For personal use. Only reproduce with permission from The Lancet Publishing Group. Clinical research provides physicians with new diagnostic and therapeutic tools for the management of their patients, and academic medical centres used to have a strong leadership role in the path from bedside clinical observation to the complex design of clinical trials. As more and more funding for clinical research has come from the pharmaceutical and biotechnology industries— a relationship that has been welcomed by both academe and industry—that leadership role has changed. At the same time there are concerns about the danger that industrially sponsored clinical research might be conditioned by the need to generate profits for shareholders. Bodenheimer 1 has reported on interviews with experts who have aired some of the problems, such as the danger that industry’s profit motive could determine how studies are designed; that industry retains control of data analysis and interpretation; and that published reports may be biased. These problems are well covered elsewhere in this Lancet series. However, there is also a concern that market forces rather than patients’ needs will establish priorities in drug development, and such a trend is especially worrying for poor countries. Rare diseases illustrate the conflict of interest in healthcare. At least 4000 diseases affect very small numbers of patients, and it is these diseases that tend to lack options for treatment. In part, this situation reflects a lack of knowledge of the pathogenesis and pathophysiology of the disease, which is in turn associated with the absence of animal models and the difficulty in recruiting enough patients for clinical study. 2 However, the rarity of these diseases means that the costs of drug research and development are unlikely ever to be recouped by future sales. The conflict of interest centres on the fact that patients with a rare disease are as entitled as anybody else to prompt and proper treatment, but companies are unlikely to invest an enormous amount of money if the potential beneficiaries are a only few thousand patients. ACADEME AND INDUSTRY 1638 THE LANCET • Vol 358 • November 10, 2001 Lancet 2001; 358: 1638–41 Mario Negri Institute for Pharmacological Research, Bergamo, Italy; and Department of Immunology and Clinical Transplantation, Azienda Ospedaliera Ospedali Riuniti, Bergamo, Italy (A Schieppati MD, Prof G Remuzzi MD, Prof S Garattini MD) Correspondence to: Prof Giuseppe Remuzzi, Laboratori NegriBergamo, via Gavazzeni 11, 24100 Bergamo, Italy (e-mail: gremuzzi@marionegri.it) Rare diseases and orphan drugs The clinical success rate for new drugs is very restricted: one in 1000 drug candidates progresses to clinical trial. Of 100 drugs entering clinical trials, about 20% are approved for marketing, with 30% rejected at phase I, 37% at phase II, 6% at phase III, and 7% at regulatory levels. 3 Experts in pharmacoeconomics think that the average investment for an innovative medicinal product is US$200–500 million. 4,5 Therefore, to translate investments into profits for the shareholder, manufacturers would need to sell millions of tablets over a long time. Moreover, many rare diseases are genetic, and new high technology treatments (eg, recombinant enzyme replacement and gene therapy) are potentially the best option for patients with rare diseases. Again, development of these approaches is costly and difficult and might not be worthwhile for industry. Patients with rare diseases have been termed health orphans and the treatments that could cure them, orphan drugs. These terms gained popularity in the mid-1980s when the Orphan Drug Act was adopted in the USA as a result of a long struggle by patients with rare diseases and their support groups. 6 The US Orphan Drug Act, signed into law in 1983, provides incentives to the pharmaceutical industry to encourage development of new drugs for rare diseases. 7 These incentives include market exclusivity for products designated as orphans with Food and Drug Administration (FDA) approval, research tax credits for clinical studies of rare diseases, and the Orphan Product Development grant programme, which has funded a total of 376 studies. 8 Before 1983, only seven drugs were available to treat rare diseases. Since then, more than 900 drugs and biologicals have been designated orphan products, and more than 200 of these have received marketing approval from the FDA. 5 Japan and Australia have followed the example set by America. 8,9 After lengthy proceedings and delays, the European Union (EU) has finally approved a regulation for orphan medicinal products. 10 The regulation is applicable to disorders with a prevalence of no more than 5 per 10 000, or for life-threatening or seriously debilitating communicable diseases even when the prevalence is higher. The regulation provides assistance in preparation of protocols, market exclusivity of the drug for 10 years, and other incentives for support of research and development. Despite the long wait, the European regulation has brought a few criticisms from industry or academia. Since taxation in the EU is individual to the member states, pharmaceutical companies are concerned that there might Modulating the profit motive to meet needs of the less-developed world Arrigo Schieppati, Giuseppe Remuzzi, Silvio Garattini The success, despite the problems, of academic/industrial collaborations over the past decade owes much to the profit motive. However, market-driven research and development has little to offer patients in the less-developed world. Some flexibility has already been demonstrated on drugs for orphan (rare or under-researched) diseases. Many diseases in less-developed countries are not rare. Academic researchers should be encouraging the establishment of funding for basic and clinical research that is directed at patients’ needs in the less-developed world and that is independent of a commercial ethos. Academe and industry