Tessa Tan Tones Edejer is a medical officer with the Global Programme on Eviderice at WHO Geneva, swlizerland Before this, she was based at the University of the Philiopines, Manila. She was trained though the international Clinical Epidemilogy Network. New types of drugs are continuously developed and marketed to meet the needs and expectations of patients, and for pharmaceutical firms to recoup investment costs and make profits. Before marketing of a new drug, many countries require registration with a central authority; requirements for registration vary greatly between developing countries. Some regulatory agencies require evidence of effectiveness; this ranges from proof of registration of the drug in the country of origin to randomised controlled trials (RCTs) conducted in the local population. There are many ethical concerns about the extent to which trials in the less developed world preserve the integrity of science, protect patients' welfare, and respect the authority of national regulatory agencies. RCTs done locally are usually organised by the branch offices of multinational pharmaceutical companies who contact principal investigators and provide administrative support. Depending on the expertise of the principal investigators, either they or the drug company will electronically enter data and undertake analysis and reporting. A report is then filed with the regulatory agency, and local authorities decide whether the drug can be marketed. RCTs provide the best evidence for effectiveness of treatment. But not all RCTs are well planned or well done. If the new drug is a product of a large multinational pharmaceutical firm, the protocol is sent by the mother office, together with forms for data collection and informed consent. The protocol may be the same as used for trials in large western markets with stringent requirements. All too often, however, there is substantial adaptation of the protocol with regard to sample size and, at times, even the informed consent form. The sample size gets trimmed down to the lowest number deemed feasible by local companies and acceptable by local regulatory authorities. This compromise sample-size is usually underpowered to detect a modest difference between the new drug and the one it is being compared with, and the locally obtained results need to be buttressed by evidence from other studies. In some cultures, informed consent is thought of as a formality, and explanations about the trial may be dispensed with entirely. Sometimes the consent form is shortened if it is felt that some of its contents might deter patients from agreeing to participate. Problems with both sample size and refusals to participate can potentially slow down recruitment and cause the company to miss deadlines for approval for registration and launching of the new drug. Because these types of studies are not initiated by researchers, principal investigators have to be invited to run the trials. They often are given an honorarium, based on the number of patients recruited. Investigators' trips to conferences are paid for, and after the trial, the principal investigators have the opportunity to present their results, both locally and internationally. Local “opinion leaders” are much sought after by pharmaceutical firms, and it is not unusual to find a few prominent practitioners running several trials simultaneously. Quality controls of trial conduct are done from two perspectives: the company, who usually employs its own clinical research associate, and the regulatory agency. A regulatory agency can exercise control over the quality of the process at different points: during approval of the protocol, monitoring of the trial, and approval of the completed study. A sufficient number of well-trained staff in regulatory agencies is needed to independently assure control. Such personnel is often not present in less developed countries. Currently, the requirement of regulatory agencies in less-developed countries for small stand-alone drug trials can be viewed as well-intentioned and consistent 'with their mandate of protecting the welfare of their population. However, by imposing this requirement, regulatory agencies may be naively serving the interests of pharmaceutical firms, by providing legitimate opportunities for premarketing promotion. The drive for international harmonisation of good clinical practice in clinical trials is laudable, more so if it can be reliably implemented in less-developed countries. But, intensive training of investigators, trial monitors, and regulatory-agency staff is needed. With trained individuals on-site, a subsequent effort to involve more developing countries in multicentre international phase III or IV trials can be legitimately advocated. These large trials would be more generalisable and would make valid and ethical claims for effectiveness of drugs in different populations and settings. And ultimately, it would be possible to use the same data for registration procedures in different countries. This article represents the personal views of the author and does not reflect those of her organisation.
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