considered beneficiaries.
The proposed Act requires insuring trials against compensation claims – but there is no mechanism to operationalize the claims, and the final arbitration committee is heavily one-sided.
The onus of detecting protocol violation (which can greatly increase the risks that the participants are exposed to) has been placed upon research ethics committees – but there is no provision for their training, capacity building or making them impervious to industrial influence. (For a local example of the last, see “Humans as medical fodder” in The Nation, 12 August 2012.) Some of these tasks are conveniently deflected to the Federation of Ethics Review Committees of Sri Lanka, which has been conducting some training programs and developing procedures, but does not have the mandate or the capacity for anything else.
The Act creates a Board to accredit ethics committees – but there is no mention about the need for its members to avoid conflicts of interest, and even their method of selection is undefined. This accreditation is merely a rubber stamp in the hands of those with cozy relationships with CROs, who will know which research ethics committees are ‘friendly.’
There is only perfunctory mention of conflicts of interest of regulators, experts, trialists, academics, ethics committee members, doctors, businessmen running CROs or academics running public-private partnerships – all of whom, in a small country, perform multiple tasks and come from a small bunch of schoolmates, batchmates, work colleagues and other sorts of ‘jolly good fellows.’
There is evidently an asymmetry in the way power has worked here. All the power has focused on creating the industrial machinery, and the interest of participants has been sidelined. Those who would be at the receiving end – the poor, ignorant patients attending state hospitals seeking free medical care, who would become the participants – have not got the attention they deserved.
In other words, the framework is flawed by unduly focusing on facilitating the benefits of the proposed industry and sidelining its potential human and societal costs.
Clinical trials are different to other forms of scientific experimentation: they take place in society rather than laboratories, utilizing human beings rather than Petri dishes or guinea pigs. The scientific issue is overshadowed by human and societal issues; even excellent scientific robustness can be overridden by ethical misdemeanor, as in the Nazi experiments and theTuskegeeaffair. To have a one-sided approach and leave matters in the hands of doctors and scientists, who are increasingly swayed by industrial interests in today’s economistic world, is to re-invite such disasters.
Clinical trials are forays into the benefits and the risks of the unknown, where the risks are borne entirely by the participants. The only valid reason why they should consent to participate is altruism: the desire to contribute to the advancement of medical scientific knowledge, for the benefit of future patients. Participants should not accede for any other reason, such as fear of reprisals, inducement by the offer of healthcare that they need but do not have, or a feeling of obligation towards their doctors. To ensure this, a robust research ethics environment and public awareness are necessary.
Even in the US, where robust ethics mechanisms have existed since the 1980s, empirical evidence shows that all such safeguards are sometimes not enough. For instance, Americans without health insurance (hence without access to healthcare) are seven times more likely to be participants than those with health insurance: subjecting oneself to a human experiment has become a method for Americans without healthcare access to gain such access. Most studies show that participants decide on whether or not to participate before reading the informed consent form, and that these forms have little impact on their decision. InIndia, only 11% of participants gave their reason for participation as helping science, while 41% said it was to obtain free, “better” or “high quality” healthcare, 38% to obtain “cure” or “observed benefits” (which shows that they had misconceived the nature of the experiment), 15% because of doctor’s advice, and 5% for the money. It is the distribution of life chances in society – not personal choice – that determines who become participants and who do not.
It is folly to equate ethics to approving research protocols and signing consent forms – and this is very much where things are right now in our country. It is also folly to assume that doctors will not abuse their power in the future merely because they haven’t yet abused it – the inducements of global clinical trials, which can be considerable, haven’t yet come their way.
We need two significant changes. First, research ethics committees, which are supposed to be the watchdogs of the rights of participants, must be strengthened to have the independence, capacity and funding to evaluate trial protocols properly, monitor them for compliance with the approved protocols and take effective remedial action where necessary. Although medical and scientific experts are needed in such committees (to assess protocols for risk-benefit analysis, scientific validity and trialists’ professional competence), the prominent role must be played by its other members.
At present our committees do not have all these features, and they are not likely to have them any time soon in the ordinary course of events.
Secondly, public awareness about clinical trials must be improved. The average patient attending a state hospital should be at least minimally aware of the implications of becoming a participant.
If global clinical trials are to take place here painlessly – especially on an ‘industrial’ scale – we must take care to institute these two changes.
A legal authority
The most disconcerting point in the whole process is the asymmetrical operation of power in it. The policy elite are drafting legislation, creating frameworks and establishing an “industry,” ignoring the ordinary, albeit ignorant, citizen. This citizen will be pre-selected by the distribution of life chances in society to bear the adverse consequences of the process. In such an environment, how can we as a society ensure that the ordinary, ignorant citizen need not fear hospitals? How can we re-establish a balance of power? What countervailing mechanisms do we need?
Sri Lankaneeds a statutory legal authority to ensure participant protection, made up of completely independent persons unconnected to biomedical research, clinical trials, the pharmaceuticals industry, state economic planning or state regulators. It must be made up of respected, knowledgeable patient rights activists, human rights activists and lawyers, ethicists, social scientists, public intellectuals and members of civil society groups with an abiding interest in protecting the rights of the ordinary, ignorant citizen.
This authority must be statutorily funded. Facilities must be provided for its training, capacity building and administration. It must determine rules, regulations, norms and customs for the ethical conduct of biomedical research involving human participants – the regulatory framework coming under the proposed Clinical Trials Act should only be guided by these, not dictate them. It must supervise the training and certification of the ethical competence of researchers and trialists. It must develop, accredit, fund and supervise research ethics committees. It must stand up for their independence when industrial interests try to bulldoze over them. It should conduct public awareness campaigns.
Ethics, science and scandal
Global clinical trials can certainly benefit both individuals and the collectivity of our society, but the human and societal costs must be minimized. For this, a robust research ethics environment is essential. The only way to have this in the current scenario of the asymmetrical operation of power is to have a separate, effective and independent authority for participant protection.
Good ethics promotes good science and prevents scandal – the responsibility for funding the authority thus lies with those who want to promote good science, be it for knowledge hubs or forex-spinning industries.
People with an interest in good science, professional integrity or the rights of the common, ignorant citizen must rise to the occasion now.
*The writer teaches medicine at the University of Colombo.