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BACKGROUND: Rapid and widespread increases in carbapenem resistance (CR) necessitate identification of risk factors to guide appropriate interventions.
OBJECTIVES: We aimed to identify risk factors for CR Gram-negative infection through a systematic literature review.
DATA SOURCES: We searched MEDLINE (via OvidSP and PubMed) and Embase (via OvidSP) databases and the Cochrane Central Register of Controlled Trials.
STUDY ELIGIBILITY CRITERIA: Prospective or retrospective cohort and case-control studies reporting quantitative data on risk factors associated with infections due to CR Gram-negative pathogens in hospitalized patients were eligible.
PARTICIPANTS: Studies included hospitalized patients with CR infection caused by Gram-negative bacterial pathogens (Enterobacterales and non-fermenters).
METHODS: Searches were conducted in January 2018/December 2019 to identify studies published since 2007. Risk factor data were extracted and grouped by factor. The primary metric was proportion of studies reporting a significant association with CR infection for each factor.
RESULTS: In total, 92 studies were identified. Risk factors most frequently reported as significantly associated with CR infection (>10 studies) were previous antibiotic use (91.1%; 72/79 studies); previous carbapenem use (82.6%; 57/69); previous colonization (72.7%; 8/11); mechanical ventilation (66.7%; 36/54); previous intensive care unit stay (64.4%; 38/59); dialysis (61.1%; 11/18); catheter (58.0%; 40/69); length of stay in hospital (54.5%; 30/55); comorbidities (52.7%; 39/74); APACHE II (51.7%; 15/29); and intubation (51.4%; 18/35). Risk factors were mostly consistent across different species and sites of infection.
CONCLUSIONS: Several variables, particularly previous antibiotic use, are strong risk factors for CR infection. Interventions to mitigate against CR infection should target these factors.
INTRODUCTION: The aim of the study is to estimate the cost-effectiveness of TheraSphere against other embolic treatments in a population with early to intermediate stage hepatocellular carcinoma (HCC) who are unresectable at presentation and are eligible for transarterial embolization (TAE), conventional transarterial chemoembolization (cTACE) or drug-eluting bead TACE (DEB-TACE).
MATERIALS AND METHODS: A Markov model was constructed using a UK National Health Service (NHS) perspective, a 20-year time horizon, and four-week cycles. The eight health states included 'watch and wait', 'transplantation' (pre-, post and post (No HCC)), 'resection', 'no HCC other', 'pharmacological management' and 'death'. Clinical data were sourced from literature and expert opinion. Resource use and costs were reflective of the NHS, and benefits were quantified using Quality-Adjusted Life Years (QALYs), with utility weights sourced from literature.
Comparators were TAE, cTACE and DEB-TACE. The primary output was the Incremental Cost-Effectiveness Ratio (ICER) expressed as cost per QALY gained. An ICER of under £20,000/QALY gained for an intervention is cost-effective and represents efficient use of healthcare resources. Extensive deterministic and probabilistic sensitivity analyses were undertaken.
RESULTS: TheraSphere patients were predicted to gain 0.7 additional QALYs compared to all other treatments. The base case ICERs for TheraSphere were £17,300, £17,279 and £23,020 per QALY gained compared to TAE, cTACE and DEB-TACE, respectively. In the TheraSphere cohort, 87% more patients were predicted to achieve downstaging compared to all other treatment options.
CONCLUSIONS: This study indicates that treatment with TheraSphere is a potentially cost-effective option for patients with early to intermediate stage HCC.
PURPOSE: This systematic review (SR) assessed the efficacy, safety and cost-effectiveness of cell-based therapy to manage limbal stem cell deficiency (LSCD), a sight-threatening orphan condition most frequently associated with severe chemical or thermal burns. LSCD has historically been treated by transplanting limbal tissue. In 1997, a new treatment, cultured limbal epithelial autografts, was described for unilateral LSCD. In cases of bilateral disease cultured autologous oral mucosa stem cells have been used. The relative efficacy of different cultured tissue procedures is unknown.
METHODS: A protocol was registered with PROSPERO (CRD42017081117). Searches were conducted in 14 databases and 6 conference websites. Two reviewers independently selected studies, conducted data extraction and assessed risk of bias. One reviewer extracted individual patient data (IPD); a second checked extracted data. Data were assessed to determine the feasibility of statistical analysis, with Bayesian synthesis used to estimate improvement achieved by different treatments.
RESULTS: Fifty-two studies were eligible for inclusion (1113 eyes); 41 studies (716 eyes) reported IPD. No evidence was identified on cost-effectiveness. This SR was unable to confirm that any of the types of ex vivo cultured stem cell transplants identified for LSCD treatment were statistically superior when assessed against the outcomes of interest.
CONCLUSIONS: We believe this SR is the first to include IPD analysis of LSCD data. There is no evidence for the superiority of any method of limbal stem cell transplant. Confirmation of the safety and efficacy of this treatment modality is challenging due to heterogeneity within and between the studies identified. Therefore, recommendations for future research are proposed.
PURPOSE: Aromatic l-amino acid decarboxylase (AADC) deficiency is a rare genetic condition, characterised by movement disorder, and speech and cognitive functioning impairment. To enable economic evaluation of treatments, health-related quality of life or utilities need to be derived. These are currently lacking in the literature. This is challenging, where patient numbers are small, particularly in paediatric populations. This study outlines the 5-stage development of vignettes describing AADC, for use in a subsequent health-state utility elicitation study, with an emphasis on caregiver and clinician engagement.
METHODS: To align with the economic model, 5 vignettes describing 5 AADC deficiency motor milestones were developed, ranging from "bedridden" to "walking with assistance". Stage 1 comprised identification of symptoms/impairments from the literature and AADC deficiency charity websites. Stage 2 comprised group discussion with 3 caregivers. A symptoms matrix was developed, followed by draft vignettes (Stage 3). Eight clinicians reviewed these, alongside the same 3 caregivers via a survey (Stage 4). The vignettes were revised at stage 5.
RESULTS: There was high consensus regarding symptoms at Stages 1 and 2, although the literature highlighted behavioural and autonomic symptoms, which caregivers did not. The symptoms were grouped into neuromuscular, autonomic, cognitive, behavioural and functional impairments. Clinician and caregiver vignette feedback highlighted the idiopathic nature of AADC. Despite this, clinicians suggested only 2 additional symptoms. Similarly, caregivers suggested 4 symptoms and a change to the wording used for the cognitive symptoms. Not all changes were included.
CONCLUSION: The differing focus of caregivers, clinicians and the literature reinforces the importance of patient/caregiver engagement. The vignettes need to comprehensively capture what it is like to live with AADC deficiency, in order for the subsequent utilities to be robust. A focus on evidence triangulation, especially for idiopathic conditions, and how engagement is sought from caregivers are important future avenues of research.
BACKGROUND AND AIMS: A proportion of chronic heart failure (CHF) patients will experience regurgitation secondary to ventricular remodeling in CHF, known as functional mitral (MR) or tricuspid (TR) regurgitation. Its presence adversely impacts the prognosis and healthcare utilization in CHF patients. The advent of interventional devices for both atrioventricular valves modifies both aspects. We present an economic model structure suitable for comparing interventions used in MR and TR, and assess the cost-effectiveness of transcatheter mitral valve repair (TMVr) plus guideline directed medical therapy (GDMT) compared with GDMT alone in people with MR.
METHODS: An economic model with a lifetime time horizon was developed based on extrapolated survival data and using New York Heart Association classifications to describe disease severity in people with functional MR at high risk of surgical mortality or deemed inoperable. Cost and utility values (describing health-related quality-of-life) were assigned to patients dependent on their disease severity. The analysis was conducted from a UK National Health Service perspective. An incremental cost per additional quality-adjusted life year (QALY) was estimated, and sensitivity (one-way and probabilistic) and scenario analyses conducted.
RESULTS AND COMPARISONS:
Compared with GDMT, the use of TMVr results in an additional 1.07 QALYs and an increase in costs of £32,267 per patient over a lifetime time horizon. The estimated incremental cost per QALY gained is £30,057 and would therefore be on the threshold of cost-effectiveness at £30,000 per quality adjusted life year. Thus, from a UK reimbursement perspective, in patients with severe functional MR who are at high risk of surgical mortality or deemed inoperable with conventional surgery, TMVr plus medical therapy is likely to represent a cost-effective treatment option compared with GDMT alone. The choice of device (MitraClip or PASCAL) will need to be confirmed once further clinical data are reported.
The purpose of economic evaluation is to inform decisions as to the relative value of different courses of action, in a systematic, transparent way. Cost-effectiveness analysis involves assessing the costs and effects of two or more competing, alternative interventions against other uses if the same resources were used elsewhere. Applied to the social care context, a commissioner with a constrained budget might use this information to consider whether to invest public funds in a new intervention, programme or service or whether standard care represents the optimal choice of provision.
In the context of the UK, the National Institute for Health and Care Excellence (NICE) has provided methods guidance for the economic evaluation of social care interventions (NICE, 2013 & 2014). In practice, there remains considerable uncertainty on methods for social care economic evaluation; for example, in the relevant perspective, inclusion of informal care, appropriate cost-effectiveness threshold, etc. To help resolve this uncertainty, NICE commissioned a scoping review to support developing a long-term strategy for how to consider social care economics in NICE guidelines. Full details for this study are available online (see Weatherly et al., 2017). This article summarises the methods used in published economic evaluations of social care interventions, briefly noting some recent methods developments, and it highlights key methods issues and gaps for addressing in the future.
OBJECTIVES: To assess the comparative efficacy and safety of lurasidone, brexpiprazole and cariprazine in the treatment of schizophrenia in a network meta-analysis.
METHODS: A systematic review was conducted to identify randomised controlled trials comparing lurasidone, brexpiprazole and cariprazine with each other or placebo in patients with schizophrenia. Searches were carried out in a range of bibliographic databases and other information sources. The key outcomes included effect on Positive and Negative Syndrome Scales (PANSS) and Clinical Global Impression-Severity (CGI-S) scores; and cardiovascular and metabolic parameters. A feasibility assessment evaluated the trials' suitability for inclusion in a Bayesian Network Meta Analysis. Random effects models were used, with half-Cauchy priors for the between-study variance term for the continuous outcomes and informative priors from Turner et al. (2015) for the binomial outcomes. Uninformative priors were used for the treatment effects. Each drug and dose combination was considered as a separate node in the networks.
RESULTS: Searches conducted in February 2020 identified 1,138 records; 19 RCTs contributed to the NMA. There was evidence that lurasidone doses of 40mg/d and above performed better than placebo in terms of change in PANSS and CGI-S scores at 6 weeks, with increasing dose leading to higher effect estimates. The lowest doses of all treatments were not found to be better than placebo. When comparing brexpiprazole and cariprazine against lurasidone 40 mg/d, the 95% credible interval contained 'no difference' regardless of dose. The safety outcomes were relatively variable; for all treatments, the 95% credible intervals usually contained 'no difference'. Active treatments were generally associated with lower odds of discontinuation due to any cause, and higher odds of experiencing any adverse event.
CONCLUSIONS: Lurasidone was found to be comparable to brexpiprazole and cariprazine for the efficacy and safety outcomes assessed at 6 weeks.
