Ethical issues in drug testing, approval, and pricing: The clot-dissolving drugs

Abstract

Ethical issues in drug testing, approval, and pricing: The clot-dissolving drugs Baruch A. Brody, New York, 1995, Oxford University Press, 268 pages, $25. The book Ethical issues in drug testing, approval, and pricing: The clot-dissolving drugs by Baruch A. Brody is a 268-page text that outlines the development, approval process, and marketing of the thrombolytic agents streptokinase, urokinase, recombinant tissue plasminogen activator, and a variety of other experimental activators. The drugs are discussed primarily in the context of their use in the setting of acute myocardial infarction; little information exists on peripheral arterial and venous thrombosis. There is a strong bent on moral and ethical concerns throughout the text, both from the standpoint of the conduct of studies directed at gaining regulatory agency approval for clinical use of the agents, as well as with respect to ethical conflict between clinical efficacy and economic cost. The book is divided into four sections. The first section deals with the development of thrombolytic agents, beginning with the pioneering investigations of James Herrick, who in 1912 emphasized the association between acute coronary artery thrombosis and the clinical syndrome of myocardial infarction. Brody follows with an insightful account of the evolution of streptokinase, first reported by Tiller and Garner in 1933. The remainder of the section outlines the various clinical trials of thrombolysis for coronary occlusion, including those organized by the NIH and those by the pharmaceutical companies. Links between investigators and the companies are discussed, naming individuals, corporations, and their financial connections in the form of stock options. The latest trial of thrombolysis for myocardial infarction, the GUSTO trial, is outlined in the final portion of the section, discussing the possible relationship between Genentech's $55 million investment in the study, the unblinded study protocol, and the rather modest mortality differences between rt-PA (6.3%) and streptokinase (7.2% to 7.4%). The second, third, and fourth sections of the text describe ethical issues with regard to clinical trials, the approval process for new drugs, and the adoption of new agents. The use of placebos is discussed, as are conflicts of interest in the conduct of clinical trials. The history of the FDA approval procedure is outlined, along with the ethical foundations of the process. Brody succinctly summarizes the clinical conflicts that arise as a result of discrepancies between cost and clinical efficacy; for example, whether the marginal difference in mortality rate between streptokinase and rt-PA for acute myocardial infarction is worth the enormous cost differential. The text closes with a brief discussion of pricing of drugs, including an alarming table that illustrates a four-fold differential between the relative price of drugs from one country to another. In summary, the book provides a concise and easily understandable text on the development and ethical concerns of thrombolysis for acute myocardial infarction. Although similar issues occur with predictable consistency with regard to all new pharmaceutical agents, this book is not likely to be of interest to peripheral vascular surgeons other than those who are intimately involved with thrombolytic research.