Role of Perspective and Other Uncertainties in Cost-Effectiveness Assessments in Advanced Prostate Cancer

Both its natural history and typical age at presentation make prostate cancer a disease for whose treatment the largest thirdparty payer is the U.S. taxpayer. Medicare payments for prostate cancer treatment were estimated to be $1.4 billion in 1994 (1). Therefore, the cost-effectiveness analysis by Bayoumi et al. (2) in this issue of the Journal, addressing three critical issues in advanced prostate cancer—medical versus surgical castration, the role of total androgen blockade with castration plus nonsteroidal antiandrogens, and the optimal timing of any of these—is timely and appropriate. Substantial attention has been directed at potential biases in the reporting and funding of cost-effectiveness analyses of pharmaceutical agents (3,4). Identifying such biases has been easier since de facto national standards were established by the 1996 U.S. Public Health Service’s Panel on Cost-effectiveness in Health and Medicine (5). This report, commissioned by a federal agency (the Agency for Healthcare Research and Quality) at the request of the Health Care Finance Administration (Medicare), has an unusual potential bias: It assumes that the government’s perspective is aligned with that of society—i.e., one that incorporates all costs and effects regardless of who incurs them. In this editorial, we highlight a variety of methods, concerns, and clinical issues within (not against) the cost-effectiveness paradigm. The costs and quality-of-life tradeoffs associated with the form of therapy intended to lower serum testosterone levels lead to completely different conclusions about the optimal form of therapy depending on one’s perspective. The consensus is that medical and surgical castration is equally effective (or ineffective) at prolonging life and delaying disease-specific complications (6). From a societal and Medicare perspective, the obvious preferred strategy is orchiectomy based on lower cost. The current choice of 75% of U.S. men is to receive luteinizing hormone releasing-hormone (LHRH) agonists. At least three factors contribute to this choice: a preference for organ preservation, the lack of concern about societal costs on the part of patients, and financial incentives for prostate cancer physicians. From a patient’s perspective, there are usually minimal differences between the available choices, since Medicare pays 80%–100% for each type of castration, and other funds often help make up the difference. To date, our society has chosen to insure patient choices for organ preservation. Not only does Medicare pay for LHRH agonists, but it also pays for breast radiation therapy following lumpectomy for breast cancer, despite the fact that breast radiation treatment does not improve survival but only reduces the risk of subsequent local relapse and consequent mastectomy. Bayoumi et al. (2) show that, patient preferences aside, organ preservation in treating prostate cancer is costly and a poor use of societal resources. How strong is the male patient’s preference for LHRH agonists? A telephone survey by Chon et al. (7) found that 22 of 42 men currently receiving hormonal therapy would be willing to pay an additional monthly discounted expense of $386 for 30 months, based on a formula that determines the net present value of an investment, to avoid orchiectomy. Such studies that use hypothetical scenarios, however, are subject to criticism, and the true willingness to pay is, therefore, uncertain. Still, the stated willingness of only about one half of subjects to pay that amount shows that copayments effectively decrease the demand for expensive drugs and that avoiding orchiectomy for many men has more monetary value than many would predict. For the ambivalent patient, the urologist’s recommendation will influence or sway his decision-making. Surgeons are commonly criticized for being quick to cut. So why have so many urologic surgeons shifted to giving hormone injections? From the urologist’s perspective, the financial incentives clearly favor recommending LHRH agonists because of the large difference between the suggested list price and the actual acquisition price. Medicare currently pays hospitals or physician offices 95% of the list price (incorrectly called the “average wholesale price”) of injectable and intravenous therapies. The current average wholesale price of leuprolide and goserelin is about $470 per month. Because of price competition between the two products, the acquisition price is routinely discounted 40% or more. If one urologist had 40 patients over a full year on LHRH agonists, the income from this treatment (before billing expenses) would be about $100 000. An obvious partial solution to address this distortion would be if Medicare began paying prices similar to those negotiated in other Western countries, e.g., the Ontario Drug Benefit plan pays $260 (U.S.) per month (Kroll B: personal communication). Did the model by Bayoumi et al. (2) start by assuming that all forms of castration were equally effective? Not really. Orchiectomy is irreversible, while LHRH agonists are potentially reversible. Only the men taking LHRH agonists can discontinue their therapy, so the statement that LHRH agonists are less effective is inappropriate. The only “what if” analysis explored (of different relative “effectiveness” of LHRH agonists compared with orchiectomy) was to use only a single point estimate taken from the meta-analyses where LHRH agonists were 10% less effective, not the 95% confidence interval of the relative effi-