Global Clinical Trials: Sri Lanka Needs Effective Participant Protection

Filed under: Colombo Telegraph,MORE OPINION |
 

By Panduka Karunanayake -

panduka

Dr. 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.

Beneficiaries

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.

Loopholes

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.’

Asymmetry

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.

Safeguards

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.

Two requirements

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. 

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9 Responses to Global Clinical Trials: Sri Lanka Needs Effective Participant Protection

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    Pharmaceutical companies are looking for race based differences in treating patients. But, I think, Sri Lanka is highly mixed. These trials are highly controlled. Yet, sri lankan sub contractors may do anything for money. So, the govt needs guide lines, regulations and monitoring with respect to what they do.

    Jim Softy
    September 11, 2012 at 2:58 pm
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      Have we already set necessary ethical guide lines for CT performances within the nation health regulations ? if not, how have some Ctrials been carrying out in srilanka today ? Very recently, following some information of Dengue spread and alternative remedies on the web /BMJ, I was interested in gathering adequate info in terms of lanken ethics principles leading to CT trials, however my efforts ended up just checking on the MRI website.

      UG
      September 11, 2012 at 5:04 pm
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    This is a very good article that can bring me more intformation about the srilanken authority structures working on clinical trial settings. Can any kind person please explain me how the ethics commitees are structured to lanken athorities (Ministry of Healthcare & Nutrition)? Global clinical trials are generally carried out in compliance with ICH-GCP guidelines also considering national health law/regulations. I wondered why Srilanka is excluded from the global CT (paediactric) on Dengue vaccine sponsored by SANOFI-AVENTIS.

    UG
    September 11, 2012 at 4:55 pm
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    Great analysis, Thanks for this !

    Kamani
    September 11, 2012 at 7:43 pm
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    To Jim Softly, I think you are implying that (1) regulation is good and will ‘control’ what CROs can do, (2) there is a need for global clinical trials in the context of possible race-based differences in drug efficacy. My problem with (1) is that the current Sri Lankan efforts to bring regulation is flawed by being ‘asymmetrical.’ I have explained this in my article. Hence in our context, I cannot have faith that ‘regulation’ will ensure good research ethics. I agree with (2), but this is amply covered by a good research ethics environment (which ensures scientific validity and social value). So we are back to the issue of how we can have that ‘good research ethics environment.’ My whole point is that the ‘asymmetry’ at policy elite level will create the likelihood that the policy (especially the policy process, once the policy is activated) will be inimical to unsuspecting patients in state hospitals, who are seldom told even what tablets/injections they are given. My suggestion is a mechanism independent of the regulators/researchers/planners/policy elite etc, considering the Sri Lankan context. Panduka.

    Panduka Karunanayake
    September 12, 2012 at 6:41 am
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    To UG, You might like to visit the Federation of Ethics Review Committees of Sri Lanka (FERC-SL) website, which tries to give leadership to research ethics activities in SL, with very limited resources. If you are not satisfied with where you get with FERC-SL, please remember that this is a reflection of where research ethics generally stands in SL, not how in/efficient FERC-SL itself is. One research ethics committee in SL is currently CIDSER-recognized (which refers to ICH-GCP), and another one might receive recognition by the end of the year. This is perhaps not bad for a country of our size. But even these two committees do not have the capacity to MONITOR clinical trials, which is a huge drawback. I am sorry I have no idea about the dengue vaccine issue. The Epidemiology Unit of SL would know. Panduka.

    Panduka Karunanayake
    September 12, 2012 at 6:52 am
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    To Kamani, Thanks. What can we do about the issue? I hope my article will stimulate discussion and action. I am not against clinical trials (even global CTs, even on an industrial scale), but we need to put some safeguards in place first. Panduka.

    Panduka Karunanayake
    September 12, 2012 at 6:57 am
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    Clinical trials are sets of tests in medical research and drug development that generate safety and efficacy data (or more specifically, information about adverse drug reactions and adverse effects of other treatments) for health interventions (e.g., drugs, diagnostics, devices, therapy protocols). They are conducted only after satisfactory information has been gathered on the quality of the nonclinical safety, and health authority/ethics committee approval is granted in the country where approval of the drug or device is sought. “‘;’ Brand new piece of writing on our personal internet site http://picturesofherpes.co

    Cole Semmel
    June 16, 2013 at 4:58 pm
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      What is the purpose of your comments? Btw, it is not about medical research but about Clinical Research… that fits better :) The writer himself has made it clear for what purpose the clinical trials have been carried out. The problem raised the lanken ethics in terms of these trials need reforms in compliance with ICH-GCP standards. Having closely studied some experiemental data added by lanken graduated physicians about a CTrial focusing on papaya leave extracts to nearly a dozen of Dengue patients, I myself felt – the results were not in compliance with any kind of GCP regulations. So long this would remain unchanged, no pharma companies will make any efforts to include lanken patient populations such trials.

      UG
      June 16, 2013 at 6:49 pm
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