Protocol for the YORKSURe prospective multistage study testing the feasibility for early detection of bladder cancer in populations with high disease-specific mortality risk.

INTRODUCTION: Around 25% of patients with bladder cancer (BCa) present with invasive disease. Non-randomised studies of population-based screening have suggested reductions in BCa-specific mortality are possible through earlier detection. The low prevalence of lethal disease in the general population means screening is not cost-effective and there is no consensus on the best strategy. Yorkshire has some of the highest mortality rates from BCa in England. We aim to test whether population screening in a region of high mortality risk will lead to a downward stage-migration of aggressive BCa, improved survival and is cost-effective. METHODS AND ANALYSIS: YORKSURe is a tiered, randomised, multicohort study to test the feasibility of a large BCa screening randomised controlled trial. In three parallel cohorts, participants will self-test urine (at home) up to six times. Results are submitted via a mobile app or freephone. Those with a positive result will be invited for further investigation at community-based early detection clinics or within usual National Health Service (NHS) pathways. In Cohort 1, we will post self-testing kits to research engaged participants (n=2000) embedded within the Yorkshire Lung Screening Trial. In Cohort 2, we will post self-testing kits to 3000 invitees. Cohort 2 participants will be randomised between haematuria and glycosuria testing using a reveal/conceal design. In Cohort 3, we will post self-testing kits to 500 patients within the NHS pathway for investigation of haematuria. Our primary outcomes are rates of recruitment and randomisation, rates of positive test and acceptability of the design. The study is currently recruiting and scheduled to finish in June 2023. ETHICS AND DISSEMINATION: The study has received the following approvals: London Riverside Research Ethics Committee (22/LO/0018) and Health Research Authority Confidentiality Advisory Group (20/CAG/0009). Results will be made available to providers and researchers via publicly accessible scientific journals. TRIAL REGISTRATION NUMBER: ISRCTN34273159.

Economic and health impacts of the Change4Life Food Scanner app: Findings from a randomized pilot and feasibility study.

Introduction: The UK Government developed the Change4Life Food Scanner app to provide families with engaging feedback on the nutritional content of packaged foods. There is a lack of research exploring the cost-effectiveness of dietary health promotion apps. Methods: Through stakeholder engagement, a conceptual model was developed, outlining the pathway by which the Food Scanner app leads to proximal and distal outcomes. The conceptual model informed the development of a pilot randomized controlled trial which investigated the feasibility and acceptability of evaluating clinical outcomes in children and economic effectiveness of the Food Scanner app through a cost-consequence analysis. Parents of 4-11 years-olds (n = 126) were randomized into an app exposure condition (n = 62), or no intervention control (n = 64). Parent-reported Child Health Utility 9 Dimension (CHU9D) outcomes were collected alongside child healthcare resource use and associated costs, school absenteeism and parent productivity losses at baseline and 3 months follow up. Results for the CHU9D were converted into utility scores based on UK adult preference weights. Sensitivity analysis accounted for outliers and multiple imputation methods were adopted for the handling of missing data. Results: 64 participants (51%) completed the study (intervention: n = 29; control: n = 35). There was a mean reduction in quality adjusted life years between groups over the trial period of -0.004 (SD = 0.024, 95% CI: -0.005; 0.012). There was a mean reduction in healthcare costs of -£30.77 (SD = 230.97; 95% CI: -£113.80; £52.26) and a mean reduction in workplace productivity losses of -£64.24 (SD = 241.66, 95% CI: -£147.54; £19.07) within the intervention arm, compared to the control arm, over the data collection period. Similar findings were apparent after multiple imputation. Discussion: Modest mean differences between study arms may have been due to the exploration of distal outcomes over a short follow-up period. The study was also disrupted due to the coronavirus pandemic, which may have confounded healthcare resource data. Although measures adopted were deemed feasible, the study highlighted difficulties in obtaining data on app development and maintenance costs, as well as the importance of economic modeling to predict long-term outcomes that may not be reliably captured over the short-term. Clinical trial registration: https://osf.io/, identifier 62hzt.

Diagnosis, treatment and survival from bladder, upper urinary tract, and urethral cancers: real-world findings from NHS England between 2013 and 2019.

OBJECTIVE: We report NHS England data for patients with bladder cancer (BC), upper tract urothelial cancer (UTUC: renal pelvic and ureteric), and urethral cancers from 2013 to 2019. MATERIALS AND METHODS: Hospital episode statistics, waiting times, and cancer registrations were extracted from NHS Digital. RESULTS: Registrations included 128 823 individuals with BC, 16 018 with UTUC, and 2533 with urethral cancer. In 2019, 150 816 persons were living with a diagnosis of BC, of whom 113 067 (75.0%) were men, 85 117 (56.5%) were aged >75 years, and 95 553 (91.7%) were Caucasian. Incidence rates were stable (32.7-34.3 for BC, 3.9-4.2 for UTUC and 0.6-0.7 for urethral cancer per 100 000 population). Most patients 52 097 (mean [range] 41.3% [40.7-42.0%]) were referred outside the 2-week-wait pathway and 15 340 (mean [range] 12.2% [11.7-12.6%]) presented as emergencies. Surgery, radiotherapy, chemotherapy, or multimodal treatment use varied with disease stage, patient factors and Cancer Alliance. Between 27% and 29% (n = 6616) of muscle-invasive BCs did not receive radical treatment. Survival rates reflected stage, grade, location, and tumour histology. Overall survival rates did not improve over time (relative change: 0.97, 95% confidence interval 0.97-0.97) at 2 years in contrast to other cancers. CONCLUSION: The diagnostic pathway for BC needs improvement. Increases in survival might be delivered through greater use of radical treatment. NHS Digital data offers a population-wide picture of this disease but does not allow individual outcomes to be matched with disease or patient features and key parameters can be missing or incomplete.

Optimizing the Design of a Repeated Fecal Immunochemical Test Bowel Cancer Screening Programme With a Limited Endoscopy Capacity From a Health Economic Perspective.

OBJECTIVES: In 2016, it was announced that the fecal immunochemical test (FIT) would replace the guaiac fecal occult blood test in the UK Bowel Cancer Screening Programme. England has limited endoscopy capacity. This study informed decision making by determining the most cost-effective FIT screening strategy (age range, frequency, and FIT threshold) under a constrained endoscopy capacity. METHODS: An economic model with a colorectal cancer natural history component was used to model 60 221 screening strategies with first screening at age 50 to 60 years, screening interval of 1 to 6 years, 3+ screening episodes, and FIT integer threshold of 20 to 180 µg hemoglobin/g feces. Screening strategies requiring the same endoscopy capacity were compared to determine the characteristics of the most cost-effective strategies. RESULTS: With 50 000 annual screening referral colonoscopies, the 20 most cost-effective strategies had a starting age of 50 to 53 years, 2-yearly screening, 7 or 8 rounds of screening, and FIT threshold of 127 to 166. Compared with a 2-yearly screening interval, screening less frequently (3-, 4-, 5-, or 6-yearly) with a more sensitive FIT was less cost-effective. CONCLUSIONS: The UK Bowel Cancer Screening Programme should use a 2-yearly FIT screening interval. When endoscopy capacity increases, the screening starting age should be reduced first followed by reducing the FIT threshold. These findings are relevant for other colorectal cancer screening programs with constrained endoscopy capacity.

Methods for the economic evaluation of obesity prevention dietary interventions in children: A systematic review and critical appraisal of the evidence.

OBJECTIVES: We aim to describe and provide a discussion of methods used to conduct economic evaluations of dietary interventions in children and adolescents, including long-term modelling, and to make recommendations to assist health economists in the design and reporting of such evaluations. METHODS: A systematic review was conducted in 11 bibliographic databases and the grey literature with searches undertaken between January 2000 and December 2021. A study was included if it (1) was an economic evaluation or modelling study of an obesity-prevention dietary intervention and (2) targeted 2- to 18-year-olds. RESULTS: Twenty-six studies met the inclusion criteria. Twelve studies conducted an economic evaluation alongside a clinical trial, and 14 studies modelled long-term health and cost outcomes. Four overarching methodological challenges were identified: modelling long-term impact of interventions, measuring and valuing health outcomes, cost inclusions and equity considerations. CONCLUSIONS: Variability in methods used to predict, measure and value long-term benefits in adulthood from short-term clinical outcomes in childhood was evident across studies. Key recommendations to improve the design and analysis of future economic evaluations include the consideration of weight regain and diminishing intervention effects within future projections; exploration of wider intervention benefits not restricted to quality-of-life outcomes; and inclusion of parental or caregiver opportunity costs.

Evaluating the Change4Life Food Scanner app in reducing children's sugar intake: a randomised pilot and feasibility study.

BACKGROUND: The Change4Life Food Scanner app displays nutritional information using visual images alongside traffic light labels. The app's effectiveness for improving dietary choices is unknown. This study investigated the feasibility and acceptability of evaluating the effectiveness of the Food Scanner app in reducing children's sugar intake in the UK. METHODS: Adopting a non-blinded parallel trial design, we randomly assigned (1:1) 126 parents of children aged 4-11 years through block randomisation sequences into a 3-month intervention consisting of exposure to the Change4Life Food Scanner app (version 1.6; ie, the intervention group [n=62]) or no intervention (ie, the control group [n=64]). Participants completed baseline and 3-month post-intervention measures of dietary intake (3-day food diary) and trial acceptability measures. The intervention group completed fortnightly app engagement measures. Ethical approval was obtained by the University of Sheffield Research Ethics Committee (026380). FINDINGS: 64 (51%) of 126 participants completed the study (29 [45%] in the intervention group and 35 [55%] in the control group). 51 (80%) of 64 reported that the study was easy to complete and 62 (97%) found receiving task completion reminders helpful. App engagement decreased throughout the study (eg, mean engagement time was 18·01 min [SD 27·15] in week 2, and 6·76 min [11·56] in week 12). 18 (64%) of 28 participants reported high overall app acceptability; however, seven (25%) did not find the app helpful. 24 (86%) of 28 reported high acceptability for the app's use of sugar cube images, which were rated as easy to understand and useful to supplement front of package nutritional labels. Six (21%) of 28 did not find sugar cube images helpful and 20 (71%) had low acceptability of the app aiding food purchasing decisions. 45 (73%) of 62 were willing to continue with the study for a 12-month trial. INTERPRETATION: Despite a high attrition rate, study procedures were considered acceptable by most participants. Acceptability of the Food Scanner app was varied, and participants did not find the app helpful for food purchases. Analysis of preliminary efficacy of the intervention is ongoing, which will inform design parameters for a future large-scale trial. FUNDING: Wellcome Trust.

Effect of blood volume on analytical bias in dried blood spots prepared for newborn screening external quality assurance.

Aim: Dried blood spots (DBS) are used for the analysis of more than 2000 biomarkers. We assessed a range of analyte concentrations and diameters of DBS. Materials & methods: DBS samples were created by the application of increasing volumes of whole blood prepared by the UK NEQAS Quality Assurance Laboratory. Samples were analyzed in four separate laboratories. Results: Volumes less than 25 µl (8 mm) and more than 75 µl (14 mm) created unsatisfactory analytical biases. Results obtained from peripheral subpunches tended to be higher than those from a central subpunch. Conclusion: DBS diameters formed from nonvolumetric application of blood to filter paper can be used to assess whether measurement bias will be within acceptable limits according to the analyte being quantified. DBS received for newborn screening in the UK with diameters less than 8 mm and those more than 14 mm should be rejected.

Outcomes of aortic aneurysm surgery in England: a nationwide cohort study using hospital admissions data from 2002 to 2015.

BACKGROUND: The United Kingdom aortic aneurysms (AA) services have undergone reconfiguration to improve outcomes. The National Health Service collects data on all hospital admissions in England. The complex administrative datasets generated have the potential to be used to monitor activity and outcomes, however, there are challenges in using these data as they are primarily collected for administrative purposes. The aim of this study was to develop standardised algorithms with the support of a clinical consensus group to identify all AA activity, classify the AA management into clinically meaningful case mix groups and define outcome measures that could be used to compare outcomes among AA service providers. METHODS: In-patient data about aortic aneurysm (AA) admissions from the 2002/03 to 2014/15 were acquired. A stepwise approach, with input from a clinical consensus group, was used to identify relevant cases. The data is primarily coded into episodes, these were amalgamated to identify admissions; admissions were linked to understand patient pathways and index admissions. Cases were then divided into case-mix groups based upon examination of individually sampled and aggregate data. Consistent measures of outcome were developed, including length of stay, complications within the index admission, post-operative mortality and re-admission. RESULTS: Several issues were identified in the dataset including potential conflict in identifying emergency and elective cases and potential confusion if an inappropriate admission definition is used. Ninety six thousand seven hundred thirty-five patients were identified using the algorithms developed in this study to extract AA cases from Hospital episode statistics. From 2002 to 2015, 83,968 patients (87% of all cases identified) underwent repair for AA and 12,767 patients (13% of all cases identified) died in hospital without any AA repair. Six thousand three hundred twenty-nine patients (7.5%) had repair for complex AA and 77,639 (92.5%) had repair for infra-renal AA. CONCLUSION: The proposed methods define homogeneous clinical groups and outcomes by combining administrative codes in the data. These methodologically robust methods can help examine outcomes associated with previous and current service provisions and aid future reconfiguration of aortic aneurysm surgery services.

The association between long-term conditions and uptake of population-based screening for colorectal cancer: results from two English cohort studies.

INTRODUCTION: Uptake of screening for colorectal cancer (CRC) can reduce mortality, and population-based screening is offered in England. To date, there is little evidence on the association between having a long-term condition (LTC) and CRC screening uptake. The objective of this study was to examine the association between having an LTC and uptake of CRC screening in England with the guaiac fecal occult blood test, with a particular focus on common mental disorders. METHODS: The study was a preregistered secondary analysis of two cohorts: first, a linked data set between the regional Yorkshire Health Study (YHS) and the National Health Service National Bowel Cancer Screening Program (BCSP, years 2006-2014); second, the national English Longitudinal Study of Ageing (ELSA, years 2014-2015). Individuals eligible for BCSP screening who participated in either the YHS (7,142) or ELSA Wave 7 (4,099) were included. Study registration: ClinicalTrials.gov, number NCT02503969. RESULTS: In both the cohorts, diabetes was associated with lower uptake (YHS odds ratio [OR] for non-uptake 1.35, 95% CI 1.03-1.78; ELSA 1.33, 1.03-1.72) and osteoarthritis was associated with increased uptake (YHS 0.75, 0.57-0.99; ELSA 0.76, 0.62-0.93). After controlling for broader determinants of health, there was no evidence of significantly different uptake for individuals with common mental disorders. CONCLUSION: Two large independent cohorts provided evidence that uptake of CRC screening is lower among individuals with diabetes and higher among individuals with osteoarthritis. Further work should compare barriers and facilitators to screening among individuals with either of these conditions. This study also demonstrates the benefits of data linkage for improving clinical decision-making.

Cost-effectiveness of screening for ovarian cancer amongst postmenopausal women: a model-based economic evaluation.

BACKGROUND: The United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) was the biggest ovarian cancer screening trial to date. A non-significant effect of screening on ovarian cancer was reported, but the authors noted a potential delayed effect of screening, and suggested the need for four years further follow-up. There are no UK-based cost-effectiveness analyses of ovarian cancer screening. Hence we assessed the lifetime outcomes associated with, and the cost-effectiveness of, screening for ovarian cancer in the UK, along with the value of further research. METHODS: We performed a model-based economic evaluation. Effectiveness data were taken from UKCTOCS, which considered strategies of multimodal screening (MMS), ultrasound screening (USS) and no screening. We conducted systematic reviews to identify the remaining model inputs, and performed a rigorous and transparent prospective evaluation of different methods for extrapolating the effect of screening on ovarian cancer mortality. We considered costs to the UK healthcare system and measured effectiveness using quality-adjusted life years (QALYs). We used value of information methods to estimate the value of further research. RESULTS: Over a lifetime, MMS and USS were estimated to be both more expensive and more effective than no screening. USS was dominated by MMS, being both more expensive and less effective. Compared with no screening, MMS cost on average £419 more (95% confidence interval £255 to £578), and generated 0.047 more QALYs (0.002 to 0.088). The incremental cost-effectiveness ratio (ICER) comparing MMS with no screening was £8864 per QALY (£2600 to £51,576). Alternative extrapolation methods increased the ICER, with the highest value being £36,769 (£13,888 to dominated by no screening). Using the UKCTOCS trial horizon, both MMS and USS were dominated by no screening, as they produced fewer QALYs at a greater cost. The value of research into eliminating all uncertainty in long-term effectiveness was estimated to be worth up to £20 million, or approximately £5 million for four years follow-up. CONCLUSIONS: Screening for ovarian cancer with MMS is both more effective and more expensive than not screening. Compared to national willingness to pay thresholds, lifetime cost-effectiveness is promising, but there remains considerable uncertainty regarding extrapolated long-term effectiveness.

Designing and Undertaking a Health Economics Study of Digital Health Interventions.

This paper introduces and discusses key issues in the economic evaluation of digital health interventions. The purpose is to stimulate debate so that existing economic techniques may be refined or new methods developed. The paper does not seek to provide definitive guidance on appropriate methods of economic analysis for digital health interventions. This paper describes existing guides and analytic frameworks that have been suggested for the economic evaluation of healthcare interventions. Using selected examples of digital health interventions, it assesses how well existing guides and frameworks align to digital health interventions. It shows that digital health interventions may be best characterized as complex interventions in complex systems. Key features of complexity relate to intervention complexity, outcome complexity, and causal pathway complexity, with much of this driven by iterative intervention development over time and uncertainty regarding likely reach of the interventions among the relevant population. These characteristics imply that more-complex methods of economic evaluation are likely to be better able to capture fully the impact of the intervention on costs and benefits over the appropriate time horizon. This complexity includes wider measurement of costs and benefits, and a modeling framework that is able to capture dynamic interactions among the intervention, the population of interest, and the environment. The authors recommend that future research should develop and apply more-flexible modeling techniques to allow better prediction of the interdependency between interventions and important environmental influences.

Factors associated with completion of bowel cancer screening and the potential effects of simplifying the screening test algorithm.

BACKGROUND: The primary colorectal cancer screening test in England is a guaiac faecal occult blood test (gFOBt). The NHS Bowel Cancer Screening Programme (BCSP) interprets tests on six samples on up to three test kits to determine a definitive positive or negative result. However, the test algorithm fails to achieve a definitive result for a significant number of participants because they do not comply with the programme requirements. This study identifies factors associated with failed compliance and modifications to the screening algorithm that will improve the clinical effectiveness of the screening programme. METHODS: The BCSP Southern Hub data for screening episodes started in 2006-2012 were analysed for participants aged 60-69 years. The variables included age, sex, level of deprivation, gFOBt results and clinical outcome. RESULTS: The data set included 1,409,335 screening episodes; 95.08% of participants had a definitively normal result on kit 1 (no positive spots). Among participants asked to complete a second or third gFOBt, 5.10% and 4.65%, respectively, failed to return a valid kit. Among participants referred for follow up, 13.80% did not comply. Older age was associated with compliance at repeat testing, but non-compliance at follow up. Increasing levels of deprivation were associated with non-compliance at repeat testing and follow up. Modelling a reduction in the threshold for immediate referral led to a small increase in completion of the screening pathway. CONCLUSIONS: Reducing the number of positive spots required on the first gFOBt kit for referral for follow-up and targeted measures to improve compliance with follow-up may improve completion of the screening pathway.

Using whole disease modeling to inform resource allocation decisions: economic evaluation of a clinical guideline for colorectal cancer using a single model.

OBJECTIVE: To assess the feasibility and value of simulating whole disease and treatment pathways within a single model to provide a common economic basis for informing resource allocation decisions. METHODS: A patient-level simulation model was developed with the intention of being capable of evaluating multiple topics within National Institute for Health and Clinical Excellence's colorectal cancer clinical guideline. The model simulates disease and treatment pathways from preclinical disease through to detection, diagnosis, adjuvant/neoadjuvant treatments, follow-up, curative/palliative treatments for metastases, supportive care, and eventual death. The model parameters were informed by meta-analyses, randomized trials, observational studies, health utility studies, audit data, costing sources, and expert opinion. Unobservable natural history parameters were calibrated against external data using Bayesian Markov chain Monte Carlo methods. Economic analysis was undertaken using conventional cost-utility decision rules within each guideline topic and constrained maximization rules across multiple topics. RESULTS: Under usual processes for guideline development, piecewise economic modeling would have been used to evaluate between one and three topics. The Whole Disease Model was capable of evaluating 11 of 15 guideline topics, ranging from alternative diagnostic technologies through to treatments for metastatic disease. The constrained maximization analysis identified a configuration of colorectal services that is expected to maximize quality-adjusted life-year gains without exceeding current expenditure levels. CONCLUSIONS: This study indicates that Whole Disease Model development is feasible and can allow for the economic analysis of most interventions across a disease service within a consistent conceptual and mathematical infrastructure. This disease-level modeling approach may be of particular value in providing an economic basis to support other clinical guidelines.

Whole disease modeling to inform resource allocation decisions in cancer: a methodological framework.

OBJECTIVES: This article presents a methodological framework for developing health economic models of whole systems of disease and treatment pathways to inform decisions concerning resource allocation-an approach referred to as "Whole Disease Modeling." This system-level approach can provide a consistent mathematical infrastructure for the economic evaluation of virtually any intervention across a disease pathway. METHODS: The framework has been developed for cancer but is broadly generalizable to other diseases. It has been informed by pilot work, a systematic review of economic analyses, a qualitative examination of model development processes, and other literature from the fields of operational research, statistics, and health economics. RESULTS: The framework is built on three principles: 1) the model boundary and breadth should capture all relevant aspects of the disease and its treatment-from preclinical disease through to death, 2) the model should be developed such that the decision node is conceptually transferable across the model, and 3) the costs and consequences of service elements should be structurally related. A generalized process for developing Whole Disease Models is presented. DISCUSSION: Although this approach involves a nontrivial investment of time and resource, its value may be realized when 1) multiple options for service change require economic analysis at a single time point, 2) a disease service changes rapidly and the model can be reused, 3) current services within a pathway have not been subjected to economic analysis, 4) upstream events are expected to have important downstream effects, or 5) simple cost-utility decision rules fail to reflect the complexity of the decision-makers' objectives.

Bayesian calibration of a natural history model with application to a population model for colorectal cancer.

BACKGROUND: Cancer natural history models are essential when evaluating screening/preventative interventions or changes to diagnostic pathways. Natural history models commonly use a state transition structure, but it is often not possible to observe the state transition probabilities required for parameterization. AIM: . The work aimed to accurately represent the uncertainty in the parameters of a state transition model for the natural history of colorectal cancer by embedding the problem in the framework of Bayesian inference. METHODS: The Metropolis-Hastings algorithm was used to estimate natural history parameters and screening test characteristics by generating multiple sets of parameters from the posterior distribution, which is the probability distribution that is compatible with the observed data. Observed data included colorectal cancer incidence categorized by age and stage, autopsy data on polyp prevalence, and cancer and polyp detection rates from the first round of screening with the fecal occult blood test in England. The approach was implemented using Visual Basic. RESULTS: The results were subsequently examined for convergence using the package CODA in R 2.8.0. Outputs from fitting were samples from the joint posterior distribution of the natural history parameters given the epidemiological data. The parameter sets obtained are shown to have a good fit to all the observed data sets. These parameter sets are used when running probabilistic sensitivity analysis. CONCLUSION: The advantages of this strategy are that it draws efficiently from a high-dimensional correlated parameter space. The algorithm is simple to code and runs overnight on a standard desktop PC. Using this method, the parameter sets are drawn according to their posterior probability given calibration data, and thus they correctly summarize the residual uncertainty in the parameter space.

Estimating the direct costs of bowel cancer services provided by the National Health Service in England.

OBJECTIVES: Bowel cancer is the second most common cancer in England and Wales, accounting for approximately 13,000 deaths per year. Economic evaluations and national guidance have been produced for individual treatments for bowel cancer. However, it has been suggested that Primary Care Trusts develop program budgeting or equivalent methodology demonstrating a whole system approach to investment and disinvestment. The objective of this study was to provide a baseline framework for considering a whole system approach to estimate the direct costs of bowel cancer services provided by the National Health Service (NHS) in England. METHODS: A treatment pathway, developed in 2005, was used to construct a service pathway model to estimate the direct cost of bowel cancer services in England. RESULTS: The service pathway model estimated the direct cost of bowel cancer services to the NHS to be in excess of £1 billion in 2005. Thirty-five percent of the cost is attributable to the screening and testing of patients with suspected bowel cancer, subsequently diagnosed as cancer-free. CONCLUSIONS: This study is believed to be the most comprehensive attempt to identify the direct cost of managing bowel cancer services in England. The approach adopted could be useful to assist local decision makers in identifying those aspects of the pathway that are most uncertain in terms of their cost-effectiveness and as a basis to explore the implications of re-allocated resources. Research recommendations include the need for detailed costs on surgical procedures, high-risk patients and the utilization of the methods used in this study across other cancers.

Simulation sample sizes for Monte Carlo partial EVPI calculations.

Partial expected value of perfect information (EVPI) quantifies the value of removing uncertainty about unknown parameters in a decision model. EVPIs can be computed via Monte Carlo methods. An outer loop samples values of the parameters of interest, and an inner loop samples the remaining parameters from their conditional distribution. This nested Monte Carlo approach can result in biased estimates if small numbers of inner samples are used and can require a large number of model runs for accurate partial EVPI estimates. We present a simple algorithm to estimate the EVPI bias and confidence interval width for a specified number of inner and outer samples. The algorithm uses a relatively small number of model runs (we suggest approximately 600), is quick to compute, and can help determine how many outer and inner iterations are needed for a desired level of accuracy. We test our algorithm using three case studies.

Systematic review of economic evidence for the detection, diagnosis, treatment, and follow-up of colorectal cancer in the United Kingdom.

OBJECTIVES: The aim of this study was to examine the availability and consistency of economic evidence for the detection, diagnosis, treatment, and follow-up of colorectal cancer. METHODS: A systematic review of UK economic evaluations of colorectal cancer interventions was undertaken. Searches were undertaken across ten electronic databases. Studies were critically appraised through reference to a conceptual model of UK colorectal cancer services. RESULTS: Forty-seven studies met the inclusion criteria. There is a substantial economic evidence base surrounding population-level colorectal screening, surgical procedures, and cytotoxic therapies for the adjuvant and palliative treatment of colorectal cancer. There is limited evidence concerning the diagnosis of suspected colorectal cancer, curative treatments for metastatic disease and follow-up regimens for nonmetastatic disease. No studies were identified relating to the economics of radiotherapy, surveillance of increased-risk groups, end-of-life care, or the management of hereditary colorectal cancer. Where evidence is available, studies are subject to important differences concerning treatment options, decision criteria, and incongruent assumptions concerning the disease and its management. CONCLUSIONS: Across many aspects of the colorectal cancer service, current practice appears to have emerged without the consideration or support of economic evidence. There is a need to develop a common understanding how colorectal cancer models should be structured and implemented.