Commercial Versus Medicaid Insurance and Use of High-Priced Anticancer Treatments.

BACKGROUND: Because the markups on cancer drugs vary by payor, providers' financial incentive to use high-price drugs is differential according to each patient's insurance type. We evaluated the association between patient insurer (commercial vs Medicaid) and the use of high-priced cancer treatments. MATERIALS AND METHODS: We linked cancer registry, administrative claims, and demographic data for individuals diagnosed with cancer in North Carolina from 2004 to 2011, with either commercial or Medicaid insurance. We selected cancers with multiple FDA-approved, guideline-recommended chemotherapy options and large price differences between treatment options: advanced colorectal, lung, and head and neck cancer. The outcome was a receipt of a higher-priced option, and the exposure was insurer: commercial versus Medicaid. We estimated risk ratios (RRs) for the association between insurer and higher-priced treatment using log-binomial models with inverse probability of exposure weights. RESULTS: Of 812 patients, 209 (26%) had Medicaid. The unadjusted risk of receiving higher-priced treatment was 36% (215/603) for commercially insured and 27% (57/209) for Medicaid insured (RR: 1.31, 95% CI: 1.02-1.67). After adjustment for confounders the association was attenuated (RR: 1.15, 95% CI: 0.81-1.65). Exploratory subgroup analysis suggested that commercial insurance was associated with increased receipt of higher-priced treatment among patients treated by non-NCI-designated providers (RR: 1.53, 95% CI: 1.14-2.04). CONCLUSIONS: Individuals with Medicaid and commercial insurance received high-priced treatments in similar proportion, after accounting for differences in case mix. However, modification by provider characteristics suggests that insurance type may influence treatment selection for some patient groups. Further work is needed to determine the relationship between insurance status and newer, high-price drugs such as immune-oncology agents.

Vaccine patterns among patients diagnosed with Guillain-Barré Syndrome and matched counterparts in a Medicare supplemental population, 2000-2020.

Some vaccines have a small risk of Guillain-Barré Syndrome (GBS), a rare autoimmune disorder characterized by paralysis if untreated. The CDC's Advisory Committee on Immunization Practices (ACIP) guidelines do not consider GBS a precaution for future vaccines unless GBS developed within six weeks after a tetanus-toxoid-containing vaccine or influenza vaccine. Our goal was to describe vaccine patterns before and after GBS diagnosis. We matched each of 709 patients diagnosed with GBS from 2002 to 2020 with Medicare supplemental insurance to 10 counterparts without GBS (1:10) on age and sex. Propensity score-based weighting balanced covariates between groups, and we estimated weighted mean cumulative counts (wMCC) of vaccines/person before and after GBS diagnosis. Among patients with GBS, 7% were diagnosed within 42 days after a vaccine. Prior to GBS diagnosis, the wMCC of vaccines per person was similar between GBS cases and matched counterparts, but after two years of follow-up, GBS patients received 21 fewer vaccines/100 people than counterparts (wMCC difference -0.21 vaccines/person, 95% CI -0.24 to -0.18); GBS patients received 16 vaccines/100 people while matched counterparts received 36/100. Vaccine use was reduced following GBS diagnosis despite no ACIP precaution for most (93%) patients in this study. The observed drop in vaccines after GBS diagnosis indicates a disconnect between clinical practice and current recommendations.

Translation of a Claims-Based Frailty Index From the International Classification of Diseases, Ninth Revision, Clinical Modification to the Tenth Revision.

The Faurot frailty index (FFI) is a validated algorithm that uses enrollment and International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)-based billing information from Medicare claims data as a proxy for frailty. In October 2015, the US health-care system transitioned from the ICD-9-CM to the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM). Applying the Centers for Medicare and Medicaid Services General Equivalence Mappings, we translated diagnosis-based frailty indicator codes from the ICD-9-CM to the ICD-10-CM, followed by manual review. We used interrupted time-series analysis of Medicare data to assess the comparability of the pre- and posttransition FFI scores. In cohorts of beneficiaries enrolled in January 2015-2017 with 8-month frailty look-back periods, we estimated associations between the FFI and 1-year risk of aging-related outcomes (mortality, hospitalization, and admission to a skilled nursing facility). Updated indicators had similar prevalences as pretransition definitions. The median FFI scores and interquartile ranges (IQRs) for the predicted probability of frailty were similar before and after the International Classification of Diseases transition (pretransition: median, 0.034 (IQR, 0.02-0.07); posttransition: median, 0.038 (IQR, 0.02-0.09)). The updated FFI was associated with increased risks of mortality, hospitalization, and skilled nursing facility admission, similar to findings from the ICD-9-CM era. Studies of medical interventions in older adults using administrative claims should use validated indices, like the FFI, to mitigate confounding or assess effect-measure modification by frailty.

Missing data approaches in longitudinal studies of aging: A case example using the National Health and Aging Trends Study.

PURPOSE: Missing data is a key methodological consideration in longitudinal studies of aging. We described missing data challenges and potential methodological solutions using a case example describing five-year frailty state transitions in a cohort of older adults. METHODS: We used longitudinal data from the National Health and Aging Trends Study, a nationally-representative cohort of Medicare beneficiaries. We assessed the five components of the Fried frailty phenotype and classified frailty based on their number of components (robust: 0, prefrail: 1-2, frail: 3-5). One-, two-, and five-year frailty state transitions were defined as movements between frailty states or death. Missing frailty components were imputed using hot deck imputation. Inverse probability weights were used to account for potentially informative loss-to-follow-up. We conducted scenario analyses to test a range of assumptions related to missing data. RESULTS: Missing data were common for frailty components measured using physical assessments (walking speed, grip strength). At five years, 36% of individuals were lost-to-follow-up, differentially with respect to baseline frailty status. Assumptions for missing data mechanisms impacted inference regarding individuals improving or worsening in frailty. CONCLUSIONS: Missing data and loss-to-follow-up are common in longitudinal studies of aging. Robust epidemiologic methods can improve the rigor and interpretability of aging-related research.

Optimizing therapeutic decision-making for off-label medicines use: A scoping review and consensus recommendations for improving practice and research.

PURPOSE: Off-label medicines use is a common and sometimes necessary practice in many populations, with important clinical, ethical and financial consequences, including potential unintended harm or lack of effectiveness. No internationally recognized guidelines exist to aid decision-makers in applying research evidence to inform off-label medicines use. We aimed to critically evaluate current evidence informing decision-making for off-label use and to develop consensus recommendations to improve future practice and research. METHODS: We conducted a scoping review to summarize the literature on available off-label use guidance, including types, extent and scientific rigor of evidence incorporated. Findings informed the development of consensus recommendations by an international multidisciplinary Expert Panel using a modified Delphi process. Our target audience includes clinicians, patients and caregivers, researchers, regulators, sponsors, health technology assessment bodies, payers and policy makers. RESULTS: We found 31 published guidance documents on therapeutic decision-making for off-label use. Of 20 guidances with general recommendations, only 35% detailed the types and quality of evidence needed and the processes for its evaluation to reach sound, ethical decisions about appropriate use. There was no globally recognized guidance. To optimize future therapeutic decision-making, we recommend: (1) seeking rigorous scientific evidence; (2) utilizing diverse expertise in evidence evaluation and synthesis; (3) using rigorous processes to formulate recommendations for appropriate use; (4) linking off-label use with timely conduct of clinically meaningful research (including real-world evidence) to address knowledge gaps quickly; and (5) fostering partnerships between clinical decision-makers, researchers, regulators, policy makers, and sponsors to facilitate cohesive implementation and evaluation of these recommendations. CONCLUSIONS: We provide comprehensive consensus recommendations to optimize therapeutic decision-making for off-label medicines use and concurrently drive clinically relevant research. Successful implementation requires appropriate funding and infrastructure support to engage necessary stakeholders and foster relevant partnerships, representing significant challenges that policy makers must urgently address.

Impact of COVID-related policies on gunshot wound assault hospitalizations in the United States: a statewide time series analysis.

BACKGROUND: The CDC recently reported that firearm homicide rates in the United States increased in 2020, particularly among Black/African American individuals and men 25-44 years old. It is unclear whether firearm hospitalizations also increased, and more importantly, what impact the COVID-19 pandemic and COVID-related policies had. Using the North Carolina Trauma Registry, a statewide registry of trauma admissions to eighteen North Carolina hospitals, we calculated weekly GSW hospitalization rates from 1/2019 to 12/2020, overall and stratified by race-ethnicity, age, and sex. Interrupted time-series design and segmented linear regression were used to estimate changes in weekly hospitalization rates over time after (1) U.S. declaration of a public health emergency; (2) statewide Stay-at-Home order; (3) Stay-at-Home order lifted with restrictions (Phase 2: Safer-at-Home); and (4) further lifting of restrictions (Phase 2.5: Safer-at-Home). Non-GSW assault hospitalizations were used as a control to assess whether trends were observed across all assault hospitalizations or if effects were specific to gun violence. FINDINGS: Overall, 47.3% (n = 3223) of assault hospitalizations were GSW. Among GSW hospitalizations, median age was 27 years old (interquartile range [IQR] 21-25), 86.2% were male, and 49.5% occurred after the U.S. declared a public health emergency. After the Stay-at-Home order was implemented, weekly GSW hospitalization rates began increasing substantially among Black/African American residents (weekly trend change = 0.775, 95% CI = 0.254 to 1.296), peaking at an average 15.6 hospitalizations per 1,000,000 residents. Weekly hospitalization rates declined after restrictions were lifted but remained elevated compared to pre-COVID levels in this group (average weekly rate 10.6 per 1,000,000 at the end of 2020 vs. 8.9 per 1,000,000 pre-pandemic). The Stay-at-Home order was also associated with increasing GSW hospitalization rates among males 25-44 years old (weekly trend change = 1.202, 95% CI = 0.631 to 1.773); rates also remained elevated among 25-44-year-old males after restrictions were lifted in 2020 (average weekly rate 10.1 vs. 7.9 per 1,000,000). Non-GSW hospitalization rates were relatively stable in 2020. CONCLUSIONS: The COVID-19 pandemic and statewide Stay-at-Home orders appeared to have placed Black/African American residents and men ages 25-44 at higher risk for GSW hospitalizations, exacerbating pre-existing disparities. Persistent gun violence disparities must be addressed.

Effect of Stay-at-Home orders and other COVID-related policies on trauma hospitalization rates and disparities in the USA: a statewide time-series analysis.

BACKGROUND: To combat the coronavirus pandemic, states implemented several public health policies to reduce infection and transmission. Increasing evidence suggests that these prevention strategies also have had a profound impact on non-COVID healthcare utilization. The goal of this study was to determine the impact of a statewide Stay-at-Home order and other COVID-related policies on trauma hospitalizations, stratified by race/ethnicity, age, and sex. METHODS: We used the North Carolina Trauma Registry, a statewide registry of trauma hospitalizations for 18 hospitals across North Carolina, including all North Carolina trauma centers, to calculate weekly rates of assault, self-inflicted, unintentional motor vehicle collision (MVC), and other unintentional injury hospitalizations between January 1, 2019, and December 31, 2020. Interrupted time-series design and segmented linear regression were used to estimate changes in hospitalization rates after several COVID-related executive orders, overall and stratified by race/ethnicity, age, and sex. Changes in hospitalization rates were assessed after 1) USA declaration of a public health emergency; 2) North Carolina statewide Stay-at-Home order; 3) Stay-at-Home order lifted with restrictions (Phase 2: Safer-at-Home); and 4) further lifting of restrictions (Phase 2.5: Safer-at-Home). RESULTS: There were 70,478 trauma hospitalizations in North Carolina, 2019-2020. In 2020, median age was 53 years old and 59% were male. Assault hospitalization rates (per 1,000,000 NC residents) increased after the Stay-at-Home order, but substantial increases were only observed among Black/African American residents (weekly trend change = 1.147, 95% CI = 0.634 to 1.662) and 18-44-year-old males (weekly trend change = 1.708, 95% CI = 0.870 to 2.545). After major restrictions were lifted, assault rates decreased but remained elevated compared to pre-COVID levels. Unintentional non-MVC injury hospitalizations decreased after the USA declared a public health emergency, especially among women ≥ 65 years old (weekly trend change = -4.010, 95% CI = -6.166 to -1.855), but returned to pre-pandemic levels within several months. CONCLUSIONS: Statewide Stay-at-Home orders placed Black/African American residents at higher risk of assault hospitalizations, exacerbating pre-existing disparities. Males 18-44 years old were also at higher risk of assault hospitalization. Fear of COVID-19 may have led to decreases in unintentional non-MVC hospitalization rates, particularly among older females. Policy makers must anticipate policy-related harms that may disproportionately affect already disadvantaged communities and develop mitigation approaches.

Effect of Stay-at-Home Orders and Other COVID-Related Policies on Trauma Hospitalization Rates and Disparities in the United States: A Statewide Time-Series Analysis.

Background: To combat the coronavirus pandemic, states implemented several public health policies to reduce infection and transmission. Increasing evidence suggests that these prevention strategies also have had a profound impact on non-COVID healthcare utilization. The goal of this study was to determine the impact of a statewide Stay-at-Home and other COVID-related policies on trauma hospitalizations, stratified by race/ethnicity, age, and sex. Methods: We used the North Carolina Trauma Registry, a statewide registry of trauma hospitalizations to 18 hospitals across North Carolina, including all North Carolina trauma centers, to calculate weekly assault, self-inflicted, unintentional motor vehicle collision (MVC), and other unintentional injury hospitalization rates between January 1, 2019 and December 31, 2020. Interrupted time-series design and segmented linear regression were used to estimate changes in hospitalizations rates after several COVID-related executive orders, overall and stratified by race/ethnicity, age, and gender. Hospitalization rates were compared after 1) U.S. declaration of a public health emergency; 2) North Carolina statewide Stay-at-Home order; 3) Stay-at-Home order lifted with restrictions (Phase 2: Safer-at-Home); and 4) further lifting of restrictions (Phase 2.5: Safer-at-Home). Results: There were 70,478 trauma hospitalizations in North Carolina from 2019-2020. In 2020, median age was 53 years old and 59% were male. Assault hospitalization rates (per 1,000,000 NC residents) increased after the Stay-at-Home order, but only among Black/African American residents (incidence rate difference [IRD]=7.9; other racial/ethnic groups' IRDs ranged 0.9 to 1.7) and 18-44 year-old males (IRD=11.9; other sex/age groups' IRDs ranged -0.5 to 3.6). After major restrictions were lifted, assault rates returned to pre-COVID levels. Unintentional injury hospitalizations decreased after the public health emergency, especially among older adults, but returned to 2019 levels within several months. Conclusions: Statewide Stay-at-Home orders put Black/African American residents at higher risk for assault hospitalizations, exacerbating pre-existing disparities. Fear of COVID-19 may have also led to decreases in unintentional non-MVC hospitalization rates, particularly among older adults. Policy makers must anticipate possible negative effects and develop approaches for mitigating harms that may disproportionately affect already disadvantaged communities.

Correlates of Receiving Guideline-Concordant Postpartum Health Services in the Community Health Center Setting.

Introduction: New clinical guidelines recommend comprehensive and timely postpartum services across 3 months after birth. Research is needed to characterize correlates of receiving guideline-concordant, quality postpartum care in federally qualified health centers serving marginalized populations. Methods: We abstracted electronic health record data from patients who received prenatal health care at three health centers in North Carolina to characterize quality postpartum care practices and to identify correlates of receiving quality care. We used multivariable log-binomial regression to estimate associations between patient, provider, and health center characteristics and two quality postpartum care outcomes: (1) timely care, defined as an initial assessment within the first 3 weeks and at least one additional visit within the first 3 months postpartum; and (2) comprehensive care, defined as receipt of services addressing family planning, infant feeding, chronic health, mood, and physical recovery across the first 3 months. Results: In a cohort of 253 patients, 60.5% received comprehensive postpartum care and 30.8% received timely care. Several prenatal factors (adequate care use, an engaged patient-provider relationship) and postpartum factors (early appointment scheduling, exclusive breastfeeding, and use of enabling services) were associated with timely postpartum care. The most important correlate of comprehensive services was having more than one postpartum visit during the first 3 months postpartum. Discussion: Identifying best practices for quality postpartum care in the health center setting can inform strategies to reduce health inequities. Future research should engage community stakeholders to define patient-centered measures of quality postpartum care and to identify community-centered ways of delivering this care.

Did the 2015 USPSTF Abnormal Blood Glucose Recommendations Change Clinician Attitudes or Behaviors? A Mixed-Method Assessment.

BACKGROUND: In 2015, the US Preventive Services Task Force (USPSTF) revised clinical recommendations to more broadly recommend abnormal blood glucose screening and more clearly recommend referral to behavioral interventions for adults with prediabetes. OBJECTIVE: To assess the effects of the 2015 USPSTF recommendation changes on abnormal blood glucose screening and referral to behavioral interventions, and to examine physicians' perceptions of the revised recommendation. DESIGN: We utilized a sequential, dependent mixed-methods triangulation design. PARTICIPANTS: A total of 33,444 patients meeting USPSTF abnormal blood glucose screening criteria within 15 health system-affiliated primary care practices and 20 primary care physicians in North Carolina. MAIN MEASURES: We assessed monthly abnormal blood glucose screening rate and monthly referral rate to behavioral interventions. To estimate trend changes in outcomes, we used segmented linear regression analysis of interrupted time-series data. We gathered physicians' perspectives on the 2015 USPSTF abnormal blood glucose recommendation including awareness of, agreement with, adoption of, and adherence to the recommendation. To analyze qualitative data, we used directed content analysis. KEY RESULTS: There was a slight significant change in trend in abnormal blood glucose screening rates post-recommendation. There was a slight, statistically significant decrease in referral rates to behavioral interventions post-recommendation. Physicians were generally unaware of the revisions to the 2015 USPSTF abnormal blood glucose recommendation; however, once the recommendations were described, physicians agreed with the screening recommendation but felt that the behavioral intervention referral recommendation was hard to implement. CONCLUSION: The 2015 USPSTF abnormal blood glucose guideline had little to no effect on abnormal blood glucose screening or referral to behavioral interventions in North Carolina practices. Potential interventions to improve these rates could include clinical decision tools embedded in the electronic health record and better referral systems for community-based diabetes prevention programs.

Inches, Centimeters, and Yards: Overlooked Definition Choices Inhibit Interpretation of Morphine Equivalence.

OBJECTIVE: Morphine-standardized doses are used in clinical practice and research to account for molecular potency. Ninety milligrams of morphine equivalents (MME) per day are considered a "high dose" risk threshold in guidelines, laws, and by payers. Although ubiquitously cited, the "CDC definition" of daily MME lacks a clearly defined denominator. Our objective was to assess denominator-dependency on "high dose" classification across competing definitions. METHODS: To identify definitional variants, we reviewed literature and electronic prescribing tools, yielding 4 unique definitions. Using Prescription Drug Monitoring Programs data (July to September 2018), we conducted a population-based cohort study of 3,916,461 patients receiving outpatient opioid analgesics in California (CA) and Florida (FL). The binary outcome was whether patients were deemed "high dose" (>90 MME/d) compared across 4 definitions. We calculated I2 for heterogeneity attributable to the definition. RESULTS: Among 9,436,640 prescriptions, 42% overlapped, which led denominator definitions to impact daily MME values. Across definitions, average daily MME varied 3-fold (range: 17 to 52 [CA] and 23 to 65 mg [FL]). Across definitions, prevalence of "high dose" individuals ranged 5.9% to 14.2% (FL) and 3.5% to 10.3% (CA). Definitional variation alone would impact a hypothetical surveillance study trying to establish how much more "high dose" prescribing was present in FL than CA: from 39% to 84% more. Meta-analyses revealed strong heterogeneity (I2 range: 86% to 99%). In sensitivity analysis, including unit interval 90.0 to 90.9 increased "high dose" population fraction by 15%. DISCUSSION: While 90 MME may have cautionary mnemonic benefits, without harmonization of calculation, its utility is limited. Comparison between studies using daily MME requires explicit attention to definitional variation.

Comparative Effectiveness and Harms of Antibiotics for Outpatient Diverticulitis : Two Nationwide Cohort Studies.

BACKGROUND: Outpatient diverticulitis is commonly treated with either a combination of metronidazole and a fluoroquinolone (metronidazole-with-fluoroquinolone) or amoxicillin-clavulanate alone. The U.S. Food and Drug Administration advised that fluoroquinolones be reserved for conditions with no alternative treatment options. The comparative effectiveness of metronidazole-with-fluoroquinolone versus amoxicillin-clavulanate for diverticulitis is uncertain. OBJECTIVE: To determine the effectiveness and harms of metronidazole-with-fluoroquinolone versus amoxicillin-clavulanate for outpatient diverticulitis. DESIGN: Active-comparator, new-user, retrospective cohort studies. SETTING: Nationwide population-based claims data on U.S. residents aged 18 to 64 years with private employer-sponsored insurance (2000 to 2018) or those aged 65 years or older with Medicare (2006 to 2015). PARTICIPANTS: Immunocompetent adults with diverticulitis in the outpatient setting. INTERVENTION: Metronidazole-with-fluoroquinolone or amoxicillin-clavulanate. MEASUREMENTS: 1-year risks for inpatient admission, urgent surgery, and Clostridioides difficile infection (CDI) and 3-year risk for elective surgery. RESULTS: In MarketScan (IBM Watson Health), new users of metronidazole-with-fluoroquinolone (n = 106 361) and amoxicillin-clavulanate (n = 13 160) were identified. There were no differences in 1-year admission risk (risk difference, 0.1 percentage points [95% CI, -0.3 to 0.6]), 1-year urgent surgery risk (risk difference, 0.0 percentage points [CI, -0.1 to 0.1]), 3-year elective surgery risk (risk difference, 0.2 percentage points [CI, -0.3 to 0.7]), or 1-year CDI risk (risk difference, 0.0 percentage points [CI, -0.1 to 0.1]) between groups. In Medicare, new users of metronidazole-with-fluoroquinolone (n = 17 639) and amoxicillin-clavulanate (n = 2709) were identified. There were no differences in 1-year admission risk (risk difference, 0.1 percentage points [CI, -0.7 to 0.9]), 1-year urgent surgery risk (risk difference, -0.2 percentage points [CI, -0.6 to 0.1]), or 3-year elective surgery risk (risk difference, -0.3 percentage points [CI, -1.1 to 0.4]) between groups. The 1-year CDI risk was higher for metronidazole-with-fluoroquinolone than for amoxicillin-clavulanate (risk difference, 0.6 percentage points [CI, 0.2 to 1.0]). LIMITATION: Residual confounding is possible, and not all harms associated with these antibiotics, most notably drug-induced liver injury, could be assessed. CONCLUSION: Treating diverticulitis in the outpatient setting with amoxicillin-clavulanate may reduce the risk for fluoroquinolone-related harms without adversely affecting diverticulitis-specific outcomes. PRIMARY FUNDING SOURCE: National Institutes of Health.

The Affordable Care Act and Ethnic Disparities in Colorectal Cancer Screening.

INTRODUCTION: Cost sharing can deter the use of health services and act as a potential contributor to racial/ethnic disparities in cancer. The Affordable Care Act required most health plans to cover, without cost sharing, preventive services, including colorectal cancer screening. Population-based data were used to estimate the impact of the Affordable Care Act's cost-sharing provision (together with other Affordable Care Act provisions targeting preventive care) on ethnic disparities in colorectal cancer screening, comparing Hispanics with non-Hispanics. METHODS: An interrupted time series quasi-experimental analysis was used to examine ethnic differences in colorectal cancer screening pre- and post-implementation of the Affordable Care Act (analysis performed in 2018). The study cohort included insured individuals aged 50-64 years who participated in the Medical Expenditure Panel Survey from 2007 through 2015 (n=44,343). RESULTS: During the pre-Affordable Care Act period, screening rates decreased annually for non-Hispanics by -0.38 per 100 adults per year (95% CI= -0.55, -0.22) but remained level for Hispanics (annual trend per 100 adults: 0.01, 95% CI= -0.34, 0.35). After cost sharing was eliminated in 2011, colorectal cancer screening rates increased for both Hispanics (by 1.29 per 100 adults, 95% CI=0.69, 1.89) and non-Hispanics (by 0.58 per 100 adults, 95% CI=0.18, 0.99). The difference in trend increases between Hispanics and non-Hispanics was not statistically significant (0.70%, 95% CI= -0.24, 1.64). CONCLUSIONS: These findings suggest that Affordable Care Act implementation resulted in increased colorectal cancer screening; however, the effect of the law was not significantly different between Hispanics and non-Hispanics. These results provide indications that more needs to be done to reduce racial/ethnic disparities in colorectal cancer screening.

Use of High-Cost Cancer Treatments in Academic and Nonacademic Practice.

BACKGROUND: Academic physicians, such as those affiliated with National Cancer Institute (NCI)-designated Comprehensive Cancer Centers, may have different practice patterns regarding the use of high-cost cancer drugs than nonacademic physicians. MATERIALS AND METHODS: For this cohort study, we linked cancer registry, administrative, and demographic data for patients with newly diagnosed cancer in North Carolina from 2004 to 2011. We selected cancer types with multiple U.S. Food and Drug Administration-approved, National Comprehensive Cancer Network-recommended treatment options and large differences in reimbursement between higher-priced and lower-priced options (stage IV colorectal, stage IV lung, and stage II-IV head-and-neck cancers). We assessed whether provider's practice setting-NCI-designated Comprehensive Cancer Center ("NCI") versus other location ("non-NCI")-was associated with use of higher-cost treatment options. We used inverse probability of exposure weighting to control for patient characteristics. RESULTS: Of 800 eligible patients, 79.6% were treated in non-NCI settings. Patients treated in non-NCI settings were more likely to receive high-cost treatment than patients treated in NCI settings (36.0% vs. 23.2%), with an unadjusted prevalence difference of 12.7% (95% confidence interval [CI], 5.1%-20.0%). After controlling for potential confounding factors, non-NCI patients remained more likely to receive high-cost treatment, although the strength of association was attenuated (adjusted prevalence difference, 9.6%; 95% CI -0.1%-18.7%). Exploratory analyses suggested potential heterogeneity across cancer type and insurance status. CONCLUSION: Use of higher-cost cancer treatments may be more common in non-NCI than NCI settings. This may reflect differential implementation of clinical evidence, local practice variation, or possibly a response to the reimbursement incentives presented by chemotherapy billing. IMPLICATIONS FOR PRACTICE: Oncology care delivery and practice patterns may vary between care settings. By comparing otherwise similar patients treated in National Cancer Institute (NCI)-designated Comprehensive Cancer Centers with those treated elsewhere, this study suggests that patients may be more likely to receive treatment with certain expensive cancer drugs if treated in the non-NCI setting. These practice differences may result in differences in patient costs and outcomes as a result of where they receive treatment.

Impact of New Medications and $4 Generic Programs on Overactive Bladder Treatment Among Older Adults in the United States, 2000-2015.

BACKGROUND: Despite several new medications being Food and Drug Administration-approved for overactive bladder (OAB) and new prescription drug payment programs, there are limited population-based data regarding OAB medication use among older adults. OBJECTIVES: To examine: (1) impacts of new medications and $4 generic programs on time trends for OAB-related medication dispensing for older adults in the United States; (2) differences by age and sex; and (3) temporal changes in OAB-related medication payments. METHODS: Using Truven Health Analytics' Medicare Supplemental Database (2000-2015), we analyzed OAB-related medication claims for 9,477,061 Medigap beneficiaries age 65-104. We estimated dispensing rates (per 1000 person-months), assessed dispensing trends using interrupted time-series methods, compared dispensing rates by age and sex, and summarized payment trends. RESULTS: From 2000 to 2015, 771,609 individuals filled 13,863,998 OAB-related prescriptions. During 2000-2007, 3 new extended-release medications became available (tolterodine, darifenacin, solifenacin), leading to increases in overall OAB-related dispensing rates by 19.1 (99% confidence interval, 17.0-21.2), a 92% increase since 2000; overall rates remained stable during 2008-2015. By 2015, the most common medications were oxybutynin (38%), solifenacin (20%), tolterodine (19%), and mirabegron (12%). Dispensing rates peaked at age 90 (rate, 53.4; 99% confidence interval, 53.1-53.7). Women had higher rates than men at all ages (average ratewomen-ratemen, 22.0). The gap between upper and lower percentiles of medication payments widened between 2008-2015; by 2015, 25% of reimbursed dispensed prescriptions had total payments exceeding $250. CONCLUSIONS: Medication-specific dispensing rates for OAB changed when new alternatives became available. Recent changes in utilization and cost of OAB medications have implications for clinical guidelines, pharmacoepidemiologic studies, and payment policies.

Left Truncation Bias to Explain the Protective Effect of Smoking on Preeclampsia: Potential, But How Plausible?

BACKGROUND: An inverse association between maternal smoking and preeclampsia has been frequently observed in epidemiologic studies for several decades. In the May 2015 issue of this journal, Lisonkova and Joseph described a simulation study suggesting that bias from left truncation might explain the inverse association. The simulations were based on strong assumptions regarding the underlying mechanisms through which bias might occur. METHODS: To examine the sensitivity of the previous authors' conclusions to these assumptions, we constructed a new Monte Carlo simulation using published estimates to frame our data-generating parameters. We estimated the association between smoking and preeclampsia across a range of scenarios that incorporated abnormal placentation and early pregnancy loss. RESULTS: Our results confirmed that the previous authors' findings are highly dependent on assumptions regarding the strength of association between abnormal placentation and preeclampsia. Thus, the bias they described may be less pronounced than was suggested. CONCLUSIONS: Under empirically derived constraints of these critical assumptions, left truncation does not appear to fully explain the inverse association between smoking and preeclampsia. Furthermore, when considering processes in which left truncation may result from the exposure, it is important to precisely describe the target population and parameter of interest before assessing potential bias. We comment on the specification of a meaningful target population when assessing maternal smoking and preeclampsia as a public health issue. We describe considerations for defining a target population in studies of perinatal exposures when those exposures cause competing events (e.g., early pregnancy loss) for primary outcomes of interest.

Standardized binomial models for risk or prevalence ratios and differences.

BACKGROUND: Epidemiologists often analyse binary outcomes in cohort and cross-sectional studies using multivariable logistic regression models, yielding estimates of adjusted odds ratios. It is widely known that the odds ratio closely approximates the risk or prevalence ratio when the outcome is rare, and it does not do so when the outcome is common. Consequently, investigators may decide to directly estimate the risk or prevalence ratio using a log binomial regression model. METHODS: We describe the use of a marginal structural binomial regression model to estimate standardized risk or prevalence ratios and differences. We illustrate the proposed approach using data from a cohort study of coronary heart disease status in Evans County, Georgia, USA. RESULTS: The approach reduces problems with model convergence typical of log binomial regression by shifting all explanatory variables except the exposures of primary interest from the linear predictor of the outcome regression model to a model for the standardization weights. The approach also facilitates evaluation of departures from additivity in the joint effects of two exposures. CONCLUSIONS: Epidemiologists should consider reporting standardized risk or prevalence ratios and differences in cohort and cross-sectional studies. These are readily-obtained using the SAS, Stata and R statistical software packages. The proposed approach estimates the exposure effect in the total population.