Dispensing pharmacy chains and direct anticoagulants: Potential associations with patient outcomes.

PURPOSE: Pharmacy chains can differ with respect to the characteristics of their patient populations as well as their nonprescription products, services, and practices, and thus may serve as a surrogate for potential unmeasured confounding in observational studies of prescription drugs. This study evaluates whether a single-source drug can have different patient outcomes based on the dispensing pharmacy chain. METHODS: Separate analyses for two anticoagulant drugs, rivaroxaban and apixaban, were conducted using Medicare Fee-for-Service claims evaluating the association between dispensing pharmacy chain and outcomes of acute myocardial infarction, ischemic stroke, intracranial hemorrhage, gastrointestinal (GI) bleeding, all-cause mortality, and major GI bleeding. Inverse probability of treatment weighting (IPTW) was used to balance baseline covariates across pharmacy chain cohorts, and outcome association was assessed with a Cox Proportional Hazards model. RESULTS: We observed no differences in outcomes across pharmacy chains for apixaban recipients. Rivaroxaban recipients from pharmacy chain C, however, had lower rates of GI bleeding (adjusted HR 0.83; 95% CI 0.69-1.00) and ischemic stroke (adjusted HR 0.57; 95% CI 0.38-0.87) as compared to chain A in primary analyses with a 3-day grace period. The results moved closer to the null when 14- and 30-day grace periods were implemented. CONCLUSIONS: These results suggest that dispensing pharmacy chains may have the potential to act as a confounder of associations between drug exposure and outcome in some observational studies. Additional studies of potential confounding by pharmacy chain are needed. Further evaluation of potential pharmacy chain effects on safe use would be of value.

Development of a Knee Arthroplasty Episode-Based Cost Measure for Evaluating Cost in the Merit-Based Incentive Payment System.

BACKGROUND: Under the Merit-based Incentive Payment System (MIPS), the U.S. Centers for Medicare and Medicaid Services (CMS) evaluate clinicians who manage Medicare patients on the basis of cost and quality outcomes. CMS contractor Acumen, LLC, convened an expert panel to develop a knee arthroplasty episode-based cost measure (EBCM) for use in the MIPS. METHODS: A Clinical Subcommittee of 28 clinician experts affiliated with 27 specialty societies provided guidance in developing the knee arthroplasty EBCM. The Clinical Subcommittee specified all aspects of the EBCM including triggering of the episode, services within the episode, risk adjustment, subgrouping, and exclusions. Services were counted only if the Clinical Subcommittee deemed them under the influence of the clinician assigned to the EBCM (selective service assignment; SSA). We assessed the reliability of the EBCM and compared it with an alternative population-based cost measure constructed without SSA. RESULTS: We identified 249,301 knee arthroplasty episodes from June 1, 2016, to May 31, 2017, with 10,681 clinicians having at least 10 attributed episodes. The mean episode cost was $19,321 with a standard deviation of $1,816. SSA increased the reliability score from 0.71 to 0.81 relative to an alternative measure that counted all patient costs. SSA also led to reclassification of 41.8% of clinicians into different quintiles of performance. CONCLUSIONS: We found that the use of SSA in the creation of the EBCM substantially reduces random noise (i.e., unrelated medical procedures or costs) and offers a tool for assessing clinicians' costs of management that is focused on care directly related to knee arthroplasty.

Guillain-Barré Syndrome After High-Dose Influenza Vaccine Administration in the United States, 2018-2019 Season.

BACKGROUND: The Vaccine Safety Datalink (VSD) identified a statistical signal for an increased risk of Guillain-Barré syndrome (GBS) in days 1-42 after 2018-2019 high-dose influenza vaccine (IIV3-HD) administration. We evaluated the signal using Medicare. METHODS: We conducted early- and end-of-season claims-based self-controlled risk interval analyses among Medicare beneficiaries ages ≥65 years, using days 8-21 and 1-42 postvaccination as risk windows and days 43-84 as control window. The VSD conducted chart-confirmed analyses. RESULTS: Among 7 453 690 IIV3-HD vaccinations, we did not detect a statistically significant increased GBS risk for either the 8- to 21-day (odds ratio [OR], 1.85; 95% confidence interval [CI], 0.99-3.44) or 1- to 42-day (OR, 1.31; 95% CI, 0.78-2.18) risk windows. The findings from the end-of-season analyses were fully consistent with the early-season analyses for both the 8- to 21-day (OR, 1.64; 95% CI, 0.92-2.91) and 1- to 42-day (OR, 1.12; 95% CI, 0.70-1.79) risk windows. The VSD's chart-confirmed analysis, involving 646 996 IIV3-HD vaccinations, with 1 case each in the risk and control windows, yielded a relative risk of 1.00 (95% CI, 0.06-15.99). CONCLUSIONS: The Medicare analyses did not exclude an association between IIV3-HD and GBS, but it determined that, if such a risk existed, it was similar in magnitude to prior seasons. Chart-confirmed VSD results did not confirm an increased risk of GBS.

A simulation study of the statistical power and signaling characteristics of an early season sequential test for influenza vaccine safety.

PURPOSE: The US Food and Drug Administration monitors the risk of Guillain-Barré syndrome (GBS) following influenza vaccination using several data sources including Medicare. In the 2017 to 2018 season, we transitioned our near real-time surveillance in Medicare to more effectively detect large GBS risk increases early in the season while avoiding false positives. METHODS: We conducted a simulation study examining the ability of the updating sequential probability ratio test (USPRT) to detect substantially elevated GBS risk in the 8- to 21-day postvaccination versus 5× to 30× the historical rate. We varied the first testing week (weeks 5-8) and the null rate (1×-3×) and evaluated power. We estimated signal probability and the risk ratio (RR) after signaling when high-risk seasons were rare. RESULTS: Applying fixed alternatives, we found >80% power to detect a risk 30× the historical rate in week 5 for the 1× null and in week 6 for the 1.5× to 3× nulls. Nearly all testing schedules had >80% power for a 5× risk by week 11. To test the robustness of USPRT, we further simulated seasons where 1% were true high-risk seasons. Using a 1× null led to 10% of seasons signaling by week 11 (median RR approximately 1.4), which decreased to approximately 1% with the ≥2.5× null (median RR approximately 16.0). CONCLUSIONS: On the basis of the results from this simulation and subsequent consultations with experts and stakeholders, we specified USPRT to test continuously from weeks 7 to 11 using the null hypothesis that the observed GBS rate was 2.5× the historical rate. This helped improve the ability of USPRT to provide early detection of GBS risk following influenza vaccination as part of a multilayered system of surveillance.

Trends in Influenza and Pneumococcal Vaccination Among US Nursing Home Residents, 2006-2014.

BACKGROUND: Institutionalized adults are at increased risk of morbidity and mortality from influenza and pneumococcal infection. Influenza and pneumococcal vaccination have been shown to be effective in reducing hospitalization and deaths due to pneumonia and influenza in this population. OBJECTIVE: To assess trends in influenza vaccination coverage among US nursing home residents from the 2005-2006 through 2014-2015 influenza seasons and trends in pneumococcal vaccination coverage from 2006 to 2014 among US nursing home residents, by state and demographic characteristics. METHODS: Data were analyzed from the Centers for Medicare and Medicaid Services' (CMS's) Minimum Data Set (MDS). Influenza and pneumococcal vaccination status were assessed for all residents of CMS-certified nursing homes using data reported to the MDS by all certified facilities. RESULTS: Influenza vaccination coverage increased from 71.4% in the 2005-2006 influenza season to 75.7% in the 2014-2015 influenza season and pneumococcal vaccination coverage increased from 67.4% in 2006 to 78.4% in 2014. Vaccination coverage varied by state, with influenza vaccination coverage ranging from 50.0% to 89.7% in the 2014-2015 influenza season and pneumococcal vaccination coverage ranging from 55.0% to 89.7% in 2014. Non-Hispanic black and Hispanic residents had lower coverage compared with non-Hispanic white residents for both vaccines, and these differences persisted over time. CONCLUSION: Influenza and pneumococcal vaccination among US nursing home residents remains suboptimal. Nursing home staff can employ strategies such as provider reminders and standing orders to facilitate offering vaccination to all residents along with culturally appropriate vaccine promotion to increase vaccination coverage among this vulnerable population.

Effectiveness and Duration of Protection Provided by the Live-attenuated Herpes Zoster Vaccine in the Medicare Population Ages 65 Years and Older.

Background: Tens of millions of seniors are at risk of herpes zoster (HZ) and its complications. Live attenuated herpes zoster vaccine (HZV) reduces that risk, although questions regarding effectiveness and durability of protection in routine clinical practice remain. We used Medicare data to investigate HZV effectiveness (VE) and its durability. Methods: This retrospective cohort study included beneficiaries ages ≥65 years during January 2007 through July 2014. Multiple adjustments to account for potential bias were made. HZV-vaccinated beneficiaries were matched to unvaccinated beneficiaries (primary analysis) and to HZV-unvaccinated beneficiaries who had received pneumococcal vaccination (secondary analysis). HZ outcomes in community and hospital settings were analyzed, including ophthalmic zoster (OZ) and postherpetic neuralgia (PHN). Results: Among eligible beneficiaries (average age 77 years), the primary analysis found VE for community HZ of 33% (95% CI: 32%-35%) and 19% (95% CI: 17%-22%), for the first 3, and subsequent 4+ years postvaccination, respectively. In the secondary analysis, VE was, respectively, 37% (95% CI: 36%-39%) and 22% (95% CI: 20%-25%). In the primary analysis, VE for PHN was 57% (95% CI: 52%-61%) and 45% (95% CI: 36%-53%) in the first 3 and subsequent 4+ years, respectively; VE for hospitalized HZ was, respectively, 74% (95% CI: 67%-79%) and 55% (95% CI: 39%-67%). Differences in VE by age group were not significant. Conclusions: In both the primary and secondary analyses, HZV provided protection against HZ across all ages, but effectiveness declined over time. VE was higher and better preserved over time for PHN and HZ-associated hospitalizations than for community HZ.