Abstract

INTRODUCTION Cerebral vasospasm (VSP) is the leading risk factor of neurological deterioration (i.e., delayed cerebral ischemia [DCI] and cerebral infarction) after aneurysmal subarachnoid hemorrhage (aSAH) and a cause of morbidity and mortality. The objective of this systematic literature review is to summarize the economic and humanistic burden of VSP and its related complications after aSAH. METHODS A predefined protocol was designed, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Systematic searches were conducted in MEDLINE, Embase, and Cochrane (in January 2021) to identify studies reporting economic and/or humanistic (i.e., health-related quality of life [HRQoL]) outcomes for patients with asymptomatic and symptomatic VSP after aSAH. Related conferences and additional sources were searched manually. Dual screening, data extraction, and qualitative analysis were conducted. RESULTS Of 3818 abstracts identified for review, 43 full-text articles representing 42 single studies met the inclusion criteria and were included. Most studies (33) were observational; nine were randomized clinical trials (RCTs). Economic outcomes were reported in 31 studies, and alongside HRQoL outcomes in 4 studies; 7 studies reported HRQoL outcomes only. Forty studies were conducted in single countries, while only 2 RCTs were conducted in multiple countries. Patients diagnosed with VSP or DCI spent between 2.1 and 7.4 days longer in intensive care and between 4.7 and 17 days longer in hospital (total) compared with patients without VSP or DCI. A significantly higher cost burden of US$33,945 (2021 £26,712) was identified for patients with VSP and £9370 (2021 £13,733) for patients with DCI compared with patients without. Patients with DCI were also disadvantaged by being employed for 62 fewer days (during 24-month follow-up), with an estimated mean cost of £3821 (2021 £5600) for days off work. Poor HRQoL was associated with ≥ 1 days with VSP symptoms (odds ratio [OR]: 2.8, 95% confidence interval [CI]: 1.4-5.3), symptomatic VSP (OR: 1.9, 95% CI: 1.0-3.6), and DCI (OR: 2.3, 95% CI: 1.3-4.2), although this was not consistent across all studies. Symptomatic VSP and DCI were identified as significant risk factors for depressed mood (OR: 2.2, 95% CI: 1.0-4.9) and global cognitive impairment (OR: 2.3) at 12 months, respectively. The severity of VSP was a critical predictor of post-aSAH economic and humanistic burden. Similar trends in economic and humanistic burden were identified in the general aSAH patient population. Study design and patient heterogeneity precluded direct metaanalysis of the results. CONCLUSION A substantial direct and indirect economic burden is linked to VSP and its related complications after aSAH. Although limited evidence was identified for humanistic burden, these patients seem to suffer from poor HRQoL with long-lasting burden. Overall, there is an urgent need to understand better the concept of "burden of illness" of VSP and its related complications after aSAH. Aneurysmal subarachnoid hemorrhage is a sudden, life-threatening emergency caused by bleeding in the subarachnoid space between the brain and skull. Vasospasm of the arteries surrounding the hemorrhage occurs in most patients and may lead to permanent brain damage. This study summarizes the published literature to describe the burden that patients may experience due to vasospasm and its related complications after aneurysmal subarachnoid hemorrhage, focusing on financial and life quality aspects. We show that the burden of vasospasm, and its related complications, is huge. Patients often experience reduced quality of life due to their poor health and are more likely to suffer from depression and intellectual impairment. There is also a substantial financial burden linked to vasospasm and its related complications, driven by the need for more intensive care, hospitalization, and higher investigative costs associated with the treatment and management of these patients. In addition, days off work and unemployment can cause a substantial indirect financial burden. Our study highlights the need for additional research to understand further the “burden of illness” of vasospasm and its related complications after aneurysmal subarachnoid hemorrhage. eng

Abstract

Endovascular coiling (EC) has been identified in systematic reviews and meta-analyses to produce more favourable clinical outcomes in comparison to neurosurgical clipping (NC) when surgically treating a subarachnoid haemorrhage from a ruptured aneurysm. Cost-effectiveness analyses between both interventions have been done, but no cost-utility analysis has yet been published. This systematic review aims to perform an economic analysis of the relative utility outcomes and costs from both treatments in the UK. A cost-utility analysis was performed from the perspective of the National Health Service (NHS), over a 1-year analytic horizon. Outcomes were obtained from the randomised International Subarachnoid Aneurysm Trial (ISAT) and measured in terms of the patient's modified Rankin scale (mRS) grade, a 6-point disability scale that aims to quantify a patient's functional outcome following a stroke. The mRS score was weighted against the Euro-QoL 5-dimension (EQ-5D), with each state assigned a weighted utility value which was then converted into quality-adjusted life years (QALYs). A sensitivity analysis using different utility dimensions was performed to identify any variation in incremental cost-effectiveness ratio (ICER) if different input variables were used. Costs were measured in pounds sterling (£) and discounted by 3.5% to 2020/2021 prices. The cost-utility analysis showed an ICER of - £144,004 incurred for every QALY gained when EC was utilised over NC. At NICE's upper willingness-to-pay (WTP) threshold of £30,000, EC offered a monetary net benefit (MNB) of £7934.63 and health net benefit (HNB) of 0.264 higher than NC. At NICE's lower WTP threshold of £20,000, EC offered an MNB of £7478.63 and HNB of 0.374 higher than NC. EC was found to be more 'cost-effective' than NC, with an ICER in the bottom right quadrant of the cost-effectiveness plane-indicating that it offers greater benefits at lower costs. This is supported by the ICER being below the NICE's threshold of £20,000-£30,000 per QALY, and both MNB and HNB having positive values (> 0).

Abstract

BACKGROUND Sickle cell disease (SCD) is a complex genetic disorder that manifests in infancy and progresses throughout life in the form of acute and chronic complications. As the upfront costs of potentially curative, genetic therapies will likely be high, an assessment and comprehensive characterization of the medical and non-medical cost burden will inform future decision making. OBJECTIVE We sought to systematically summarize the existing literature surrounding SCD medical and non-medical costs. METHODS We searched MEDLINE and EMBASE (2008-2020) and identified US-based studies that detailed medical or non-medical costs. Eligible studies provided empirical estimates about any aspect of cost or SCD individuals of all ages and their caregivers. Study quality was assessed using the Newcastle-Ottawa Scale, and costs were adjusted to 2019 US$. RESULTS Search queries returned 479 studies, with 342 from medical burden searches and 137 from non-medical burden searches, respectively. Herein, we report the results of the 40 studies that contained relevant cost information: 39 detailed medical costs and 1 detailed non-medical costs. Costs were higher for SCD patients when compared with non-SCD individuals (cost difference range: $6636-$63,436 annually). The highest medical cost component for SCD patients was inpatient ($11,978-$59,851 annually), followed by outpatient and then pharmacy. No studies characterized the cost burden throughout the lifetime disease trajectory of an SCD individual, and no studies captured caregiver or productivity costs. CONCLUSION Our results reveal an incomplete characterization of medical and non-medical costs within SCD. A deeper understanding of the medical and non-medical cost burden requires completion of additional studies that capture the burden across the patient's lifetime, in addition to expression of the impact of existing and emergent health technologies on disease trajectory.

Abstract

INTRODUCTION There are two treatment modalities for aneurysmal subarachnoid hemorrhage: endovascular treatment and neurosurgical clipping. Results of economic evaluations are needed to gain insight into the relationship between clinical effectiveness and costs of these treatment modalities. This important information can inform both clinical decision-making processes and policymakers in facilitating Value-Based Healthcare. EVIDENCE ACQUISITION Databases (PubMed, Embase, Cochrane Library, the Centre for Reviews and Dissemination, EBSCO, and Web of Science) were searched for studies published until October 2020 that had performed economic evaluations in aneurysmal subarachnoid hemorrhage patients by comparing endovascular treatment with neurosurgical clipping. The quality of reporting and methodology of these evaluations was assessed using the associated instruments (i.e. CHEERS statement and CHEC-list, respectively). EVIDENCE SYNTHESIS A total of six studies met the inclusion criteria. All included studies reported both effects and costs, however five did not relate effects to costs. Only one study related effects directly to costs, thus conducted a full economic evaluation. The reporting quality scored 81% and the methodological quality scored 30%. CONCLUSIONS The quality of published cost-effectiveness studies on the treatment of aneurysmal subarachnoid hemorrhage is poor. Six studies reported both outcomes and costs, however only one study performed a full economic evaluation comparing endovascular treatment to neurosurgical clipping. Although the reporting quality was sufficient, the methodological quality was poor. Further research that relates health-related quality of life measures to costs of endovascular treatment and neurosurgical clipping is required-specifically focusing on both reporting and methodological quality. Different subgroup analyses and modeling could also enhance the findings.

Abstract

BACKGROUND While clinical guidelines provide a framework for hospital management of spontaneous intracerebral hemorrhage (ICH), variation in the resource utilization and costs of these services exist. OBJECTIVES Perform a systematic literature review to assess the evidence on hospital resource utilization and costs associated with management of adult ICH patients, as well as identify factors that impact variation in such hospital resource utilization and costs, regarding clinical characteristics and delivery of services. METHODS A systematic literature review was performed using PubMed, Cochrane Central Register of Controlled Trials, and Ovid MEDLINE(R) 1946 to Present. Articles were assessed against inclusion and exclusion criteria. Study design, ICH sample size, population, setting, objective, hospital characteristics, hospital resource utilization and cost data, and main study findings were abstracted. RESULTS 43 studies met the inclusion criteria. Pertinent clinical characteristics that increased hospital resource use included presence of comorbidities and baseline ICH severity. Aspects of service delivery that greatly impacted hospital resource consumption included ICU length of stay and performance of surgical procedures and intensive care procedures. CONCLUSION Hospital resource utilization and costs for ICH patients were high and differed widely across studies. Making concrete conclusions on hospital resources and costs for ICH care was constrained given methodological and patient variation in the studies. Future research should evaluate the long-term cost-effectiveness of ICH treatment interventions and use specific economic evaluation guidelines and common data elements to mitigate study variation.

Abstract

BACKGROUND Technologies used in the processing of whole blood and blood component products, including pathogen reduction, are continuously being adopted into blood transfusion workflows to improve process efficiencies. However, the economic implications of these technologies are not well understood. With the advent of these new technologies and regulatory guidance on bacterial risk-control strategies, an updated systematic literature review on this topic was warranted. OBJECTIVE The objective of this systematic literature review was to summarize the current literature on the economic analyses of pathogen-reduction technologies (PRTs). METHODS A systematic literature review was conducted using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines to identify newly published articles in PubMed, MEDLINE Complete, and EconLit from 1 January 2000 to 17 July 2019 related to economic evaluations of PRTs. Only full-text studies in humans published in English were included in the review. Both budget-impact and cost-effectiveness studies were included; common outcomes included cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS The initial searches identified 433 original abstracts, of which 16 articles were included in the final data extraction and reporting. Seven articles presented cost-effectiveness analyses and nine assessed budget impact. The introduction of PRT increased overall costs, and ICER values ranged widely across cost-effectiveness studies, from below $US150,000/QALY to upwards of $US20,000,000/QALY. This wide range of results was due to a multitude of factors, including comparator selection, target patient population, and scenario analyses included. CONCLUSIONS Overall, the results of economic evaluations of bacterial risk-control strategies, regardless of mechanism, were highly dependent on the current screening protocols in place. The optimization of blood transfusion safety may not result in decisions made at the willingness-to-pay thresholds commonly seen in pharmaceutical evaluations. Given the critical public health role of blood products, and the potential safety benefits introduced by advancements, it is important to continue building this body of evidence with more transparency and data source heterogeneity. This updated literature review provides global context when making local decisions for the coverage of new and emerging bacterial risk-control strategies.

Abstract

BACKGROUND Postpartum hemorrhage (PPH) is responsible for nearly one quarter of maternal deaths. A 2017 multicountry trial found that incorporating tranexamic acid (TXA) into the PPH management package was effective in reducing maternal death due to bleeding. OBJECTIVE To systematically review studies assessing the cost-effectiveness of tranexamic acid for PPH treatment. SEARCH STRATEGY Nine databases were searched using variations of keywords 'tranexamic acid', 'postpartum hemorrhage' and 'cost effectiveness'. SELECTION CRITERIA Eligible studies were any type of economic or effectiveness evaluation studies on tranexamic acid for treating women with PPH. DATA COLLECTION AND ANALYSIS Two reviewers independently screened citations and extracted data on cost effectiveness measures. Quality was assessed using the Consensus on Health Economic Criteria list. MAIN RESULTS Four studies were included, of which two were abstracts. Three studies concluded that early administration of TXA was cost-saving or cost-effective. One abstract reported TXA was not cost-effective in the USA unless the probability of death due to hemorrhage is higher. CONCLUSION Available evidence (four studies in three countries) suggests that this life-saving intervention may be below willingness to pay thresholds (cost-effective) or cost saving. Further studies conducted in different populations and settings are needed to inform health policy decision-making to reduce PPH-associated morbidity and mortality.

Abstract

Novel interventions for sickle cell disease (SCD) bring hope to patients, yet concern about the associated economic costs exists. Cost-effectiveness analysis (CEA) uses standardized methods, with robust underpinnings in health economics, to estimate the value of these interventions compared with usual care. However, because of the complexity and lifetime trajectory of SCD, CEAs are challenging to conduct. The objectives of this rapid review were to summarize the main characteristics, components, and results of published CEAs of existing interventions for SCD, identify research gaps, and provide directions for future analyses. We identified records through searches of bibliographic databases, from reference lists of relevant review articles, and through consultation with experts. A total of 13 CEAs met our inclusion criteria and were qualitatively synthesized. These evaluated blood transfusions (n = 2), hematopoietic stem cell transplantation (n = 1), pharmaceuticals (n = 2), hypothetical cell or genetic therapy (n = 1), screening programs (n = 4), and interventions for SCD treatment complications (n = 3). A limited number of potential SCD and treatment complications were evaluated. No study adopted a societal perspective in the base case, six studies examined lifetime cost-effectiveness, seven studies employed a Markov or discrete-event simulation model, and eight studies used an outcome metric that captured both quality and length of life. To better compare the value of emerging and current therapies, future CEAs should adopt a societal perspective incorporating both medical and nonmedical costs, comprehensively model SCD complexity using robust health economic simulation models over the patient's entire lifespan, and capture the intervention's effect on both survival and quality of life.

Abstract

OBJECTIVES The objective of our study was to conduct a systematic literature review of economic costs (henceforth costs) associated with myasthenia gravis (MG). METHODS We searched MEDLINE (through PubMed), CINAHL, Embase, PsycINFO, and Web of Science for studies reporting costs of MG published from inception up until March 18, 2020, without language restrictions. Two reviewers independently screened records for eligibility, extracted the data, and assessed included studies for risk of bias using the Newcastle-Ottawa Scale. Costs were inflated and converted to 2018 United States dollars ($). RESULTS The search identified 16 articles for data extraction and synthesis. Estimates of costs of MG were found for samples from eight countries spanning four continents (Europe, North America, South America, and Asia). Across studies, the mean per-patient annual direct medical cost of illness was estimated at between $760 and $28,780, and cost per hospitalization between $2550 and $164,730. The indirect cost of illness was estimated at $80 and $3550. Costs varied considerably by patient characteristics, and drivers of the direct medical cost of illness included intravenous immunoglobulin and plasma exchange, myasthenic crisis, mechanical ventilatory support, and hospitalizations. CONCLUSIONS We show that the current body of literature of costs of MG is sparse, limited to a few geographical settings and resource categories, mostly dated, and subject to non-trivial variability, both within and between countries. Our synthesis will help researchers and decision-makers identify gaps in the local health economic context of MG and inform future cost studies and economic evaluations in this patient population.

Abstract

INTRODUCTION An estimated 69 million traumatic brain injuries (TBI) occur each year worldwide, with most in low-income and middle-income countries. The CRASH-3 randomised trial found that intravenous administration of tranexamic acid within 3 hours of injury reduces head injury deaths in patients sustaining a mild or moderate TBI. We examined the cost-effectiveness of tranexamic acid treatment for TBI. METHODS A Markov decision model was developed to assess the cost-effectiveness of treatment with and without tranexamic acid, in addition to current practice. We modelled the decision in the UK and Pakistan from a health service perspective, over a lifetime time horizon. We used data from the CRASH-3 trial for the risk of death during the trial period (28 days) and patient quality of life, and data from the literature to estimate costs and long-term outcomes post-TBI. We present outcomes as quality-adjusted life years (QALYs) and 2018 costs in pounds for the UK, and US dollars for Pakistan. Incremental cost-effectiveness ratios (ICER) per QALY gained were estimated, and compared with country specific cost-effective thresholds. Deterministic and probabilistic sensitivity analyses were also performed. RESULTS Tranexamic acid was highly cost-effective for patients with mild TBI and intracranial bleeding or patients with moderate TBI, at £4288 per QALY in the UK, and US$24 per QALY in Pakistan. Tranexamic acid was 99% and 98% cost-effective at the cost-effectiveness thresholds for the UK and Pakistan, respectively, and remained cost-effective across all deterministic sensitivity analyses. Tranexamic acid was even more cost-effective with earlier treatment administration. The cost-effectiveness for those with severe TBI was uncertain. CONCLUSION Early administration of tranexamic acid is highly cost-effective for patients with mild or moderate TBI in the UK and Pakistan, relative to the cost-effectiveness thresholds used. The estimated ICERs suggest treatment is likely to be cost-effective across all income settings globally.