Drug Trials—the Dark Side: This WorldBMJ 2006; 332 doi: https://doi.org/10.1136/bmj.332.7548.1039 (Published 27 April 2006) Cite this as: BMJ 2006;332:1039
- Ike Iheanacho, editor, Drug and Therapeutics Bulletin ()
An advert posted inside some London buses shrieks, “Drop by today—it could be a beneficial visit!” Placed by the pharmaceutical services company PAREXEL, it seeks volunteers for research—at Northwick Park Hospital. The recent disastrous trial of the monoclonal antibody TGN 1412 at that venue has heightened the public's interest in clinical drug studies. And the long term result may be increased scepticism, such that fewer people in the United Kingdom will be willing to participate in clinical research, no matter how upbeat the recruitment messages.
In addressing this problem, the pharmaceutical industry is, predictably, well ahead of the game. For instance, clinical trials are increasingly being conducted in developing countries that offer a rich source of suitable and apparently willing patients. Drug Trials—the Dark Side was a compelling documentary on how drug companies are targeting India for this purpose.
The scene was set by the comments of a patient-recruitment agent, who boasted how much quicker and cheaper it was to enrol patients for trials in India, compared with, for example, the United States and countries in western Europe. He also emphasised how India had a huge supply of “treatment-naive” people, or in the words of Paul Kenyon, the programme's presenter, “patients offering a blank canvas to the drug companies.” From this starting point, Kenyon set out to discover just why so many people are ready to take part in clinical studies, even though they receive no financial reward.
Through interviews, case studies, and on the spot reporting, Kenyon showed how the rapid recruitment commonly relies on insufficient regard for ensuring that patients give informed consent. This abuse of a fundamental principle of research in humans can be attributed largely to a poisonous combination of four factors: ill health, poverty, ignorance, and blind faith in the medical profession. Patients too poor to afford standard therapy, and with little or no understanding of clinical research, are only too happy to accept what appears to be “free” treatment from doctors they revere.
In such circumstances, the notion of truly informed and freely given consent becomes highly questionable, as the documentary made clear. And it was easy to sympathise with the consultant who dismissed as a myth the idea that such consent was possible where patients felt so obligated to their doctors and would consequently “agree” to anything they were asked to do. Acting on his ethical objections, this doctor had taken a brave, atypical stand in refusing to allow trials in his hospital. Others are not so fastidious, seemingly wary of ostracism by colleagues and frightened of upsetting the drug companies.
Testimony to how little some patients really knew was their thumbprints (rather than signatures) on consent forms written in English, a foreign language. Of particular concern were examples of where patients' supposedly informed consent to take part in trials had meant that essential treatment had been delayed or stopped in favour of untested interventions.
There was a particularly eye-opening demonstration of failure to inform a potential trial participant. In an unusual move, one drug company allowed Kenyon to film the recruitment of a patient to a study of a drug for rheumatoid arthritis. Even in this heavily stage-managed setting (where the film crew could not arrive unannounced) and despite the well meaning efforts of the recruiting doctor, it was obvious that the patient had “consented” to enter the (placebo controlled) trial without really knowing he was agreeing to an experiment. More worrying still, he appeared to believe that the treatment would cure his arthritis, an assumption apparently unchallenged during the consent-seeking process.
Whatever the faults in how participants are recruited, the boom in India's clinical trial industry is set to continue. Indeed, drug companies may become ever more dependent on carrying out research on compliant patients in developing countries, to help minimise the cost of acquiring data needed for the licensing of new medicines.
What is more, Western countries may find it convenient to have such treatments tested elsewhere, especially if this obviates TGN 1412-type incidents on their own doorstep. Drug Trials—the Dark Side should help to ensure that such delegation of risk does not blind us to the costs borne on our behalf by others far away. Crucially, the programme also highlighted how in India at least, taking part in a trial does not guarantee subsequent affordable access to the tested medicines, even for the study patients, let alone the population in general. This is a pointed corrective to any suggestion that unknowing participation in a study might be justifiable if it is the only means of access to “free” treatment.
One final point: randomised clinical trials are often called the “gold standard of medical research.” Overuse of this intellectually sloppy phrase has much to answer for. In particular, it can mean that trials are too often considered intrinsically worthwhile, with too little attention being paid to whether, where, and how they should be conducted. To help foster such scrutiny, it is better to view clinical studies as the least bad way available of answering certain health care questions. Sometimes, as Kenyon's important film showed, they are not even that.
BBC1, 27 April at 9 pm
Items reviewed are rated on a 4 star scale (4=excellent)