Changes in opioid marketing practices after release of the CDC guidelines.

OBJECTIVES: After the release of the CDC guidelines in March 2016, the rate of opioid prescriptions decreased. How or whether pharmaceutical companies changed their opioid marketing practices post release of the CDC guidelines is unknown. Our objectives were to (1) evaluate whether the release of the guidelines was associated with changes in total monthly marketing spending received per physician, monthly marketing encounter frequency per physician, and spending per encounter during opioid marketing; and (2) evaluate whether such changes in marketing differed between specialist physicians and primary care physicians (PCPs) and between urban and rural primary care service areas (PCSAs). STUDY DESIGN: Retrospective observational cross-sectional study using opioid marketing spending data from the CMS Open Payments database between August 2013 and December 2017. METHODS: Single-group and multiple-group interrupted time series analyses were used to evaluate differences in the immediate changes in level and trend over time in opioid marketing practices post release of the CDC guidelines. RESULTS: Post release of the CDC guidelines, the monthly number of marketing encounters per physician and total monthly amount received per physician decreased. However, the amount spent at each marketing encounter increased. The release of the CDC guidelines was associated with an immediate increase in level of opioid marketing spending per encounter by $0.59 (95% CI, $0.51-$0.68; P < .001) and an over-time increase in rate of spending per encounter of $0.04 per month (95% CI, $0.03-$0.05; P < .001). These changes differed between specialists and PCPs and between urban and rural PCSAs. CONCLUSIONS: It is important to continue ongoing education for physicians on changes in pharmaceutical opioid marketing practices.

Analysis of Affordable Health Care.

BACKGROUND: Lack of affordable health care affects the uninsured, commercially insured, and Medicare beneficiaries. Yet, the wide variation in providers' prices and practice styles suggests that more affordable care already may be available and data on low value and wasteful care suggest that lower cost care need not come at the expense of better quality. Although price variation has received the most attention in the literature and legislation, total cost of care is a function of both unit prices (fees) and the quantity of services. OBJECTIVE: To partition provider-specific variation in total annual risk-adjusted per capita expenditures on health care services into variation in unit prices (fees) versus quantities of services, and to explore the relationship between low value, avoidable, discretionary, and recommended care to total health expenditures. The analysis is important because both prices and quantities of services can affect affordability and reductions in prices versus quantities have very different effects on providers' profits. SETTING: 2018 data from the Minnesota State Employees Group Insurance Program (SEGIP) that offers a tiered cost-sharing health insurance benefit design to 130,000 State employees and their dependents (SEGIP "members"). EXPOSURE: Each year during open enrollment, SEGIP members choose a primary care clinic (PCC). The PCC can make decisions regarding both unit prices and prescribed services. PCCs are placed in one of four cost-sharing tiers based on the total annual risk-adjusted per capita health expenditures for the SEGIP members who choose their clinic. Members choosing higher cost PCCs face higher deductibles, copayments, and maximum out-of-pocket spending limits. MEASURES: Overall prices and use of inpatient, outpatient hospital, professional, and pharmaceutical services, total and avoidable use of emergency department visits and inpatient admissions, low value care, testing for patients with pneumonia, and recommended preventive care. RESULTS: Differences in total risk-adjusted annual per capita health expenditures across the care systems were substantial. Higher cost providers had both higher unit prices and higher use of services. Variation in the quantity of health care services explained more of the variance in total spending than variation in prices. Prices for professional services and use of inpatient, outpatient hospital, and pharmaceutical services, and ambulatory care sensitive admissions, contributed significantly to high total expenditures. Lower cost PCCs in the lowest cost-sharing tier had higher rates of low value care and lower emergency department visits per capita. Neither the number of investigations for patients with pneumonia nor the receipt of recommended mammography screening varied systematically by tier. CONCLUSIONS: Efforts to identify and expand sources of affordable care, including improved information and incentives for consumers, need to account for variation in both prices and quantities of services. Efforts to encourage more efficient use of health care services by providers need to consider the effect of those efforts on the provider's internal costs and thus their profits.

FDA safety warnings and trends in testosterone marketing to physicians.

In response to study findings showing the risk of cardiovascular adverse events associated with testosterone therapy, the FDA issued safety warnings in 2014 and modified testosterone labeling in March 2015 to indicate the increased risk of stroke and heart attack. It is unknown whether there were changes in testosterone marketing practices by pharmaceutical companies following the FDA label warning. Both primary care physicians (PCPs) and non-PCPs prescribe testosterone and are targeted by pharmaceutical marketing representatives to encourage testosterone prescribing. Likewise, pharmaceutical marketing occurs in both urban and rural areas. Our study is the first to examine testosterone marketing practices around the period of the testosterone label warning by physician specialty and rural vs urban primary care service area. In this study, we found that testosterone marketing efforts such as marketing spending per encounter, quarterly marketing spending per physician, and quarterly number of encounters per physician increased among non-PCPs and urban physicians for 4 quarters following an FDA boxed warning in 2015 on testosterone prescriptions. After the black box warning, off-label testosterone advertisements stopped. This reduction in advertising could have made it more attractive for pharmaceutical companies to increase their marketing spending targeting non-PCPs and physicians in urban areas. Understanding responses of pharmaceutical companies to FDA guidelines is important and can help inform future guideline initiatives.

Association of opioid fills with centers for disease control and prevention opioid guidelines and payer coverage policies: physician, insurance and geographic factors.

Background The Centers for Disease Control and Prevention (CDC) issued guidelines and certain healthcare payers have made pharmacy coverage changes (PCC) focusing on regulating prescription opioids. Aim We evaluated differences in the rate of first-time opioid fills at doses ≥ 50 morphine milligram equivalents (MME)/day and first-time opioid fills with benzodiazepine fill overlap following the CDC guidelines and following a PCC between provider types, geographic locations, and insurance types. Method We used OptumLabs® Data Warehouse claims data between 2014 and 2018. Subjects were opioid naïve non-cancer care patients, 18 years and older who had an identified chronic pain condition ICD diagnosis within 2 weeks prior to their first-time opioid fill. We used multiple treatment period segmented regression analysis with interaction terms to test the differences between primary care providers (PCPs) and specialist providers (SPs), urban and rural primary care service areas (PCSAs), and Medicare Advantage (MA) and commercially insured patients (CIPs) in their first-time opioid fill patterns. Results Prescribing first-time opioid fills at doses ≥ 50MME/day declined following the CDC guidelines and PCC, the decline was greater among SPs than PCPs and in rural PCSAs than urban PCSAs. Also, following the CDC guidelines, the decline was greater among MA patients however following the PCC the decline was greater among CIPs. There were no differences in rate of first-time opioid fill with benzodiazepine overlap between groups. Conclusion Responses to the CDC opioid guidelines and a PCC differed between PCPs and SPs, urban and rural PCSAs, and when prescribing to MA and CIPs. Understanding these differences is important to help inform future guidelines.

Influence of Histologic Types and Subtypes on Survival Outcomes of Intermediate-High and High-Risk Renal Cell Carcinoma Following Nephrectomy: Findings From the SEER Database.

OBJECTIVE: To understand the influence of histologic subtypes on the survival outcomes of intermediate-high and high-risk renal cell carcinoma (RCC) following nephrectomy. METHODS: This study employed data files from the SEER Program to identify patients diagnosed with intermediate-high or high risk RCC and treated with nephrectomy. Unadjusted Kaplan Meier curves, and multivariable Cox regression analyses were applied to estimate the hazards of histologic types for overall survival (OS) and cancer-specific survival (CSS). RESULTS: OS was higher for chromophobe (HR=0.58, 95% CI 0.47-0.70; P<.0001), similar for papillary (HR=0.90, 95% CI 0.80-1.02; P=.11) and worse for sarcomatoid (HR=3.17, 95% CI 2.70-3.72; P<.0001) subtypes relative to the clear cell subtype. OS was lower in the high-risk disease (HR=2.35, 95% CI 2.01-2.74; P <.0001) versus intermediate-high risk disease. CSS was higher for chromophobe (HR=0.47, 95% CI 0.35-0.63; P<.0001), similar for papillary (HR=0.91, 95% CI 0.77-1.08; P=.28) and worse for sarcomatoid (HR=4.19, 95% CI 3.50-5.02; P<.0001) subtypes relative to the clear cell subtype. CSS was lower for the high-risk disease (HR=2.86, 95%CI 2.39-3.43; P <.0001) relative to intermediate-high risk disease.

Association of 3 CDC opioid prescription guidelines for chronic pain and 2 payer pharmacy coverage changes on opioid initiation practices.

BACKGROUND: Due to the US opioid epidemic, in March of 2016, the Centers for Disease Control and Prevention (CDC) published new guidelines for primary care providers on opioid prescribing for chronic pain. Payer coverage changes were also implemented to help modify opioid prescribing behavior. Whether these initiatives were associated with changes in opioid initiation patterns is unknown. OBJECTIVE: To assess the association between 3 of the 2016 CDC guidelines and 2 subsequent payer pharmacy coverage changes with changes in opioid initiation behavior across different provider specialties. METHODS: We conducted a real-world evidence study using claims data from OptumLabs Data Warehouse between January of 2014 and December of 2018. Subjects were continuously enrolled opioid naive patients, aged at least 18 years, who had at least 1 chronic pain diagnosis within 2 weeks before their first (first-time) opioid prescription. The study used multiple treatment period segmented regression analysis to evaluate the association, across different provider specialties, between the CDC guideline release and the payer pharmacy coverage changes with immediate change in level and overall change in the rate of first-time extended-release opioid prescriptions, firsttime opioid prescriptions at doses of at least 50 MME (morphine milligram equivalent) per day, and first-time opioid prescriptions with overlapping benzodiazepine prescription. RESULTS: The CDC guidelines were not associated with any change in the rate of first-time prescriptions of extended-release opioids. However, a January 2017 payer pharmacy coverage change was associated with a reduction over time in first-time extended-release opioid prescription rates by 22.15 in every 100,000 prescriptions (CI = -40.04 to -2.92, P = 0.013). The CDC guidelines were associated with an immediate decline in level of first-time opioid prescription at doses of at least 50 MME per day by 74.00 in every 10,000 prescriptions (CI = -124.86 to -23.13, P = 0.004) and an increased rate of decline over time by 13.64 in every 10,000 prescriptions (CI = -17.07 to -10.21, P < 0.001). These associations varied across provider types and specialties. The March 2018, payer coverage change was associated with an immediate reduction in level of first-time opioid prescriptions at doses of at least 50 MME per day across all specialties and an increased reduction over time among surgeons. The CDC guidelines were associated, respectively, with a reduction in the rate of overlapping first-time opioid prescriptions with benzodiazepines among family medicine, internal medicine, surgeons, emergency medicine providers, and providers with unknown specialty by 6.11, 5.10, 2.89, 11.43, and 9.11 in every 10,000 prescriptions monthly (CI = -9.48 to -2.73, -9.86 to -0.35, -5.40 to -0.38, -17.26 to -5.61 and -11.96 to -6.25, respectively, P < 0.001, P = 0.035, P = 0.024, P < 0.001 and P < 0.001). CONCLUSIONS: Some specialist providers also adopted the CDC guidelines, and the response to the guidelines differed across various provider specialties. Some CDC guidelines were associated with a reduction in high-risk first-time opioid prescriptions. Payer pharmacy coverage changes reinforced the guidelines both in situations where the CDC guidelines did and did not show any association. DISCLOSURE: This research was funded by Agency for Healthcare Research and Quality (R01 HS025164; PI: Karaca-Mandic). Karaca-Mandic reports grants from the American Cancer Society and Sempre Health, along with fees from Tactile Medical and Precision Health Economics, unrelated to this study. The other authors have nothing to disclose.

Association between preoperative prostate-specific antigen levels and mortality in high- and intermediate-grade prostate cancer patients who received radical prostatectomy: Findings from the SEER database.

BACKGROUND: The degree of expression of prostate-specific antigen (PSA) has been applied for the purpose of screening and monitoring the progression of prostate cancer. The goal of this study was to evaluate the association between preoperative PSA levels and mortality outcomes in men with high- and intermediate-grade prostate cancer who received radical prostatectomy. METHODS: The 2004-2014 files of the Surveillance, Epidemiology, and End Result database were analyzed. A total of 97,357 patients with non-metastatic high- and intermediate-grade adenocarcinoma of the prostate who received radical prostatectomy were identified. Using Kaplan-Meier estimates and multivariable Cox proportional hazard models, the relationship between preoperative PSA values and cancer-specific mortality outcomes in men with high- and intermediate-grade prostate cancer who received radical prostatectomy was tested. RESULTS: Of 97,357 patients with high- and intermediate-grade prostate cancer who received radical prostatectomy from 2001 to 2014, there were 983 cancer-specific deaths, and the average follow-up time for the cohort was 85.0 (34.6) months. Preoperative PSA values > 10 ng/ml were associated with greater risk of cancer-specific mortality (hazard ratio 2.3, P < 0.0001) when compared to the referent/normal values for preoperative PSA (<4 ng/ml). Individuals with preoperative PSA values 4-10 ng/ml had lower risk of prostate cancer-specific mortality (hazard ratio 0.80, P = 0.03) when compared to individuals with normal preoperative PSA values. CONCLUSIONS: Individuals with preoperative PSA values 4-10 ng/ml had 20% lower risk of prostate cancer-specific mortality when compared to individuals with preoperative PSA values of <4 ng/dl. The findings from this study suggest that low or normal preoperative PSA values may not always mean that prostate cancer is indolent, and more work needs to be done to better classify risk in men with prostate cancer.