Cost-effectiveness models of clinical trials of new pharmaceuticals for AIDS-related Pneumocystis carinii pneumonia: are they helpful to policy makers?

BACKGROUND

Pneumocystis carinii pneumonia (PCP) has been the most common and most costly complication of acquired immunodeficiency syndrome (AIDS). Because of concern over the high costs of care for persons with AIDS, policy makers have instituted a number of new measures to encourage cost-effectiveness. Although the clinical efficacy of new pharmaceutical agents is evaluated extensively before approval, comparative trials of a new agent with its major competitor are sometimes not carried out, and estimates of cost-effectiveness are therefore difficult to obtain.

METHODS

We describe methodologic issues associated with the development of economic models of new pharmaceutical agents and illustrate these issues with an analysis of second-line therapeutic options for PCP.

RESULTS

A new drug, trimetrexate, and the standard second-line therapy, pentamidine, are both inferior to the standard first-line therapy, trimethoprim/sulfamethoxazole, as initial therapy for moderate to severe PCP. However, as many as half of the patients with PCP are either intolerant or refractory to trimethoprim/sulfamethoxazole therapy for PCP. Economic models suggest that, if the two drugs have identical survival rates, then trimetrexate, despite a higher acquisition cost, is both less expensive and more effective in achieving toxicity-free survival than pentamidine in patients who require second-line therapy for PCP. Sensitivity analyses indicate that trimetrexate is less expensive than pentamidine over a wide range of estimates of costs and effectiveness.

CONCLUSIONS

To make well-informed therapeutic decisions, policy makers and physicians require head-to-head studies of a new pharmaceutical agent with its major competitor. However, economic models can be used to derive estimates of cost-effectiveness of new pharmaceutical agents when such data are lacking. The interpretation of these models raises general issues related to the perspective of the investigators, study design, estimation of costs of care, rates of response, toxicity, and survival, and generalizability of the results to other settings as well as methodologic issues that are unique to human immunodeficiency virus (HIV) disease. If a comparative trial found better survival rates, then cost-effectiveness models would be of limited usefulness; almost all physicians would use the drug with the higher survival rate.