A cost-utility analysis of two Clostridioides difficile infection guideline treatment pathways.

OBJECTIVES: Treatment guidelines are key drivers of prescribing practice in the management of Clostridioides difficile infection (CDI), but recommendations on best practice can vary. We conducted a cost-utility analysis to compare the treatment pathway recommended by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guideline with the pathway proposed by the National Institute for Health and Care Excellence (NICE) guideline, from the perspective of the UK National Health Service. METHODS: A decision tree modelling approach was adopted to reflect the treatment pathway for CDI as outlined in ESCMID and NICE guidelines. Patients experiencing a CDI infection received up to three treatments per infection to achieve a response and could subsequently experience up to two recurrences. Data on patient demographics, treatment response, recurrence, utilities, CDI-related mortality, and costs were taken from published literature. RESULTS: The ESCMID treatment pathway was cost-effective versus the NICE treatment pathway at a threshold of £20 000 per quality-adjusted life year gained, with an incremental cost-effectiveness ratio of £4931. Cost-effectiveness was driven by differences in index infection recommendations (ESCMID recommends fidaxomicin as first-line treatment whereas NICE recommends vancomycin). The model results were robust to variations in inputs investigated in scenarios and sensitivity analyses, and probabilistic sensitivity analysis demonstrated that the ESCMID guideline treatment strategy had a 100% likelihood of being cost-effective versus the NICE treatment strategy. DISCUSSION: Compared with the NICE guideline, the ESCMID guideline recommendations for treating an index CDI represent the most cost-effective use of healthcare resources from the perspective of the UK National Health Service.

Economic evaluation of Cytosponge®-trefoil factor 3 for Barrett esophagus: A cost-utility analysis of randomised controlled trial data.

BACKGROUND: Esophageal adenocarcinoma has a very poor prognosis unless detected early. The Cytosponge-trefoil factor 3 (TFF3) is a non-endoscopic test for Barrett esophagus, a precursor of esophageal adenocarcinoma. Randomised controlled trial data from the BEST3 trial has shown that an offer of Cytosponge-TFF3 in the primary care setting in England to individuals on medication for acid reflux increases detection of Barrett esophagus 10-fold over a year compared with standard care. This is an economic evaluation of Cytosponge-TFF3 screening versus usual care using data from the BEST3 trial which took place between 20th March 2017 and 21st March 2019. METHODS: A Markov model with a one-year cycle-length and a lifetime time horizon was created, adapting previous modeling work on Cytosponge screening. The impact of one round of Cytosponge screening was modelled in patients with a median age of 69 years (based on BEST3 trial population). Cost-effectiveness was expressed as an incremental cost-effectiveness ratio (ICER). Deterministic and probabilistic sensitivity analyses were conducted on model parameters. FINDINGS: Per person, one round of Cytosponge-TFF3 screening, including confirmatory endoscopy and treatment, in the intervention arm costed £82 more than usual care and generated an additional 0.015 quality-adjusted life-years (QALYs) at an ICER of £5,500 per QALY gained. Probabilistic sensitivity analysis gave an ICER of £5,405 (95% CI -£6,791 to £17,600). The average QALY gain per person is small because the majority of patients in the model will not develop BE and therefore will have no resulting change in their utility, however the small proportion of patients who are identified with BE dysplasia or cancer derive large benefit. At a willingness-to-pay threshold of £20,000 per QALY, the probability that Cytosponge-TFF3 was cost-effective was over 90%. INTERPRETATION: Using data from a pragmatic randomised trial, one-off Cytosponge-TFF3 screen is cost-effective relative to usual care for patients with gastro-esophageal reflux disease, despite relatively low uptake and an older population in this trial setting than previously modelled. Improving Cytosponge-TFF3 uptake and targeting younger patients is likely to further improve cost-effectiveness.

Economic value of clinical decision support allied to direct data feedback to clinicians: blood usage in haematology.

BACKGROUND AND OBJECTIVES: Responding to national and local pressures to reduce the amount of blood transfused, the haematology department of Oxford University Hospitals (OUH), UK implemented an electronic blood-ordering system with clinical decision support. This intervention targeted junior doctors, giving regular feedback on their transfusion practices with respect to clinical guidelines. METHODS: We evaluated the incremental costs of the intervention using interrupted time series methods to compare red blood cell and platelet usage before and after the intervention was implemented. Difference-in-differences analysis was used to control for external factors that would affect the use of blood products over time. Reductions in blood usage were balanced against intervention costs. RESULTS: The base case analysis showed an average cost saving to the department of £89 304 annually as a result of the intervention. Scenario analyses suggested that the savings may have been greater still, had the increasing trend in blood use prior to the intervention continued in the absence of the intervention. CONCLUSION: An electronic blood-ordering system with clinical decision support can reduce blood transfusions and associated healthcare costs. Focusing on improving junior doctors' transfusion practice is expected to have a knock-on benefit in terms of dissemination of good transfusion practice both within their own department and others as they continue their training.

Faecal immunochemical tests versus colonoscopy for post-polypectomy surveillance: an accuracy, acceptability and economic study.

BACKGROUND: In the UK, patients with one or two adenomas, of which at least one is ≥ 10 mm in size, or three or four small adenomas, are deemed to be at intermediate risk of colorectal cancer (CRC) and referred for surveillance colonoscopy 3 years post polypectomy. However, colonoscopy is costly, can cause discomfort and carries a small risk of complications. OBJECTIVES: To determine whether or not annual faecal immunochemical tests (FITs) are effective, acceptable and cost saving compared with colonoscopy surveillance for detecting CRC and advanced adenomas (AAs). DESIGN: Diagnostic accuracy study with health psychology assessment and economic evaluation. SETTING: Participants were recruited from 30 January 2012 to 30 December 2013 within the Bowel Cancer Screening Programme in England. PARTICIPANTS: Men and women, aged 60-72 years, deemed to be at intermediate risk of CRC following adenoma removal after a positive guaiac faecal occult blood test were invited to participate. Invitees who consented and returned an analysable FIT were included. INTERVENTION: We offered participants quantitative FITs at 1, 2 and 3 years post polypectomy. Participants testing positive with any FIT were referred for colonoscopy and not offered further FITs. Participants testing negative were offered colonoscopy at 3 years post polypectomy. Acceptibility of FIT was assessed using discussion groups, questionnaires and interviews. MAIN OUTCOME MEASURES: The primary outcome was 3-year sensitivity of an annual FIT versus colonoscopy at 3 years for detecting advanced colorectal neoplasia (ACN) (CRC and/or AA). Secondary outcomes included participants' surveillance preferences, and the incremental costs and cost-effectiveness of FIT versus colonoscopy surveillance. RESULTS: Of 8008 invitees, 5946 (74.3%) consented and returned a round 1 FIT. FIT uptake in rounds 2 and 3 was 97.2% and 96.9%, respectively. With a threshold of 40 µg of haemoglobin (Hb)/g faeces (hereafter referred to as µg/g), positivity was 5.8% in round 1, declining to 4.1% in round 3. Over three rounds, 69.2% (18/26) of participants with CRC, 34.3% (152/443) with AAs and 35.6% (165/463) with ACN tested positive at 40 µg/g. Sensitivity for CRC and AAs increased, whereas specificity decreased, with lower thresholds and multiple rounds. At 40 µg/g, sensitivity and specificity of the first FIT for CRC were 30.8% and 93.9%, respectively. The programme sensitivity and specificity of three rounds at 10 µg/g were 84.6% and 70.8%, respectively. Participants' preferred surveillance strategy was 3-yearly colonoscopy plus annual FITs (57.9%), followed by annual FITs with colonoscopy in positive cases (31.5%). FIT with colonoscopy in positive cases was cheaper than 3-yearly colonoscopy (£2,633,382), varying from £485,236 (40 µg/g) to £956,602 (10 µg/g). Over 3 years, FIT surveillance could miss 291 AAs and eight CRCs using a threshold of 40 µg/g, or 189 AAs and four CRCs using a threshold of 10 µg/g. CONCLUSIONS: Annual low-threshold FIT with colonoscopy in positive cases achieved high sensitivity for CRC and would be cost saving compared with 3-yearly colonoscopy. However, at higher thresholds, this strategy could miss 15-30% of CRCs and 40-70% of AAs. Most participants preferred annual FITs plus 3-yearly colonoscopy. Further research is needed to define a clear role for FITs in surveillance. FUTURE WORK: Evaluate the impact of ACN missed by FITs on quality-adjusted life-years. TRIAL REGISTRATION: Current Controlled Trials ISRCTN18040196. FUNDING: National Institute for Health Research (NIHR) Health Technology Assessment programme, NIHR Imperial Biomedical Research Centre and the Bobby Moore Fund for Cancer Research UK. MAST Group Ltd provided FIT kits.

Faecal immunochemical tests (FIT) versus colonoscopy for surveillance after screening and polypectomy: a diagnostic accuracy and cost-effectiveness study.

OBJECTIVE: The English Bowel Cancer Screening Programme (BCSP) recommends 3 yearly colonoscopy surveillance for patients at intermediate risk of colorectal cancer (CRC) postpolypectomy (those with three to four small adenomas or one ≥10 mm). We investigated whether faecal immunochemical tests (FITs) could reduce surveillance burden on patients and endoscopy services. DESIGN: Intermediate-risk patients (60-72 years) recommended 3 yearly surveillance were recruited within the BCSP (January 2012-December 2013). FITs were offered at 1, 2 and 3 years postpolypectomy. Invitees consenting and returning a year 1 FIT were included. Participants testing positive (haemoglobin ≥40 µg/g) at years one or two were offered colonoscopy early; all others were offered colonoscopy at 3 years. Diagnostic accuracy for CRC and advanced adenomas (AAs) was estimated considering multiple tests and thresholds. We calculated incremental costs per additional AA and CRC detected by colonoscopy versus FIT surveillance. RESULTS: 74% (5938/8009) of invitees were included in our study having participated at year 1. Of these, 97% returned FITs at years 2 and 3. Three-year cumulative positivity was 13% at the 40 µg/g haemoglobin threshold and 29% at 10 µg/g. 29 participants were diagnosed with CRC and 446 with AAs. Three-year programme sensitivities for CRC and AAs were, respectively, 59% and 33% at 40 µg/g, and 72% and 57% at 10 µg/g. Incremental costs per additional AA and CRC detected by colonoscopy versus FIT (40 µg/g) surveillance were £7354 and £180 778, respectively. CONCLUSIONS: Replacing 3 yearly colonoscopy surveillance in intermediate-risk patients with annual FIT could reduce colonoscopies by 71%, significantly cut costs but could miss 30%-40% of CRCs and 40%-70% of AAs. TRIAL REGISTRATION NUMBER: ISRCTN18040196; Results.

Mixed-methods evaluation of the Perioperative Medicine Service for High-Risk Patients Implementation Pilot (POMSHIP): a study protocol.

INTRODUCTION: Perioperative complications have a lasting effect on health-related quality of life and long-term survival. The Royal College of Anaesthetists has proposed the development of perioperative medicine (POM) services as an intervention aimed at improving postoperative outcome, by providing better coordinated care for high-risk patients. The Perioperative Medicine Service for High-risk Patients Implementation Pilot was developed to determine if a specialist POM service is able to reduce postoperative morbidity, failure to rescue, mortality and cost associated with hospital admission. The service involves individualised objective risk assessment, admission to a postoperative critical care unit and follow-up on the surgical ward by the POM team. This paper introduces the service and how it will be evaluated. METHODS AND ANALYSIS OF THE EVALUATION: A mixed-methods evaluation is exploring the impact of the service. Clinical effectiveness of the service is being analysed using a 'before and after' comparison of the primary outcome (the PostOperative Morbidity Score). Secondary outcomes will include length of stay, validated surveys to explore quality of life (EQ-5D) and quality of recovery (Quality of Recovery-15 Score). The impact on costs is being analysed using 'before and after' data from the Patient-Level Information and Costing System and the National Schedule of Reference Costs. The perceptions and experiences of staff and patients with the service, and how it is being implemented, are being explored by a qualitative process evaluation. ETHICS AND DISSEMINATION: The study was classified as a service evaluation. Participant information sheets and consent forms have been developed for the interviews and approvals required for the use of the validated surveys were obtained. The findings of the evaluation are being used formatively, to make changes in the service throughout implementation. The findings will also be used to inform the potential roll-out of the service to other sites.

A novel inpatient complex pain team: protocol for a mixed-methods evaluation of a single-centre pilot study.

INTRODUCTION: Complex pain is a debilitating condition that is responsible for low quality of life and significant economic impacts. Although best practice in the treatment of complex pain employs a multidisciplinary team, many patients do not have access to this care, leading to poor outcomes. METHODS AND ANALYSIS: This study evaluates a novel inpatient complex pain team at a large London teaching hospital. A multidisciplinary pain team comprising specialist doctors, nurses, psychologists and physiotherapists was instituted for inpatients with complex pain who will undergo an intense and bespoke evidence-based programme which will then be integrated into the community. A mixed-methods evaluation will take place and patients will be recruited over the course of 1 year. A qualitative arm will interview 15 staff and 15 patients on recruitment and again 6 months later looking to compare and contrast the new pain team with past experiences of pain management. A quantitative arm will assess clinical outcomes using validated scoring tools. An economic evaluation will seek to evaluate the relative cost of the service by comparing healthcare costs before and after the intervention. ETHICS AND DISSEMINATION: The study was categorised as a service evaluation, so formal ethical approval was not considered necessary. Participant recruitment began in January 2016 and the 1-year follow-up will end in November 2017. The results of this study will be published in 2018.

The Age of BLood Evaluation (ABLE) randomised controlled trial: description of the UK-funded arm of the international trial, the UK cost-utility analysis and secondary analyses exploring factors associated with health-related quality of life and health-care costs during the 12-month follow-up.

BACKGROUND: At present, red blood cells (RBCs) are stored for up to 42 days prior to transfusion. The relative effectiveness and safety of different RBC storage times prior to transfusion is uncertain. OBJECTIVE: To assess the clinical effectiveness and cost-effectiveness of transfusing fresher RBCs (stored for ≤ 7 days) compared with current standard-aged RBCs in critically ill patients requiring blood transfusions. DESIGN: The international Age of BLood Evaluation (ABLE) trial was a multicentre, randomised, blinded trial undertaken in Canada, the UK, the Netherlands and France. The UK trial was funded to contribute patients to the international trial and undertake a UK-specific health economic evaluation. SETTING: Twenty intensive care units (ICUs) in the UK, as part of 64 international centres. PARTICIPANTS: Critically ill patients aged ≥ 18 years (≥ 16 years in Scotland) expected to require mechanical ventilation for ≥ 48 hours and requiring a first RBC transfusion during the first 7 days in the ICU. INTERVENTIONS: All decisions to transfuse RBCs were made by clinicians. One patient group received exclusively fresh RBCs stored for ≤ 7 days whenever transfusion was required from randomisation until hospital discharge. The other group received standard-issue RBCs throughout their hospital stay. MAIN OUTCOME MEASURES: The primary outcome was 90-day mortality. Secondary outcomes included development of organ dysfunction, new thrombosis, infections and transfusion reactions. The primary economic evaluation was a cost-utility analysis. RESULTS: The international trial took place between March 2009 and October 2014 (UK recruitment took place between January 2012 and October 2014). In total, 1211 patients were assigned to receive fresh blood and 1219 patients to receive standard-aged blood. RBCs were stored for a mean of 6.1 days [standard deviation (SD) ± 4.9 days] in the group allocated to receive fresh blood and 22.0 days (SD ± 8.4 days) in the group allocated to receive standard-aged blood. Patients received a mean of 4.3 RBC units (SD ± 5.2 RBC units) and 4.3 RBC units (SD ± 5.5 RBC units) in the groups receiving fresh blood and standard-aged blood, respectively. At 90 days, 37.0% of patients in the group allocated to receive fresh blood and 35.3% of patients in the group allocated to receive standard-aged blood had died {absolute risk difference 1.7% [95% confidence interval (CI) -2.1% to 5.5%]}. There were no between-group differences in any secondary outcomes. The UK cohort comprised 359 patients randomised and followed up for 12 months for the cost-utility analysis. UK patients had similar characteristics and outcomes to the international cohort. Mean total costs per patient were £32,346 (95% CI £29,306 to £35,385) in the group allocated to receive fresh blood and £33,353 (95% CI £29,729 to £36,978) in the group allocated to receive standard-aged blood. Approximately 85% of the total costs were incurred during the index hospital admission. There were no significant cost differences between the two groups [mean incremental costs for those receiving fresh vs. standard-aged blood: -£231 (95% CI -£4876 to £4415)], nor were there significant differences in outcomes (mean difference in quality-adjusted life-years -0.010, 95% CI -0.078 to 0.057). LIMITATIONS: Adverse effects from the exclusive use of older RBCs compared with standard or fresh RBCs cannot be excluded. CONCLUSIONS: The use of RBCs aged ≤ 7 days confers no clinical or economic benefit in critically ill patients compared with standard-aged RBCs. FUTURE WORK: Future studies should address the safety of RBCs near the end of the current permitted storage age. TRIAL REGISTRATION: Current Controlled Trials ISRCTN44878718. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 62. See the NIHR Journals Library website for further project information. The international ABLE trial was also supported by peer-reviewed grants from the Canadian Institutes of Health Research (177453), Fonds de Recherche du Québec - Santé (24460), the French Ministry of Health Programme Hospitalier de Recherche Clinique (12.07, 2011) and by funding from Établissement Français du Sang and Sanquin Blood Supply.

Recompression of JPEG images by requantization.

In this paper, we report a novel heuristic for requantizing JPEG images. The resulting images are generally smaller and often have improved perceptual image quality over a "blind" requantization approach, that is, one that does not consider the properties of the quantization matrices. The heuristic is supported by a detailed mathematical treatment which incorporates the well-known Laplacian distribution of the AC discrete cosine transform (DCT) coefficients with an analysis of the error introduced by requantization. We note that the technique is applicable to any image compression method which employs discrete cosine transforms and quantization.