Regulatory and HTA Considerations for Development of Real-World Data Derived External Controls.

Regulators and Health Technology Assessment (HTA) bodies are increasingly familiar with, and publishing guidance on, external controls derived from real-world data (RWD) to generate real-world evidence (RWE). We recently conducted a systematic literature review (SLR) evaluating publicly available information on the use of RWD-derived external controls to contextualize outcomes from uncontrolled trials submitted to the European Medicines Agency (EMA), the US Food and Drug Administration (FDA), and/or select HTA bodies. The review identified several key operational and methodological aspects for which more detailed guidance and alignment within and between regulatory agencies and HTA bodies is necessary. This paper builds on the SLR findings by delineating a set of key takeaways for the responsible generation of fit-for-purpose RWE. Practical methodological and operational guidelines for designing, conducting, and reporting RWD-derived external control studies are explored and discussed. These considerations include: (i) early engagement with regulators and HTA bodies during the study planning phase; (ii) consideration of the appropriateness and comparability of external controls across multiple dimensions, including eligibility criteria, temporality, population representation, and clinical evaluation; (iii) ensuring adequate sample sizes, including hypothesis testing considerations; (iv) implementation of a clear and transparent strategy for assessing and addressing data quality, including data missingness across trials and RWD; (v) selection of comparable and meaningful endpoints that are operationalized and analyzed using appropriate analytic methods; and (vi) conduct of sensitivity analyses to assess the robustness of findings in the context of uncertainty and sources of potential bias.

Effectively Leveraging RWD for External Controls: A Systematic Literature Review of Regulatory and HTA Decisions.

Real-world data (RWD)-derived external controls can be used to contextualize efficacy findings for investigational therapies evaluated in uncontrolled trials. As the number of submissions to regulatory and health technology assessment (HTA) bodies using external controls rises, and in light of recent regulatory and HTA guidance on the appropriate use of RWD, there is a need to address the operational and methodological challenges impeding the quality of real-world evidence (RWE) generation and the consistency in evaluation of RWE across agencies. This systematic review summarizes publicly available information on the use of external controls to contextualize outcomes from uncontrolled trials for all indications from January 1, 2015, through August 20, 2021, that were submitted to the European Medicines Agency, the US Food and Drug Administration, and/or select major HTA bodies (National Institute for Health and Care Excellence (NICE), Haute Autorité de Santé (HAS), Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG), and Gemeinsamer Bundesausschuss (G-BA)). By systematically reviewing submissions to regulatory and HTA bodies in the context of recent guidance, this study provides quantitative and qualitative insights into how external control design and analytic choices may be viewed by different agencies in practice. The primary operational and methodological aspects identified for discussion include, but are not limited to, engagement of regulators and HTA bodies, approaches to handling missing data (a component of data quality), and selection of real-world endpoints. Continued collaboration and guidance to address these and other aspects will inform and assist stakeholders attempting to generate evidence using external controls.

Patient-reported outcomes labeling for oncology drugs: Multidisciplinary perspectives on current status and future directions.

Introduction: Regulatory agencies encourage the incorporation of the patient voices throughout clinical drug development. Patient-Reported Outcomes (PROs) offer one way of doing this and their use has markedly increased in many therapeutic areas, particularly oncology, in recent years. However, few oncology drug labels include PRO data and those which do, offer little consistency. Objective: To provide multidisciplinary perspectives (patient, pharmaceutical industry, PRO researcher, regulatory expert) on PRO data in oncology drug labels. Methods: PRO data in the labels of drugs approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for oncology indications between 2010 and 2020 were critically reviewed by authors who provided their insights on the advantages and disadvantages/gaps. Results: Forty-six oncology drugs included PRO data in their labels. Differences were observed between FDA and EMA PRO labeling (e.g., PRO concept, use of tables and graphs to display PROs or reference to clinical meaningfulness). In providing their perspectives on the number and nature of PROs in labels, authors noted limitations including: the low proportion of oncology drugs with PRO labeling, limited PRO information in labels, lack of patient-friendly language, and potential bias towards positive outcomes. Lack of consistency within- and between-agencies was noted. Conclusion: Despite regulatory agencies' commitment to incorporate patient voices in regulatory decisions, availability of PRO information is limited in oncology drug labels. While several PRO guidance documents are available from regulatory and Health Technology Assessment agencies, harmonization of PRO guidance for labeling inclusion around the world is needed to better inform prescribers and consequently their patients in the process of shared medical decisions.

The value of new drugs for advanced prostate cancer.

BACKGROUND: The US Food and Drug Administration has recently approved a number of new cancer drugs. The clinical trials that serve as the basis for new cancer drug approvals may not reflect how the drugs will perform in routine practice and do not measure the impact of the drugs on spending. The authors sought to evaluate the real-world effectiveness and value of drugs recently approved for advanced prostate cancer. METHODS: Using Surveillance, Epidemiology, and End Results-Medicare data, the authors identified fee-for-service Medicare beneficiaries aged 65 years or older who began treatment with a drug approved for metastatic castration-resistant prostate cancer in 2007-2009, when only 1 drug was approved for metastatic castration-resistant prostate cancer, and in 2014-2016, when 5 additional drugs were approved. They calculated life expectancy and lifetime medical costs (ie, Medicare reimbursements) for each group. RESULTS: Between 2007-2009 and 2014-2016, life expectancy increased by 12.6 months. Lifetime medical costs increased by $87,000. The incremental cost per life-year gained was $83,000. CONCLUSION: The release of 5 new drugs coincided with increases in survival rates and spending. This study's estimates indicate that the new drugs collectively were cost-effective.

Patterns of Bicalutamide Use in Prostate Cancer Treatment: A U.S. Real-World Analysis Using the SEER-Medicare Database.

INTRODUCTION: Bicalutamide (BIC), a non-steroidal anti-androgen, is FDA-indicated for use in combination with a luteinizing hormone-releasing hormone (LHRH) analog for treatment of Stage D2 metastatic carcinoma of the prostate. Lack of consensus exists regarding the clinical benefit of BIC use, either alone or combined use of BIC with an LHRH analog or antagonist (combined androgen blockade or CAB), versus treatment with androgen deprivation therapy (ADT) alone. METHODS: The SEER-Medicare database was used to identify prostate cancer patients aged ≥ 66 years diagnosed between 2007 and 2011 and who filled at least one prescription for BIC. Duration of BIC treatment was assessed in relation to ADT use; either alone (monotherapy), as part of CAB only, and as part of CAB followed by monotherapy. Additionally, we assessed use of BIC during or outside a potential testosterone flare prevention period (initiation within 2 months of an LHRH agonist). RESULTS: A total of 7521 prostate cancer patients who filled a prescription for BIC were identified. Eighteen percent of the cohort used BIC alone, over half the patients (54%) used BIC as part of CAB and 27% used BIC as part of CAB followed by monotherapy. Among men treated with BIC as part of CAB, 58% received BIC only within the potential flare period. CONCLUSIONS: Although there is no FDA indication for BIC use as monotherapy, > 44% of patients in this study used BIC alone or as part of CAB followed by monotherapy. Further research is necessary to understand the outcomes of BIC utilization in these settings, particularly compared with newer second-generation anti-androgens. FUNDING: Medivation LLC, a Pfizer company, and Astellas, Pharma, Inc.

Clinical and economic burden associated with stage III to IV triple-negative breast cancer: A SEER-Medicare historical cohort study in elderly women in the United States.

BACKGROUND: The current study was performed to describe patient characteristics, treatment patterns, survival, health care resource use (HRU), and costs among older women in the United States with advanced (American Joint Committee on Cancer stage III/IV) triple-negative breast cancer (TNBC) in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. METHODS: Women who were aged ≥66 years at the time of diagnosis and diagnosed with advanced TNBC between January 1, 2007, and January 1, 2011, in the SEER-Medicare database and who were followed for survival through December 31, 2013, were eligible. Patient demographic and clinical characteristics at the time of diagnosis, subsequent treatment patterns, and survival outcomes were analyzed. HRU and costs for the first 3 months after diagnosis, the last 3 months of life, and the time in between are summarized. All analyses were stratified by American Joint Committee on Cancer stage of disease. RESULTS: There were 1244 patients newly diagnosed with advanced TNBC; the majority were aged ≥75 years (61% with stage III disease and 57.4% with stage IV disease) and white (>70% of patients in both disease stage groups). The most common treatment approaches were surgery combined with chemotherapy for patients for stage III disease (50.6%) and chemotherapy alone or with radiotherapy for patients with stage IV disease (31.3%). Diverse chemotherapy regimens were administered for each line of therapy; nevertheless, the medications used were consistent with national guidelines. Patients with stage III and stage IV disease were found to have a similar mean number of hospitalizations and outpatient visits, but mean monthly costs were greater for patients with stage IV disease at all 3 time points. The mean cost per patient-month (in 2013 US dollars) was $4810 for patients with stage III disease and $9159 for patients with stage IV disease. CONCLUSIONS: Among older women with advanced TNBC, significant treatment variations and considerable HRU and costs exist. Further research is needed to find effective treatments with which to reduce the clinical and economic burden of this disease. Cancer 2018;124:2104-14. © 2018 American Cancer Society.

Revisiting the utility of technical performance scores following tetralogy of Fallot repair.

OBJECTIVE: Although an important quality metric, current technical performance scores may not be generalizable and may omit operative factors that influence outcomes. We examined factors not included in current technical performance scores that may contribute to increased postoperative length of stay, major complications, and cost after primary repair of tetralogy of Fallot. METHODS: This is a retrospective single site study of patients younger than age 2 years with tetralogy of Fallot undergoing complete repair between 2007 and 2015. Medical record data and discharge echocardiograms were reviewed to ascertain component and composite technical performance scores. Primary outcomes included postoperative length of stay, major complications, and total hospital costs. Multivariable logistic and linear regression identified determinants of each outcome. RESULTS: Patient population (n = 115) had a median postoperative length of stay of 8 days (interquartile range, 6-10 days), and a median total cost of $71,147. Major complications occurred in 33 patients (29%) with 1 death. Technical performance scores assigned were optimum in 28 patients (25%), adequate in 59 patients (52%), and inadequate in 26 patients (23%). Neither technical performance score components nor composite scores were associated with increased postoperative length of stay. Optimum or adequate repairs versus inadequate had equal risk of a complication (P = .79), and equivalent mean total cost ($100,000 vs $187,000; P = .25). Longer cardiopulmonary bypass time per 1-minute increase (P < .01) was associated with longer postoperative length of stay and reintervention (P = .02). The need to return to bypass also increased total cost (P < .01). CONCLUSIONS: Current tetralogy of Fallot technical performance scores were not associated with selected outcomes in our postoperative population. Although returning to bypass and bypass length are not included as components in the current score, these are important factors influencing complications and resource use in our population. Revisions anticipated from a prospective trial should consider including these variables.

A systematic review to assess adherence and persistence with statins.

OBJECTIVE: To identify and assess studies published over a 10 year period up to February 2016 which measure adherence or persistence with statins, to summarize their methods, strengths and weaknesses and to summarize evidence linking statin adherence/persistence with risk of cardiovascular events. METHODS: Electronic databases and abstracts from four major cardiovascular disease conferences were searched from January 2005 to February 2016. The study selection process was performed by two reviewers working independently. Studies were included if they reported data regarding patient adherence or persistence with statins in adults with primary hypercholesterolemia, using any type of study design or length of follow-up. One reviewer extracted the study data and assessed study quality, which was checked by a second reviewer independently. Given the heterogeneity between the included studies a narrative critique and summary is presented. RESULTS: We report on 84 real world studies which aimed to assess adherence or persistence with statins. The majority of studies concluded that good adherence/persistence was associated with reduction in cardiovascular events and mortality. In two studies high intensity statin regimens were associated with poorer patient adherence when compared to low intensity statins. Adherence and persistence with statin therapy also has an impact on hospitalization costs and other cardiovascular disease (CVD) related costs. CONCLUSIONS: Adherence and persistence are associated with a reduction in CVD events and mortality. There was limited evidence to suggest that high intensity statin regimens are associated with poorer treatment adherence when compared to lower intensity regimens. Hence, more robust studies are required to establish this association. As recommended by the 2013 ACC/AHA, 2016 ESC and several other clinical guidelines, clinicians and pharmacy managers should regularly monitor statin therapy adherence.

A Systematic Review of Cardiovascular Outcomes-Based Cost-Effectiveness Analyses of Lipid-Lowering Therapies.

BACKGROUND: Previous reviews have evaluated economic analyses of lipid-lowering therapies using lipid levels as surrogate markers for cardiovascular disease. However, drug approval and health technology assessment agencies have stressed that surrogates should only be used in the absence of clinical endpoints. OBJECTIVE: The aim of this systematic review was to identify and summarise the methodologies, weaknesses and strengths of economic models based on atherosclerotic cardiovascular disease event rates. METHODS: Cost-effectiveness evaluations of lipid-lowering therapies using cardiovascular event rates in adults with hyperlipidaemia were sought in Medline, Embase, Medline In-Process, PubMed and NHS EED and conference proceedings. Search results were independently screened, extracted and quality checked by two reviewers. RESULTS: Searches until February 2016 retrieved 3443 records, from which 26 studies (29 publications) were selected. Twenty-two studies evaluated secondary prevention (four also assessed primary prevention), two considered only primary prevention and two included mixed primary and secondary prevention populations. Most studies (18) based treatment-effect estimates on single trials, although more recent evaluations deployed meta-analyses (5/10 over the last 10 years). Markov models (14 studies) were most commonly used and only one study employed discrete event simulation. Models varied particularly in terms of health states and treatment-effect duration. No studies used a systematic review to obtain utilities. Most studies took a healthcare perspective (21/26) and sourced resource use from key trials instead of local data. Overall, reporting quality was suboptimal. CONCLUSIONS: This review reveals methodological changes over time, but reporting weaknesses remain, particularly with respect to transparency of model reporting.

Systematic Review of Low-Density Lipoprotein Cholesterol Apheresis for the Treatment of Familial Hypercholesterolemia.

BACKGROUND: Apheresis is an important treatment for reducing low-density lipoprotein cholesterol (LDL-C) in patients with familial hypercholesterolemia (FH). We systematically reviewed the current literature surrounding LDL-C apheresis for FH. METHODS AND RESULTS: Electronic databases were searched for publications of LDL-C apheresis in patients with FH. Inclusion criteria include articles in English published in 2000-2013 that provide descriptions of practice patterns, efficacy/effectiveness, and costs related to LDL-C apheresis in patients with FH. Data were stratified by country and FH genotype where possible. Thirty-eight studies met the inclusion criteria: 8 open-label clinical trials, 11 observational studies, 17 reviews/guidelines, and 2 health technology assessments. The prevalence of FH was not well characterized by country, and underdiagnosis was a barrier to FH treatment. Treatment guidelines varied by country, with some guidelines recommending LDL-C apheresis as first-line treatment in patients with homozygous FH and after drug therapy failure in patients with heterozygous FH. Additionally, guidelines typically recommended weekly or biweekly LDL-C apheresis treatments conducted at apheresis centers that may last 2 to >3 hours per session. Studies reported a range for mean LDL-C reduction after apheresis: 57-75% for patients with homozygous FH and 58-63% for patients with heterozygous FH. Calculated annual costs (in US$2015) may reach US$66 374 to US$228 956 per patient for weekly treatment. CONCLUSIONS: LDL-C apheresis treatment may be necessary for patients with FH when drug therapy is inadequate in reducing LDL-C to target levels. While apheresis reduces LDL-C, high per-session costs and the frequency of guideline-recommended treatment result in substantial annual costs, which are barriers to the optimal treatment of FH.

Cardiovascular Disease, Mortality Risk, and Healthcare Costs by Lipoprotein(a) Levels According to Low-density Lipoprotein Cholesterol Levels in Older High-risk Adults.

BACKGROUND: The value of lipoprotein(a) (Lp[a]) for predicting cardiovascular disease (CVD) across low-density lipoprotein cholesterol (LDL-C) is uncertain. HYPOTHESIS: In older high-risk adults, higher LDL and Lp(a) combined would be associated with higher CVD risk and more healthcare costs. METHODS: We included 3251 high-risk subjects (prior CVD, diabetes, or 10-year Framingham CVD risk >20%) age ≥65 years from the Cardiovascular Health Study and examined the relation of Lp(a) tertiles with incident CVD, coronary heart disease (CHD), and all-cause mortality within LDL-C strata (spanning <70 mg/dL to ≥160 mg/dL). We also examined 1-year all-cause and CVD healthcare costs from Medicare claims. RESULTS: Over a 22.5-year follow-up, higher Lp(a) levels predicted CVD and total mortality (both standardized hazard ratio [HR]: 1.06, P < 0.01), whereas higher LDL-C levels predicted higher CHD (standardized HR: 1.09, P < 0.01) but lower total mortality (standardized HR: 0.94, P < 0.001). Adjusted HRs in the highest (vs lowest) tertile of Lp(a) level were 1.95 (P = 0.06) for CVD events and 2.68 (P = 0.03) for CHD events when LDL-C was <70 mg/dL. One-year all-cause healthcare costs were increased for Lp(a) ($771 per SD of 56 µg/mL [P = 0.03], $1976 for Lp(a) 25-64 µg/mL vs <25 µg/mL [P = 0.02], and $1648 for Lp(a) ≥65 µg/mL vs <25 µg/mL [P = 0.054]) but not LDL-C. CONCLUSIONS: In older high-risk adults, increased Lp(a) levels were associated with higher CVD risk, especially in those with LDL-C <70 mg/dL, and with higher healthcare costs.

Assessment of statin therapy, LDL-C levels, and cardiovascular events among high-risk patients in the United States.

BACKGROUND: Statins have demonstrated significant benefit in reducing cardiovascular disease (CVD) risk. OBJECTIVE: To evaluate statin treatment patterns by intensity, elevated low-density lipoprotein cholesterol (LDL-C) levels, and cardiovascular (CV) events in high-risk CVD patients. METHODS: Patients included were aged ≥ 18 years, with a coronary heart disease (CHD; Jan 1, 2007-Dec 31, 2011, index date) or CHD risk equivalent (CHD RE) diagnosis (Jan 1, 2007-Dec 31, 2010, index date), in the Truven MarketScan claims database, continuously enrolled for 2 years pre- and up to 1 (CHD) or 2 (CHD RE) years post-index. Patients with CHD, CHD RE, rhabdomyolysis, or chronic kidney disease any time pre-index were excluded. Statin therapy was assessed at baseline, 30, 90, and 365 days post-index. LDL-C values were captured in patients with available data at 30-day intervals up to 1 year. CV events were evaluated up to 1 year post-index. Descriptive statistics were used to report results. RESULTS: There were 175,103 CHD and 68,290 CHD RE patients; 3333 CHD RE patients had post-index CV events. At 1 year, 38.7% of CHD patients and 44.3% of CHD RE patients with post-index CV events were not prescribed statins. Most patients who were prescribed statins, received a moderate-intensity statin. The percentage of patients with LDL-C ≥ 100 mg/dL reduced over time, but at 1 year, 29.3% of CHD and 30.0% of CHD RE patients with post-index CV events had LDL-C ≥ 100 mg/dL. At 1 year post-index, 9.9% CHD and 7.3% CHD RE patients had at least 1 CV event. CONCLUSION: There is room for better LDL-C management among high-risk CVD patients to reduce their overall CV risk.

A US Claims-Based Analysis of Real-World Lipid-Lowering Treatment Patterns in Patients With High Cardiovascular Disease Risk or a Previous Coronary Event.

The objective was to examine real-world treatment patterns of lipid-lowering therapies and their possible associated intolerance and/or ineffectiveness in patients with high cardiovascular disease (CVD) risk initiating statins and/or ezetimibe. Patients aged ≥18 years who initiated statins and/or ezetimibe from January 01, 2007, to June 30, 2011, were retrospectively identified from the IMS LifeLink PharMetrics Plus commercial claims database. Patients were further classified into 2 cohorts: (1) history of cardiovascular event (CVE) and (2) history of coronary heart disease risk equivalent (CHD RE). Patients had continuous health plan enrollment ≥1 year pre- and post-index date (statin and/or ezetimibe initiation date). Primary outcomes were index statin intensity, treatment modifications, possible associated statin/nonstatin intolerance and/or ineffectiveness issues (based on treatment modification), and time-to-treatment modifications. Analyses for each cohort were stratified by age group (<65 and ≥65 years). A total of 41,934 (history of CVE) and 170,344 patients (history of CHD RE) were included. On the index date, 8.8% to 25.1% of patients were initiated on high-intensity statin. Among patients aged <65, 79.2% and 48.8% of those with history of CVE and 78.6% and 47.3% of those with a history of CHD RE had ≥1 and 2 treatment modifications, respectively. Among all patients, 24.6% to 25.6% had possible statin intolerance and/or ineffectiveness issues after accounting for second treatment modification (if any). In conclusion, in patients with high CVD risk, index statin treatment modifications that imply possible statin intolerance and/or ineffectiveness were frequent; low use of high-intensity statins indicates unmet need in the management of hyperlipidemia and possible remaining unaccounted CVD residual risk.

Clinical and economic burden associated with cardiovascular events among patients with hyperlipidemia: a retrospective cohort study.

BACKGROUND: Annual direct costs for cardiovascular (CV) diseases in the United States are approximately $195.6 billion, with many high-risk patients remaining at risk for major cardiovascular events (CVE). This study evaluated the direct clinical and economic burden associated with new CVE up to 3 years post-event among patients with hyperlipidemia. METHODS: Hyperlipidemic patients with a primary inpatient claim for new CVE (myocardial infarction, unstable angina, ischemic stroke, transient ischemic attack, coronary artery bypass graft, percutaneous coronary intervention and heart failure) were identified using IMS LifeLink PharMetrics Plus data from January 1, 2006 through June 30, 2012. Patients were stratified by CV risk into history of CVE, modified coronary heart disease risk equivalent, moderate- and low-risk cohorts. Of the eligible patients, propensity score matched 243,640 patients with or without new CVE were included to compare healthcare resource utilization and direct costs ranging from the acute (1-month) phase through 3 years post-CVE date (follow-up period). RESULTS: Myocardial infarction was the most common CVE in all the risk cohorts. During the acute phase, among patients with new CVE, the average incremental inpatient length of stay and incremental costs ranged from 4.4-6.2 days and $25,666-$30,321, respectively. Acute-phase incremental costs accounted for 61-75% of first-year costs, but incremental costs also remained high during years 2 and 3 post-CVE. CONCLUSIONS: Among hyperlipidemic patients with new CVE, healthcare utilization and costs incurred were significantly higher than for those without CVE during the acute phase, and remained higher up to 3 years post-event, across all risk cohorts.

Productivity loss and indirect costs associated with cardiovascular events and related clinical procedures.

BACKGROUND: The high acute costs of cardiovascular disease and acute cardiovascular events are well established, particularly in terms of direct medical costs. The costs associated with lost work productivity have been described in a broad sense, but little is known about workplace absenteeism or short term disability costs among high cardiovascular risk patients. The objective of this study was to quantify workplace absenteeism (WA) and short-term disability (STD) hours and costs associated with cardiovascular events and related clinical procedures (CVERP) in United States employees with high cardiovascular risk. METHODS: Medical, WA and/or STD data from the Truven Health MarketScan® Research Databases were used to select full-time employees aged 18-64 with hyperlipidemia during 2002-2011. Two cohorts (with and without CVERP) were created and screened for medical, drug, WA, and STD eligibility. The CVERP cohort was matched with a non-CVERP cohort using propensity score matching. Work loss hours and indirect costs were calculated for patients with and without CVERP and by CVERP type. Wages were based on the 2013 age-, gender-, and geographic region-adjusted wage rate from the United States Bureau of Labor Statistics. RESULTS: A total of 5,808 WA-eligible, 21,006 STD-eligible, and 3,362 combined WA and STD eligible patients with CVERP were well matched to patients without CVERP, creating three cohorts of patients with CVERP and three cohorts of patients without CVERP. Demographics were similar across cohorts (mean age 52.2-53.1 years, male 81.3-86.8%). During the first month of follow-up, patients with CVERP had more WA/STD-related hours lost compared with patients without CVERP (WA-eligible: 23.4 more hours, STD-eligible: 51.7 more hours, WA and STD-eligible: 56.3 more hours) (p < 0.001). Corresponding costs were $683, $895, and $1,119 higher, respectively (p < 0.001). Differences narrowed with longer follow-up. In the first month and year of follow-up, patients with coronary artery bypass graft experienced the highest WA/STD-related hours lost and costs compared with patients with other CVERP. CONCLUSIONS: CVERP were associated with substantial work loss and indirect costs. Prevention or reduction of CVERP could result in WA and STD-related cost savings for employers.

Association of reimbursement policy and urologists' characteristics with the use of medical androgen deprivation therapy for clinically localized prostate cancer.

OBJECTIVES: Physician characteristics and changes in drug reimbursement rates have been shown to influence practice patterns regardless of clinical guidelines, patient, clinical, or sociodemographic factors. We concurrently examined the association between urologists׳ characteristics and non-evidence-based use of primary medical androgen deprivation therapy (ADT) for clinically localized patients with prostate cancer, before and after the 2003 Medicare Modernization Act׳s reductions in ADT reimbursement rates. METHODS AND MATERIALS: The Surveillance, Epidemiology, and End Results-Medicare-linked database and the American Medical Association Physician Masterfile are used in a retrospective analysis of 12,255 patients diagnosed between 2001 and 2007 with clinical stage T1-T2, low- to intermediate-grade prostate cancer, and the 1,863 urologists who treated them. Logistic multilevel regression analyses are used to evaluate the association of urologists׳ characteristics on ADT use among patients within 6 months of diagnosis. RESULTS: Overall, 3,866 (32%) patients received non-evidence-based ADT. After adjusting for patient and urologist characteristics, patients treated by urologists with no medical school affiliations, compared with those treated by urologists with major medical school affiliations, are significantly more likely to receive non-evidence-based medical ADT (odds ratio = 2.35; 95% CI: 1.71-3.23; P<0.0001). Non-US-trained urologists are also more likely to prescribe non-evidence-based medical ADT (odds ratio = 1.64; 95% CI: 1.33-2.04; P<0.0001). CONCLUSIONS: Patients treated by non-medical school-affiliated or non-US-trained urologists or both are significantly more likely to receive non-evidence-based ADT before and after the passage of the Medicare Modernization Act. Better strategies to encourage evidence-based ADT use on clinically localized patients with prostate cancer may be of benefit especially among non-medical school-affiliated or non-US-trained urologists or both.

Determinants of the combined use of external beam radiotherapy and brachytherapy for low-risk, clinically localized prostate cancer.

BACKGROUND: Prostate cancer treatment choices have been shown to vary by physician and patient characteristics. For patients with low-risk, clinically localized prostate cancer, the authors examined the impact of their clinical, sociodemographic, and radiation oncologists' (RO) characteristics on the likelihood that the patients would receive combined external beam radiotherapy and brachytherapy, a treatment regimen that is at variance with clinical guidelines. METHODS: The Surveillance, Epidemiology and End Results (SEER)-Medicare linked database and the American Medical Association Physician Masterfile were used in a retrospective analysis of 5531 patients with low-risk, clinically localized prostate cancer who were diagnosed between 2004 and 2007, and the 708 ROs who treated them. Hierarchical logistic regression analyses were used to evaluate the relationship between patient and RO characteristics and the use of combined therapy within 6 months of diagnosis. RESULTS: Overall, 356 patients (6.4%) received combined therapy. Nonclinical factors were found to be associated with combined therapy. After adjusting for patient and RO characteristics, the odds of receiving combined therapy for patients residing in Georgia were found to be significantly greater than for all other SEER regions. Black patients were significantly less likely to receive combined therapy (odds ratio, 0.62; 95% confidence interval, 0.40-0.96 [P= .03]) compared with white patients. In addition, ROs accounted for 36.6% of the variation in patients receiving combined therapy. CONCLUSIONS: Geographic and sociodemographic factors were found to be significantly associated with guideline-discordant combined therapy for patients diagnosed with low-risk, clinically localized prostate cancer. Which RO a patient consults is important in determining whether they receive combined therapy.