Comparing Preferences for Disease Profiles: A Discrete Choice Experiment from a US Societal Perspective.

OBJECTIVES: There is increasing interest in expanding the elements of value to be considered when making health policy decisions. To help inform value frameworks, this study quantified preferences for disease attributes in a general public sample and examined which combination of attributes (disease profiles) are considered most important for research and treatment. METHODS: A discrete choice experiment (DCE) was conducted in a US general population sample, recruited through online consumer panels. Respondents were asked to select one of a set of health conditions they believed to be most important, characterized by attributes defined by a previous qualitative study: onset age; cause of disease; life expectancy; caregiver requirement; symptom burden (characterized by the Health Utilities Index with varying levels of ambulation independence, dexterity limitations, and degree of pain and discomfort); and disease prevalence. A fractional factorial DCE design was implemented using R, and 60 choice sets were generated (separated into blocks of 10 per participant). Data were analyzed using a mixed-logit regression model, and results used to assess the likelihood of preferring disease profiles. Based on individual attribute preferences, overall preferences for disease profiles, including a profile aligned with Duchenne muscular dystrophy (DMD), were compared. RESULTS: Fifty-two percent of respondents (n = 537) were female, and 70.6% were aged 18-54 years. Attributes considered most important were those related to life expectancy (odds ratio [OR], 95% confidence interval [CI] 1.88 [1.56-2.27] for a 50% reduction in remaining life expectancy vs no impact), and symptom burden (OR [95% CI] 1.84 [1.47-2.31] for severe vs mild burden). Greater importance was also found for pediatric onset, caregiver requirement, and diseases affecting more people. As an example of disease profile preferences, a DMD-like pediatric inherited disease with 50% reduction in life expectancy, extensive caregiver requirement, severe symptom burden, and 1:5000 prevalence had 2.37-fold higher odds of being selected as important versus an equivalent disease with adult onset and no life expectancy reduction. CONCLUSIONS: Of disease attributes included in this DCE, respondents valued higher prevalence of disease, life expectancy and symptom burden as most important for prioritizing research and treatment. Based on expressed attribute preferences, a case study of an inherited pediatric disease involving substantial reductions to length and quality of life and requiring caregiver support has relatively high odds of being identified as important compared to diseases reflecting differing attribute profiles. These findings can help inform expansions of value frameworks by identifying important attributes from the societal perspective.

Rimegepant, Ubrogepant, and Lasmiditan in the Acute Treatment of Migraine Examining the Benefit-Risk Profile Using Number Needed to Treat/Harm.

OBJECTIVES: To develop and compare benefit-risk profiles for rimegepant, ubrogepant, and lasmiditan based on a network meta-analysis (NMA) of published clinical trials. METHODS: A fixed-effects Bayesian NMA of randomized controlled trials of lasmiditan, rimegepant, and ubrogepant for the acute treatment of adults with migraine were used to determine risk differences for efficacy and safety outcomes of the 3 treatments compared with pooled placebo. Risk differences were used to calculate number needed to treat (NNT) for pain relief and pain freedom at 2 and 2 to 24 hours and freedom from most bothersome symptoms at 2 hours; and number needed to harm (NNH) for dizziness and nausea, relative to placebo. RESULTS: Results were based on 5 randomized controlled trials (NCT03461757, NCT02828020, NCT02867709, NCT02439320, and NCT02605174). NNT to achieve sustained pain relief at 2 to 24 hours was lowest for rimegepant 75 mg (5; 95% credible interval [Crl]: 4, 7) and ubrogepant 100 mg (5; 95% Crl: 4, 8) and highest for ubrogepant 25 mg (8; 95% Crl: 5, 16). Rimegepant had the lowest NNT to achieve sustained pain freedom at 2 to 24 hours and lasmiditan 50 mg had the highest (7; 95% Crl: 5, 12 vs. 26; 95% Crl: 13, 95). NNH for dizziness and nausea was highest for ubrogepant 25 mg (28; 95% Crl: 15, 62 and 99; 95% Crl: -2580, 2378, respectively). Lasmiditan 200 mg had the lowest NNH for dizziness and rimegepant 75 mg had the lowest NNH for nausea. CONCLUSIONS: The benefit-risk profiles of lasmiditan, rimegepant, and ubrogepant may improve clinical decision-making.

SABA use as an indicator for asthma exacerbation risk: an observational cohort study (SABINA Canada).

Background: Patients with asthma use short-acting ß-agonists (SABA) to relieve symptoms but SABA alone does not treat underlying inflammation. Thus, over-reliance on SABA may result in poor asthma control and negative health outcomes. Objective: To describe use of SABA and characterise the relationship with severe exacerbations in the Canadian provinces of Nova Scotia (NS) and Alberta (AB). Methods: In this longitudinal Canadian SABA In Asthma (SABINA) study, patients with an asthma diagnosis were identified between 2016 and 2020 within two provincial administrative datasets (Health Data Nova Scotia and Alberta Health Services). All patients were followed for ≥24 months, with the first 12 months used to measure baseline asthma severity. Medication use and the relationship of SABA overuse (three or more canisters per year) with severe asthma exacerbations were characterised descriptively and via regression analysis. Results: A total of 115 478 patients were identified (NS: n=8034; AB: n=107 444). SABA overuse was substantial across both provinces (NS: 39.4%; AB: 28.0%) and across all baseline disease severity categories. Patients in NS with SABA overuse had a mean±sd annual rate of 0.46±1.11 exacerbations, compared to 0.30±1.36 for those using fewer than three canisters of SABA. Patients in AB had mean±sd exacerbation rates of 0.31±0.86 and 0.17±0.62, respectively. The adjusted risk of severe exacerbation was associated with SABA overuse (NS: incidence ratio rate 1.36, 95% CI 1.18-1.56; AB: incidence ratio rate 1.32, 95% CI 1.27-1.38). Conclusion: This study supports recent updates to Canadian Thoracic Society and Global Initiative for Asthma guidelines for asthma care. SABA overuse is associated with increased risk of severe exacerbations and can be used to identify patients at a higher risk for severe exacerbations.

The cost-effectiveness of abobotulinumtoxinA (Dysport) and onabotulinumtoxinA (Botox) for managing spasticity of the upper and lower limbs, and cervical dystonia.

OBJECTIVE: To evaluate the costs and benefits associated with the use of abobotulinumtoxinA (aboBoNT-A) and onabotulinumtoxinA (onaBoNT-A) for lower limb spasticity in children, upper and lower limb spasticity in adults, and cervical dystonia in adults. METHODS: This pharmacoeconomic analysis compared aboBoNT-A with onaBoNT-A. A decision tree model with a 1-year time horizon was conducted from a UK National Health Service (NHS) perspective using data from a variety of sources: randomized controlled trials (RCTs), network meta-analyses (NMAs), observational studies, and a physician survey investigating treatment patterns and resource utilization. Four patient populations were included: pediatric patients with lower limb spasticity (PLL), and adults with upper limb spasticity (AUL), lower limb spasticity (ALL), and cervical dystonia (CD). Outcomes included costs, quality-adjusted life years (QALYs) gained, cost per responder, and incremental cost per QALY gained. The effectiveness of each treatment was evaluated as a response to treatment. The base case assumption was that all patients in the model continued to receive botulinum toxin type A (BoNT-A) treatments at regular intervals regardless of treatment response status. Scenario analysis evaluated the impact of discontinuing BoNT-A for patients without a response to the first injection. RESULTS: The model found that aboBoNT-A resulted in greater quality-of-life and lower costs compared with onaBoNT-A for the management of spasticity and CD in all included indications. Across populations, cost savings ranged from £304 to £3,963 and QALYs gained ranged from 0.010 to 0.02 over a 1-year time horizon. Results were robust to scenario analyses and were driven by the impact of treatment response on health-related quality-of-life. CONCLUSIONS: AboBoNT-A was associated with higher treatment response, improved quality-of-life, and reduced costs in spasticity and CD versus onaBoNT-A. These findings could help deliver more effective and efficient healthcare in the NHS.

The objective of this study was to compare the costs and health outcomes associated with abobotulinumtoxinA (aboBoNT-A; Dysport) and onabotulinumtoxinA (onaBoNT-A; Botox) for treating children and adults with a variety of conditions related to limb spasticity and cervical dystonia. Therapies such as aboBoNT-A and onaBoNT-A have been shown to reduce spasticity, deformity, pain, and cervical dystonia symptoms. They can also improve function, movement, and self-care abilities. We estimated the treatment costs for patients with spasticity and patients with cervical dystonia receiving aboBoNT-A and onaBoNT-A in the UK. We also estimated other health-related costs that patients were expected to incur while receiving these treatments, as well as their quality of life.For each indication (spasticity in the upper and lower limbs in adults and children, cervical dystonia in adults), research studies were identified to estimate the likelihood of patient response for aboBoNT-A and onaBoNT-A. Survey studies were assessed to understand use of health services and costs for patients who respond to therapy vs. those who do not. We estimated total costs over one year and expected quality of life for patients. Costs included the costs of aboBoNT-A and onaBoNT-A treatments, as well as other health services.In all identified studies, the likelihood of response was higher for aboBoNT-A than for onaBoNT-A. This was associated with reduced need for other health services (and therefore lower costs), and better quality of life for patients receiving aboBoNT-A. In addition, the cost per year of aboBoNT-A treatment was lower than onaBoNT-A treatment for all indications. Therefore, treatment with aboBoNT-A was consistently associated with lower costs and better quality of life. This outcome is referred to as "economically dominant," meaning that from a health economic perspective, aboBoNT-A would be preferred to onaBoNT-A for treating patients with spasticity or cervical dystonia.

A Method for Reconstructing Individual Patient Data From Kaplan-Meier Survival Curves That Incorporate Marked Censoring Times.

Introduction. Access to individual patient data (IPD) can be advantageous when conducting cost-effectiveness analyses or indirect treatment comparisons. While exact times of censoring are often marked on published Kaplan-Meier (KM) curves, an algorithm for reconstructing IPD from such curves that allows for their incorporation is presently unavailable. Methods. An algorithm capable of incorporating marked censoring times was developed to reconstruct IPD from KM curves, taking as additional inputs the total patient count and coordinates of the drops in survival. The reliability of the algorithm was evaluated via a simulation exercise, in which survival curves were simulated, digitized, and then reconstructed. To assess the reliability of the reconstructed curves, hazard ratios (HRs) and quantiles of survival were compared between the original and reconstructed curves, and the reconstructed curves were visually inspected. Results. No systematic differences were found in HRs and quantiles in the original versus reconstructed curves. Upon visual inspection, the reconstructed IPD provided a close fit to the digitized data from the published KM curves. Inherent to the algorithm, censoring times were incorporated into the reconstructed data exactly as specified. Conclusion. This new algorithm can reliably be used to reconstruct IPD from reported KM survival curves in the presence of extractable censoring times. Use of the algorithm will allow health researchers to reconstruct IPD more closely by incorporating censoring times exactly as marked, requiring as additional inputs the total patient count and coordinates of the drops in survival.

Health expenditures after first hospital admission for heart failure in Nova Scotia, Canada: a retrospective cohort study.

BACKGROUND: Although the frequency of heart failure makes it among the costliest of illnesses, there are scant Canadian data on annual costs of treatment or the costs as the condition advances. Our objective was to estimate mean prevalence- and incidence-based direct medical costs among older adults discharged alive after a first hospital admission for heart failure. METHODS: We conducted a retrospective cohort study using population-based administrative health databases for Nova Scotia. The cohort comprised persons 50 years of age or older with an incident hospital admission for heart failure between 2009 and 2012. We considered the costs (expressed as 2020 Canadian dollars) of hospital admissions, physician visits and, for patients 65 years of age or older, outpatient cardiac medications. We estimated costs for calendar years, longitudinally and in the last 2 years of life. We analyzed costs from the perspective of a third-party public payer. RESULTS: The cohort consisted of 3327 patients (mean age 77.6 yr; 1605 [48.2%] women). Median survival was 2.5 and 2.2 years among men and women, respectively. Annual prevalence-based costs were about $7100. Mean incidence-based costs ranged between $65 000 and $164 000 in the year after diagnosis and decreased by 90% subsequently. Costs were 4 to 7 times higher in the year before death than in the period from 1 to 2 years before death. INTERPRETATION: The direct medical costs of treating patients with heart failure in Nova Scotia displayed a reverse J shape, with costs highest after diagnosis, declining subsequently and then increasing during the final year of life. Strategies designed to improve the quality of care immediately after diagnosis and during more advanced stages of disease might reduce these costs.

Mapping Migraine-Specific Quality of Life to Health State Utilities in Patients Receiving Rimegepant.

INTRODUCTION: Migraine is a debilitating neurological condition, affecting up to 15% of Americans. Recent estimates from a long-term safety study of rimegepant showed evidence of decreased monthly migraine days (MMD) in people with episodic migraine treated with rimegepant 75 mg. The objective of this study was to characterize migraine-specific quality of life version 2.1 (MSQv2) scores and corresponding mapped EuroQol-5 Dimensions-3 Level (EQ-5D-3L) utility values. METHODS: Study participants were randomized into two treatment regimens: individuals with 2-14 MMD received rimegepant 75 mg as needed (PRN), and those with 4-14 MMD at baseline who received rimegepant on a fixed every-other-day schedule plus an as needed dose on days they did not treat (QOD + PRN). MSQv2 was mapped to EQ-5D-3L utilities using a validated algorithm. Outcomes were assessed for the PRN arm at baseline weeks 12, 24, 36, and 52 and for the QOD + PRN arm at baseline and week 12. RESULTS: At baseline, MSQv2 data were available for 1,800 patients: 1,033 with 2-8 MMD in the PRN group, 481 with 9-14 MMD in the PRN group, and 286 with 4-14 MMD in the QOD + PRN group. For all MSQv2 domains as well as mapped utility values, outcomes improved over each study visit. At baseline, EQ-5D-3L utilities were 0.66, 0.63, and 0.65 for the 2-8 MMD PRN, 9-14 MMD PRN, and 4-14 MMD QOD + PRN groups, respectively. At end-of-study, utilities had increased by + 0.09, + 0.10, and + 0.12 for the three groups, respectively (p < 0.001 for all comparisons with baseline). Similar trends in improvement were observed across MSQv2 subdomains; all differences were statistically significant. CONCLUSIONS: Rimegepant 75 mg, which has been shown to be associated with reduced MMD, is associated with improvement in MSQv2 domains over time, leading to estimated improvement in EQ-5D-3L utilities. While this improvement was observed in all patient-groups, it was most pronounced in those with higher MMD and those taking rimegepant QOD + PRN. TRIAL REGISTRATION: Clinical Trials NCT03266588.

Cost burden of breakthrough hemolysis in patients with paroxysmal nocturnal hemoglobinuria receiving ravulizumab versus eculizumab.

Objectives: Although complement inhibition is highly effective, patients with paroxysmal nocturnal hemoglobinuria (PNH) may experience intravascular breakthrough hemolysis (BTH). Underlying causes may include elevated free C5, pregnancy, or non-pregnancy complement-activating conditions (e.g. infections). This study compared BTH-related resource utilization and costs in PNH patients treated with eculizumab versus ravulizumab. Methods: A cost model was developed using data from a targeted literature review and a survey of experienced clinicians. Costs associated with BTH episodes were calculated by cause and weighted by the proportion attributed to each cause and the cost of treating each episode. The model captured direct medical costs in 2018 US dollars. Annual BTH-related healthcare resource utilization was also calculated. Results: BTH episodes in the literature were commonly associated with elevated lactate dehydrogenase and aspartate aminotransferase, hemoglobinuria, transfusion needs, and/or recurrence of PNH symptoms. The majority of BTH management costs in eculizumab-treated patients related to changing from the approved dosing regimen following an episode of BTH, rather than acute management. No ongoing dosing changes were expected for ravulizumab-treated patients following episodes of BTH, substantially reducing its ongoing management costs. Resource utilization was greater for eculizumab-treated patients than ravulizumab-treated patients due to higher incidence of BTH, and risk of elevated free C5-related BTH. Total incremental cost was substantially lower for ravulizumab- vs eculizumab-treated patients ($407 vs $9379); results were consistent when pregnant women were not included ($386 vs $3472). Conclusion: Overall resource use and costs for BTH are estimated to be lower for PNH patients receiving ravulizumab compared with eculizumab.

Costs of in-house genomic profiling and implications for economic evaluation: a case example of non-small cell lung cancer (NSCLC).

OBJECTIVES: Genomic profiling in oncology is vital for determining eligible patients for mutation-specific targeted therapies. Use of commercial genomic testing has the potential to improve patient outcomes. Economic evaluations of in-house genomic profiling typically only include material costs while external commercial services include many other factors. Using non-small cell lung cancer (NSCLC) as an example, this study sought to characterize the unique challenges of costing testing services and their impact on results of economic evaluations. METHODS: Structured interviews with Canadian oncologists, pathologists, and laboratory directors were conducted to identify material and non-material costs associated with genomic-testing laboratories to allow estimation of a more complete cost of in-house testing, with NSCLC cost-per-test calculated using annual operational costs and NSCLC-specific testing volume. A health and budget impact model of in-house versus external commercial profiling services was used to compare the impact of non-material costs on results. RESULTS: In-house testing costs, limited to materials, was $133/single-gene test and $1,400/panel. For a laboratory running 1,300 in-house tests/year, total annual non-material costs included equipment maintenance ($6,842), labor ($502,313; technicians, administrative, and medical staff), shipping/reporting and software updates ($146,050), for an additional $519/test. The combined cost of $652/single-gene and $1,919/panel was compared to a cost of $6,194 for a commercial external test. Based on current Canadian testing patterns and anticipated utilization of external testing, inclusion of in-house non-material costs reduced the estimated 3-year budget impact by 12%. CONCLUSION: When conducting economic evaluation to assess the value of introducing external tests, it is critical that non-material costs of standard testing strategies be measured and incorporated.

Undertreatment of overactive bladder among men with lower urinary tract symptoms in the United States: A retrospective observational study.

AIMS: To characterize the epidemiology and treatment patterns of adult men (≥40 years) diagnosed with, or treated for, overactive bladder (OAB) and/or benign prostatic hyperplasia (BPH). METHODS: This retrospective observational study used data extracted from the IBM MarketScan Commercial Claims and Encounters database and the Medicare Supplemental Coordination of Benefits database. Men with BPH and/or OAB were identified and observed to assess treatment and diagnostic patterns. RESULTS: Within the entire study sample (N = 462 400), BPH diagnosis (61.5%) and BPH treatment (73.7%) were more common than the corresponding values for OAB (25.8% and 7.0%, respectively). Notably, among diagnosed individuals, the dispensation of a corresponding treatment was more likely in individuals diagnosed with BPH (183 672 out of 284 416 = 64.6%) compared with OAB (16 468 out of 119 236 = 13.8%). Among newly diagnosed and/or treated patients (n = 196 576), only 60.3% received treatment. Among treated patients, most experienced only a single type of treatment (93.4%), 6.6% went on to receive a secondary treatment and 3.5% a tertiary. The most common primary treatment was alpha-blocker monotherapy (76.9%) followed by tadalafil monotherapy (16.4%). Among those untreated at first diagnosis, the median time between diagnosis and treatment initiation was 128 days. CONCLUSIONS: Diagnosis and management of OAB among males are challenging given the inherent overlap in symptoms observed with BPH. Unsurprisingly, we found that BPH is diagnosed and treated more frequently than OAB; but the differences between diagnosis and treatment patterns for the two conditions highlight the potential undertreatment of OAB and misdirection of therapy for men with a combination of voiding and storage symptoms.

A review of published anticholinergic scales and measures and their applicability in database analyses.

BACKGROUND/OBJECTIVES: Available metrics for characterizing cumulative anticholinergic exposure over time may not be well suited for use across all US data sources. In this review, the properties of existing anticholinergic scales and measures were evaluated to determine their suitability for implementation in observational studies relying on administrative data. METHODS: A targeted literature review was conducted to identify available anticholinergic scales and measures. Suitability of the identified scales and measures for quantification of anticholinergic exposure was evaluated based on pre-defined criteria. Agreement between selected scales was characterized by the percentage overlap of included drugs and inter-scale Spearman's correlation of scores. RESULTS: Sixteen scales were identified; six were relevant and suitable for the quantification of anticholinergic exposure. When implemented on administrative data the Anticholinergic Drug Scale and Anticholinergic Cognitive Burden scale demonstrated the most agreement, with an inter-scale correlation coefficient of 0.82. Scale performance varied by outcome of interest, and underlying disease profile of the population of interest. Variability across the two measures ("average daily dose" and "cumulative dose") was observed, with neither considering both dose and anticholinergic potency in score calculations. CONCLUSIONS: Accurate quantification of anticholinergic burden is important in assessing relative risks versus benefits of prescribing anticholinergic medications. In this review, the Anticholinergic Drug Scale and the Anticholinergic Cognitive Burden scale and the average daily dose and cumulative dose measures, were determined to be well suited for the quantification of anticholinergic exposure, particularly in the context of administrative data analyses; however, methods to characterize anticholinergic burden through consideration of both anticholinergic dose and potency are needed.

Advanced Data Visualisation in Health Economics and Outcomes Research: Opportunities and Challenges.

Data visualisation techniques are valuable tools for exploring, synthesising and communicating the results of research studies. Advanced data visualisation techniques, including dynamic and interactive visualisations, are just beginning to be used in health economics and outcome research (HEOR). In HEOR, there is the potential to use these techniques both to explore methodological challenges that are central to the design and interpretation of the findings of pharmacoeconomic and outcomes research studies, but also to communicate research findings to various stakeholders. In this manuscript, we discuss opportunities and methodological challenges for data visualisation specific to HEOR, describe external barriers that may impact the use of data visualisation methods, and discuss future applications of this technology in HEOR. While there are a number of obvious applications within the data-heavy field of HEOR, caution is required to ensure that visualisations, particularly advanced ones, accurately and fairly reflect the underlying data. However, researchers will benefit from adopting these increasingly sophisticated techniques to help ensure that decisionmakers and other stakeholders can understand, digest and communicate the data-which is critical for achieving the ultimate goal of improving patient outcomes.

Characterizing the Health-Related Quality of Life Burden of Overactive Bladder Using Disease-Specific Patient-Reported Outcome Measures: A Systematic Literature Review.

INTRODUCTION: The objective was to identify the most commonly used patient-reported outcome (PRO) instruments for overactive bladder (OAB), determine which are the most useful for measuring burden in OAB and characterize the findings of recent studies that have employed PRO instruments to assess OAB symptoms and the effects of treatment. METHODS: A systematic search of OAB literature published between January 2006 and November 2017 using Medline/PubMed and EMBASE databases. RESULTS: Of 3425 abstracts and 500 full-text articles reviewed, 58 studies (both clinical trials and observational studies) were included in the review. The most commonly used PRO instruments were the OAB Questionnaire (OAB-q; 64%), followed by the King's Health Questionnaire (KHQ; 31%) and the Patient Perception of Bladder Condition (PCBC; 21%). Synthesis of data from studies using the OAB-q showed that OAB treatment with antimuscarinics, mirabegron and onabotulinumtoxinA all improve health-related quality of life (HRQoL) and symptoms beyond the benefits observed with placebo. The OAB-q could detect dose-response relationships in some studies and demonstrated there were no significant differences across therapies from different drug classes. CONCLUSION: The HRQoL burden of OAB and response to treatment can be reliably measured by PRO instruments, and the OAB-q is the most commonly used instrument in OAB, particularly in clinical trials of OAB interventions. These data will be useful to provide benchmarks of burden levels for PRO scores obtained among those on contemporary therapies for comparison with outcomes from patients managed with emerging treatments. FUNDING: Astellas Pharma Global Development, Inc.

Methods of sample size calculation in descriptive retrospective burden of illness studies.

BACKGROUND: Observational burden of illness studies are used in pharmacoepidemiology to address a variety of objectives, including contextualizing the current treatment setting, identifying important treatment gaps, and providing estimates to parameterize economic models. Methodologies such as retrospective chart review may be utilized in settings for which existing datasets are not available or do not include sufficient clinical detail. While specifying the number of charts to be extracted and/or determining whether the number that can feasibly extracted will be clinically meaningful is an important study design consideration, there is a lack of rigorous methods available for sample size calculation in this setting. The objective of this study was to develop recommended sample size calculations for use in such studies. METHODS: Calculations for identifying the optimal feasible sample size calculations were derived, for studies characterizing treatment patterns and medical costs, based on the ability to comprehensively observe treatments and maximize precision of resulting 95% confidence intervals. For cost outcomes, if the standard deviation is not known, the coefficient of variation cv can be used as an alternative. A case study of a chart review of advanced melanoma (MELODY) was used to characterize plausible values for cv in a real-world example. RESULTS: Across sample sizes, any treatment given with greater than 1% frequency has a high likelihood of being observed. For a sample of size 200, and a treatment given to 5% of the population, the precision of a 95% confidence interval (CI) is expected to be ±0.03. For cost outcomes, for the median cv value observed in the MELODY study (0.72), a sample size of approximately 200 would be required to generate a 95% CI precise to within ±10% of the mean. CONCLUSION: This study presents a formal guidance on sample size calculations for retrospective burden of illness studies. The approach presented here is methodologically rigorous and designed for practical application in real-world retrospective chart review studies.

The burden of treatment-resistant depression: A systematic review of the economic and quality of life literature.

BACKGROUND: Major depressive disorder (MDD) is a global public health concern. In particular, treatment-resistant depression (TRD) represents a key unmet need in the management of MDD. A systematic review of the epidemiological and economic literature on the burden associated with an increasing number of treatment steps due to TRD/non-response within an MDD episode was performed to quantify the burden of TRD. METHODS: Studies were identified in the PubMed/Medline databases through April 27th, 2017. Articles were limited to full-length peer-reviewed journal publications with no date restrictions. Economic and patient health-related quality of life (HRQoL) data on non-response by the number of treatment steps were quantified and, where appropriate, compared across studies; otherwise, comparative data within studies were reported. RESULTS: The 12 studies on economic burden found an association between increasing levels of TRD/non-response and elevations in direct and indirect costs. Likewise, the 19 studies studying HRQoL burden found that increasing levels of TRD/non-response correlated with reduced patient HRQoL and health status. LIMITATIONS: TRD is defined inconsistently, which results in notable heterogeneity between published studies and poses methodological challenges for between-study comparisons. It is unknown if the increased economic and patient HRQoL burden are due to factors associated with TRD/non-response in addition to those due to depression persistence or severity. CONCLUSIONS: A consistent trend was observed such that medical costs increased and patient HRQoL and health status decreased by increasing level of TRD/non-response within an MDD episode. These findings highlight the need for improved therapies for TRD to help reduce disease burden.

The Association Between Overactive Bladder and Falls and Fractures: A Systematic Review.

INTRODUCTION: Urinary symptoms are associated with an increased risk of falls, but few studies have focused on patients with overactive bladder (OAB). This study aimed to synthesize estimates of the risk of falls and fractures in patients with OAB. METHODS: Medline, EMBASE, the Cumulative Index to Nursing and Allied Health Literature, and Scopus were systematically searched for observational studies that focused on patients with OAB. When available, data from a non-OAB comparison sample were included. Double independent review and data extraction were performed. Falls and fractures data were summarized by unadjusted and adjusted risks, and percent attributable risk (PAR) of falls and fractures associated with OAB. RESULTS: Fifteen studies were included in the analyses. The proportion of patients with OAB experiencing at least one fall over a year ranged from 18.9% to 50.0%, and the proportion of patients with OAB experiencing recurrent or serious falls ranged from 10.2% to 56.0%. In studies that included a non-OAB comparison sample, a higher risk of falls was observed in patients with OAB compared to those without. A significantly increased (1.3- to 2.3-fold) adjusted OAB-associated risk of falls was reported, while unadjusted PARs for OAB associated falls ranged from 3.7% to 15.5%. Risk was higher among women and those 65 years of age or older. While analysis of fractures showed elevated point estimates, most studies were underpowered to detect a statistically significant difference between groups. CONCLUSIONS: Evidence from the published literature clearly demonstrates the importance of OAB and its symptoms as risk factors for falls and fractures. FUNDING: Astellas.

Treatment patterns and costs of care for patients with relapsed and refractory Hodgkin lymphoma treated with brentuximab vedotin in the United States: A retrospective cohort study.

OBJECTIVES: Although brentuximab vedotin (BV) has changed the management of patients with relapsed or refractory Hodgkin lymphoma (RRHL), little information is available on routine clinical practice. We identified treatment patterns and costs of care among RRHL patients in the United States (US) treated with BV. METHODS: A retrospective observational study of adults initiating BV for RRHL from 2011-2015, with ≥6 months of data prior to and following BV initiation, was conducted. Treatments were classified based on dispensations and chemotherapy administration. Median total and monthly costs were estimated based on all-cause healthcare resource use in 2015 US dollars (USD). RESULTS: The cohort comprised 289 patients (59% male; mean age at diagnosis, 42 years) with a mean follow-up of 250 weeks. Eleven percent had BV salvage therapy prior to ASCT, and 32% had BV for a relapse post-ASCT. 43% received treatment post-BV, most commonly allogeneic stem cell transplant (SCT) and bendamustine (both 10.2%). Median (IQR) total costs from BV initiation to censoring were 294,790 (142,110-483,360) USD; and were highest among those treated with BV prior to ASCT (up to 421,900 [300,940-778,970] USD). Median monthly costs were almost 20,000 USD per month, and up to 25,000 USD per month among those with BV and ASCT. Medications were the greatest driver of median monthly costs. CONCLUSIONS: Median total all-cause costs were almost 300,000 USD, and median monthly costs approximately 20,000 USD, per patient treated. Patients requiring treatment following BV continue to incur high costs, highlighting the economic burden associated with managing patients in the RRHL setting.

Health-related quality-of-life implications of cardiovascular events in individuals with type 2 diabetes mellitus: A subanalysis from the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR)-TIMI 53 trial.

BACKGROUND: The impact of cardiovascular complications on health-related quality-of-life (HRQoL) in type 2 diabetes mellitus has not been clearly established. Using EQ5D utility data from SAVOR-TIMI 53, a large phase IV trial of saxagliptin versus placebo, we quantified the impact of cardiovascular and other major events on HRQoL. METHODS: EQ5D utilities were recorded annually and following myocardial infarction (MI) or stroke. Utilities among patients experiencing major cardiovascular events were analyzed using linear mixed-effects regression, adjusting for baseline characteristics (including EQ5D utility), and compared to those not experiencing major cardiovascular events. Mean utility decrements with standard errors (SE) were estimated as the difference in utility before and after the event. FINDINGS: The mean EQ5D utility of the sample was 0.776 at all time points, and did not differ by treatment. However, mean baseline and month 12 utilities among those with a major cardiovascular event were 0.751 and 0.714. Mean utilities were 0.691 within 3months of, 0.691 3-6months after, and 0.714 6-12months after, a major cardiovascular event. Cardiovascular event-specific utility decrements were 0.05 (0.007) for major cardiovascular events over the same time periods. Decrements of 0.051 (0.012; myocardial infarction), 0.111 (0.022; stroke), 0.065 (0.014; hospitalization for heart failure) 0.019 (0.024; hospitalization for hypoglycemia) were estimated; all coefficients were statistically significant. INTERPRETATION: Consistent with clinical outcomes reported elsewhere, saxagliptin did not improve HRQoL. Cardiovascular complications were associated with significantly decreased HRQoL, most substantial earlier after the event. FUNDING: BMS/AZ.

Evaluation of psoriasis patients' attitudes toward benefit-risk and therapeutic trade-offs in their choice of treatments.

OBJECTIVE: Treatment options for psoriasis offer trade-offs in terms of efficacy, convenience, and risk of adverse events. We evaluated patients' preferences with respect to benefit-risk in the treatment of psoriasis. METHODS: A discrete choice experiment was conducted in adults from the UK with moderate-to-severe psoriasis using an orthogonal design with 32 hypothetical choice sets. Participants were randomly assigned to one of two surveys with 16 choice sets. Patients' preferences were investigated with respect to the following attributes: reduction in body surface area affected by psoriasis, treatment administration (frequency and mode of delivery), short-term diarrhea or nausea risk, and 10-year risk of developing melanoma or nonmelanoma skin cancer, tuberculosis, or serious infections. A mixed effects logistic regression model generated relative preferences between treatment profiles. RESULTS: Participants (N=292) had a strong preference to avoid increased risk of melanoma or nonmelanoma skin cancer (odds ratio [OR]: 0.44 per 5% increased 10-year risk) and increased risks of tuberculosis and serious infections (both ORs: 0.73 per 5% increased 10-year risk) and preferred once-weekly to twice-daily tablets (OR: 0.76) and weekly (OR: 0.56) or fortnightly (OR: 0.65) injections. Participants preferred avoiding treatments that may cause diarrhea or nausea in the first 2 weeks (OR: 0.87 per 5% increase) and preferred treatments that effectively resolved plaque lesions (OR: 0.93 for each palm area still affected). CONCLUSION: All attributes were significant predictors of choice. Patients' preference research complements clinical trial data by providing insight regarding the relative weight of efficacy, tolerability, and other factors for patients when making treatment choices.