The economic burden of overactive bladder in the United States: A systematic literature review.

AIMS: Overactive bladder (OAB) affects up to 17% of the United States (US) population. This study aimed to synthesize estimates of direct and indirect costs of OAB in the US and compare costs among those with and without OAB. METHODS: A systematic review was performed using MEDLINE/PubMed and Embase, from 2003 to 2016, following PRISMA guidelines. The target population was adults with idiopathic OAB or urge urinary incontinence from the US. Data were extracted on study and patient characteristics, all-cause and OAB-specific direct costs, resource use, and indirect costs. Costs were inflated to a common price year of 2016 USD. RESULTS: Eighteen studies were included. Mean insurer paid all-cause total direct healthcare costs ranged from 8168 to 15 569 USD, and OAB-specific costs ranged from 656 to 860 USD per-patient annually. Estimates of the incremental costs for OAB patients compared to non-OAB comparators ranged from 43% to 117%. One study estimated total annual indirect costs of OAB at 11 134 USD per-patient. CONCLUSIONS: The range of direct healthcare costs reported for managing patients with OAB varied, but was relatively small given the differing contributing data sources, study designs, and cost definitions. Direct costs were consistently higher among patients with OAB versus non-OAB comparisons, from a 1.4- to >2-fold increase annually. OAB-specific costs made up a small proportion of all-cause costs, highlighting the clinical and economic impact of OAB-related conditions such as falls, urinary tract infection, and depression. Few studies were identified that examined the indirect costs of OAB in the US.

Development of a General Composite Scale (GENCOMS) for Progressive Neurodegenerative Diseases and Implications for the Assessment of Disease-Modifying Therapies.

INTRODUCTION: The reliable assessment of treatment outcomes for disease-modifying therapies (DMT) in neurodegenerative disease is challenging. The objective of this paper is to describe a generalized framework for developing composite scales that can be applied in diverse, degenerative conditions, termed "GENCOMS." Composite scales optimize the sensitivity for detecting clinically meaningful effects that slow disease progression. METHODS: The GENCOMS method relies on robust natural history data and/or placebo arm data from DMT trials. Validated scales that are core to the disease process have been identified, and item level data obtained to standardize the response outcomes from 0 (best possible score) to 1 (worst possible score). A partial least squares regression analysis was conducted with temporal change as the dependent variable and change scores in standardized items as the explanatory variables. The derived model coefficients constitute a weighted sum of items that most effectively measure disease progression. RESULTS: The resultant composite scale was optimized to detect disease progression and can be examined in a range of slow or fast progressing populations. The scale can be used in studies with comparable patient populations as an endpoint optimized to measure disease progression and therefore ideally suited to assess treatment effects in DMTs. CONCLUSION: The methodology presented here provides a generalizable framework for developing composite scales in the assessment of neurodegenerative disease progression and evaluation of DMT effects. By objectively selecting and weighting items from previously validated measures based solely on their sensitivity to disease progression, this methodology allows for the creation of a more responsive measurement of clinical decline. This heightened sensitivity to clinical decline can be utilized to detect modest yet meaningful treatment effects in the early stages of neurogenerative diseases, when it is optimal to begin a DMT.

Cost-effectiveness of rimegepant oral lyophilisate compared to best supportive care for the acute treatment of migraine in the UK.

AIMS: Migraine is the most common disabling headache disorder and is characterized by recurrent throbbing head pain and symptoms of photophobia, phonophobia, nausea, and vomiting. Rimegepant 75 mg, an oral lyophilisate calcitonin gene-related peptide antagonist, is the first treatment approved for both the acute and preventative treatment of migraine, and the first acute therapy approved in over 20-years. The objective was to assess the cost-utility of rimegepant compared with best supportive care (BSC) in the UK, for the acute treatment of migraine in the adults with inadequate symptom relief after taking at least 2 triptans, or for whom triptans are contraindicated or not tolerated. MATERIALS AND METHODS: A de novo model was developed to estimate incremental costs and quality-adjusted life years (QALYs), structured as a decision tree followed by Markov model. Patients received rimegepant or BSC for a migraine attack and were assessed for response (pain relief at 2-h). Responders and non-responders followed different pain trajectories over 48-h cycles. Non-responders discontinued treatment while responders continued treatment for subsequent attacks, with a proportion discontinuing over time. Data sources included a post-hoc pooled analysis of the phase 3 acute rimegepant trials (NCT03235479, NCT03237845, NCT03461757), and a long-term safety study (NCT03266588). The analysis was conducted from the perspective of the UK National Health Service and Personal Social Services over a 20-year time horizon. RESULTS: Rimegepant resulted in an incremental cost-utility ratio (ICUR) of £10,309 per QALY gained vs BSC, which is cost-effectiveness at a willingness to pay threshold of £30,000/QALY. Rimegepant generated +0.44 incremental QALYs and higher incremental lifetime costs (£4,492). Improved QALYs for rimegepant were a result of less time spent with severe and moderate headache pain. CONCLUSION: This study highlights the economic value of rimegepant which was found to be cost-effective for the acute treatment of migraine in adults unsuitable for triptans.

Health State Utility Mapping of Rimegepant for the Preventive Treatment of Migraine: Double-Blind Treatment Phase and Open Label Extension (BHV3000-305).

INTRODUCTION: The objectives of this study were to (1) report long-term health-related quality of life (HRQoL) outcomes among patients using rimegepant preventatively in BHV3000-305 (NCT03732638) open-label extension (OLE) and (2) map Migraine-Specific Quality of Life questionnaire version 2.1 (MSQv2) to EQ-5D-3L utility values over the double-blind treatment (DBT; 0-12 weeks) and the OLE (13-64 weeks) to assess the influence of treatment on these values. METHODS: This was a post hoc analysis using data from a rimegepant study for the prevention of migraine (BHV3000-305). Adult patients with migraine took either rimegepant 75 mg or placebo every other day (EOD) during the DBT phase. All patients received rimegepant during the OLE. MSQv2 was measured at baseline, weeks 12, 24, and 64. A validated algorithm was used to map MSQv2 scores to EQ-5D utilities. RESULTS: Baseline data were available for 347 patients treated with placebo and 348 treated with rimegepant in the DBT period, who continued to the OLE. Baseline EQ-5D utilities were similar between trial arms: 0.598 for placebo and 0.614 for rimegepant. EQ-5D improved from baseline to week 12 and utilities increased by + 0.09 for placebo and + 0.10 for rimegepant (p value = 0.011). By 24 weeks, at which point patients who were originally randomized to placebo had received rimegepant 75 mg EOD for 12 weeks, HRQoL measures (MSQv2 and EQ-5D) were similar across groups, demonstrating rapid onset of treatment effect. This HRQoL improvement was durable out to 64 weeks. CONCLUSION: Compared to placebo, treatment with rimegepant 75 mg was associated with greater improvement in EQ-5D utilities during the 12-week DBT phase. Patients originally randomized to placebo experienced a similar improvement in EQ-5D utilities after switching to rimegepant during the OLE, demonstrating that benefits are realized within 12 weeks of active treatment. This preventive effect was durable out to 64 weeks and was associated with an additional increase in HRQoL over time. TRIAL REGISTRATION: NCT03732638.

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.

Frequency and age at occurrence of clinical manifestations of disease in patients with hypophosphatasia: a systematic literature review.

BACKGROUND: Hypophosphatasia (HPP) is a rare, inherited, metabolic disease caused by tissue-nonspecific alkaline phosphatase deficiency, characterized by bone mineralization defects and systemic complications. Understanding of the clinical course and burden of HPP is limited by its rarity. This systematic literature review and synthesis of case report data aimed to determine the frequency and timing of clinical HPP manifestations and events. METHODS: Case reports and series of patients with HPP who had been followed longitudinally for ≥1 year were identified. Demographics and clinical data of interest, identified through consultation with clinical experts in HPP, were extracted. Occurrences of clinical manifestations/events of interest were categorized, classified by age at first reported occurrence of HPP manifestations and visualized over time. Clinical manifestations/events considered to contribute to the clinical burden of HPP were identified. Kaplan-Meier curves were used to estimate the median (range) age at first occurrence of the most frequently reported manifestations/events. RESULTS: From the 283 studies that met the inclusion criteria, 265 patients with HPP with ≥1 year of longitudinal follow-up were identified (median [interquartile range] age 4 [0-34] years; 45% male). The types of clinical manifestations/events of interest experienced by individuals with ≥1 such manifestation/event (n = 261) often differed between older and younger patients. Most (94%) of the 265 patients experienced ≥1 manifestation/event deemed to contribute to the clinical burden of HPP; premature tooth loss (53.5%), fractures (35.8%), pain (33.6%), and gross motor/ambulation difficulties (30.9%) were most frequently reported. The median (range) age at first reported occurrence of respiratory symptoms, cranial abnormalities, and premature tooth loss ranged from 0.3 to 10 years, whereas the median age at first reported occurrence of fractures, pain, gross motor/ambulation difficulties, and surgery ranged from 33 to 70 years. CONCLUSIONS: HPP is associated with a high clinical burden of disease, regardless of age at first reported occurrence of HPP manifestations. Over an individual's lifetime, the types of manifestations/events experienced can change and multiple HPP-related clinical manifestations/events can accumulate. These observations may reflect evolution and progression of the disease.