Reimbursement Policy and Androgen- Deprivation Therapy for Prostate Cancer

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1 T h e n e w e ngl a nd j o u r na l o f m e dic i n e special article Reimbursement Policy and Androgen- Deprivation Therapy for Prostate Cancer Vahakn B. Shahinian, M.D., Yong-Fang Kuo, Ph.D., and Scott M. Gilbert, M.D. A bs tr ac t From the Department of Internal Medicine, University of Michigan, Ann Arbor (V.B.S.); the Departments of Internal Medicine and Preventive Medicine and Community Health, and the Sealy Center on Aging, University of Texas Medical Branch, Galveston (Y.-F.K.); and the Department of Urology, University of Florida College of Medicine, Gainesville (S.M.G.). Address reprint requests to Dr. Shahinian at the Department of Internal Medicine, University of Michigan, 28 Simpson Memorial Institute, 12 Observatory Rd., Ann Arbor, MI , or at vahakn@umich.edu. N Engl J Med 21;363: Copyright 21 Massachusetts Medical Society. Background The Medicare Modernization Act led to moderate reductions in reimbursement for androgen-deprivation therapy () for prostate cancer, starting in 24 and followed by substantial changes in 25. We hypothesized that these reductions would lead to decreases in the use of for indications that were not evidence based. Methods Using the Surveillance, Epidemiology, and End Results (SEER) Medicare database, we identified 54,925 men who received a diagnosis of incident prostate cancer from 23 through 25. We divided these men into groups according to the strength of the indication for use. The use of was deemed to be inappropriate as primary therapy for men with localized cancers of a low-to-moderate grade (for whom a survival benefit of such therapy was improbable), appropriate as adjuvant therapy with radiation therapy for men with locally advanced cancers (for whom a survival benefit was established), and discretionary for men receiving either primary or adjuvant therapy for localized but high-grade tumors. The proportion of men receiving was calculated according to the year of diagnosis for each group. We used modified Poisson regression models to calculate the effect of the year of diagnosis on the use of. Results The rate of inappropriate use of declined substantially during the study period, from 38.7% in 23 to 3.6% in 24 to 25.7% in 25 (odds ratio for use in 25 vs. 23,.72; 95% confidence interval [CI],.65 to.79). There was no decrease in the appropriate use of adjuvant (odds ratio, 1.1; 95% CI,.86 to 1.19). In cases involving discretionary use, there was a significant decline in use in 25 but not in 24. Conclusions Changes in the Medicare reimbursement policy in 24 and 25 were associated with reductions in use, particularly among men for whom the benefits of such therapy were unclear. (Funded by the American Cancer Society.) 1822 n engl j med 363;19 nejm.org november 4, 21

2 A ndrogen-deprivation therapy (), through orchiectomy or the use of gonadotropin-releasing hormone (GnRH) agonists, has been a mainstay for palliation in men with prostate cancer. 1,2 In the 199s, Medicare policies made the subcutaneous or intramuscular administration of GnRH agonists profitable for physicians, with reimbursement based on 95% of the average wholesale price. Later, the Government Accountability Office reported that physicians acquired GnRH agonists at an average of 82% of the average wholesale price and sometimes at a much lower price, which allowed profits constituting up to 4% of urologists revenues in private practice. 3,4 Remarkable changes in patterns of use of followed. Orchiectomy was almost completely replaced by the use of GnRH agonists as the predominant form of. 5 The overall use of doubled during the 199s, and by 1999, nearly half of all patients with prostate cancer were receiving such therapy for various indications within a year after diagnosis. This increase occurred frequently among patients for whom such therapy had an unproven benefit. During the 199s, the use of primary increased by a factor of eight among men who were 8 years of age or older and had low-risk, localized tumors, patients who would almost certainly be asymptomatic and die from causes unrelated to prostate cancer. 5,6 Patients of nonacademic urologists (who are usually reimbursed on a fee-for-service basis, whereas academic urologists are usually salaried) were 6% more likely to receive in cases of uncertain benefit, further implicating a financial motive for the use of. 7 In 23, payments from Medicare Part B for GnRH agonists amounted to nearly $1 billion. 8 The drug-reimbursement policy of Medicare Part B changed substantially as a result of the Medicare Modernization Act. 9 In 24, reimbursement was generally reduced to 85% of the average wholesale price (and to about 8% of the average wholesale price for GnRH agonists). In 25, reimbursement was set at 16% of the average sale price (in contrast to the average wholesale price) on the basis of actual transactions reported quarterly by pharmaceutical companies. These changes represented a reduction of 5% or more in reimbursement for GnRH agonists. A study that was based on public-use data from Medicare showed that the use of GnRH agonists declined by 14% from 23 to 25. However, since only counts of services were available, rates could not be calculated and indications for use could not be assessed. 8 Given the drastic cuts in reimbursements, we hypothesized that the use of would decline markedly for indications for which there was limited evidence of efficacy but that would continue to be used for evidence-based indications. Me thods Data Sources We used the Surveillance, Epidemiology, and End Results (SEER) Medicare database, which links two large population-based data sources that together provide information about older adults with newly diagnosed cancer, to identify men who had received a diagnosis of prostate cancer. The SEER program consists of regional and state-based tumor registries located throughout the country, representing approximately 14% of the U.S. population before 21 and 26% thereafter. The study was conducted in accordance with the protocol, which was approved by the institutional review board at the University of Michigan. Informed consent was waived since the analyzed data had no personal identifiers. Study Subjects The main analysis included 8,457 men who received a diagnosis of incident prostate cancer from 23 through 25 who were at least 65 years of age at diagnosis. We excluded 6591 men who were not enrolled in both Medicare Part A and Part B for at least 6 months after the cancer diagnosis, 1874 who died within 6 months after diagnosis, 16,38 who were members of a health maintenance organization, and 129 whose cancer was diagnosed on autopsy or was recorded on a death certificate. After these exclusions, 54,925 eligible subjects remained in the analysis. Indications for We defined three groups of men, according to the strength of the indication for use: inappropriate use, appropriate use, and discretionary use. Inappropriate use consisted of a scenario in which there was no reasonable expectation of benefit. This group included men with stage T1 or T2 tumors of a low-to-moderate grade with a Gleason score of 2 to 6 (on a scale of 2 to 1, with higher scores indicating a higher grade of tumor) who did not undergo radiation therapy or radical prostatectomy. In this group, if was used, it would n engl j med 363;19 nejm.org november 4,

3 T h e n e w e ngl a nd j o u r na l o f m e dic i n e A Appropriate Indication for Use No Men Receiving (%) B Inappropriate Indication for Use 5 Men Receiving (%) No Figure 1. Annual Rate of Use of Androgen-Deprivation Therapy () within 6 Months after the Diagnosis of Prostate Cancer from 1994 through 25, According to Indication for Use. Shown are the proportions of men receiving (at least one dose of a gonadotropin-releasing hormone agonist or orchiectomy) who also underwent radiation therapy for the treatment of clinical stage T3 or T4 tumors (a prespecified appropriate indication for 3419 men) (Panel A) and those who had clinical stage T1 or T2 tumors and did not undergo radiation therapy or radical prostatectomy (a prespecified inappropriate indication for 34,957 men) (Panel B). be considered as primary therapy for localized, lowrisk disease, for which there was no evidence of efficacy in clinical trials. 6,1 Furthermore, in such cases, it is difficult to show a survival benefit from any intervention because of the slow natural progression of disease and the competing risk of death from causes other than prostate cancer. 6,11 Appropriate use consisted of a scenario in which treatment was considered to be necessary on the basis of evidence of efficacy and limited alternative treatment options. This group included men with T3 or T4 tumors who underwent radiation therapy, and if were used, it would be considered as adjuvant therapy for locally advanced disease. The use of clearly would represent the best choice for these men, since an overall survival benefit was well established with that regimen. 6,12-15 (Within the framework of this study, adjuvant refers to the use of together with radiation therapy but not radical prostatectomy.) Discretionary use consisted of a scenario in which treatment either was of uncertain benefit because of insufficient evidence or was based on evidence but reasonable alternatives existed. The group included men with T1 or T2 tumors with a high-grade Gleason score (7 to 1). These men were further subdivided into two subgroups. One subgroup included men who did not undergo radiation therapy or radical prostatectomy. If were used in that subgroup, it would be considered primary therapy for localized but high-risk prostate cancer. Although there was no evidence of a survival benefit for primary in clinical trials involving men with such tumors, the increased risk of disease progression or death from prostate cancer would have made use of more compelling. The other subgroup included men who received radiation therapy. If were used in that subgroup, it would be considered adjuvant together with radiation for localized but high-risk prostate cancer. Although the findings of a clinical trial 13 that were reported midway through 24 provided support for the use of adjuvant in such patients, the regimen was included in the discretionary group, since alternative approaches, such as radiation therapy or radical prostatectomy alone, would also be viable treatment options, particularly for men with Gleason 7 tumors. In additional analyses that were designed to provide an overview of trends in the use of starting in the 199s, we defined a cohort of men who received a diagnosis of incident prostate cancer from 1994 through 25. For consistency, because of changes in the composition of SEER registries and in the coding of tumor grade over time, this cohort was limited to patients in the SEER 11 tumor registries, and we expanded the indications for inappropriate use of to include men with T1 or T2 tumors of any Gleason score who did not undergo radiation therapy or radical prostatectomy n engl j med 363;19 nejm.org november 4, 21

4 Study Definitions Study variables are described in Table 1 in the Supplementary Appendix, available with the full text of this article at NEJM.org. Briefly, we used SEER records to categorize men according to age, race or ethnic group, SEER region, year of diagnosis, tumor grade, clinical stage (on the basis of SEER variables Extent of Disease Clinical Extension before 24 and Collaborative Stage Clinical Extension since 24), and prostate-specific antigen (PSA) level. 16 (Before 24, the PSA level was reported only as elevated, borderline, or normal, with reporting of numbers starting in 24.) Since 23, tumor grade has been grouped as low (Gleason score, 2 to 4), moderate (Gleason score, 5 to 6), or high (Gleason score, 7 to 1). We assessed the severity of coexisting illnesses using a modification of the Charlson comorbidity index for use with Medicare claims data. 17,18 The study outcome was the receipt of, which was defined as at least one dose of a GnRH agonist or orchiectomy in the first 6 months after the diagnosis of prostate cancer. 16,19 We obtained data regarding Medicare reimbursement for GnRH agonists from payment variables on the claims files. The dollar amount for a given claim was standardized to a 1-month dose (e.g., the dollar amount was divided by 3 if the claim was for a 3-month depot injection). This standardized amount was then averaged for all claims per quarter. Statistical Analysis For the cohort of men who received a diagnosis of incident prostate cancer from 1994 through 25, we calculated the proportion in each study group who received within 6 months after diagnosis, according to year. For the cohort of men who received a diagnosis of incident prostate cancer from 23 through 25, we calculated the proportion receiving within 6 months after diagnosis in each group, stratified according to the demographic and clinical characteristics of the men. We also calculated the use of according to quarter from 23 through 25 and plotted the data against the average reimbursement per monthly dose of a GnRH agonist. To further examine the effect of reimbursement changes on use, we modeled the effect of the date of diagnosis, since policies changed on January 1, 24, and January 1, 25. We conducted analyses using modified Poisson regression models with as the outcome and with the date of diagnosis (in quarterly increments from 23 through 25) and available characteristics of the men as independent variables. 2 We considered the change in use over time in a piecewise fashion (steady change over each quarter) or in a discontinuous pattern (sudden change in use in 24 or 25) and chose the best-fitting model on the basis of the maximum log-likelihood ratio. For all groups, the best model was one in which the change in use was discontinuous at the start of 24 and 25, and the results are accordingly presented with the year of diagnosis as a categorical variable. We also evaluated shifts in how was implemented. In response to drastic cuts in reimbursement for GnRH agonists, there may have been a shift from use in physicians offices to use in hospital outpatient departments or a shift toward the use of orchiectomy. There may also have been a shift to increased use of the GnRH agonist triptorelin, which was introduced in 23 and had an efficacy similar to that of previously approved GnRH agonists but had a higher level of reimbursement during the study period, since changes in reimbursement policy applied only to older drugs that had been introduced before passage of the Medicare Modernization Act. We therefore examined men who received any during the study period from 23 through 25 and calculated the proportion who were treated with orchiectomy, triptorelin (on the basis of a first claim for a GnRH agonist), or a GnRH agonist in a hospital outpatient setting (on the basis of the site of administration of a first claim) for each year. All tests were two-sided, and a P value of less than.5 was considered to indicate statistical significance. All analyses were performed with the use of SAS statistical software, version 9.1 (SAS Institute). R esult s Rate of Use Figure 1 shows trends in use from 1994 through 25 for appropriate indications (adjuvant with radiation therapy in men with T3 or T4 tumors) and inappropriate indications (primary for men with T1 or T2 tumors). The rate of appropriate use increased from 4.7% to a peak of 85.1% in 24. The rate of inappropri- n engl j med 363;19 nejm.org november 4,

5 T h e n e w e ngl a nd j o u r na l o f m e dic i n e Table 1. Rate of Use of Androgen-Deprivation Therapy () among Men with a Diagnosis of Incident Prostate Cancer from 23 through 25, According to Demographic and Clinical Characteristics of the Subjects.* Variable No. of Subjects Any Inappropriate Appropriate percent of subjects Discretionary Primary Adjuvant Men receiving Age yr 16, yr 15, yr 12, yr 1, Race or ethnic group White 41, Black 5, Hispanic 3, Other 4, SEER region Connecticut 3, Detroit 4, Hawaii Iowa 3, New Mexico 1, Seattle 3, Utah 2, Atlanta/rural Georgia 1, Kentucky 3, Louisiana 4, New Jersey 8, California 17, Marital status Married 36, Not married 18, Census tract Proportion of adults who did not complete high school <8.4% 13, to <14.7% 13, to <25.1% 13, % 13, Proportion of residents below poverty level <4.1% 13, to <7.7% 13, to <15.1% 13, % 13, n engl j med 363;19 nejm.org november 4, 21

6 Table 1. (Continued.) Variable Score on comorbidity index No. of Subjects Any Inappropriate Appropriate percent of subjects Discretionary Primary Adjuvant 35, , , , Year of diagnosis 23 18, , , Clinical stage T1 24, NA T2 25, NA T3 1, NA 79.7 NA NA T4 2, NA 83.1 NA NA Tumor grade Low NA NA NA Moderate 27, NA NA High 24, NA * Among the 54,925 men with a diagnosis of incident prostate cancer from 23 through 25, the total numbers who had clinical indications for the various categories of were 9221 for inappropriate use, 1377 for appropriate use, and 16,984 for discretionary use (with the third category subdivided into 6377 men who had indications for primary and 1,67 who had indications for adjuvant ). The remaining 27,343 men did not fall into the categories defined in the study. NA denotes not applicable, and SEER Surveillance, Epidemiology, and End Results. Race or ethnic group was determined from the SEER database. Scores on the modified Charlson comorbidity index can range from to 24, with higher scores indicating more coexisting conditions. The overall sample size for this index was 5,413 because of the need to exclude patients who did not have at least 12 months of Medicare Part A and Part B coverage before the diagnosis of prostate cancer (for calculation of the score). ate use increased steadily from 3.1% in 1994 to a peak of 44.9% in 22. However, the rate of use dropped rapidly starting in 24, to 35.5% in 25, which was similar to the rate in Of 54,925 men who received a diagnosis of incident prostate cancer from 23 through 25, a total of 43.2% received within 6 months after diagnosis (Table 1). Overall, use declined slightly in 24 and more substantially in 25. For all categories of indications, use was more common in older men, those with coexisting illnesses, and those with advanced-stage or high-grade tumors. The inappropriate use of was more common among black and Hispanic men, unmarried men, and those residing in census tracts with higher rates of poverty or lower rates of education. In contrast, married men and those residing in census tracts with lower rates of poverty or higher rates of education more commonly received for appropriate indications. Use According to Reimbursement In Figure 2, the proportion of men receiving within 6 months after diagnosis for various indications from 23 through 25 according to quarter is plotted against the average reimbursement per monthly dose of GnRH agonist. Reimbursement for GnRH agonists per monthly dose fell from $356 in 23 to $311 in 24 to $176 in 25. n engl j med 363;19 nejm.org november 4,

7 T h e n e w e ngl a nd j o u r na l o f m e dic i n e In the appropriate-use group, there was no decline in use (Fig. 2A). In the inappropriate-use group, there was a dramatic drop in rates in 24, from 39.% in the fourth quarter of 23 to 3.3% in the first quarter of 24, with a continued decline to 22.4% by the end of 25 (Fig. 2B). In the discretionary-use subgroups, the rates of use of were highest through 23 and then gradually declined in 24 and dropped more markedly in 25 (Fig. 2C). Odds of Use over Time Table 2 presents the adjusted odds of use over time. The odds of overall use decreased throughout the study period, with a decrease of nearly 2% in 25, as compared with 23 (odds ratio,.82; 95% confidence interval [CI],.79 to.84). For the inappropriate-use group, there were substantial and significant decreases in the odds of use both in 24 and in 25, with a nearly 3% decline in 25, as compared with 23 (odds ratio,.72; 95% CI,.65 to.79). There was no significant decline in the appropriate-use group in 25, as compared with 23 (odds ratio, 1.1; 95% CI,.86 to 1.19). For both discretionary-use groups, there was no significant decline in the odds of use in 24, whereas there was a significant decline in 25. To determine whether there were regional variations in the change in use over time, we tested for an interaction between SEER region and year of diagnosis on the rate of use in the models of overall and inappropriate use. The results were not significant. As quantitative PSA levels became available as part of the SEER data in 24, we performed further analyses to include the PSA level at diagnosis as a variable in the models of change in use from 24 to 25. The results were essentially unchanged. Changes in Implementation of over Time We also evaluated changes in how was implemented during the study period. Table 3 shows the proportion of men receiving for any indication, according to whether they underwent orchiectomy, received the GnRH agonist triptorelin (reimbursed at an average of $27 per monthly dose in 25 vs. an average of $176 for all GnRH agonists combined), or who received a GnRH agonist in a hospital outpatient setting versus a physician s office. There were significant trends toward increased use of orchiectomy, triptorelin, and Figure 2 (facing page). Rate of Use of Androgen- Deprivation Therapy () within 6 Months after the Diagnosis of Prostate Cancer per Quarter from 23 through 25, According to Indication for Use and Level of Reimbursement. Shown are the proportions of men who received among those with stage T3 or T4 tumors who also underwent radiation therapy (adjuvant, appropriate use) (Panel A), those with stage T1 or T2 tumors of low-to-moderate grade (Gleason score, 2 to 6) who did not undergo radiation therapy or radical prostatectomy (primary, inappropriate use) (Panel B), and those who had stage T1 or T2 tumors of a high grade (Gleason score, 7 to 1) and who either did not undergo radiation therapy or radical prostatectomy (primary, discretionary use) or underwent radiation therapy (adjuvant, discretionary use) (Panel C). All panels include values for the average reimbursement for gonadotropin-releasing hormone (GnRH) agonists per monthly dose (plotted on the y axis at the right side of the graph). Vertical dashed lines represent dates of specific interest, which are numbered as follows: 1 represents January 1, 24, when reimbursement for gonadotropinreleasing hormone (GnRH) agonists was reduced from 95% to 8 to 81% of the average wholesale price; 2 represents August 18, 24, when findings of a prominent clinical trial 13 were published, showing an overall survival benefit for the use of adjuvant with radiation therapy in clinically localized prostate cancer; 3 represents January 1, 25, when reimbursement for GnRH agonists was set at 16% of the average sale price (as compared with the average wholesale price); and 4 represents January 13, 25, when findings of a prominent study 16 were published, showing that use was associated with a risk of fracture. hospital outpatient administration of GnRH agonists, although absolute rates of use in each case remained low. Discussion We found a substantial decline in the use of in close association with reductions in reimbursement for GnRH agonists in 24 and 25. Notably, reductions were most dramatic for indications that were not compatible with available evidence of efficacy. These findings are consistent with previous research on the influence of financial incentives on the delivery of health care. Financial incentives are most likely to have an effect on physicians behavior in cases in which medical uncertainty exists, as opposed to cases in which care is clearly lifesaving. 21 The degree of financial incentive is also important Our results show a gradient, 1828 n engl j med 363;19 nejm.org november 4, 21

8 A Appropriate Indication for Use Men Receiving (%) Adjuvant Dollar amount Reimbursement ($ per dose) B Inappropriate Indication for Use Men Receiving (%) Primary Dollar amount Reimbursement ($ per dose) C Discretionary Indication for Use Men Receiving (%) Primary Adjuvant Dollar amount Reimbursement ($ per dose) n engl j med 363;19 nejm.org november 4,

9 T h e n e w e ngl a nd j o u r na l o f m e dic i n e Table 2. Odds Ratio for the Use of Androgen-Deprivation Therapy (), According to Category of Indication for Use and.* Indication Category 24 vs vs vs. 23 odds ratio (95% confidence interval) Any.93 (.9.96).88 (.85.91).82 (.79.84) Appropriate use (adjuvant, T3 or T4 tumors) 1.3 ( ).98 ( ) 1.1 ( ) Inappropriate use (primary, T1 or T2, low-tomoderate-grade.83 (.77.91).86 (.78.95).72 (.65.79) tumors) Discretionary use Adjuvant, T1 or T2, high-grade tumors.97 ( ).9 (.85.96).88 (.82.94) Primary, T1 or T2, high-grade tumors.98 ( ).87 (.8.94).85 (.78.92) * Odds ratios were calculated from individual modified Poisson regression models for each group. For all models, the dependent variable was the use of within 6 months after diagnosis, and independent variables were the calendar year of diagnosis (as a categorical variable), age at diagnosis, race, SEER region, marital status, score on the comorbidity index, census-tract educational level, census-tract poverty level, clinical stage, tumor grade, and prostate-specific antigen level. Only results for the year of diagnosis are presented. with the greatest drop in use in the context of greatest uncertainty about efficacy and no drop in use where benefits are clearest, findings that are consistent with the hypothesis that financial incentives may be driving the observed trends. In addition, there were changes in how was used, such as an increase in orchiectomy, which may have been financially motivated. However, these shifts were small and probably had a limited clinical effect. In addition, the increased use of triptorelin, a GnRH agonist with a higher level of reimbursement during the study period, may have been related to the expected uptake of a newly introduced product. 25 Alternative explanations for the findings must also be considered. Trends in patterns of administration, such as the increasing use of intermittent therapy or a shift to a longer-acting depot preparation (from 1 month to 3 or 4 months), may have increased the difficulty of capturing the use of in the claims algorithms, leading to an apparent reduction in use. We minimized this problem by requiring the submission of only one claim for a GnRH agonist to define the use of. Furthermore, we directly determined whether claims for GnRH agonists were intended for periods of 1, 3, or 4 months and noted a reduction in all three categories (Table 2 in the Supplementary Appendix). Relevant practice guidelines during the study period were from the National Comprehensive Cancer Network (NCCN), which published guidelines annually, and from the American Society of Clinical Oncology (ASCO), which in April 24 first published recommendations for use in patients with metastatic, progressive, or recurrent prostate cancer There were only subtle changes in the NCCN guidelines over the study period. In 23 but not thereafter, primary was listed as an option for localized but high-risk prostate cancer in patients with a limited life expectancy. The ASCO guidelines, which did not directly address the clinical scenarios that we examined in this study, made no specific recommendations about the early use of primary for asymptomatic metastatic disease, which may have potentially influenced physicians behavior regarding primary use of for localized but high-risk disease. Ongoing clinical trials involving may also have influenced trends in use. An example is the high-profile study, 13 published in August 24, that showed an overall survival benefit when adjuvant was used with radiation therapy for localized but high-risk disease. Despite the additional supportive evidence, this use of declined in 25. Finally, increasing recognition of the adverse effects of is likely to have contributed to some of the observed reductions in use, particularly starting in 25. A major study 16 published in 25 showed an association between and a risk of fracture. Since this study was published shortly after the second change in reimbursement took effect on January 1, 25, it is difficult to separate out the contributions of these influences. Our findings suggest that reductions in reimbursement may influence the delivery of care in 183 n engl j med 363;19 nejm.org november 4, 21

10 Table 3. Change in Type or Place of Administration of Androgen-Deprivation Therapy () from 23 through 25.* Received as Orchiectomy Received as a GnRH Agonist Hospital Outpatient Department Physician Office Triptorelin number (percent) (1.4) 361 (4.2) 822 (94.6) 111 (1.3) (1.9) 419 (5.) 7745 (93.3) 55 (.7) (2.5) 445 (6.6) 6176 (91.2) 428 (6.3) * Denominators include all men with incident prostate cancer who received at least one dose of a gonadotropin-releasing hormone (GnRH) agonist or orchiectomy within 6 months after diagnosis for any indication: 8685 in 23, 832 in 24, and 677 in 25. P<.1 for the test of linear trend in use from 23 to 25. Numbers are based on the first claim submitted for a GnRH agonist within 6 months after diagnosis. a potentially beneficial way, with even the modest changes in 24 associated with a substantial decrease in the use of inappropriate therapy. The corollary is that reimbursement policies should be carefully considered to avoid providing incentives for care for which no clear benefit has been established. The extreme profitability of the use of GnRH agonists during the 199s probably contributed to the rapid growth in the use of for indications that were not evidence based. Supported by a Research Scholar Grant ( RSGI CPHPS, to Dr. Shahinian) from the American Cancer Society. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. We thank members of the Applied Research Program of the National Cancer Institute, the Office of Research, Development, and Information of the Centers for Medicare and Medicaid Services, Information Management Services, and the SEER program. References 1. Crawford ED, Eisenberger MA, McLeod DG, et al. A controlled trial of leuprolide with and without flutamide in prostatic carcinoma. N Engl J Med 1989; 321: [Erratum, N Engl J Med 1989; 321:142.] 2. Huggins C, Hodges CV. Studies on prostatic cancer: I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. J Urol 22;168: Medicare: payments for covered outpatient drugs exceed providers costs. Washington, DC: General Accounting Office, 21. (GAO ) 4. Painter MR. Reimbursement issues with hormonal therapies for prostate cancer. Rev Urol 25;7:Suppl 5:S44-S Shahinian VB, Kuo YF, Freeman JL, Orihuela E, Goodwin JS. Increasing use of gonadotropin-releasing hormone agonists for the treatment of localized prostate carcinoma. Cancer 25;13: Welch HG, Albertsen PC, Nease RF, Bubolz TA, Wasson JH. Estimating treatment benefits for the elderly: the effect of competing risks. Ann Intern Med 1996; 124: Shahinian VB, Kuo YF, Freeman JL, Orihuela E, Goodwin JS. Characteristics of urologists predict the use of androgen deprivation therapy for prostate cancer. J Clin Oncol 27;25: Weight CJ, Klein EA, Jones JS. Androgen deprivation falls as orchiectomy rates rise after changes in reimbursement in the U.S. Medicare population. Cancer 28; 112: Report to the Congress: effects of Medicare payment changes on oncology services. Washington, DC: Medicare Payment Advisory Commission, Chodak GW, Keane T, Klotz L. Critical evaluation of hormonal therapy for carcinoma of the prostate. Urology 22; 6: Chodak GW, Thisted RA, Gerber GS, et al. Results of conservative management of clinically localized prostate cancer. N Engl J Med 1994;33: Bolla M, Collette L, Blank L, et al. Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial. Lancet 22;36: D Amico AV, Manola J, Loffredo M, Renshaw AA, DellaCroce A, Kantoff PW. 6-Month androgen suppression plus radiation therapy vs radiation therapy alone for patients with clinically localized prostate cancer: a randomized controlled trial. JAMA 24;292: Granfors T, Modig H, Damber JE, Tomic R. Combined orchiectomy and external radiotherapy versus radiotherapy alone for nonmetastatic prostate cancer with or without pelvic lymph node involvement: a prospective randomized study. J Urol 1998;159: Pilepich MV, Caplan R, Byhardt RW, et al. Phase III trial of androgen suppression using goserelin in unfavorable-prognosis carcinoma of the prostate treated with definitive radiotherapy: report of Radiation Therapy Oncology Group Protocol J Clin Oncol 1997;15: Shahinian VB, Kuo YF, Freeman JL, Goodwin JS. Risk of fracture after androgen deprivation for prostate cancer. N Engl J Med 25;352: Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987;4: Klabunde CN, Potosky AL, Legler JM, Warren JL. Development of a comorbidity index using physician claims data. J Clin Epidemiol 2;53: Lu-Yao G, Moore DF, Oleynick J, Dipaola RS, Yao SL. Use of hormonal therapy in men with metastatic prostate cancer. J Urol 26;176: Zou G. A modified Poisson regression approach to prospective studies with binary data. Am J Epidemiol 24;159: Shen J, Andersen R, Brook R, Kominski G, Albert PS, Wenger N. The effects of payment method on clinical decisionmaking: physician responses to clinical scenarios. Med Care 24;42: Christianson JB, Knutson DJ, Mazze RS. Physician pay-for-performance: implementation and research issues. J Gen Intern Med 26;21:Suppl 2:S9-S Conrad DA, Christianson JB. Penetrating the black box : financial incentives n engl j med 363;19 nejm.org november 4,

11 for enhancing the quality of physician services. Med Care Res Rev 24;61: Suppl:37S-68S. 24. Hillman AL, Ripley K, Goldfarb N, Nuamah I, Weiner J, Lusk E. Physician financial incentives and feedback: failure to increase cancer screening in Medicaid managed care. Am J Public Health 1998; 88: Chang SL, Liao JC, Shinghal R. Decreasing use of luteinizing hormonereleasing hormone agonists in the United States is independent of reimbursement changes: a Medicare and Veterans Health Administration claims analysis. J Urol 29;182: National Comprehensive Cancer Network. Prostate cancer: NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 24;2: Loblaw DA, Mendelson DS, Talcott JA, et al. American Society of Clinical Oncology recommendations for the initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer. J Clin Oncol 24;22: [Erratum, J Clin Oncol 24;22:4435.] 28. Scardino P. Update: NCCN prostate cancer clinical practice guidelines. J Natl Compr Canc Netw 25;3:Suppl 1:S29-S Scherr D, Swindle PW, Scardino PT. National Comprehensive Cancer Network guidelines for the management of prostate cancer. Urology 23;61:Suppl 1: Copyright 21 Massachusetts Medical Society n engl j med 363;19 nejm.org november 4, 21