Bennett C L, Oddone E, Matchar D
Northwestern University, Chicago, IL 60611, USA.
Clin Perform Qual Health Care. 1995 Jul-Sep;3(3):156-64.
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.
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.
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.
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.
卡氏肺孢子虫肺炎（PCP）一直是获得性免疫缺陷综合征（AIDS）最常见且花费最高的并发症。由于担心艾滋病患者的高昂治疗费用，政策制定者已采取了多项新措施以鼓励成本效益。尽管新药物在批准前会对其临床疗效进行广泛评估，但新药物与其主要竞争对手的对比试验有时并未开展，因此难以获得成本效益的评估结果。
我们描述了与新药物经济模型开发相关的方法学问题，并通过对PCP二线治疗方案的分析来说明这些问题。
一种新药三甲曲沙和标准二线疗法喷他脒，作为中度至重度PCP的初始治疗，均不如标准一线疗法甲氧苄啶/磺胺甲恶唑。然而，多达一半的PCP患者对PCP的甲氧苄啶/磺胺甲恶唑治疗不耐受或难治。经济模型表明，如果两种药物的生存率相同，那么对于需要PCP二线治疗的患者，尽管三甲曲沙的购置成本较高，但在实现无毒性生存方面，它比喷他脒更便宜且更有效。敏感性分析表明，在广泛的成本和效益估计范围内，三甲曲沙比喷他脒便宜。
为了做出明智的治疗决策，政策制定者和医生需要对新药物与其主要竞争对手进行直接对比研究。然而，当缺乏此类数据时，经济模型可用于推导新药物的成本效益估计值。这些模型的解释引发了一些一般性问题，涉及研究者的视角、研究设计、护理成本估计、反应率、毒性和生存率，以及结果对其他环境的可推广性，还有人类免疫缺陷病毒（HIV）疾病特有的方法学问题。如果一项对比试验发现了更高的生存率，那么成本效益模型的作用将有限；几乎所有医生都会使用生存率更高的药物。
