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BackgroundTo the extent that outcomes are mediated through negative perceptions of generics (the nocebo effect), observational studies comparing brand-name and generic drugs are susceptible to bias favoring the brand-name drugs. We used authorized generic (AG) products, which are identical in composition and appearance to brand-name products but are marketed as generics, as a control group to address this bias in an evaluation aiming to compare the effectiveness of generic versus brand medications.Methods and findingsFor commercial health insurance enrollees from the US, administrative claims data were derived from 2 databases: (1) Optum Clinformatics Data Mart (years: 2004–2013) and (2) Truven MarketScan (years: 2003–2015). For a total of 8 drug products, the following groups were compared using a cohort study design: (1) patients switching from brand-name products to AGs versus generics, and patients initiating treatment with AGs versus generics, where AG use proxied brand-name use, addressing negative perception bias, and (2) patients initiating generic versus brand-name products (bias-prone direct comparison) and patients initiating AG versus brand-name products (negative control). Using Cox proportional hazards regression after 1:1 propensity-score matching, we compared a composite cardiovascular endpoint (for amlodipine, amlodipine-benazepril, and quinapril), non-vertebral fracture (for alendronate and calcitonin), psychiatric hospitalization rate (for sertraline and escitalopram), and insulin initiation (for glipizide) between the groups. Inverse variance meta-analytic methods were used to pool adjusted hazard ratios (HRs) for each comparison between the 2 databases. Across 8 products, 2,264,774 matched pairs of patients were included in the comparisons of AGs versus generics. A majority (12 out of 16) of the clinical endpoint estimates showed similar outcomes between AGs and generics. Among the other 4 estimates that did have significantly different outcomes, 3 suggested improved outcomes with generics and 1 favored AGs (patients switching from amlodipine brand-name: HR [95% CI] 0.92 [0.88–0.97]). The comparison between generic and brand-name initiators involved 1,313,161 matched pairs, and no differences in outcomes were noted for alendronate, calcitonin, glipizide, or quinapril. We observed a lower risk of the composite cardiovascular endpoint with generics versus brand-name products for amlodipine and amlodipine-benazepril (HR [95% CI]: 0.91 [0.84–0.99] and 0.84 [0.76–0.94], respectively). For escitalopram and sertraline, we observed higher rates of psychiatric hospitalizations with generics (HR [95% CI]: 1.05 [1.01–1.10] and 1.07 [1.01–1.14], respectively). The negative control comparisons also indicated potentially higher rates of similar magnitude with AG compared to brand-name initiation for escitalopram and sertraline (HR [95% CI]: 1.06 [0.98–1.13] and 1.11 [1.05–1.18], respectively), suggesting that the differences observed between brand and generic users in these outcomes are likely explained by ...

Background and Purpose: Although stroke is the leading cause of death in Brazil, little information exist on the acute treatment provided for stroke and its associated costs. This study addresses this gap by both clinically and economically characterizing the acute treatment of first-ever intracerebral hemorrhage (ICH) and ischemic stroke (IS) in Brazil. Methods: Retrospective medical chart review using data from two high-volume stroke centers in São Paulo, Brazil. Clinical and resource utilization data for all patients admitted to the stroke centers with a first-ever stroke between January 1, 2006 and May 31, 2007 were collected and the mean acute treatment costs per person were calculated by assigning appropriate unit cost data to all resource use. Cost estimates in Brazilian reals (BRL) were converted to US dollars (USD) using the 2005 purchasing power parity index. National costs of acute treatment for incident strokes were estimated by extrapolation of mean cost estimate per person to national incidence data for the two types of stroke. The mean costs of acute treatment on a national scale were examined in sensitivity analysis. Results: A total of 316 stroke patients were identified and their demographic and clinical characteristics, patterns of care, and outcomes were examined. Mean length of hospital stay was 12.0 ± 8.8 days for ICH and 13.3 ±23.4 days for IS. Ninety-one percent of the ICH patients and 68% of the IS patients were admitted to an intensive care unit (ICU). Mean total costs of initial hospitalization were USD 4,101 (SD ±4,254) for ICH and USD 1,902 (SD ±1,426) for IS. In multivariate analysis, hemorrhagic stroke, development of pneumonia, neurosurgical intervention, stay in ICU, and physical therapy were all significant independent predictors of acute treatment costs. Aggregate national health care expenditures for acute treatment of incident ICH were USD 122.4 million (range 30.8–274.2) and USD 326.9 million for IS (range 82.4–732.2). Conclusion: Acute treatment costs of incident ICH and IS in Brazil are substantial and primarily driven by the intensity of hospital treatment and in-hospital complications. With the expected increase in the incidence of stroke in Brazil over the coming decades, these results emphasize the need for effective preventive and acute medical care.

ObjectivesTo compare rates of switchbacks to branded drug products for patients switched from branded to authorized generic drug products, which have the same active ingredients, appearance, and excipients as the branded product, with patients switched from branded to generic drug products, which have the same active ingredients as the branded product but may differ in appearance and excipients.DesignObservational cohort study.SettingPrivate (a large commercial health plan) and public (Medicaid) insurance programs in the US.ParticipantsBeneficiaries of a large US commercial health insurer between 2004 and 2013 (primary cohort) and Medicaid beneficiaries between 2000 and 2010 (replication cohort).Main outcome measuresPatients taking branded products for one of the study drugs (alendronate tablets, amlodipine tablets, amlodipine-benazepril capsules, calcitonin salmon nasal spray, escitalopram tablets, glipizide extended release tablets, quinapril tablets, and sertraline tablets) were identified when they switched to an authorized generic or a generic drug product after the date of market entry of generic drug products. These patients were followed for switchbacks to the branded drug product in the year after their switch to an authorized generic or a generic drug product. Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals after adjusting for demographics, including age, sex, and calendar year. Inverse variance meta-analysis was used to pool adjusted hazard ratios across all drug products.ResultsA total of 94 909 patients switched from branded to authorized generic drug products and 116 017 patients switched from branded to generic drug products and contributed to the switchback analysis. Unadjusted incidence rates of switchback varied across drug products, ranging from a low of 3.8 per 100 person years (for alendronate tablets) to a high of 17.8 per 100 person years (for amlodipine-benazepril capsules), with an overall rate of 8.2 per 100 person years across all drug products. Adjusted switchback rates were consistently lower for patients who switched from branded to authorized generic drug products compared with branded to generic drug products in the primary cohort (pooled hazard ratio 0.72, 95% confidence interval 0.64 to 0.81). Similar results (0.75, 0.62 to 0.91) were observed in the replication cohort.ConclusionSwitching from branded to authorized generic drug products was associated with lower switchback rates compared with switching from branded to generic drug products.

Objectives To describe population-based use of cognitive-enhancing and psychopharmacological medications across care settings among Medicare beneficiaries with dementia. Design One-year (2008) cross-sectional study Setting Medicare administrative claims froma 5% random sample Participants 52,754 Medicare beneficiaries with dementia aged ≥65 years with continuous Medicare Parts A, B, and D coverage and alive throughout 2008. To ascertain dementia, ≥1 medical claim with a dementia ICD-9-CM code was required prior to 2008 and an additional claim was required in 2008 to confirm active disease. Measurements Use of medications commonly prescribed in managing dementia (cognitive enhancers, antidepressants, antipsychotics, and mood stabilizers) was assessed using three separate measures: 1) Annual prevalence of use; 2) Consistency of use; 3) Count of psychopharmacological medication classes. Care setting was determined using the number of months of nursing home (NH) residency: no-NH (zero months), partial-NH (1–11 months), and full-NH (12 months). Results Community-dwellers represented 41.3% of the cohort, while 42.4% and 16.3% resided partially and fully in a NH, respectively. Annual prevalence of use was 57.1% for cognitive enhancers, 56.4% for antidepressants, 34.0% for antipsychotics, and 8.8% for mood stabilizers. Cognitive enhancer use was significantly lower among those with any NH-stay [adjusted-prevalence-ratio (99% CI) partial-NH vs. no-NH 0.84 (0.83–0.86); full-NH versus no-NH0.83 (0.81–0.85)]. In contrast, those with any NH residence had significantly higher use for all psychopharmacological medication classes compared with community-dwellers. Over half the cohort had consistent medication regimens during 2008 (64.8%). The number of psychopharmacological medication classes used increased with increasing NH-stay duration. Conclusion This population-based study documents significant differences in medication use for managing dementia across care settings and substantial use of psychopharmacological medications among older adults with dementia.

To estimate real-world off-label use of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 1 diabetes, estimate rates of diabetic ketoacidosis (DKA), and compare them with DKA rates observed in sotagliflozin clinical trials. RESEARCH DESIGN AND METHODSWe identified initiators of SGLT2 inhibitors in the Sentinel System from March 2013 to June 2018, determined the prevalence of type 1 diabetes using a narrow and a broad definition, and measured rates of DKA using administrative claims data. Standardized incidence ratios (SIRs) were calculated using age-and sexspecific follow-up time in Sentinel and age-and sex-specific DKA rates from sotagliflozin trials 309, 310, and 312. RESULTSAmong 475,527 initiators of SGLT2 inhibitors, 0.50% and 0.92% met narrow and broad criteria for type 1 diabetes, respectively. Rates of DKA in the narrow and broad groups were 7.1/100 person-years and 4.3/100 person-years, respectively. Among patients who met narrow criteria for type 1 diabetes, rates of DKA were highest for patients aged 25-44 years, especially females aged 25-44 years (19.7/100 person-years). More DKA events were observed during off-label use of SGLT2 inhibitors in Sentinel than would be expected based on sotagliflozin clinical trials (SIR 5 1.83; 95% CI 1.45-2.28). CONCLUSIONSReal-world off-label use of SGLT2 inhibitors among patients with type 1 diabetes accounted for a small proportion of overall SGLT2 inhibitor use. However, the risk for DKA during off-label use was notable, especially among young, female patients. Although real-word rates of DKA exceeded the expectation based on clinical trials, results should be interpreted with caution due to differences in study methods, patient samples, and study drugs.Inhibition of sodium-glucose cotransporter 2 (SGLT2) in the proximal tubules suppresses renal glucose reabsorption, resulting in urinary glucose excretion and lowering of blood glucose in patients with diabetes. Canagliflozin (1), dapagliflozin (2), empagliflozin (3), and ertugliflozin (4) are SGLT2 inhibitors indicated as adjuncts to diet and exercise to improve glycemic control in adults with type 2 diabetes. Because of proven cardiovascular benefits (5,6

Background Older adults with dementia are vulnerable to the central deteriorating effects of drugs with anticholinergic properties (DAP). These effects include falls and confusion and may exacerbate dementia-related symptoms. Many individuals with dementia also receive acetylcholinesterase inhibitors (AChEI), indicated for mild to moderate Alzheimer's disease. AChEI have opposing effects to DAP and consequently, concomitant use of DAP and AChEI may further impair cognition among patients with dementia. Objectives Our objectives were to 1) evaluate the anticholinergic burden among nursing home (NH) residents with dementia; 2) characterize trends in use of DAP and concomitant use of DAP and AChEI among NH residents with dementia; and 3) identify factors associated with the use of DAP and concomitant use of DAP and AChEI. Methods We conducted a retrospective analysis of Medicare data from 2007-2008 linked to the Minimum Data Set. Results During the study period, 53,805 (77%) NH residents with dementia used at least one DAP each month. Sixty-seven percent of residents with dementia used Anticholinergic Burden Scale (ACBS) level 1 DAPs, 3% used level 2 and 31% used level 3 DAP. Thirteen percent of NH residents with dementia concomitantly used ACBS levels 2 or3 DAPs and AChEI. Conclusions This study sheds new light on the prevalence of DAP use and concomitant use of DAP and AChEI among NH residents with dementia. Clinicians should consider alternatives with lower anticholinergic effects, particularly in patients already taking DAP.

Authorized generics are identical in formulation to brand drugs, manufactured by the brand company but marketed as a generic. Generics, marketed by generic manufacturers, are required to demonstrate pharmaceutical and bioequivalence to the brand drug, but repetition of clinical trials is not required. This retrospective cohort study compared outcomes for generics and authorized generics, which serves as a generic vs. brand proxy that minimizes bias against generics. For the seven drugs studied between 1999 and 2014, 5,234 unique patients were on brand drugs prior to generic entry and 4,900 (93.6%) switched to a generic. During the 12 months following the brand-to-generic switch, patients using generics vs. authorized generics were similar in terms of outpatient visits, urgent care visits, hospitalizations, and medication discontinuation. The likelihood of emergency department (ED) visits was slightly higher for authorized generics compared with generics. These data suggest that generics were clinically no worse than their proxy brand comparators.