Boston Partners in Education

BackgroundMigraine affects 1.1 billion people globally and is the second leading cause of disability worldwide. In clinical trials, treatment efficacy is evaluated by comparing the differential responses in the treatment and placebo arms. Although placebo response in preventive migraine trials has been studied, there is limited research examining temporal trends. This study evaluates the trend of placebo response over thirty years in migraine prevention trials and investigates the association of potential confounders, such as patient, treatment, and study characteristics on placebo response using meta-analysis with regression.MethodsWe conducted literature searches from January 1990 to August 2021 in bibliographical databases (PubMed, Cochrane Library, and EMBASE). Studies were selected according to PICOS criteria and included randomized, double-blind, placebo-controlled trials evaluating preventive migraine treatments in adult patients diagnosed with episodic or chronic migraine, with or without aura. The protocol was registered with PROSPERO (CRD42021271732). Migraine efficacy outcomes included were either continuous (e.g., monthly migraine days) or dichotomous (e.g., ≥ 50% responder rate (yes/no)). We assessed the correlation of the change in outcome from baseline in the placebo arm, with the year of publication. The relationship between placebo response and year of publication was also assessed after accounting to confounders.ResultsA total of 907 studies were identified, and 83 were found eligible. For the continuous outcomes, the change from baseline in mean placebo response showed an increase over the years (rho = 0.32, p = 0.006). The multivariable regression analysis also showed an overall increase in placebo response over the years. The correlation analysis of dichotomous responses showed no significant linear trend between publication year and mean placebo response (rho = 0.08, p = 0.596). Placebo response also varied by route of administration.ConclusionPlacebo response increased over the past 30 years in migraine preventive trials. This phenomenon should be considered when designing clinical trials and conducting meta-analyses.

PurposeTo evaluate the utilization of hypotension diagnosis codes by shock type and year in known hypotensive patients.Patients and MethodsRetrospective analysis of the Medicare fee-for-service claims database. Patients with a shock diagnosis code between 2011 and 2017 were identified using the International Classification of Diseases, Ninth and Tenth Revision, Clinical Modification (ICD-9-CM and ICD-10-CM). Based on specific ICD codes corresponding to each shock type, patients were classified into four mutually exclusive cohorts: cardiogenic shock, hypovolemic shock, septic shock, and other/unspecified shock. Annual proportion and counts of cases with at least one hypotension ICD code for each shock cohort were generated to produce 7-year medical code utilization trends. A Cochran-Armitage test for trend was performed to evaluate the statistical significance.ResultsA total of 2,200,275 shock patients were analyzed, 13.3% (n=292,192) of which received a hypotension code. Hypovolemic shock cases were the most likely to receive a hypotension code (18.02%, n=46,544), while septic shock cases had the lowest rate (11.48%, n=158,348). The proportion of patients with hypotension codes for other cohorts were 18.0% (n=46,544) for hypovolemic shock and 16.9% (n=32,024) for other/unspecified shock. The presence of hypotension codes decreased by 0.9% between 2011 and 2014, but significantly increased from 10.6% in 2014 to 17.9% in 2017 (p <0.0001, Z=−105.05).ConclusionHypotension codes are remarkably underutilized in known hypotensive patients. Patients, providers, and researchers are likely to benefit from improved hypotension coding practices.

For managing overactive bladder (OAB), mirabegron, a β3 adrenergic receptor agonist, is typically used as second-line pharmacotherapy after antimuscarinics. Therefore, patients initiating treatment with mirabegron and antimuscarinics may differ, potentially impacting associated clinical outcomes. When using observational data to evaluate real-world safety and effectiveness of OAB treatments, residual bias due to unmeasured confounding and/or confounding by indication are important considerations. Falsification analysis, in which clinically irrelevant endpoints are tested as a reference, can be used to assess residual bias. The objective in this study was to compare baseline cardiovascular risk among OAB patients by treatment, and assess the presence of residual bias via falsification analysis of OAB patients treated with mirabegron or antimuscarinics, to determine whether clinically relevant comparisons across groups would be feasible. Linked electronic health record and claims data (Optum/Humedica) for OAB patients in the United States from 2011–2015 were available, with index defined as first date of OAB treatment during this period. Unadjusted characteristics were compared across groups at index and propensity-matching conducted. Falsification endpoints (hepatitis C, shingles, community-acquired pneumonia) were compared between groups using odds ratios (ORs) and 95% confidence intervals (CI). The study identified 10,311 antimuscarinic- and 408 mirabegron-treated patients. Mirabegron patients were predominantly older males, with more comorbidities. The analytic sample included 1,188 antimuscarinic patients propensity-matched to 396 mirabegron patients; after matching, no significant baseline differences remained. Estimates of falsification ORs were 0.7 (CI:0.3–1.7) for shingles, 1.5 (CI:0.3–8.2) for hepatitis C, 0.8 (CI:0.4–1.8) and 0.9 (CI:0.6–1.4) for pneumonia. While propensity matching successfully balanced observed covariates, wide CIs prevented definitive conclusions regarding residual bias. Accordingly, further observational comparisons by treatment group were not pursued. In real-world analysis, bias-detection methods could not confirm that differences in cardiovascular risk in patients receiving mirabegron versus antimuscarinics were fully adjusted for, precluding clinically relevant comparisons across treatment groups.

Objectives: Utilization of opioid-free analgesia (OFA) for post-surgical pain is a growing trend to counter the risks of opioid abuse and opioid-related adverse drug events (ORADEs). However, utilization patterns of OFA have not been examined. In this study, we investigated the utilization patterns and predictors of OFA in a surgical population in the United States.Methods: Analysis of the Cerner Health Facts database (January 2011 to December 2015) was conducted to describe hospital and patient characteristics associated with OFA. Baseline characteristics, such as age, gender, race, discharge status, year of admission and chronic comorbidities at index admission were collected. Hospital characteristics and payer type at index admission were collected as reported in the electronic health record database. Descriptive statistics and logistic regression were used to identify statistically significant predictors of OFA on patient and institutional levels.Results: The study identified 10,219 patients, from 187 hospitals, who received post-surgical OFA and 255,196 patients who received post-surgical opioids. OFA rates varied considerably by hospital. Patients more likely to receive OFA were older (OR = 1.06, 95% CI [1.03, 1.10]; p < .001), or had neurological disorders (OR = 1.24, 95% CI [1.10, 1.39]; p < .001), diabetes (OR = 1.20, 95% CI [1.08, 1.33]; p = .001) or psychosis (OR = 1.18, 95% CI [1.01, 1.37]; p = .030). Patients with obesity and depression were less likely to receive OFA (OR = 0.80, 95% CI [0.67, 0.95]; p = .010 OR = 0.85, 95% CI [0.73, 0.98]; p = .030, respectively).Conclusions: Use of post-surgical OFA was limited overall and was not favored in some patient groups prone to ORADEs, indicating missed opportunities to reduce opioid use and ORADE incidence. A substantial proportion of OFA patients was contributed by a few hospitals with especially high rates of OFA, suggesting that hospital policies, institutional structure and cross-functional departmental commitment to reducing opioid use may play a large role in the implementation of OFA.