Association of psychological distress, quality of life and costs with carpal tunnel syndrome severity: a crosssectional analysis of the PALMS cohort

Objectives: The PALMS study is designed to identify prognostic factors for outcome from corticosteroid injection and surgical decompression for carpal tunnel syndrome (CTS) and predictors of cost over 2 years. The aim of this paper is to explore the cross-sectional association of baseline patient-reported and clinical severity with anxiety, depression, health-related quality of life and costs of CTS in patients referred to secondary care. Methods: Prospective, multi-centre cohort study initiated in 2013. We collected baseline data on patientreported symptom severity (CTS-6), psychological status (HADS), hand function (Michigan Hand Questionnaire) comorbidities, EQ5D-3L and sociodemographic variables. Nerve conduction tests classified patients into five severity grades (mild to very severe). Data were analysed using a general linear model. Results: 753 patients with CTS provided complete baseline data. Multivariable linear regression adjusting for age, sex, ethnicity, duration of CTS, smoking status, alcohol consumption, employment status, body mass index and comorbidities showed a highly statistically significant relationship between CTS-6 and anxiety, depression and the EQ-5D (p<0.0001 in each case). Likewise, a significant relationship was observed between electrodiagnostic severity and anxiety (p=0.027) but not with depression (p=0.986) or the EQ-5D (p=0.257). NHS and societal costs in the 3 months prior to enrolment were significantly associated with self-reported severity (p<0.0001) but not with electrodiagnostic severity. Conclusions: Patient-reported symptom severity in carpal tunnel syndrome is significantly and positively associated with anxiety, depression, health-related quality of life and NHS and societal costs even when adjusting for age, gender, body mass index, comorbidities, smoking, drinking and occupational status. In contrast there is little or no evidence of any relationship with objectively derived CTS severity. Future research is needed to understand the impact of approaches and treatments that address psychosocial stressors as well as biomedical factors on relief of symptoms from carpal tunnel syndrome.CJH was funded by the National Institute for Health Research (NIHR) through a NIHR Senior Research Fellowship. ECFW is funded by the NIHR Cambridge Biomedical Research Centre

Retrospective, multicohort analysis of the Clinical Practice Research Datalink (CPRD) to determine differences in the cost of medication wastage, dispensing fees and prescriber time of issuing either short (&lt;60 days) or long (≥60 days) prescription lengths in primary care for common, chronic conditions in the UK

Objectives: To investigate patterns of early repeat prescriptions and treatment switching over an 11-year period to estimate differences in the cost of medication wastage, dispensing fees and prescriber time for short (<60 days) and long (≥60 days) prescription lengths from the perspective of the National Health Service in the United Kingdom. Setting: Retrospective, multiple cohort study of primary care prescriptions from the Clinical Practice Research Datalink. Participants: Five random samples of 50,000 patients each prescribed oral drugs for (1) glucose control in type 2 diabetes mellitus (T2DM), (2) hypertension in T2DM, (3) statins (lipid management) in T2DM, (4) secondary prevention of myocardial infarction and (5) depression. Primary and secondary outcome measures: The volume of medication wastage from early repeat prescriptions and three other types of treatment switches was quantified and costed. Dispensing fees and prescriber time were also determined. Total unnecessary costs (TUC, cost of medication wastage, dispensing fees, and prescriber time) associated with <60 day and ≥60 day prescriptions, standardised to a 120-day period, were then compared. Results: Longer prescription lengths were associated with more medication waste per prescription. However, when including dispensing fees and prescriber time, longer prescription lengths resulted in lower TUC. This finding was consistent across all five cohorts. Savings ranged from £8.38 to £12.06 per prescription per 120 days if a single long prescription were issued instead of multiple short prescriptions. Prescriber time costs accounted for the largest component of TUC. Conclusions: Shorter prescription lengths could potentially reduce medication wastage, but they may also increase dispensing fees and/or the time burden of issuing prescriptions

How good are GPs at adhering to a pragmatic trial protocol in primary care? Results from the ADDITION-Cambridge cluster-randomized pragmatic trial

Objective: To assess the fidelity of general practitioners’ (GP) adherence to a long term pragmatic trial protocol. Design: Retrospective analyses of electronic primary care records of participants in the pragmatic cluster-randomised ADDITION (Anglo-Danish-Dutch Study of Intensive Treatment In People with Screen Detected Diabetes in Primary Care)-Cambridge trial, comparing intensive multi-factorial treatment (IT) vs. routine care (RC). Data were collected from the date of diagnosis until December 2010. Setting: Primary care surgeries in the East of England Study sample/participants: A subsample (n=189, RC-arm: n=99, IT-arm: n=90) of patients from the ADDITION-Cambridge cohort (867 patients), consisting of 40-69 year old patients with screen detected diabetes mellitus. Interventions: In the RC-arm treatment was delivered according to concurrent treatment guidelines. Surgeries in the IT-arm received funding for additional contacts between GPs/nurses and patients, and GPs were advised to follow more intensive treatment algorithms for the management of glucose, lipids and blood pressure and aspirin therapy than in the RC-arm. Outcome measures: The number of annual contacts between patients and GPs/nurses, the proportion of patients receiving prescriptions for cardio-metabolic medication in years 1 to 5 after diabetes diagnosis, and the adherence to prescription algorithms. Results: The difference in the number of annual GP contacts (β=0.65) and nurse contacts (β=-0.15) between the study arms was small and insignificant. Patients in the IT-arm were more likely to receive glucose-lowering (OR=3.27), ACE-inhibiting (OR=2.03) and lipid-lowering drugs (OR=2.42, all p-values<0.01) than patients in the RC-arm. The prescription adherence varied between medication classes, but improved in both trial arms over the 5 year follow-up. Conclusions: The adherence of GPs to different aspects of the trial protocol was mixed. Background changes in health care policy need to be considered as they have the potential to dilute differences in treatment intensity and hence incremental effect. Clinical trial number: ISRCTN8676908

The HTA risk analysis chart: visualising the need for and potential value of managed entry agreements in health technology assessment

Background Recent changes to the regulatory landscape of pharmaceuticals may sometimes require reimbursement authorities to issue guidance on technologies that have a less mature evidence base. Decision makers need to be aware of risks associated with such health technology assessment (HTA) decisions and the potential to manage this risk through managed entry agreements (MEAs). Objective This work develops methods for quantifying risk associated with specific MEAs and for clearly communicating this to decision makers. Methods We develop the ‘HTA risk analysis chart’, in which we present the payer strategy and uncertainty burden (P-SUB) as a measure of overall risk. The P-SUB consists of the payer uncertainty burden (PUB), the risk stemming from decision uncertainty as to which is the truly optimal technology from the relevant set of technologies, and the payer strategy burden (PSB), the additional risk of approving a technology that is not expected to be optimal. We demonstrate the approach using three recent technology appraisals from the UK National Institute for Health and Clinical Excellence (NICE), each of which considered a price-based MEA. Results The HTA risk analysis chart was calculated using results from standard probabilistic sensitivity analyses. In all three HTAs, the new interventions were associated with substantial risk as measured by the P-SUB. For one of these technologies, the P-SUB was reduced to zero with the proposed price reduction, making this intervention cost effective with near complete certainty. For the other two, the risk reduced substantially with a much reduced PSB and a slightly increased PUB. Conclusions The HTA risk analysis chart shows the risk that the healthcare payer incurs under unresolved decision uncertainty and when considering recommending a technology that is not expected to be optimal given current evidence. This allows the simultaneous consideration of financial and data-collection MEA schemes in an easily understood format. The use of HTA risk analysis charts will help to ensure that MEAs are considered within a standard utility-maximising health economic decision-making framework

Decision Frameworks for Assessing Cost-Effectiveness Given Previous Nonoptimal Decisions

Introduction: Economic evaluations identify the best course of action by a decision maker with respect to the level of health within the overall population. Traditionally, they identify 1 optimal treatment choice. In many jurisdictions, multiple technologies can be covered for the same heterogeneous patient population, which limits the applicability of this framework for directly determining whether a new technology should be covered. This article explores the impact of different decision frameworks within this context. Methods: Three alternate decision frameworks were considered: the traditional normative framework in which only the optimal technology will be covered (normative); a commonly adopted framework in which the new technology is recommended for reimbursement only if it is optimal, with coverage of other technologies remaining as before (current); and a framework that assesses specifically whether coverage of the new technology is optimal, incorporating previous reimbursement decisions and the market share of current technologies (positivist). The implications of the frameworks were assessed using a simulated probabilistic Markov model for a chronic progressive condition. Results: Results illustrate how the different frameworks can lead to different reimbursement recommendations. This in turn produces differences in population health effects and the resultant price reductions required for covering the new technology. Conclusion: By covering only the optimal treatment option, decision makers can maximize the level of health across a population. If decision makers are unwilling to defund technologies, however, the second best option of adopting the positivist framework has the greatest relevance with respect to deciding whether a new technology should be covered.The authors received no financial support for the research, authorship, and/or publication of this article

A Decision Analysis Evaluating Screening for Kidney Cancer Using Focused Renal Ultrasound

Background Screening for renal cell carcinoma (RCC) has been identified as a key research priority; however, no randomised control trials have been performed. Value of information analysis can determine whether further research on this topic is of value. Objective To determine (1) whether current evidence suggests that screening is potentially cost effective and, if so, (2) in which age/sex groups, (3) identify evidence gaps, and (4) estimate the value of further research to close those gaps. Design, setting, and participants A decision model was developed evaluating screening in asymptomatic individuals in the UK. A National Health Service perspective was adopted. Intervention A single focused renal ultrasound scan compared with standard of care (no screening). Outcome measurements and statistical analysis Expected lifetime costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER), discounted at 3.5% per annum. Results and limitations Given a prevalence of RCC of 0.34% (0.18–0.54%), screening 60-yr-old men resulted in an ICER of £18 092/QALY (€22 843/QALY). Given a prevalence of RCC of 0.16% (0.08–0.25%), screening 60-yr-old women resulted in an ICER of £37 327/QALY (€47 129/QALY). In the one-way sensitivity analysis, the ICER was <£30 000/QALY as long as the prevalence of RCC was ≥0.25% for men and ≥0.2% for women at age 60 yr. Given the willingness to pay a threshold of £30 000/QALY (€37 878/QALY), the population-expected values of perfect information were £194 million (€244 million) and £97 million (€123 million) for 60-yr-old men and women, respectively. The expected value of perfect parameter information suggests that the prevalence of RCC and stage shift associated with screening are key research priorities. Conclusions Current evidence suggests that one-off screening of 60-yr-old men is potentially cost effective and that further research into this topic would be of value to society. Patient summary Economic modelling suggests that screening 60-yr-old men for kidney cancer using ultrasound may be a good use of resources and that further research on this topic should be performed

Measuring Health Utilities in Children and Adolescents: A Systematic Review of the Literature.

BACKGROUND: The objective of this review was to evaluate the use of all direct and indirect methods used to estimate health utilities in both children and adolescents. Utilities measured pre- and post-intervention are combined with the time over which health states are experienced to calculate quality-adjusted life years (QALYs). Cost-utility analyses (CUAs) estimate the cost-effectiveness of health technologies based on their costs and benefits using QALYs as a measure of benefit. The accurate measurement of QALYs is dependent on using appropriate methods to elicit health utilities. OBJECTIVE: We sought studies that measured health utilities directly from patients or their proxies. We did not exclude those studies that also included adults in the analysis, but excluded those studies focused only on adults. METHODS AND FINDINGS: We evaluated 90 studies from a total of 1,780 selected from the databases. 47 (52%) studies were CUAs incorporated into randomised clinical trials; 23 (26%) were health-state utility assessments; 8 (9%) validated methods and 12 (13%) compared existing or new methods. 22 unique direct or indirect calculation methods were used a total of 137 times. Direct calculation through standard gamble, time trade-off and visual analogue scale was used 32 times. The EuroQol EQ-5D was the most frequently-used single method, selected for 41 studies. 15 of the methods used were generic methods and the remaining 7 were disease-specific. 48 of the 90 studies (53%) used some form of proxy, with 26 (29%) using proxies exclusively to estimate health utilities. CONCLUSIONS: Several child- and adolescent-specific methods are still being developed and validated, leaving many studies using methods that have not been designed or validated for use in children or adolescents. Several studies failed to justify using proxy respondents rather than administering the methods directly to the patients. Only two studies examined missing responses to the methods administered with respect to the patients' ages

Computing the Expected Value of Sample Information Efficiently: Practical Guidance and Recommendations for Four Model-Based Methods

Value of information (VOI) analyses can help policy makers make informed decisions about whether to conduct and how to design future studies. Historically a computationally expensive method to compute the expected value of sample information (EVSI) restricted the use of VOI to simple decision models and study designs. Recently, 4 EVSI approximation methods have made such analyses more feasible and accessible. Members of the Collaborative Network for Value of Information (ConVOI) compared the inputs, the analyst's expertise and skills, and the software required for the 4 recently developed EVSI approximation methods. Our report provides practical guidance and recommendations to help inform the choice between the 4 efficient EVSI estimation methods. More specifically, this report provides: (1) a step-by-step guide to the methods' use, (2) the expertise and skills required to implement the methods, and (3) method recommendations based on the features of decision-analytic problems

Ozanimod for treating moderately to severely active ulcerative colitis [ID3841] A Single Technology Appraisal

This report was commissioned by the NIHR Systematic Reviews Programme as project number 13/54/43Executive Summary: This summary provides a brief overview of the key issues identified by the evidence review group (ERG) as being potentially important for decision-making. It also includes the ERG’s preferred assumptions and the resulting incremental cost-effectiveness ratios (ICERs). • Section 1.1 provides an overview of the key issues and the differences in the assumptions of the company and the ERG in economic analysis. • Section 1.2 provides an overview of key model outcomes and the modelling assumptions that have the greatest effect on the ICER. • Sections 1.3 to 1.5 explain the key issues in more detail. Background information on the condition, technology and evidence and information on non-key issues are in the main ERG report. • Sections 1.6 and 1.7 provide an overview of the ERG’s preferred base case and sensitivity analyses undertaken by the ERG. All issues identified represent the ERG’s view, not the opinion of the National Institute for Health and Care Excellence (NICE)

Clinical and cost-effectiveness of detailed anomaly ultrasound screening in the first trimester: a mixed-methods study

Background In the United Kingdom, pregnant women are offered two scans: at 11–14 and 18–20 weeks’ gestation. Current guidance supports fetal anatomical screening at the second scan, but evidence suggests earlier detection is possible. Objectives To determine clinical and cost-effectiveness of a detailed two-dimensional ultrasound scan in the first trimester for detection of fetal anomalies, in addition to usual practice. Design Systematic review and meta-analysis. Nationwide survey. Analysis of National Congenital Anomaly Disease Registry data. Consensus procedure. Prospective survey of parental opinions. Probabilistic decision-analytic model for cost-effectiveness. Value-of-information analysis. Setting United Kingdom National Health Service. Participants Pregnant women and partners. Interventions Detailed anomaly ultrasound at 11–14 weeks’ gestation, in addition to usual practice. Main outcome measures Diagnostic accuracy, protocol development, health economic modelling and value-of-information analysis. Data sources MEDLINE (OvidSP), EMBASE (OvidSP), Science Citation Index and Conference Proceedings Citation Index-Science (Web of Science Core Collection); National Congenital Anomaly Disease Registry; European Congenital Anomalies Registry; Surveys of National Health Service Trusts; screening sonographers, midwives and doctors; and parents; National Schedule of National Health Service Costs (2019–20). Review methods Systematic review and meta-analysis for diagnostic accuracy. Results First-trimester ultrasound detects 93.3% (95% confidence interval 90.4% to 95.7%) of a pre-selected group of eight major anomalies with specificity of 99.99% (95% confidence interval 99.98% to 99.99%) and positive predictive value of 96.5% (95% confidence interval 93.3 to 98.8, 416,877 fetuses, 40 studies). For major cardiac anomalies, the respective data are 55.8% (95% confidence interval 45.9% to 65.5%), 99.98% (95% confidence interval 99.97% to 99.99%) and 94.85% (95% confidence interval 91.63% to 97.32%, 306,872 fetuses, 45 studies). Of NHS trusts surveyed, 77% currently perform first-trimester anatomy assessment, with evidence of inequity of care; earlier screening resulted in more diagnoses before 16 weeks’ gestation. A consensus procedure (n = 172) developed an anatomical protocol and minimum targets for diagnosis. Parental survey (n = 1374) indicated that over 90% would opt for such screening. Modelling of singleton pregnancies undergoing earlier anomaly screening using two-dimensional ultrasound was associated with increased mean healthcare costs per woman (£11, 95% confidence interval £1 to £29) and maternal quality-adjusted life-years (0.002065, 95% confidence interval 0.000565 to 0.00358), an incremental cost per quality-adjusted life-year of £5270, with likelihood of being cost-effective at £20,000 per quality-adjusted life-year of over 95%. Additional modelling predicted reductions in infant healthcare costs and quality-adjusted life-years. Decision uncertainty was low. Value-of-information analysis of cost-effectiveness results showed no groups of parameters for which further research to reduce uncertainty would likely prove cost-effective. Limitations Study heterogeneity; the lack of a universal reference standard; simplifying assumptions relating to economic model structure; and estimation of some parameters are documented and justified. The rarity of the conditions made estimation of longer-term maternal and infant costs and quality-adjusted life-years challenging, resulting in likely under-estimation of healthcare costs. Conclusions With standardisation and training, first-trimester ultrasound screening for fetal anomalies is clinically effective with over 90% detection for eight major conditions and low false-positive rates. Decision uncertainty around implementation is low and a prospective study would not be an efficient investment. Adding first-trimester anomaly screening to the current screening likely represents a cost-effective use of resources and is acceptable to parents. Future work Focus on developing an implementation framework to modify the current United Kingdom Fetal Anomaly Screening Programme. Study registration This study is registered as PROSPERO CRD42018111781 and CRD42018112434. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/19/10) and is published in full in Health Technology Assessment; Vol. 29, No. 22. See the NIHR Funding and Awards website for further award information