Drug studies in developing countries.

Abstract

One of the common features of "developing countries" in terms of pharmaceuticals is the lack of ability to generate independently the drugs that they need. These countries have to rely primarily upon products researched and developed by the pharmaceutical industry of richer countries -- indeed, generics are often produced and used in the developing countries when proprietary compounds outrun their patent restrictions. This dependency has vast repercussions, but here we will focus only on the clinical end of the spectrum. With few exceptions, drugs are researched and developed by the pharmaceutical industry of industrialized countries for the diseases prevalent in those countries, and their profiles are tailored to their own customers, including dosage, acceptability, and -- not least -- pricing. Therefore, the problem to be faced is the availability of the right drug, or even any drug at all, in developing countries. The western pharmaceutical industry has produced only a negligible number of so-called "orphan drugs" for tropical or "neglected" diseases (Trouiller P, Olliaro P. Drug development output: what proportion for tropical diseases? Lancet, 1999, 354 (9173): 164). There are other ramifications as well. Several regulatory authorities in developing countries do not have a system to deal with new chemical entities, as only products that have been developed, reviewed and registered elsewhere are considered. Local regulations may require a clinical trial to be repeated in a developing country when a new compound is submitted for marketing authorization. Thus, clinical researchers often do only studies of secondary importance and limited scientific interest on drugs that have been already researched. We believe that such an approach is inadequate. Ethical aspects related to research in the tropical world should not be forgotten, though they have no easy solution. Fortunately, there are some notable exceptions in the field of research into tropical and other diseases: China, India, Malaysia and Thailand, for instance, have been contributing pivotal studies of drugs for malaria and leishmaniasis with undeviating commitment. In addition to providing meaningful information on drug efficacy and safety, a drug's pharmaceutical development project should also provide prescribing information so that the drug is used in an optimal manner. In this respect, it is becoming increasingly obvious that not all individuals respond uniformly to drugs and that ethnic variability necessitates better-adapted treatment recommendations (Wood AJ, Zhou HH. Ethnic differences in drug disposition and responsiveness. Clinical Pharmacokinetics, 1992, 70: 350-373; Lang CC et al. Attenuation of isoproteronol-mediated vasodilatation in blacks. New England Journal of Medicine, 1995, 333: 155-160). The use of a population approach to pharmacokinetics and pharmacodynamics is growing in modern pharmacology, in order to consider these differences between population subgroups and to provide information that will generate guidelines for individualizing dose regimens. Traditionally, the role of individual variables has been underestimated, and a drug's development programme that deals properly with dose adaptation based on, for example, ethnic differences in metabolism or mean body weight is very much needed. We believe that developing countries do not need to conduct small clinical trials to duplicate information that already exists on drugs which are being considered for registration. …