The Orphan Drug Act of 1983, along with the discovery of a new use for a known drug and an investor willing to assume the necessary risk, brought about the formation of a start-up pharmaceutical company. The primary incentive of the Orphan Drug Act of seven years of marketing exclusivity provided the protection from competition necessary for recovery of the significant research and development and marketing costs. The orphan product, MetroGel®, for the treatment of rosacea, required approximately five years of development before it was approved for marketing by the Food and Drug Administration. MetroGel® has become the number one drug in the United States for the treatment of rosacea. It currently is marketed in other countries through a licensing agreement with a major pharmaceutical company.

The 1983 Orphan Drug Act was designed in response to market and regulatory disincentives that limited industrial interest in developing drugs needed by people in the United States with rare diseases and conditions. These disincentives evolved from changes in the pharmaceutical industry and in regulatory testing requirements. In the eight years since the Act and subsequent amendments have been in effect, the law has been associated with the new development and approval of 40 marketed drugs and 12 biologicals to treat rare (orphan) diseases. An additional 281 drugs and 141 biologicals have been entered into development and designated as orphans. Finally, the law has mandated exploration of whether the incentives of the Act are necessary and appropriate for stimulating industrial development of orphan medical drugs and devices. Despite this progress, controversies have arisen over three profitable orphan products that have benefited from the law's provisions. This has created the need for continued assessment of the Act's benefits and costs.

The FDA recently approved Ceredase™, a new treatment for Gaucher's disease, under the provisions of the Orphan Drug Act. Ceredase™ is unusually expensive, but there are no satisfactory alternative therapies. It appears likely that Ceredase™would not have become available without the protection of the Orphan Drug Act, but its expense and the lack of information about its long-term effects on health raise questions about whether the ODA provides appropriate incentives to develop cost-effective technologies.

Automated ambulatory medical records systems (AAMRSs) have been operational for over 20 years but have not been adopted by more than a small fraction of their potential users. This paper presents a detailed analysis of the uses and benefits of the COSTAR-based AAMRS at the Harvard Community Health Plan and of the factors which have inhibited the dissemination of COSTAR. We conclude that AAMRSs have been an orphan technology and cite trends in health care that favor the future development of AAMRSs.

Positron emission tomography (PET) is a method of nuclear medicine imaging that uses short-lived radiopharmaceuticals to detect and quantify the metabolic abnormalities of disease processes. PET initially was developed in a research environment as a research tool; data from these research studies resulted in the gradual recognition that PET studies would be useful for various routine clinical applications. The diffusion of PET into clinical practice has been slow in comparison with other new imaging methods (e.g., magnetic resonance imaging). This slow diffusion is attributable to several factors, including the complexity and high cost of PET, the uncertain role of the U.S. Food and Drug Administration in regulating the radiopharmaceuticals that are produced and used on-site for PET studies, and the apparent slow pace at which the Health Care Financing Administration and other third-party payers are developing policies for reimbursing for PET.

This paper provides a critical overview of several strategies and mechanisms that have been employed by the Program for Appropriate Technology in Health over the past decade to address the unmet needs for health technologies in the developing world. Partnerships between public and private-sector organizations are emphasized in order to share risks, encourage efficiency, and ensure the availability of priority products for health care in resource-poor settings. Incentives for the involvement of the commercial sector, the means to protect the interest of the public sector, and the role of bridging organizations are discussed in the light of the shifting goals of the public sector.

The U.S. Food and Drug Administration's (FDA) approval of the orphan biological product recombinant erythropoietin (rEPO) in June 1989 resulted both in a breakthrough treatment for the chronic anemia of people who suffer from chronic renal failure and a powerful argument for change in the legislation that spawned its development: the Orphan Drug Act of 1983. At a cost of over $6,000 per patient per year, Congress could not understand how a product that no manufacturer wanted to produce was suddenly costing the federal government hundreds of millions of dollars each year. Congress attempted to change the act in 1990 to preclude a manufacturer from using its provisions to secure lucrative monopolies in certain drug markets. In early 1991, the FDA finally issued regulations to implement the act that addressed some of the very concerns that were caused by rEPO.

Orphan drug products generally are used in treating or preventing rare diseases. The small number of patients available for study may create special problems in the evaluation of these products. This paper examines some of the special problems that are associated with the design and implementation of studies to evaluate the safety and efficacy of orphan drugs. The U.S. Food and Drug Administration (FDA) has not established special criteria for evaluating orphan drugs per se, but the FDA has been flexible in evaluating drug products that present special problems, especially when these products are for treatment of serious of life-threatening illnesses. The FDA and other U.S. governmental agencies also have taken steps to promote the development and availability of drugs for rare diseases, including making these products available to patients who are in need, even before the drugs have full FDA marketing approval.

Despite the need for more safe and effective contraceptive drugs and devices, enormous barriers to contraceptive research and development have been raised in the United States. The designation of contraceptives as orphan drugs, with concomitant incentives, may be warranted to encourage private manufacturers to reenter the field.

With the growing international literature in economic evaluation and the rapid spread of new health technologies, there is a need to undertake, or at least interpret, economic evaluations on the international level. However, the ways in which cross-national differences affect the cost-effectiveness of health technologies or their evaluations have never been studied. This paper explores these issues by taking advantage of a unique situation in which the same economic evaluation of a new indication for a health technology was conducted simultaneously in four countries using an identical methodology. The study showed that if prior agreement on methods can be reached and local data applied, economic evaluations can be undertaken in a way that facilitates the extrapolation of results from country to country.

The treatment of prostate cancer was reviewed at a U.S. National Institutes of Health Consensus Development Conference in June 1987. Data from the U.S. National Cancer Institute's Surveillance, Epidemiology, and End Results tumor registries were analyzed and showed that the proportion of eligible prostate cancer patients receiving the recommended therapies did not increase at a faster rate after the conference than before.

Diabetic retinal disease remains a leading cause of visual disability among those of working age. Controlled trials have demonstrated that timely diagnosis and photocoagulation treatment can reduce significantly the likelihood of visual impairment in affected diabetic patients. Using a prospective simulation model, we show that an annual screening and treatment program saves thousands of years of vision and reduces medical expenditures over the lifetime of a cohort of Swedish Type I diabetic patients.

A study was initiated to investigate the impact of information dissemination in Illinois upon the projected rise in the cesarean birth rate over the period from 1986 through 1988. The total cesarean birth rate in Illinois had not changed significantly during this period, whereas the rate of vaginal births after cesarean sections (VBAC) increased by 58.4% (p <.001). Information dissemination may have contributed to stemming an increase in the cesarean birth rate in Illinois while promoting VBAC deliveries.

We describe and illustrate the use of a generalizable model for evaluating the cost-effectiveness of alternative cholesterol-lowering treatments. We combine standard incidence-based techniques for measuring the cost of illness with logistic risk functions from the Framingham Heart Study to project, for persons with known coronary risk characteristics, the likelihood of developing coronary heart disease (CHD) over a lifetime as well as a number of related outcomes, including the expected loss of years of life due to CHD, the expected lifetime direct and indirect costs of CHD, and the changes in these outcomes that would result from cholesterol-lowering treatment.