Few would disagree that the diseases which affect poor people in tropical countries are neglected, and more should be done to address this inequity. That means improving and deploying interventions which work, and developing new ones. Fortunately, there has been an upsurge in interest in neglected diseases, and a considerable increase in support for the development of new vaccines, drugs and methods of vector control. Clinical trials are essential to evaluate these new interventions, and also to improve existing ones.
The standards increasingly demanded by funders and review committees are those of Good Clinical Practice, a rubric which has a little to do with good clinical practice, i.e. taking good care of patients, and a lot to do with documentation. I am not against the principles of good clinical practice, of course they are excellent, but I am concerned about the recommended practices and their blind adoption in poor settings. The mountains of paper and the burgeoning e-mail traffic, conference calls, committees, international air flights and meetings that characterize clinical research in the 21st century are supposed to ensure quality, and therefore facilitate progress. Whether all the procedural aspects and paperwork are truly necessary or even useful is a moot point. They are certainly very expensive and demanding.
I fear that adoption of ‘industry standards’ in tropical medicine research will actually limit important post-registration research, particularly for groups with limited funds, will promote bad clinical practice by encouraging greater attention to the case record form than the patient, and that the ever-increasing bureaucratic burden will bury innovation and dissuade clinical investigators from entering this important field.
‘Industry standard’ good clinical practice does not ensure the research question is a good one, or the design of the trial is appropriate and I do not believe that it guarantees a better (i.e. more likely to be true) result. It has to be set against the impoverished reality of under-resourced and under-staffed health structures in countries which often have < US$10 per person per year to spend on all aspects of health. The usual trappings of a regulatory study, viz Contract Research Organizations (highly expensive commercial entities), Data and Safety Monitoring Committees, Trial Monitors (who are often part of the CRO, and usually pay more attention to the CRFs than the clinical procedures), may all do a good job, but they do not guarantee the probity of the trial, the appropriateness of the informed consent process, the quality of the clinical observations, or the accuracy of the result. More importantly, they do not guarantee that the patients or volunteers are well cared for.
There may be an inverse correlation between the thickness of the case record form and the reliability of its contents. Is there really any need for a CRF to have more than 30 pages or weigh more than 1 kg? Try filling one in properly in a busy hospital ward or out-patients department at the end of a long day at an ambient temperature of 33°C and with humidity approaching 100%. Clinical researchers are being encouraged to be process rather than patient orientated. The case record form, rather than the patient, has become the focus of attention. Sometimes large financial incentives to investigators (remuneration per case studied as much as 50 times the average per capita income of the patient) encourage dishonest practices. The spiralling costs of such studies and the spiralling perceived requirements for committees make it difficult for small under-funded groups to conduct clinical research, thereby concentrating resources in large powerful established groups or consortia (often based in wealthier countries).
Because Good Clinical Practice implies good clinical practice ethical review committees are increasingly insisting on these bureaucratic details, considering them to be an essential element of ethical conduct. Funding bodies often follow suit. Whilst the principles of good clinical practice to ensure that clinical research is correctly planned, supervised, recorded and reported are laudable, the increasing complexity and costs of the process imported from organizations and companies in rich countries may be unaffordable and unworkable in poorer countries. This increasing bureaucracy is not a necessary evil. It requires very careful appraisal and evaluation, and imaginative counter-measures. We need to distil the valuable essence of good clinical practice into something simple and workable, and concentrate on answering the really important questions in the simplest and most effective ways.
Large, simple, low cost, high-quality clinical studies with sensible appropriate informed consent procedures and user-friendly case record forms are possible and should be encouraged. Funders should concentrate more on supporting infrastructural costs and clinical and laboratory training. More attention to clinical practice, more common sense, and less bureaucracy would serve our patients better, lead to better clinical research and faster improvements in the health of people living in tropical countries.