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.

Gene Therapy Versus Common Care for Eligible Individuals With Sickle Cell Disease in the United States : A Cost-Effectiveness Analysis.

BACKGROUND: Sickle cell disease (SCD) and its complications contribute to high rates of morbidity and early mortality and high cost in the United States and African heritage community. OBJECTIVE: To evaluate the cost-effectiveness of gene therapy for SCD and its value-based prices (VBPs). DESIGN: Comparative modeling analysis across 2 independently developed simulation models (University of Washington Model for Economic Analysis of Sickle Cell Cure [UW-MEASURE] and Fred Hutchinson Institute Sickle Cell Disease Outcomes Research and Economics Model [FH-HISCORE]) using the same databases. DATA SOURCES: Centers for Medicare & Medicaid Services claims data, 2008 to 2016; published literature. TARGET POPULATION: Persons eligible for gene therapy. TIME HORIZON: Lifetime. PERSPECTIVE: U.S. health care sector and societal. INTERVENTION: Gene therapy versus common care. OUTCOME MEASURES: Incremental cost-effectiveness ratios (ICERs), equity-informed VBPs, and price acceptability curves. RESULTS OF BASE-CASE ANALYSIS: At an assumed $2 million price for gene therapy, UW-MEASURE and FH-HISCORE estimated ICERs of $193 000 per QALY and $427 000 per QALY, respectively, under the health care sector perspective. Corresponding estimates from the societal perspective were $126 000 per QALY and $281 000 per QALY. The difference in results between models stemmed primarily from considering a slightly different target population and incorporating the quality-of-life (QOL) effects of splenic sequestration, priapism, and acute chest syndrome in the UW model. From a societal perspective, acceptable (>90% confidence) VBPs ranged from $1 million to $2.5 million depending on the use of alternative effective metrics or equity-informed threshold values. RESULTS OF SENSITIVITY ANALYSIS: Results were sensitive to the costs of myeloablative conditioning before gene therapy, effect on caregiver QOL, and effect of gene therapy on long-term survival. LIMITATION: The short-term effects of gene therapy on vaso-occlusive events were extrapolated from 1 study. CONCLUSION: Gene therapy for SCD below a $2 million price tag is likely to be cost-effective when applying a societal perspective at an equity-informed threshold for cost-effectiveness analysis. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute.

Estimated Savings After Stopping Tyrosine Kinase Inhibitor Treatment Among Patients With Chronic Myeloid Leukemia.

Importance: Patients with chronic myeloid leukemia (CML) who have a sustained deep molecular response using tyrosine kinase inhibitors (TKIs) can safely attempt to stop their use. As these medications are very costly, this change in treatment protocols may result in large savings. Objective: To estimate future savings from attempting to stop TKI use among patients with CML who have deep molecular response. Design, Setting, and Participants: A microsimulation model was developed for this decision analytical modeling study to estimate costs for US adults moving from using a TKI, to attempting discontinuation and then reinitiating TKI therapy, if clinically appropriate. Estimates were calculated for US patients who currently have CML and simulated newly diagnosed cohorts of patients over the next 30 years. Exposure: Attempting to stop using a TKI. Main Outcomes and Measures: Estimated savings after attempted discontinuation of TKI use. Results: A simulated population of individuals with CML in 2018 and future populations were created using estimates from the SEER*Explorer website. The median age at diagnosis was 66 years for men and 65 years for women. Between 2022 and 2052, the savings associated with eligible patients attempting discontinuation of TKI therapy was estimated at more than $30 billion among those currently diagnosed and over $15 billion among those who will develop CML in the future, for a total savings of over $54 billion by 2052 for drug treatment and polymerase chain reaction testing. The estimate is conservative as it does not account for complications and other health care-associated costs for patients continuing TKI therapy. Conclusions and Relevance: The findings of this decision analytical modeling study of patients with CML suggest that attempting discontinuation of TKI therapy could save over $54 billion during the next 30 years. Further education for patients and physicians is needed to safely increase the number of patients who can successfully attain treatment-free remission.

From localized to well mixed: How commuter interactions shape disease spread.

Interactions between commuting individuals can lead to large-scale spreading of rumors, ideas, or disease, even though the commuters have no net displacement. The emergent dynamics depend crucially on the commuting distribution of a population, that is how the probability to travel to a destination decays with distance from home. Applying this idea to epidemics, we will demonstrate the qualitatively different infection dynamics emerging from populations with different commuting distributions. If the commuting distribution is exponentially localized, then we recover a reaction-diffusion system and observe Fisher waves traveling at a speed proportional to the characteristic commuting distance. If the commuting distribution has a long tail, then no finite-velocity waves can form, but we show that, in some regimes, there is nontrivial spatial dependence that the well-mixed approximation neglects. We discuss how, in all cases, an initial dispersal-dominated regime can allow the disease to go undetected for a finite amount of time before exponential growth takes over. This "offset time" is a quantity of huge importance for epidemic surveillance and yet largely ignored in the literature.

Referral and Prescription Patterns for Female Patients With Urinary Incontinence.

IMPORTANCE: Although behavioral modifications, medications, and other interventions can improve urinary incontinence (UI), many women never receive them. OBJECTIVES: To better characterize UI treatment patterns in primary care, we examined prescriptions and referrals to pelvic floor physical therapy (PFPT) and specialist physicians within a large Midwestern academic health system. STUDY DESIGN: Electronic health records were queried to identify a cohort of adult female patients receiving a new UI diagnosis during outpatient primary care visits from 2016 to 2020. Urinary incontinence referrals and referral completion were examined for the overall cohort, and medication prescriptions were examined for women with urgency or mixed UI. Logistic regression was used to assess the association of prescriptions and/or referrals with patient demographics, comorbidities, and UI diagnosis dates. RESULTS: In the year after primary care UI diagnosis, 37.2% of patients in the overall cohort (n = 4,382) received guideline-concordant care. This included 20.6% of women who were referred for further management: 17.7% to urology/urogynecology and 3.2% to PFPT. Most women who were referred attended an initial appointment. Among those with urgency (n = 2,398) or mixed UI (n = 552), 17.1% were prescribed medication. Women with stress (odds ratio [OR], 3.10; 95% CI, 2.53-3.79) and mixed UI (OR, 6.17; 95% CI, 4.03-9.66) were more likely to be referred for further management, and women diagnosed during the COVID-19 pandemic were less likely to be referred for further care (OR, 0.39; 95% CI, 0.29, 0.48). CONCLUSION: Only slightly above 1 in 3 women with a new diagnosis of UI in primary care received guideline-based medications or referrals within 1 year, suggesting missed opportunities for timely care.

Pharmaceutical industry payments and delivery of non-recommended and low value cancer drugs: population based cohort study.

OBJECTIVE: To estimate the association between oncologists' receipt of payments from the pharmaceutical industry and delivery of non-recommended or low value interventions among their patients. DESIGN: Cohort study. SETTING: Fee-for-service Medicare claims. PARTICIPANTS: Medicare beneficiaries with a diagnosis of incident cancer (new occurrence of a cancer diagnosis code in proximity to claims for cancer treatment, and no such diagnosis codes during a ≥1 year washout period) during 2014-19, who met additional requirements identifying them as at risk for one of four non-recommended or low value interventions: denosumab for castration sensitive prostate cancer, granulocyte colony stimulating factors (GCSF) for patients at low risk for neutropenic fever, nab-paclitaxel for cancers with no evidence of superiority over paclitaxel, and a branded drug in settings where a generic or biosimilar version was available. MAIN OUTCOME MEASURES: Receipt of the non-recommended or low value drug for which the patient was at risk. The primary association of interest was the assigned oncologist's receipt of any general payments from the manufacturer of the corresponding non-recommended or low value drug (measured in Open Payments) within 365 days before the patient's index cancer date. The two modeling approaches used were general linear model controlling for patients' characteristics and calendar year, and general linear model with physician level indicator variables. RESULTS: Oncologists were in receipt of industry payments for 2962 of 9799 patients (30.2%) at risk for non-recommended denosumab (median $63), 76 747 of 271 485 patients (28.3%) at risk for GCSF (median $60); 18 491 of 86 394 patients (21.4%) at risk for nab-paclitaxel (median $89), and 4170 of 13 386 patients (31.2%) at risk for branded drugs (median $156). The unadjusted proportion of patients who received non-recommended denosumab was 31.4% for those whose oncologist had not received payment and 49.5% for those whose oncologist had (prevalence difference 18.0%); the corresponding values for GCSF were 26.6% v 32.1% (5.5%), for nab-paclitaxel were 7.3% v 15.1% (7.8%), and for branded drugs were 88.3% v 83.5% (-4.8%). Controlling for patients' characteristics and calendar year, payments from industry were associated with increased use of denosumab (17.5% (95% confidence interval 15.3% to 19.7%)), GCSF (5.8% (5.4% to 6.1%)), and nab-paclitaxel (7.6% (7.1% to 8.1%)), but lower use of branded drugs (-4.6% (-5.8% to -3.3%)). In physician level indicator models, payments from industry were associated with increased use of denosumab (7.4% (2.5% to 12.2%)) and nab-paclitaxel (1.7% (0.9% to 2.5%)), but not with GCSF (0.4% (-0.3% to 1.1%)) or branded drugs (1.2% (-6.0 to 8.5%)). CONCLUSIONS: Within some clinical scenarios, industry payments to physicians are associated with non-recommended and low value drugs. These findings raise quality of care concerns about the financial relationships between physicians and industry.

A Framework for a Health Economic Evaluation Model for Patients with Sickle Cell Disease to Estimate the Value of New Treatments in the United States of America.

BACKGROUND: Sickle cell disease (SCD) is an inherited blood disorder associated with lifelong morbidity and increased risk of mortality that affects approximately 100,000 individuals in the United States (US), primarily of African-American descent. Due to these complications, individuals with SCD typically incur high healthcare costs. With a number of costly but potentially curative SCD therapies on the horizon, understanding the progression of SCD and economic burden to insurers and patients is vital. OBJECTIVE: The aim is to develop a framework to understand the progression and costs of SCD that could be used to estimate how new treatments can impact the progression and costs of the disease. METHODS: We detail how we will create a simulation model that represents the natural history of a population and allows for the characterization of the impact of novel therapies on the disease, associated costs, and outcomes in comparison to current management. CONCLUSION: In this report, we describe a conceptual approach to modeling SCD to determine the relative clinical and economic impact of new gene therapies compared to conventional therapies with a goal of providing a flexible approach that could inform the clinical management of SCD for patients, payers, and policy makers.

Medication delivery factors and adjuvant endocrine therapy adherence in breast cancer.

PURPOSE: Over 50% of breast cancer patients prescribed a 5-year course of daily oral adjuvant endocrine therapy (ET) are nonadherent. We investigated the role of costs and cancer medication delivery mode and other medication delivery factors on adherence. METHODS: We conducted a retrospective cohort study of commercially insured and Medicare advantage patients with newly diagnosed breast cancer in 2007-2015 who initiated ET. We examined the association between 12-month ET adherence (proportion of days covered by fills ≥ 0.80) and ET copayments, 90-day prescription refill use, mail order pharmacy use, number of pharmacies, and synchronization of medications. We used regression models to estimate nonadherence risk ratios adjusted for demographics (age, income, race, urbanicity), comorbidities, total medications, primary cancer treatments, and generic AI availability. Sensitivity analyses were conducted using alternative specifications for independent variables. RESULTS: Mail order users had higher adherence in both commercial and Medicare-insured cohorts. Commercially insured patients who used mail order were more likely to be adherent if they had low copayments (< $5) and 90-day prescription refills. For commercially insured patients who used local pharmacies, use of one pharmacy and better synchronized refills were also associated with adherence. Among Medicare patients who used mail order pharmacies, only low copayments were associated with adherence, while among Medicare patients using local pharmacies both low copayments and 90-day prescriptions were associated with ET adherence. CONCLUSION: Out-of-pocket costs, medication delivery mode, and other pharmacy-related medication delivery factors are associated with adherence to breast cancer ET. Future work should investigate whether interventions aimed at streamlining medication delivery could improve adherence for breast cancer patients.

Racial and Ethnic Differences in Medication Initiation Among Adults Newly Diagnosed with Type 2 Diabetes.

OBJECTIVE: Given persistent racial/ethnic differences in type 2 diabetes outcomes and the lasting benefits conferred by early glycemic control, we examined racial/ethnic differences in diabetes medication initiation during the year following diagnosis. METHODS: Among adults newly diagnosed with type 2 diabetes (2005-2016), we examined how glucose-lowering medication initiation differed by race/ethnicity during the year following diagnosis. We specified modified Poisson regression models to estimate the association between race/ethnicity and medication initiation in the entire cohort and within subpopulations defined by HbA1c, BMI, age at diagnosis, comorbidity, and neighborhood deprivation index (a census tract-level socioeconomic indicator). RESULTS: Among the 77,199 newly diagnosed individuals, 47% started a diabetes medication within 12 months of diagnosis. The prevalence of medication initiation ranged from 32% among Chinese individuals to 58% among individuals of Other/Unknown races/ethnicities. Compared to White individuals, medication initiation was less likely among Chinese (relative risk: 0.78 (95% confidence interval 0.72, 0.84)) and Japanese (0.82 (0.75, 0.90)) individuals, but was more likely among Hispanic/Latinx (1.27 (1.24, 1.30)), African American (1.14 (1.11, 1.17)), other Asian (1.13 (1.08, 1.18)), South Asian (1.10 (1.04, 1.17)), Other/Unknown (1.31 (1.24, 1.39)), American Indian or Alaska Native (1.11 (1.04, 1.18)), and Native Hawaiian/Pacific Islander (1.28 (1.19, 1.37)) individuals. Racial/ethnic differences dissipated among individuals with higher HbA1c values. CONCLUSIONS: Initiation of glucose-lowering treatment during the year following type 2 diabetes diagnosis differed markedly by race/ethnicity, particularly for those with lower HbA1c values. Future research should examine how patient preferences, provider implicit bias, and shared decision-making contribute to these early treatment differences.

Twenty-first century house calls: a survey of ambulatory care providers to inform organisational telehealth strategy.

OBJECTIVES: While patient interest in telehealth increases, clinicians' perspectives may influence longer-term adoption. We sought to identify facilitators and barriers to continued clinician incorporation of telehealth into practice. METHODS: A cross-sectional 24-item web-based survey was emailed to 491 providers with ≥50 video visits (VVs) within an academic health system between 1 March 2020 and 31 December 2020. We quantitatively summarised the characteristics and perceptions of respondents by using descriptive and test statistics. We used systematic content analysis to qualitatively code open-ended responses, double coding at least 25%. RESULTS: 247 providers (50.3%) responded to the survey. Seventy-nine per cent were confident in their ability to deliver excellent clinical care through VV. In comparison, 48% were confident in their ability to troubleshoot technical issues. Most clinicians (87%) expressed various concerns about VV. Providers across specialties generally agreed that VV reduced infection risk (71%) and transportation barriers (71%). Three overarching themes in the qualitative data included infrastructure and training, usefulness and expectation setting for patients and providers. DISCUSSION: As healthcare systems plan for future delivery directions, they must address the tension between patients' and providers' expectations of care within the digital space. Telehealth creates new friction, one where the healthcare system must fit into the patient's life rather than the usual dynamic of the patient fitting into the healthcare system. CONCLUSION: Telehealth infrastructure and patient and clinician technological acumen continue to evolve. Clinicians in this survey offered valuable insights into the directions healthcare organisations can take to right-size this healthcare delivery modality.

Concurrent prescribing of opioids with other sedating medications after cancer diagnosis: a population-level analysis.

PURPOSE: Cancer is a major reason for concurrent prescription of opioids with other sedating medications-particularly benzodiazepines and gabapentinoids-yet population-based assessments of the extent and predictors of concurrent prescribing among clinically and demographically diverse patients with cancer are lacking. METHODS: We conducted a retrospective cohort study of patients with non-metastatic cancer using North Carolina cancer registry data linked with Medicare and private insurance claims (2013-2016). We used modified Poisson regression to assess associations of patient characteristic with adjusted relative risk (aRR) of new concurrent prescribing of opioids with benzodiazepines or gabapentinoids after diagnosis. RESULTS: Overall, 15% of patients were concurrently prescribed opioids with benzodiazepines or gabapentinoids. Characteristics independently associated with an increased risk of concurrent prescribing included cancer type (e.g., aRR cervical vs. colorectal cancer: 1.55, 95% CI: 1.12-2.14); prior use of opioids (aRR: 2.43, 95% CI:2.21-2.67), benzodiazepines (aRR: 4.08, 95% CI: 3.72-4.48), or gabapentinoids (3.82, 95% CI: 3.31-4.39), and premorbid mental health conditions, including substance use disorder (aRR: 1.27, 95% CI: 1.05-1.54). Black and Hispanic patients were less likely to experience concurrent prescribing (aRR, Black vs. White: 0.35, 95% CI: 0.15-0.83; aRR, Hispanic vs. White: 0.75, 95% CI: 0.66-0.85). CONCLUSION: Approximately 1 in 7 patients with cancer was concurrently prescribed opioids with other sedating medications. Associations between patient characteristics and risk of concurrent prescribing highlight predictors of concurrent prescribing and suggest a rationale for systematic assessment of substance use history at diagnosis. Future research could explore inequitable pain and symptom management and investigate risk of adverse medication-related events.

First-Line Therapy for Type 2 Diabetes With Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists : A Cost-Effectiveness Study.

BACKGROUND: Guidelines recommend sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP1) receptor agonists as second-line therapy for patients with type 2 diabetes. Expanding their use as first-line therapy has been proposed but the clinical benefits may not outweigh their costs. OBJECTIVE: To evaluate the lifetime cost-effectiveness of a strategy of first-line SGLT2 inhibitors or GLP1 receptor agonists. DESIGN: Individual-level Monte Carlo-based Markov model. DATA SOURCES: Randomized trials, Centers for Disease Control and Prevention databases, RED BOOK, and the National Health and Nutrition Examination Survey. TARGET POPULATION: Drug-naive U.S. patients with type 2 diabetes. TIME HORIZON: Lifetime. PERSPECTIVE: Health care sector. INTERVENTION: First-line SGLT2 inhibitors or GLP1 receptor agonists. OUTCOME MEASURES: Life expectancy, lifetime costs, incremental cost-effectiveness ratios (ICERs). RESULTS OF BASE-CASE ANALYSIS: First-line SGLT2 inhibitors and GLP1 receptor agonists had lower lifetime rates of congestive heart failure, ischemic heart disease, myocardial infarction, and stroke compared with metformin. First-line SGLT2 inhibitors cost $43 000 more and added 1.8 quality-adjusted months versus first-line metformin ($478 000 per quality-adjusted life-year [QALY]). First-line injectable GLP1 receptor agonists cost more and reduced QALYs compared with metformin. RESULTS OF SENSITIVITY ANALYSIS: By removing injection disutility, first-line GLP1 receptor agonists were no longer dominated (ICER, $327 000 per QALY). Oral GLP1 receptor agonists were not cost-effective (ICER, $823 000 per QALY). To be cost-effective at under $150 000 per QALY, costs for SGLT2 inhibitors would need to be under $5 per day and under $6 per day for oral GLP1 receptor agonists. LIMITATION: U.S. population and costs not generalizable internationally. CONCLUSION: As first-line agents, SGLT2 inhibitors and GLP1 receptor agonists would improve type 2 diabetes outcomes, but their costs would need to fall by at least 70% to be cost-effective. PRIMARY FUNDING SOURCE: American Diabetes Association.

Real-world implementation evaluation of an electronic health record-integrated consumer informatics tool that collects patient-generated contextual data.

OBJECTIVE: Use the RE-AIM framework to examine the implementation of a patient contextual data (PCD) Tool designed to share patients' needs, values, and preferences with care teams ahead of clinical encounters. MATERIALS & METHODS: Observational study that follows initial PCD Tool scaling across primary care at a Midwestern academic health network. Program invitations, enrollment, patient submissions, and clinician views were tracked over a 1-year study period. Logistic regression modeled the likelihood of using the PCD Tool, accounting for patient covariates. RESULTS: Of 58,874 patients who could be contacted by email, 9,183 (15.6%) became PCD Tool users. Overall, 76% of primary care providers had patients who used the PCD Tool. Older age, female gender, non-minority race, patient portal activation, and Medicare coverage were significantly associated with increased likelihood of use. Number of office visits, medical issues, and behavioral health conditions also associated with use. Primary care staff viewed 18.7% of available PCD Tool summaries, 1.1% to 57.6% per clinic. DISCUSSION: The intervention mainly reached non-minority patients and patients who used more health services. Given the requirement for an email address on file, some patients may have been underrepresented. Overall, patient reach and adoption and clinician adoption, implementation, and maintenance of this Tool were modest but stable, consistent with a non-directive approach to fostering adoption by introducing the Tool in the absence of clear expectations for use. CONCLUSION: Healthcare organizations must implement effective methods to increase the reach, adoption, implementation, and maintenance of PCD tools across all patient populations. Assisting people, particularly racial minorities, with PCD Tool registration and actively supporting clinician use are critical steps in implementing technology that facilitates care.

Feasibility of a pharmacist-led symptom monitoring and management intervention to improve breast cancer endocrine therapy adherence.

BACKGROUND: Adjuvant endocrine therapy (AET) for breast cancer reduces mortality, but one-third to one-half of patients discontinue it early or are nonadherent. OBJECTIVE: We developed a pilot single-site study of patients with evidence of early nonadherence to AET to assess the feasibility of a novel, clinical pharmacist-led intervention targeting symptom and medication management. METHODS: Patients with prescription fill records showing nonadherence were enrolled in a single-arm feasibility study. Automated reminders were sent by e-mail or text with a link to symptom monitoring assessments weekly for 1 month and monthly until 6 months. Clinical oncology pharmacists used guideline-based symptom management and other medication management tools to support adherence and ameliorate symptoms reported on the assessments. Patient-reported outcome assessments included physical, mental, and social health domains and self-efficacy to manage symptoms and medications. Feasibility outcomes included completion of symptom reports and pharmacist recommendations. RESULTS: Of 19 participants who were nonadherent who enrolled and completed initial assessments, 18 completed all final study procedures, with 14 completing all assessments and no patient missing more than 3 assessments. All 18 participants reported at least one of 3 symptom types, and the majority reported attempting pharmacist recommendations. Patient-reported measures of physical, mental, and social health and self-efficacy improved, and 44% of the patients became adherent. CONCLUSION: An intervention using pharmacists in an oncology practice to systematically monitor and manage symptoms shows promise to reduce symptoms, enhance support and self-efficacy, and improve adherence to AET.

The Longer-Term Benefits and Harms of Glucagon-Like Peptide-1 Receptor Agonists: a Systematic Review and Meta-Analysis.

BACKGROUND: Previous meta-analyses of the benefits and harms of glucagon-like peptide-1 receptor agonists (GLP1RAs) have been limited to specific outcomes and comparisons and often included short-term results. We aimed to estimate the longer-term effects of GLP1RAs on cardiovascular risk factors, microvascular and macrovascular complications, mortality, and adverse events in patients with type 2 diabetes, compared to placebo and other anti-hyperglycemic medications. METHODS: We searched PubMed, Scopus, and clinicaltrials.gov (inception-July 2019) for randomized controlled trials ≥ 52 weeks' duration that compared a GLP1RA to placebo or other anti-hyperglycemic medication and included at least one outcome of interest. Outcomes included cardiovascular risk factors, microvascular and macrovascular complications, all-cause mortality, and treatment-related adverse events. We performed random effects meta-analyses to give summary estimates using weighted mean differences (MD) and pooled relative risks (RR). Risk of bias was assessed using the Cochrane Collaboration risk of bias in randomized trials tool. Quality of evidence was summarized using the Grading of Recommendations, Assessment, Development, and Evaluation approach. The study was registered a priori with PROSPERO (CRD42018090506). RESULTS: Forty-five trials with a mean duration of 1.7 years comprising 71,517 patients were included. Compared to placebo, GLP1RAs reduced cardiovascular risk factors, microvascular complications (including renal events, RR 0.85, 0.80-0.90), macrovascular complications (including stroke, RR 0.86, 0.78-0.95), and mortality (RR 0.89, 0.84-0.94). Compared to other anti-hyperglycemic medications, GLP1RAs only reduced cardiovascular risk factors. Increased gastrointestinal events causing treatment discontinuation were observed in both comparisons. DISCUSSION: GLP1RAs reduced cardiovascular risk factors and increased gastrointestinal events compared to placebo and other anti-hyperglycemic medications. GLP1RAs also reduced MACE, stroke, renal events, and mortality in comparisons with placebo; however, analyses were inconclusive for comparisons with other anti-hyperglycemic medications. Given the high costs of GLP1RAs, the lack of long-term evidence comparing GLP1RAs to other anti-hyperglycemic medications has significant policy and clinical practice implications.

The cost, survival, and quality-of-life implications of guideline-discordant imaging for prostate cancer.

BACKGROUND: National Comprehensive Cancer Network (NCCN) guidelines for incident prostate cancer staging imaging have been widely circulated and accepted as best practice since 1996. Despite these clear guidelines, wasteful and potentially harmful inappropriate imaging of men with prostate cancer remains prevalent. AIM: To understand changing population-level patterns of imaging among men with incident prostate cancer, we created a state-transition microsimulation model based on existing literature and incident prostate cancer cases. METHODS: To create a cohort of patients, we identified incident prostate cancer cases from 2004 to 2009 that were diagnosed in men ages 65 and older from SEER. A microsimulation model allowed us to explore how this cohort's survival, quality of life, and Medicare costs would be impacted by making imaging consistent with guidelines. We conducted a probabilistic analysis as well as one-way sensitivity analysis. RESULTS: When only imaging high-risk men compared to the status quo, we found that the population rate of imaging dropped from 53 to 38% and average per-person spending on imaging dropped from $236 to $157. The discounted and undiscounted incremental cost-effectiveness ratios indicated that ideal upfront imaging reduced costs and slightly improved health outcomes compared with current practice patterns, that is, guideline-concordant imaging was less costly and slightly more effective. CONCLUSION: This study demonstrates the potential reduction in cost through the correction of inappropriate imaging practices. These findings highlight an opportunity within the healthcare system to reduce unnecessary costs and overtreatment through guideline adherence.