In a cohort of men newly diagnosed with low risk prostate cancer between 1992–2005, a 64% reduction in reimbursement for AST was associated with a 40% relative reduction in the prevalence of non-indicated AST (10.2% vs. 6.1%) and a 39% reduction in the adjusted odds of receiving non-indicated AST. There was no statistically significant change for indicated AST in the same time period among men with metastatic disease.The effect for non-indicated AST was stable over alternative definitions of low-risk localized disease and variations in the number of SEER registries included in the analysis. The decline in primary AST could not be attributed to a growth in the preference for competing treatment choices such as radical prostatectomy or radiotherapy because the effect was still seen when eliminating such patients from the low-risk cohort, which is relevant because minimally invasive radical prostatectomy (21
) and intensity modulated radiotherapy increased in popularity during the same period.
Weight et al. (18
) measured the total number of annual Medicare prescriptions for AST from 2001 to 2005 and found a 14% decline in 2005. Their study suggested several alternative explanations beyond financial incentives for an observed decline in Medicare prescriptions for AST. First, there may have been a shift in the presentation of prostate cancer toward lower risk disease. We controlled for such a shift through stratification by tumor characteristics and indications for AST use. Second, there may have been a trend toward using longer acting agents, leading to a reduction in the number of prescriptions per year. We controlled for the possibility of such a trend by operationalizing longer acting agents as several doses of a 1-month agent. Third, there may have been a shift toward intermittent AST, which is a strategy of delivering AST for a limited period, beginning only when the PSA starts to rise and typically ending several months later, after PSA levels fall (22
). By limiting our investigation to the receipt of at least 3 months of AST in the first year, we minimized the possibility of this confounding. Specifically, among non-indicated AST prescriptions, receipt of 1–2 months of AST without receiving a third month was rare (<5% in 2000 and 2005). Last, Weight et al. (18
) hypothesized that the decline in prescription rates might represent a decrease in the use of neoadjuvant AST. We controlled for such a decrease by limiting our non-indicated cases to primary AST monotherapy.
The growing body of evidence of harms attributable to AST may be argued to have resulted in the observed decline in AST use. However, post hoc analyses and administrative database studies documenting high-risk complications of AST such as osteoporotic fractures, metabolic syndrome, and cardiovascular morbidity were mostly published after 2005 (9
). If physicians were increasingly aware of the unintended consequences of AST before the publication of these results, this could have accounted for the decline in AST utilization in 2004–2005. Similar analyses of trends in communities less prone to financial incentives such as the US Veterans Affairs or Canadian health system may shed light on this matter. However, trends in other disease models (ie, perioperative beta blockers) demonstrate that even evidence from randomized trials is slow to affect clinical practice (23
). Thus, the observed pattern of declining AST use in 2004–2005 likely represents a real effect of reimbursement change and not physician awareness of clinical evidence.
We chose to explore AST utilization trends in the extremes of indication—definitely indicated and non-indicated—so as to more clearly explore the effect of payment change on these two groups. Thus, we did not investigate AST utilization trends in intermediate groups such as locally advanced prostate cancer, for which indications for AST utilization in combination with radiotherapy or surgery have changed over our period of investigation (24
). Furthermore, we emphasize that this investigation does not suggest that financial incentives led to the increase in AST seen in the 1990s. Our analysis only allows us to conclude that the reduction in reimbursement is associated with a decline in use in 2004–2005.
The national SEER registry with Medicare follow-up represents a relevant and robust method for examining trends in cancer care. Claims-based research has been shown to reliably collect treatment information when the claim is associated with a physician payment, especially high-reimbursing procedures such as surgery or chemotherapy (28
). However, this study has several limitations. We followed a cohort of Medicare patients; thus, findings may not be valid in younger men. The change in the way SEER classified Gleason scores into WHO grade categories introduced some uncertainty into our trend analysis. Using our primary definition of low-risk disease, men in 2003–2005 had lower grade disease than men before 2003. This shift in the tumor grade of our low-risk cohort led to a false peak in the proportion and the odds of receiving primary AST in 2003. However, there was no change in the definition after 2003; thus, it did not affect measurement of our primary outcome (2004–2005 vs 2003). In addition, whereas methods were designed to minimize bias, residual confounding may exist. Until 2004, SEER did not report the PSA value, only whether it was elevated or not. Thus, our risk stratification did not include an important variable. Moreover, because our analysis covered a long period there is a risk that grade migration may have had an impact on prescription rates. The trend has been to classify the same tumor as higher grade in recent years (31
), which could lead to less AST used in low-grade tumors; however, such migration would be expected to have a gradual impact on AST utilization rates, not the sudden impact that we observed.
Medicare changed the profitability of AST delivery in several ways in 2004–2005. Reimbursement for the drug itself was changed from paying 95% of the average wholesale price through 2003 to 80%–85% of the average wholesale price in 2004 to 106% of the average sales price in 2005 ($190 per 1-month depot in 2005) (32
). These changes in pricing accounted for the decreased reimbursement we explored in this study. In 2004, Medicare also stopped paying for the nursing visit (CPT code 99211) associated with chemotherapy administration and in 2005 lowered the reimbursement for intramuscular or subcutaneous drug injection (CPT code 96400) by about $30. Because these latter reductions were relatively minor and would have introduced additional variability into our model, we did not include them in our analysis. However, future analyses may inquire about how the structure and timing of office visits for drug delivery changed as a result of these other payment changes.
Although the decline in non-indicated AST prescriptions was associated with a coincident decrease in AST payment, the payment change did not affect indicated therapy. Whereas only about 60% of men with metastatic disease receive indicated AST, this frequency did not suffer when reimbursement declined. The lack of a negative impact on indicated therapy may reflect the possibility that Medicare has identified a reimbursement level that is not far below the provider’s true cost of administration or it may represent an ethical constraint on withholding unprofitable beneficial therapy.
AST is one of the many classes of drugs covered under Medicare Part B, including other chemotherapeutics and asthma inhalers that were affected by recent payment changes; thus, our work has broad implications. Indeed, similar to our findings, Jacobson et al. showed that regional variations in payment for other chemotherapeutics in the 1990s did not affect the overall utilization rate of chemotherapy for metastatic breast, lung, or gastrointestinal tumors but did affect the selection of chemotherapeutic agents (33
). Specifically, highly reimbursed physicians were more likely to prescribe more expensive agents. The interesting parallel to our study is that rates of indicated treatment (chemotherapy given or not) were not affected by reimbursement, but where discretion was allowed (ie, choice of which drug to use), reimbursement did affect practice. Future analyses should investigate the AST data with attention to whether the change in prescribing patterns in 2004–2005 was associated with particular physician characteristics. Such analyses could also exploit regional variations in physician reimbursement for AST that occurred because of variations in procedures used by National Drug Code carriers in setting the average wholesale price for AST within each code of the Healthcare Common Procedure Coding System before October 2002 (33
). Similarly, one could examine how AST utilization is affected by regional variation in the adoption of the least costly alternative option for setting reimbursement, a policy that ended on April 19, 2010 (34