Methods for the cost-effectiveness modelling of screening interventions in an uncertain landscape:Application to screening for prostate cancer

Decisions need to be made about who and how to screen for diseases to optimise health inthe population. Cost-effectiveness analyses of screening interventions can be associatedwith many areas of uncertainty due to a constantly changing landscape in screeningmethods, diagnostic tests, treatments and understanding of natural history. A failure toaccount for such uncertainty may result in incorrect or poorly informed decisions. Prostatecancer is an example of a disease where recent developments in the understanding of whoand how to screen have provided challenges to the analyst trying to makerecommendations on the most cost-effective screening strategy.Using prostate cancer screening as a case study, this dissertation explores methods tohandle uncertainty when modelling the cost-effectiveness of screening interventions in anuncertain landscape. The dissertation shows how a systematic review of previous modelscan identify areas of parameter and structural uncertainty, how to gain expert consensuswith respect to relevant screening strategies, and how to appropriately adapt and calibratean existing natural history model to a new setting.  It will demonstrate how the 22 studies identified in the systematic review informed thestructure and data parameters of the natural history model and how a modified-Delphiprocess identified prostate cancer screening strategies that were deemed relevant byexperts, including risk-stratified and adaptive approaches. It will also show how a decisionmodel was adapted and calibrated to UK data to find that, of the strategies identified in theDelphi, a once-off screening at age 50 years was most cost-effective.  Many methods are available for dealing with uncertainty in cost-effectiveness modelling ofscreening interventions. The dissertation will conclude with a discussion on the merits andlimitations of the methods used, with recommendations given for practice. The aim is toprovide a guide to identifying and addressing the uncertainty inherent in cost-effectivenessanalyses of screening strategies.

An observational cohort study of health outcomes and costs associated with early pregnancy assessment units in the UK

BACKGROUND: The objective of this study was to assess the impact of consultant presence, volume of patients seen and weekend opening on the health and cost-related outcomes associated with different Early Pregnancy Assessment Unit (EPAU) configurations. METHODS: This was an observational study with a prospective cohort design. Six thousand six hundred six pregnant women (16 years of age and over) attending EPAUs because of suspected early pregnancy complications were recruited from 44 EPAUs across the UK. The main outcome measures were quality of life, costs, and anxiety. RESULTS: Costs, quality of life and anxiety scores were similar across configurations with little evidence to suggest an impact of consultant presence, weekend opening or volume of patients seen. Mean overall costs varied from £92 (95% CI £85 - £98) for a diagnosis of normally developing pregnancy to £1793 (95% CI £1346 - £2240) for a molar pregnancy. EQ-5D-5L score increased from 0.85 (95% CI 0.84–0.86) at baseline to 0.91 (95% CI 0.90–0.92) at 4 weeks for the 573 women who completed questionnaires at both time points, largely due to improvements in the pain/discomfort and anxiety/depression dimensions. 78% of women reported a decrease in their anxiety score immediately following their EPAU appointment. CONCLUSIONS: EPAU configuration, as specified in this study, had limited impact on any of the outcomes examined. However, it is clear that care provided in the EPAU has a positive overall effect on women’s health and emotional wellbeing, with significant improvements in EQ-5D and anxiety shown following an EPAU visit. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12913-022-07709-9

Labour induction with prostaglandins: a systematic review and network meta-analysis

Abstract OBJECTIVES: To assess the effectiveness and safety of prostaglandins used for labour induction. DESIGN: Systematic review with Bayesian network meta-analysis DATA SOURCES: The Cochrane Pregnancy and Childbirth Group's Database of Trials (which incorporates the results of a broad generic search for all pregnancy and postpartum trials). Sources included are CENTRAL, Medline, Embase, NHS Economic Evaluation Database, CINAHL, relevant journals, conference proceedings, and registries of ongoing trials. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised clinical trials of prostaglandin or prostaglandin analogues used for third trimester cervical ripening or labour induction versus placebo or no treatment, alternative prostaglandin dose or administration, or a different type of prostaglandin. We included studies recruiting women with a viable fetus, but had no other restrictions relating to indication for labour induction or language of publication. Outcomes assessed were serious neonatal morbidity (trialist defined) or perinatal death; serious maternal morbidity (trialist defined) or death; vaginal delivery not achieved within 24 hours, caesarean section, and uterine hyperstimulation with fetal heart rate changes. RESULTS: 280 randomised clinical trials were included (48 068 women) in the review. Maternal and neonatal mortality and serious morbidity were rarely reported and are summarized narratively. Unresolved inconsistency was observed for the hyperstimulation outcome. Relative to placebo, the odds of failing to achieve a vaginal delivery were lowest for vaginal misoprostol (≥50 µg) (odds ratio 0.06 (95% credible interval 0.02 to 0.12)), with a 39% absolute probability of event (95% credible interval 1% to 94%). Compared with placebo, odds of caesarean section were lowest for titrated oral misoprostol solution

Methods to induce labour:A systematic review, network meta-analysis and cost-effectiveness analysis

OBJECTIVES: To compare the clinical effectiveness and cost‐effectiveness of labour induction methods. METHODS: We conducted a systematic review of randomised trials comparing interventions for third‐trimester labour induction (search date: March 2014). Network meta‐analysis was possible for six of nine prespecified key outcomes: vaginal delivery within 24 hours (VD24), caesarean section, uterine hyperstimulation, neonatal intensive care unit (NICU) admissions, instrumental delivery and infant Apgar scores. We developed a decision‐tree model from a UK NHS perspective and calculated incremental cost‐effectiveness ratios, expected costs, utilities and net benefit, and cost‐effectiveness acceptability curves. MAIN RESULTS: In all, 611 studies comparing 31 active interventions were included. Intravenous oxytocin with amniotomy and vaginal misoprostol (≥50 μg) were most likely to achieve VD24. Titrated low‐dose oral misoprostol achieved the lowest odds of caesarean section, but there was considerable uncertainty in ranking estimates. Vaginal (≥50 μg) and buccal/sublingual misoprostol were most likely to increase uterine hyperstimulation with high uncertainty in ranking estimates. Compared with placebo, extra‐amniotic prostaglandin E(2) reduced NICU admissions. There were insufficient data to conduct analyses for maternal and neonatal mortality and serious morbidity or maternal satisfaction. Conclusions were robust after exclusion of studies at high risk of bias. Due to poor reporting of VD24, the cost‐effectiveness analysis compared a subset of 20 interventions. There was considerable uncertainty in estimates, but buccal/sublingual and titrated (low‐dose) misoprostol showed the highest probability of being most cost‐effective. CONCLUSIONS: Future trials should be designed and powered to detect a method that is more cost‐effective than low‐dose titrated oral misoprostol. TWEETABLE ABSTRACT: New study ranks methods to induce labour in pregnant women on effectiveness and cost

Matching-Adjusted Indirect Comparison of Crisaborole Ointment 2% vs. Topical Calcineurin Inhibitors in the Treatment of Patients with Mild-to-Moderate Atopic Dermatitis

INTRODUCTION: Crisaborole topical ointment, 2%, is a nonsteroidal, topical anti-inflammatory phosphodiesterase-4 (PDE4) inhibitor that is approved for the treatment of mild-to-moderate atopic dermatitis (AD). The objective of the current analysis was to compare the efficacy of crisaborole 2% relative to pimecrolimus 1%, tacrolimus 0.03% and tacrolimus 0.1% in patients aged ≥ 2 years with mild-to-moderate AD by comparing improvement in Investigator’s Static Global Assessment scores ( (ISGA scores of 0/1 indicating “clear or almost clear”). ISGA was selected as the primary efficacy outcome given the US Food and Drug Administration’s recommendations on the use of ISGA for assessment of global severity in AD and to align with efficacy measurements in the crisaborole registration trials. Safety endpoints could not be analyzed due to differences in outcome definitions across studies. METHODS: Efficacy of crisaborole was evaluated using individual patient data (IPD) from two pivotal phase III randomized controlled trials (RCTs), and efficacy of comparators was evaluated using published RCTs included in a previous network meta-analysis. Vehicle controls were not comparable due to differences in ingredients and population imbalance and, therefore, an unanchored matching-adjusted indirect comparison (MAIC) was used, which reweighted IPD for crisaborole to estimate absolute response in comparator populations. RESULTS: The odds of achieving an improvement in ISGA score was higher with crisaborole 2% versus pimecrolimus 1% (odds ratio [OR] 2.03; 95% confidence interval [CI] 1.45–2.85; effective sample size =  627, reduced from 1021; p value < 0.001) and for crisaborole 2% versus tacrolimus 0.03% (OR 1.50; 95% CI 1.09–2.05; effective sample size = 311, reduced from 1021; p = 0.012). CONCLUSION: The unanchored MAIC suggests that the odds of achieving an improvement in ISGA score is greater with crisaborole 2% than with pimecrolimus 1% or tacrolimus 0.03% in patients aged ≥ 2 years with mild-to-moderate AD. These results are consistent with findings from the previously published network meta-analysis, which used a different methodology for performing indirect treatment comparisons. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13555-021-00646-1

Treatments for bulimia nervosa: a network meta-analysis

Background Bulimia nervosa (BN) is a severe eating disorder that can be managed using a variety of treatments including pharmacological, psychological, and combination treatments. We aimed to compare their effectiveness and to identify the most effective for the treatment of BN in adults. Methods A search was conducted in Embase, Medline, PsycINFO, and Central from their inception to July 2016. Studies were included if they reported on treatments for adults who fulfilled diagnostic criteria for BN. Only randomised controlled trials (RCTs) that examined available psychological, pharmacological, or combination therapies licensed in the UK were included. We conducted a network meta-analysis (NMA) of RCTs. The outcome analysed was full remission at the end of treatment. Results We identified 21 eligible trials with 1828 participants involving 12 treatments, including wait list. The results of the NMA suggested that individual cognitive behavioural therapy (CBT) (specific to eating disorders) was most effective in achieving remission at the end of treatment compared with wait list (OR 3.89, 95% CrI 1.19–14.02), followed by guided cognitive behavioural self-help (OR 3.81, 95% CrI 1.51–10.90). Inconsistency checks did not identify any significant inconsistency between the direct and indirect evidence. Conclusions The analysis suggested that the treatments that are most likely to achieve full remission are individual CBT (specific to eating disorders) and guided cognitive behavioural self-help, although no firm conclusions could be drawn due to the limited evidence base. There is a need for further research on the maintenance of treatment effects and the mediators of treatment outcome

Differences in the organisation of early pregnancy units and the effect of senior clinician presence, volume of patients and weekend opening on emergency hospital admissions: Findings from the VESPA Study

OBJECTIVE: To determine whether the participation of consultant gynaecologists in delivering early pregnancy care results in a lower rate of acute hospital admissions. DESIGN: Prospective cohort study and emergency hospital care audit; data were collected as part of the national prospective mixed-methods VESPA study on the “Variations in the organization of EPAUs in the UK and their effects on clinical, Service and PAtient-centred outcomes”. SETTING: 44 Early Pregnancy Assessment Units (EPAUs) across the UK randomly selected in balanced numbers from eight pre-defined mutually exclusive strata. PARTICIPANTS: 6606 pregnant women (≥16 years old) with suspected first trimester pregnancy complications attending the participating EPAUs or Emergency Departments (ED) from December 2016 to July 2017. EXPOSURES: Planned and actual senior clinician presence, unit size, and weekend opening. MAIN OUTCOME MEASURES: Unplanned admissions to hospital following any visit for investigations or treatment for first trimester complications as a proportion of women attending EPAUs. RESULTS: 205/6397 (3.2%; 95% CI 2.8–3.7) women were admitted following their EPAU attendance. The admission rate among 44 units ranged from 0% to 13.7% (median 2.8). Neither planned senior clinician presence (p = 0.874) nor unit volume (p = 0.247) were associated with lower admission rates from EPAU, whilst EPAU opening over the weekend resulted in lower admission rates (p = 0.027). 1445/5464 (26.4%; 95%CI 25.3 to 27.6) women were admitted from ED. There was little evidence of an association with planned senior clinician time (p = 0.280) or unit volume (p = 0.647). Keeping an EPAU open over the weekend for an additional hour was associated with 2.4% (95% CI 0.1% to 4.7%) lower odds of an emergency admission from ED. CONCLUSIONS: Involvement of senior clinicians in delivering early pregnancy care has no significant impact on emergency hospital admissions for early pregnancy complications. Weekend opening, however, may be an effective way of reducing emergency admissions from ED