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

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

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

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.

Abstract

Introduction:: Use of tranexamic acid (TXA) in trauma has been the subject of growing interest by researchers and health professionals. However, there are still several open questions regarding its use. In some aspects medical literature is controversial. The points of disagreement among experts include questions such as: Which patients should receive TXA in trauma? Should treatment be performed in the pre-hospital environment? Is there any need for laboratory parameters before starting TXA treatment? What is the drug safety profile? The main issue on which there is still no basis in literature is: What is the indication for treatment within massive transfusion protocols? Objective:: Answer the questions proposed based on critical evaluation of the evidence gathered so far and carry out a study of cost-effectiveness of TXA use in trauma adapted to the Brazilian reality. Methods:: A literature review was performed through searching Pubmed.com, Embase and Cab Abstract by headings "tranexamic AND trauma", in all languages, yielding 426 articles. Manuscripts reporting on TXA utilization for elective procedures were excluded, remaining 79 articles. Fifty-five articles were selected, and critically evaluated in order to answer study questions. The evaluation of cost effectiveness was performed using CRASH-2 trial data and Brazilian official population data. Results:: TXA is effective and efficient, and should be administered to a wide range of patients, including those with indication evaluated in research protocols and current indication criteria for TXA should be expanded. As for the cost-effectiveness, the TXA proved to be cost-effective with an average cost of R$ 61.35 (currently US$16) per year of life saved. Conclusion:: The use of TXA in trauma setting seems to be effective, efficient and cost-effective in the various groups of polytrauma patients. Its use in massive transfusion protocols should be the subject of further investigations. Introducao:: O uso do acido tranexamico (TXA) no trauma tem sido alvo de interesse crescente por parte de pesquisadores e profissionais de saude. No entanto, seus beneficios ainda nao foram completamente definidos. Os pontos de divergencia entre especialistas incluem questoes como: quais pacientes devem receber TXA no trauma? O tratamento deve ser realizado em ambiente pre-hospitalar? Ha necessidade de exames laboratoriais para indicar o tratamento? Qual o perfil de seguranca da droga? A principal questao para a qual ainda nao existe qualquer embasamento na literatura e: qual a indicacao do tratamento dentro de protocolos de transfusao macica? Objetivo:: Responder as questoes propostas, com base em avaliacao critica da evidencia reunida ate o momento e realizar estudo de custo-efetividade do uso do TXA no trauma adaptado a realidade brasileira. Metodos:: Foi realizada revisao da literatura atraves de estrategia de busca: PubMed.com, Embase e no Cab Abstract pelos descritores "tranexamic AND trauma", em todos idiomas, resultando em 426 artigos. Foram excluidos aqueles relativos as operacoes eletivas, restando 79 artigos. Cinquenta e cinco foram selecionados e avaliados criticamente com vistas a responder as questoes em estudo. A avaliacao de custo-efetividade foi realizada utilizando dados do estudo CRASH-2 e populacionais oficiais brasileiros. Resultados:: Atraves da analise da evidencia disponivel chegou-se a conclusao de que o acido tranexamico e tratamento eficaz e efetivo, devendo ser administrado a ampla gama de pacientes, incluindo todos aqueles com indicacao ja avaliada nos protocolos de pesquisa publicados e provavelmente devam-se expandir os criterios de indicacao. Quanto a avaliacao de custo-efetividade, o TXA mostrou-se bastante custo-eficaz com gasto medio de R$ 61,35 por ano de vida salvo. Conclusao:: O uso do acido tranexamico no trauma parece ser eficaz, efetivo e custo-eficaz nos diversos grupos de pacientes politraumatizados. Seu uso em protocolos de transfusao macica ainda deve ser objeto de futuras investigacoes.

Abstract

OBJECTIVE To assess the cost effectiveness of giving tranexamic acid (TXA) to bleeding trauma patients in low, middle and high income settings. METHODS The CRASH-2 trial showed that TXA administration reduces the risk of death in bleeding trauma patients with a small but statistically significant increase in non-intensive care stay. A Markov model was used to assess the cost effectiveness of TXA in Tanzania, India and the United Kingdom (UK). The health outcome was the number of life years gained (LYs). Two costs were considered: the cost of administering TXA and the cost of additional days in hospital. Cost data were obtained from hospitals, World Health Organization (WHO) database and UK reference costs. Cost-effectiveness was measured in international dollars ($) per LY. Both deterministic and probabilistic sensitivity analyses were performed to test the robustness of the results to model assumptions. FINDINGS Administering TXA to bleeding trauma patients within three hours of injury saved an estimated 372, 315 and 755 LYs per 1,000 trauma patients in Tanzania, India and the UK respectively. The cost of giving TXA to 1,000 patients was $17,483 in Tanzania, $19,550 in India and $30,830 in the UK. The incremental cost of giving TXA versus not giving TXA was $18,025 in Tanzania, $20,670 in India and $48,002 in the UK. The estimated incremental cost per LY gained of administering TXA is $48, $66 and $64 in Tanzania, India and the UK respectively. CONCLUSION Early administration of TXA to bleeding trauma patients is likely to be highly cost effective in low, middle and high income settings. TRIAL REGISTRATION This paper uses data collected by the CRASH 2 trial: Controlled-Trials.com ISRCTN86750102, Clinicaltrials.gov NCT00375258 and South African Clinical Trial Register DOH-27-0607-1919.

Abstract

Respiratory syncytial virus (RSV) is the leading cause of infant hospitalization in the US. The economic burden of severe disease is substantial, including hospitalization costs and out-of-pocket expenses. RSV prophylaxis with either RSV immune globulin intravenous (RSV-IGIV) or palivizumab has been shown to be effective in reducing RSV-related hospitalizations. Motavizumab, a new enhanced-potency humanized RSV monoclonal antibody, is presently in clinical trials. RSV-IGIV and palivizumab are associated with high acquisition costs. Cost-effectiveness analyses are therefore of great importance in helping to determine who should receive RSV prophylaxis. Six studies have analysed the cost effectiveness of RSV-IGIV, 14 have analysed the cost effectiveness of palivizumab and five have analysed the cost effectiveness of both agents, two of which directly compared palivizumab with RSV-IGIV. The cost effectiveness of motavizumab has not been studied. Significant variation exists in the modelling used in these analyses. Many studies have examined short-term benefits such as reducing hospitalizations and associated costs, while fewer studies have examined long-term benefits such as QALYs or life-years gained. The payer and society have been the most common perspectives used. The endpoints examined varied and generally did not account for the potential impact of RSV prophylaxis on RSV-related complications such as asthma. While some studies have reported acceptable cost-effectiveness ratios for RSV prophylaxis, the majority failed to show cost savings or cost-effectiveness ratios below commonly accepted thresholds for either RSV-IGIV or palivizumab. Cost effectiveness of RSV prophylaxis tended to be more favourable in populations with specific risk factors, including premature infants < or =32 weeks' gestational age, and infants or children aged < 2 years with chronic lung disease or congenital heart disease. Comparing the results of economic analyses of the two agents suggests palivizumab may be the more cost-effective option in the population for which RSV prophylaxis is recommended. Over time, the acquisition cost of RSV prophylaxis agents, a major cost driver, may decrease, and more acceptable outcomes of economic analyses may result. Albeit important, the results of economic analyses are not the only tool that decision makers rely on, as population-specific risk factors, and efficacy and safety data must be considered when developing treatment guidelines and making clinical decisions.

Abstract

PURPOSE To measure the cost-effectiveness of a specific polyclonal intravenous immune globulin preparation (Pentaglobin) in adult patients treated for severe sepsis and septic shock. MATERIALS AND METHODS Effectiveness data from a meta-analysis of 9 randomized trials (N=435) were used to populate a decision model to estimate the cost-effectiveness of Pentaglobin and its comparator standard therapy from the hospital perspective in Germany. Primary outcome: all-cause morality; secondary outcome: intensive care unit (ICU) length of stay. Benefit was expressed as lives saved (LS). Published cost data were applied to assess differences in ICU treatment costs. Cost- effectiveness was calculated as incremental cost per LS. RESULTS Pentaglobin reduced the risk of mortality (P<.001) but had no effect on ICU length of stay. A baseline risk of mortality of 0.4434 (risk ratio=0.5652; absolute risk reduction=0.1928; number-needed-to-treat =5.19) increased ICU treatment costs with Pentaglobin by 2,037 (22,711 vs 24,747) with a cost per LS of 10,565. Sensitivity analyses on baseline mortality risk (95% confidence interval 0.3293-0.5162) and risk ratio (95% confidence interval 0.4306-0.7420) yielded a cost per LS range of 5,715 to 28,443 with a 56.3% probability of cost- effectiveness of 12,000 or less. CONCLUSIONS Pentaglobin is a promising adjuvant therapy both clinically and economically for treatment of adults with severe sepsis and septic shock.