Association of Fluoroquinolone Prescribing Rates With Black Box Warnings from the US Food and Drug Administration.

Importance: In 2013 and 2016, the US Food and Drug Administration (FDA) issued warnings and recommended limited use of fluoroquinolones for patients with certain acute conditions. It is not clear how prescribers have responded to these warnings. Objective: To analyze changes in prescribing of fluoroquinolones after the 2013 and 2016 FDA warnings and to examine the physician characteristics associated with these changes. Design, Setting, and Participants: This cross-sectional study used Medicare administrative claims data on Medicare fee-for-service beneficiaries and OneKey data on physicians and their organizations from January 1, 2011, to December 31, 2017. The sample was restricted to outpatient visits for sinusitis, bronchitis, and uncomplicated urinary tract infections. An interrupted time series approach was used to analyze the changes in the prescription rate after each FDA warning. Data analysis was performed between January 1, 2011, and December 31, 2017. Interventions: Two FDA black box warnings released in August 2013 and July 2016. Main Outcomes and Measures: The main outcome was an indicator for fluoroquinolone prescriptions in 3 periods: before the 2013 warning (baseline period), after the 2013 warning but before the 2016 warning (postwarning period 1), and after the 2016 warning (postwarning period 2). Results: The sample comprised 1 238 397 unique patients with a total of 2 720 071 outpatient acute care visits. Of this sample, 848 360 were women (68.5%), and the mean (SD) age was 69.7 (12.6) years. The immediate prescribing levels of fluoroquinolones in postwarning period 1 increased by 3.42 percentage points (95% CI, 3.23-3.62; P < .001) and declined by -0.77 percentage points (95% CI, -1.00 to -0.54; P < .001) in postwarning period 2. The prescribing trend increased by 0.08 percentage points per month (95% CI, 0.08-0.10; P < .001) in postwarning period 1 and 0.06 percentage points per month (95% CI, 0.04-0.08; P < .001) in postwarning period 2. In postwarning period 1, the prescribing levels for physicians who were affiliated with hospitals with a top 10th percentile case mix index vs those without such affiliation decreased by -1.13 percentage points (95% CI, -1.92 to -0.34; P = .005), whereas the levels for primary care physicians declined by -1.34 percentage points (95% CI, -1.78 to -0.88; P < .001) compared with non-primary care physicians in postwarning period 2. Physicians at teaching hospitals were the only ones who showed a decline in prescribing trend in postwarning period 1. Conclusions and Relevance: This cross-sectional study found an overall decline in prescribing of fluoroquinolones after the release of FDA warnings. Understanding the association of physician and organizational characteristics with fluoroquinolone prescribing behavior may ultimately help to identify mechanisms to improve de-adoption.

A model-based cost-effectiveness analysis of pharmacogenomic panel testing in cardiovascular disease management: preemptive, reactive, or none?

PURPOSE: Pharmacogenomics (PGx) studies how inherited genetic variations in individuals affect drug absorption, distribution, and metabolism. PGx panel testing can potentially help improve efficiency and accuracy in individualizing therapy. This study compared the cost-effectiveness between preemptive PGx panel testing, reactive PGx panel testing and usual care (no testing) in cardiovascular disease management. METHODS: We developed a decision analytic model from the US payer's perspective for a hypothetical cohort of 10,000 patients ≥45 years old, using a short-term decision tree and long-term Markov model. The testing panel included the following gene-drug pairs: CYP2C19-clopidogrel, CYP2C9/VKORC1-warfarin, and SLCO1B1-statins with 30 test-return days. Costs were reported in 2019 US dollars and effectiveness was measured in quality-adjusted life years (QALYs). The primary outcome was incremental cost-effectiveness ratio (ICER = ΔCost/ΔQALY), assuming 3% discount rate for costs and QALYs. Scenario and probabilistic sensitivity analyses were performed to assess the impact of demographics, risk level, and follow-up timeframe. RESULTS: Preemptive testing was found to be cost-effective compared with usual care (ICER $86,227/QALY) at the willingness-to-pay threshold of $100,000/QALY while reactive testing was not (ICER $148,726/QALY). Sensitivity analyses suggested that our cost-effectiveness results were sensitive to longer follow-up, and the age group 45-64 years. CONCLUSION: Compared with usual care, preemptive PGx panel testing was cost-effective in cardiovascular disease management.

Comparing outcomes and costs among warfarin-sensitive patients versus warfarin-insensitive patients using The Right Drug, Right Dose, Right Time: Using genomic data to individualize treatment (RIGHT) 10K warfarin cohort.

Oral anticoagulant (OAC) therapy has been the main treatment approach for stroke prevention for decades. Warfarin is the most widely prescribed OAC in the United States, but is difficult to manage due to variability in dose requirements across individuals. Pharmacogenomics may mitigate risk concerns related to warfarin use by fostering the opportunity to facilitate individualized medicine approaches to warfarin treatment (e.g., genome-guided dosing). While various economic evaluations exist examining the cost-effectiveness of pharmacogenomics testing for warfarin, few observational studies exist to support these studies, with even fewer using genotype as the main exposure of interest. We examined a cohort of individuals initiating warfarin therapy between 2004 and 2017 and examined bleeding and cost outcomes for the year following initiation using Mayo Clinic's billing and administrative data, as well the Mayo Clinic Rochester Cost Data Warehouse. Analyses included descriptive summaries, comparison of characteristics across exposure groups, reporting of crude outcomes, and multivariate analyses. We included N = 1,143 patients for analyses. Just over a third of our study population (34.9%) carried a warfarin-sensitive phenotype. Sensitive individuals differed in their baseline characteristics by being of older age and having a higher number of comorbid conditions; myocardial infarction, diabetes, and cancer in particular. The occurrence of bleeding events was not significantly different across exposure groups. No significant differences across exposure groups existed in either the likelihood of incurring all-cause healthcare costs or in the magnitude of those costs. Warfarin-sensitive individuals were no more likely to utilize cardiovascular-related healthcare services; however, they had lower total and inpatient cardiovascular-related costs compared to warfarin-insensitive patients. No significant differences existed in any other categories of costs. We found limited evidence that warfarin-sensitive individuals have different healthcare spending than warfarin-insensitive individuals. Additional real-world studies are needed to support the traditional economic evaluations currently existing in the literature.

Systematic review of the evidence on the cost-effectiveness of pharmacogenomics-guided treatment for cardiovascular diseases.

PURPOSE: To examine the evidence on the cost-effectiveness of implementing pharmacogenomics (PGx) in cardiovascular disease (CVD) care. METHODS: We conducted a systematic review using multiple databases from inception to 2018. The titles and abstracts of cost-effectiveness studies on PGx-guided treatment in CVD care were screened, and full texts were extracted. RESULTS: We screened 909 studies and included 46 to synthesize. Acute coronary syndrome and atrial fibrillation were the predominantly studied conditions (59%). Most studies (78%) examined warfarin-CYP2C9/VKORC1 or clopidogrel-CYP2C19. A payer's perspective was commonly used (39%) for cost calculations, and most studies (46%) were US-based. The majority (67%) of the studies found PGx testing to be cost-effective in CVD care, but cost-effectiveness varied across drugs and conditions. Two studies examined PGx panel testing, of which one examined pre-emptive testing strategies. CONCLUSION: We found mixed evidence on the cost-effectiveness of PGx in CVD care. Supportive evidence exists for clopidogrel-CYP2C19 and warfarin-CYP2C9/VKORC1, but evidence is limited in other drug-gene combinations. Gaps persist, including unclear explanation of perspective and cost inputs, underreporting of study design elements critical to economic evaluations, and limited examination of PGx panel and pre-emptive testing for their cost-effectiveness. This review identifies the need for further research on economic evaluations of PGx implementation.

Identifying high-cost episodes in lower extremity joint replacement.

OBJECTIVES: To evaluate the ability of claims-based risk adjustment and incremental components of clinical data to identify 90-day episode costs among lower extremity joint replacement (LEJR) patients according to the Centers for Medicare & Medicaid Services (CMS) Comprehensive Care for Joint Replacement (CJR) program provisions. DATA SOURCES: Medicare fee-for-service (FFS) data for qualifying CJR episodes in the United States, and FFS data linked with clinical data from CJR-qualifying LEJR episodes performed at High Value Healthcare Collaborative (HVHC) and Mayo Clinic in 2013. HVHC and Mayo Clinic populations are subsets of the total FFS population to assess the additive value of additional pieces of clinical data in correctly assigning patients to cost groups. STUDY DESIGN: Multivariable logistic models identified high-cost episodes. DATA COLLECTION/EXTRACTION METHODS: Clinical data from participating health care systems merged with Medicare FFS data. PRINCIPAL FINDINGS: Our three populations consisted of 363 621 patients in the CMS population, 4881 in the HVHC population, and 918 in the Mayo population. When modeling per CJR specifications, we observed low to moderate model performance (CMS C-Stat = 0.714; HVHC C-Stat = 0.628; Mayo C-Stat = 0.587). Adding CMS-HCC categories improved identification of patients in the top 20% of episode costs (CMS C-Stat = 0.758, HVHC C-Stat = 0.692, Mayo C-Stat = 0.677). Clinical variables, particularly functional status in the population for which this was available (Mayo C-Stat = 0.783), improved ability to identify patients within cost groups. CONCLUSIONS: Policy makers could use these findings to improve payment adjustments for bundled LEJR procedures and in consideration of new data elements for reimbursement.

Incorporating the Last Four Digits of Social Security Numbers Substantially Improves Linking Patient Data from De-identified Hospital Claims Databases.

OBJECTIVE: Assess algorithms for linking patients across de-identified databases without compromising confidentiality. DATA SOURCES/STUDY SETTING: Hospital discharges from 11 Mayo Clinic hospitals during January 2008-September 2012 (assessment and validation data). Minnesota death certificates and hospital discharges from 2009 to 2012 for entire state (application data). STUDY DESIGN: Cross-sectional assessment of sensitivity and positive predictive value (PPV) for four linking algorithms tested by identifying readmissions and posthospital mortality on the assessment data with application to statewide data. DATA COLLECTION/EXTRACTION METHODS: De-identified claims included patient gender, birthdate, and zip code. Assessment records were matched with institutional sources containing unique identifiers and the last four digits of Social Security number (SSNL4). PRINCIPAL FINDINGS: Gender, birthdate, and five-digit zip code identified readmissions with a sensitivity of 98.0 percent and a PPV of 97.7 percent and identified postdischarge mortality with 84.4 percent sensitivity and 98.9 percent PPV. Inclusion of SSNL4 produced nearly perfect identification of readmissions and deaths. When applied statewide, regions bordering states with unavailable hospital discharge data had lower rates. CONCLUSION: Addition of SSNL4 to administrative data, accompanied by appropriate data use and data release policies, can enable trusted repositories to link data with nearly perfect accuracy without compromising patient confidentiality. States maintaining centralized de-identified databases should add SSNL4 to data specifications.

Cervical cancer screening: a prospective cohort study of the effects of historical patient compliance and a population-based informatics prompted reminder on screening rates.

AIMS AND OBJECTIVES: The aim of this study was to assess the impact of historical screening compliance with the effectiveness of patient reminder letters on cervical cancer screening rates. METHOD: Using population-based informatics systems, women with no cervical cancer screening in the prior 3 years were identified in two primary care clinics, Mayo Family Clinic Northeast (NE; n = 1613) and Northwest (NW; n = 1088). Patients were divided into two compliance groups: overdue/unknown screening status at study start or previously compliant. The NE Clinic sent reminder letters over a 6 months window to patients eligible for screening at the study start or during the study that were also identified as employees/dependents (E/D). There were 795 intervention (NE Clinic E/D patients) and 1906 control subjects. Using an intent-to-treat analysis, differences in screening rates were assessed. RESULTS: A higher unadjusted screening rate was observed for the E/D group than the non-E/D group at both sites (32.7 versus 18.2% at NW, P < 0.001; 39.0 versus 14.7% at NE, P < 0.001). For the historically compliant group, unadjusted screening rates were higher for those who received letters (E/D subjects at NE) versus those who did not (E/D subjects at NW; 56.1 versus 44.5%, P = 0.01). No difference was observed between E/D subjects at NE (received letters) and NW (no letters) for the overdue/unknown group (27.4 versus 25.9%, P = 0.62). There was no difference in screening rates for non-E/D subjects at NE versus at NW (none of whom received letters) for both the compliant (24.2 versus 30.6%, P = 0.18) and the overdue/unknown groups (11.9 versus 13.0%, P = 0.59). Multivariate logistic regression models showed a significant overall effect of E/D status (P = 0.006), compliance group (P < 0.001), and the interaction between clinic site and E/D status (P = 0.04). CONCLUSION: Among insured women, reminder letters appear to improve cervical cancer screening rates for those with a history of screening compliance. Reminder letters appear insufficient to motivate women if screening is overdue. Further investigation of the cohort of women overdue for screening is needed to develop interventions to successfully target this group.