Six neonates with hematological and clinical pictures indistinguishable from acute myeloid leukemia were studied. Two patients had Down syndrome and three others had either +21 or i(21q) chromosomal abnormalities in their blood cells at presentation. Granulocyte-macrophage colony-forming unit assays performed in bone marrow and peripheral blood mononuclear cells revealed abnormal growth patterns in two patients; both died of progressive disease of acute myeloid leukemia. All the other four neonates with normal in vitro cell growth pattern had spontaneous remission within 7 months. Of these four patients, one remains well and in remission for 8 years and the other three developed acute myeloid leukemia at the ages of 15, 32 and 19 months, respectively. We conclude that the in vitro cell growth pattern is helpful to distinguish transient myeloproliferative disorder from congenital acute myeloid leukemia and that patients with the former condition are at risk to develop acute myeloid leukemia subsequently.

The effort to discover and develop new pharmaceuticals is a risky and costly enterprise. For diseases that affect few patients, the barriers to development maybe especially great, since the drugs' small markets may make it difficult for firms to recoup their initial research and development investments. The Federal Government has sought to reduce these barriers through incentives first adopted in the Orphan Drug Act of 1983 (Public Law 97-414). The transfer of technology from Federal laboratories such as the National Institutes of Health to the pharmaceutical industry can also reduce the cost and risk of drug development for firms. Although such incentives may result in important new therapies, their price to patients and insurers may still be high.

As part of our assessment, Government Policies and Pharmaceutical Research and

Development, requested by the House Committee on Energy and Commerce and its

Subcommittee on Health and the Environment and the Subcommittee on Antitrust,

Monopolies, and Business Rights of the Senate Committee on the Judiciary, OTA

commissioned researchers at Stanford University to examine the development and provision of alglucerase, an important new treatment for Gaucher disease. Gaucher disease is a rare inherited disorder in which the body lacks an enzyme necessary to break down fats. This background paper describes the development of alglucerase, illustrates the role that both the Federal Government and private sector can have in making new therapies available for orphan diseases, and lays out some of the tradeoffs that can exist between developing new medical technologies and controlling health care costs.

EXOSURF is a protein-free surfactant composed of 85% dipalmitoylphosphatidylcholine, 9% hexadecanol, and 6% tyloxapol by weight. A single dose of 5 mL of EXOSURF per kilogram body weight, which gave 67 mg of dipalmitoylphosphatidylcholine per kilogram body weight, or 5 mL/kg air was given intratracheally in each of two controlled trials: at birth to neonates 700 through 1350 g (the prophylactic trial, n = 74) or at 4 to 24 hours after birth to neonates greater than 650 g who had hyaline membrane disease severe enough to require mechanical ventilation (the rescue trial, n = 104). In both studies, time-averaged inspired oxygen concentrations and mean airway pressures during the 72 hours after entry decreased significantly (P less than .05) in the treated neonates when compared with control neonates. Thirty-six percent of the treated neonates in the rescue study had an incomplete response to treatment or relapsed within 24 hours, suggesting the need for retreatment in some neonates. In the rescue trial, risk-adjusted survival increased significantly in the treated group. There were no significant differences in intracranial hemorrhages, chronic lung disease, or symptomatic patent ductus arteriosus between control and treated infants in either trial.

One of the most striking pieces of medical news in the 1980s revealed the connection between high blood cholesterol and a person's likelihood of developing coronary artery disease. In 1985, the National Heart, Lung, and Blood Institute of the National Institutes of Health began the National Cholesterol Education Program, whose goal was to develop a national policy for reducing serum cholesterol. However, the panel that convened to formulate recommendations for screening and treatment was instructed not to consider cost in its deliberations. As Alan Garber and Judy Wagner point out in this article, failure to include costs in the development of guidelines such as these can have "far-reaching, unanticipated effects." This point is especially relevant to the new Agency for Health care Policy and Research (AHCPR) , which was formed as part of the 1989 budget reconciliation law. One of AHCPR's express mandates is to develop condition-specific treatment guidelines for nationwide use. "If the AHCPR guidelines show the same disregard for costs" that the cholesterol guidelines showed, the authors state, "they cannot be expected to guide health dollars to their most effective use."