We thank Dr. Avins for his interest and cautionary comments. Assuming the stability of the relative risk reductions demonstrated in trials such as the Helsinki Heart Study [1], a cumulative increase in coronary events would indeed reduce the number of patients who must be treated to prevent one event (the number needed to treat). In highlighting the potential merits of long-term investments in prevention, however, one cannot overlook the continuing effort of treatment in relation to deferred yields. Such situations run counter to innate "time preferences"—our natural tendency to want benefits as soon as possible while deferring burdensome or unpleasant events as long as possible. This phenomenon leads many health economists to apply a discount rate of 5% per annum to future costs and effects in their calculations of cost-effectiveness ratios [2]. Unfortunately, little research has been done into the implicit discount rates—and the expectations, realistic or otherwise—that underpin patients' willingness to take preventive treatment for years in hopes of deferring some future event.

More generally, this phenomenon means that the number-needed-to-treat concept is most pertinent for immediate interventions with immediate payoffs, such as life-saving surgery or thrombolytic therapy for acute myocardial infarction. For long-term interventions with deferred benefits, or for any situation where the burdens or benefits of treatment are not constant as a function of time, the number needed to treat must be used with caution.

Lastly, the number needed to treat also fails to capture the uncertain payoff of preventive investments. It tells us how many patients are exposed to drug treatment for every one who directly benefits but does not tell us about those who have events despite preventive maneuvers. In the Helsinki Heart Study [1], for example, the cumulative proportion over 5 years was 2.73% in the gemfibrozil group and 4.14% in the placebo group. Among 710 treated patients, 10 will avoid cardiac events, but 19 patients will still have an event—a figure that may be sobering for patients with unsullied faith in prevention.

That is why we argued [3] for the adoption of alternative indices of clinical efficiency to enhance physician and patient appreciation of the real ratios of efforts to yields and risks to benefits for the growing number of drugs, devices, and procedures.