Covariates of success in quitting smoking: a systematic review of studies from 2008 to 2021 conducted to inform the statistical analyses of quitting outcomes of a hospital-based tobacco dependence treatment service in the United Kingdom.

Background: Smoking cessation interventions are being introduced into routine secondary care in the United Kingdom (UK), but there are person and setting-related factors that could moderate their success in quitting smoking. This review was conducted as part of an evaluation of the QUIT hospital-based tobacco dependence treatment service ( https://sybics-quit.co.uk). The aim of the review was to identify a comprehensive set of variables associated with quitting success among tobacco smokers contacting secondary healthcare services in the UK who are offered support to quit smoking and subsequently set a quit date. The results would then be used to inform the development of a statistical analysis plan to investigate quitting outcomes. Methods: Systematic literature review of five electronic databases. Studies eligible for inclusion investigated quitting success in one of three contexts: (a) the general population in the UK; (b) people with a mental health condition; (c) quit attempts initiated within a secondary care setting. The outcome measures were parameters from statistical analysis showing the effects of covariates on quitting success with a statistically significant (i.e., p-value <0.05) association. Results: The review identified 29 relevant studies and 14 covariates of quitting success, which we grouped into four categories: demographics (age; sex; ethnicity; socio-economic conditions; relationship status, cohabitation and social network), individual health status and healthcare setting (physical health, mental health), tobacco smoking variables (current tobacco consumption, smoking history, nicotine dependence; motivation to quit; quitting history), and intervention characteristics (reduction in amount smoked prior to quitting, the nature of behavioural support, tobacco dependence treatment duration, pharmacological aids). Conclusions: In total, 14 data fields were identified that should be considered for inclusion in datasets and statistical analysis plans for evaluating the quitting outcomes of smoking cessation interventions initiated in secondary care contexts in the UK. PROSPERO registration: CRD42021254551 (13/05/2021).

Stop smoking interventions are being incorporated as a systematic and opt-out component of secondary care services in the UK's National Health Service (NHS), driven by the NHS's Long Term Plan. This review was conducted as part of an evaluation of the QUIT hospital-based tobacco dependence treatment service ( https://sybics-quit.co.uk). To support the development of statistical analyses to find out what affects smokers' success in quitting smoking after contacting the service, research was needed to identify what characteristics of the individual smokers and the healthcare setting might be important for success in quitting. The main purpose of the review was to support the development of a statistical analysis plan of quitting outcomes. We looked at academic papers published between 2008 and 2021 that estimated the influence of different factors on success in quitting smoking. The results of the review summarise the list of factors that previous studies have found to have an influence on quitting outcomes. The list of factors was used to inform discussions with the service about what data fields it would be important for the service to collect because that data could be important for helping the service to understand variation in quitting outcomes.

Critical Appraisal of Decision Models Used for the Economic Evaluation of Bladder Cancer Screening and Diagnosis: A Systematic Review.

BACKGROUND AND OBJECTIVE: Bladder cancer is common among current and former smokers. High bladder cancer mortality may be decreased through early diagnosis and screening. The aim of this study was to appraise decision models used for the economic evaluation of bladder cancer screening and diagnosis, and to summarise the main outcomes of these models. METHODS: MEDLINE via PubMed, Embase, EconLit and Web of Science databases was systematically searched from January 2006 to May 2022 for modelling studies that assessed the cost effectiveness of bladder cancer screening and diagnostic interventions. Articles were appraised according to Patient, Intervention, Comparator and Outcome (PICO) characteristics, modelling methods, model structures and data sources. The quality of the studies was also appraised using the Philips checklist by two independent reviewers. RESULTS: Searches identified 3082 potentially relevant studies, which resulted in 18 articles that met our inclusion criteria. Four of these articles were on bladder cancer screening, and the remaining 14 were diagnostic or surveillance interventions. Two of the four screening models were individual-level simulations. All screening models (n = 4, with three on a high-risk population and one on a general population) concluded that screening is either cost saving or cost effective with cost-effectiveness ratios lower than $53,000/life-years saved. Disease prevalence was a strong determinant of cost effectiveness. Diagnostic models (n = 14) assessed multiple interventions; white light cystoscopy was the most common intervention and was considered cost effective in all studies (n = 4). Screening models relied largely on published evidence generalised from other countries and did not report the validation of their predictions to external data. Almost all diagnostic models (n = 13 out of 14) had a time horizon of 5 years or less and most of the models (n = 11) did not incorporate health-related utilities. In both screening and diagnostic models, epidemiological inputs were based on expert elicitation, assumptions or international evidence of uncertain generalisability. In modelling disease, seven models did not use a standard classification system to define cancer states, others used risk-based, numerical or a Tumour, Node, Metastasis classification. Despite including certain components of disease onset or progression, no models included a complete and coherent model of the natural history of bladder cancer (i.e. simulating the progression of asymptomatic primary bladder cancer from cancer onset, i.e. in the absence of treatment). CONCLUSIONS: The variation in natural history model structures and the lack of data for model parameterisation suggest that research in bladder cancer early detection and screening is at an early stage of development. Appropriate characterisation and analysis of uncertainty in bladder cancer models should be considered a priority.

Modelling the impact of the coronavirus pandemic on bowel cancer screening outcomes in England: A decision analysis to prepare for future screening disruption.

The English Bowel Cancer Screening Programme invites people between the ages of 60 and 74 to take a Faecal Immunochemical Test every two years. This programme was interrupted during the coronavirus pandemic. The research aimed: (1) to estimate the impact of colorectal cancer (CRC) Faecal Immunochemical Test screening pauses of different lengths and the actual coronavirus-related screening pause in England, and (2) to analyse the most effective and cost-effective strategies to re-start CRC screening to prepare for future disruptions. The analysis used the validated Microsimulation Model in Cancer of the Bowel built in the R programming language. The model simulated the life course of a representative English screening population from 2019, by age, sex, socio-economic deprivation, and prior screening history. The modelling scenarios were based on assumptions and data from screening centres in England. Pausing bowel screening in England due to coronavirus pandemic is predicted to increase CRC deaths by 0.73% within 10 years and 0.13% over the population's lifetime, with excess deaths due to peak in 2023. More deaths are expected in men and people aged over 70. Pausing screening for longer would result in greater additional CRC cases and deaths. Postponing screening for everyone would be the most cost-effective strategy to minimise the impact of screening disruption without any additional endoscopy capacity. If endoscopy capacity can be increased, temporarily raising the Faecal Immunochemical Test threshold to 190 µg/g may help to minimise CRC deaths, particularly if screening programmes start from age 50 in the future.

Calibrating Natural History of Cancer Models in the Presence of Data Incompatibility: Problems and Solutions.

The calibration of cancer natural history models is often challenged by a lack of representative calibration targets, forcing modellers to rely on potentially incompatible datasets. Using a microsimulation colorectal cancer model as an example, the purposes of this paper are to (1) highlight the reasons for uncertainty in calibration targets, (2) illustrate practical and generalisable approaches for dealing with incompatibility in calibration targets, and (3) discuss the importance of future research in the area of incorporating uncertainty in calibration. The low quality of data and differences in populations, outcome definitions, and healthcare systems may result in incompatibility between the model and the data. Acknowledging reasons for data incompatibility allows assessment of the risk of incompatibility before calibrating the model. Only a few approaches are available to address data incompatibility, for instance addressing biases in calibration targets and their adjustment, relaxing the goodness-of-fit metric, and validation of the calibration targets to the data not used in the calibration. However, these approaches lack explicit comparison and validation, and so more research is needed to describe the nature and causes of indirect uncertainty (i.e. uncertainty that cannot be expressed in absolute quantitative forms) and identify methods for managing this uncertainty in healthcare modelling.

Diagnostic accuracy of conventional oral examination for detecting oral cavity cancer and potentially malignant disorders in patients with clinically evident oral lesions: Systematic review and meta-analysis.

This systematic review evaluates the diagnostic accuracy of conventional oral examination (COE) versus incisional or excisional biopsy for the diagnosis of malignant and/or dysplastic lesions in patients with clinically evident lesions. Searches were conducted across five electronic databases from inception to January 2020. Meta-analyses were undertaken, where appropriate. Among 18 included studies, 14 studies were included in the meta-analysis, giving summary estimates for COE of 71% sensitivity and 85% specificity for the diagnosis of dysplastic and/or malignant lesions. The pooled diagnostic accuracy of identifying malignant-only lesions was reported in seven studies, giving a pooled estimate of 88% sensitivity and 81% specificity. Diagnostic accuracy of different types of dental/medical professionals in identifying dysplastic or malignant lesions gave varying estimates of sensitivity and specificity across three studies. Further research is needed to improve the diagnostic accuracy of COE for early detection of dysplastic and malignant oral lesions.

External Validation of a Colorectal Cancer Model Against Screening Trial Long-Term Follow-Up Data.

BACKGROUND: The University of Sheffield School of Health and Related Research (ScHARR) Bowel Cancer Screening Model has been used previously to make decisions about colorectal cancer screening strategies in England. OBJECTIVES: The objective of this study was to perform an external validation of the ScHARR model against long-term follow-up data about colorectal cancer (CRC) incidence and mortality reductions due to screening, from the Nottingham trial of guaiac faecal occult blood testing for CRC, and the UK Flexible Sigmoidoscopy Screening Trial. METHODS: The ScHARR model was adapted prior to validation to reflect the setting of each trial in terms of population characteristics, details of screening and surveillance programs, uptake of screening, and further investigations and study follow-up. The impact of using current versus historical CRC incidence and mortality data in the validation was also examined by carrying out a series of analyses in which historical data from different years was included in the model. RESULTS: The ScHARR model was able to predict CRC incidence and mortality rate/hazard ratios from both trials to well within the 95% confidence intervals in the observed data. While it was less accurate in predicting absolute incidence and mortality rates, modeling historical incidence and mortality data enabled these predictions to be improved considerably. CONCLUSION: The ScHARR model is able to replicate the long-term relative benefit from screening observed in 2 large-scale UK-based screening trials and can therefore be considered to be an appropriate tool to facilitate decision making around the English bowel cancer screening program.

Economic impact of screening for X-linked Adrenoleukodystrophy within a newborn blood spot screening programme.

BACKGROUND: A decision tree model was built to estimate the economic impact of introducing screening for X-linked adrenoleukodystrophy (X-ALD) into an existing tandem mass spectrometry based newborn screening programme. The model was based upon the UK National Health Service (NHS) Newborn Blood Spot Screening Programme and a public service perspective was used with a lifetime horizon. The model structure and parameterisation were based upon literature reviews and expert clinical judgment. Outcomes included health, social care and education costs and quality adjusted life years (QALYs). The model assessed screening of boys only and evaluated the impact of improved outcomes from hematopoietic stem cell transplantation in patients with cerebral childhood X-ALD (CCALD). Threshold analyses were used to examine the potential impact of utility decrements for non-CCALD patients identified by screening. RESULTS: It is estimated that screening 780,000 newborns annually will identify 18 (95%CI 12, 27) boys with X-ALD, of whom 10 (95% CI 6, 15) will develop CCALD. It is estimated that screening may detect 7 (95% CI 3, 12) children with other peroxisomal disorders who may also have arisen symptomatically. If results for girls are returned an additional 17 (95% CI 12, 25) cases of X-ALD will be identified. The programme is estimated to cost an additional £402,000 (95% CI £399-407,000) with savings in lifetime health, social care and education costs leading to an overall discounted cost saving of £3.04 (95% CI £5.69, £1.19) million per year. Patients with CCALD are estimated to gain 8.5 discounted QALYs each giving an overall programme benefit of 82 (95% CI 43, 139) QALYs. CONCLUSION: Including screening of boys for X-ALD into an existing tandem mass spectrometry based newborn screening programme is projected to reduce lifetime costs and improve outcomes for those with CCALD. The potential disbenefit to those identified with non-CCALD conditions would need to be substantial in order to outweigh the benefit to those with CCALD. Further evidence is required on the potential QALY impact of early diagnosis both for non-CCALD X-ALD and other peroxisomal disorders. The favourable economic results are driven by estimated reductions in the social care and education costs.

STAKEHOLDER INVOLVEMENT THROUGHOUT HEALTH TECHNOLOGY ASSESSMENT: AN EXAMPLE FROM PALLIATIVE CARE.

OBJECTIVES: Internationally, funders require stakeholder involvement throughout health technology assessment (HTA). We report successes, challenges, and lessons learned from extensive stakeholder involvement throughout a palliative care case study that demonstrates new concepts and methods for HTA. METHODS: A 5-step "INTEGRATE-HTA Model" developed within the INTEGRATE-HTA project guided the case study. Using convenience or purposive sampling or directly / indirectly identifying and approaching individuals / groups, stakeholders participated in qualitative research or consultation meetings. During scoping, 132 stakeholders, aged ≥ 18 years in seven countries (England, Italy, Germany, The Netherlands, Norway, Lithuania, and Poland), highlighted key issues in palliative care that assisted identification of the intervention and comparator. Subsequently stakeholders in four countries participated in face-face, telephone and / or video Skype meetings to inform evidence collection and / or review assessment results. An applicability assessment to identify contextual and implementation barriers and enablers for the case study findings involved twelve professionals in the three countries. Finally, thirteen stakeholders participated in a mock decision-making meeting in England. RESULTS: Views about the best methods of stakeholder involvement vary internationally. Stakeholders make valuable contributions in all stages of HTA; assisting decision making about interventions, comparators, research questions; providing evidence and insights into findings, gap analyses and applicability assessments. Key challenges exist regarding inclusivity, time, and resource use. CONCLUSION: Stakeholder involvement is feasible and worthwhile throughout HTA, sometimes providing unique insights. Various methods can be used to include stakeholders, although challenges exist. Recognition of stakeholder expertise and further guidance about stakeholder consultation methods is needed.

Lay and professional stakeholder involvement in scoping palliative care issues: Methods used in seven European countries.

BACKGROUND: Stakeholders are people with an interest in a topic. Internationally, stakeholder involvement in palliative care research and health technology assessment requires development. Stakeholder involvement adds value throughout research (from prioritising topics to disseminating findings). Philosophies and understandings about the best ways to involve stakeholders in research differ internationally. Stakeholder involvement took place in seven countries (England, Germany, Italy, Lithuania, the Netherlands, Norway and Poland). Findings informed a project that developed concepts and methods for health technology assessment and applied these to evaluate models of palliative care service delivery. AIMS: To report on stakeholder involvement in the INTEGRATE-HTA project and how issues identified informed project development. DESIGN: Using stakeholder consultation or a qualitative research design, as appropriate locally, stakeholders in seven countries acted as 'advisors' to aid researchers' decision making. Thematic analysis was used to identify key issues across countries. SETTING/PARTICIPANTS: A total of 132 stakeholders (82 professionals and 50 'lay' people) aged ⩾18 participated in individual face-to-face or telephone interviews, consultation meetings or focus groups. RESULTS: Different stakeholder involvement methods were used successfully to identify key issues in palliative care. A total of 23 issues common to three or more countries informed decisions about the intervention and comparator of interest, sub questions and specific assessments within the health technology assessment. CONCLUSION: Stakeholders, including patients and families undergoing palliative care, can inform project decision making using various involvement methods according to the local context. Researchers should consider local understandings about stakeholder involvement as views of appropriate and feasible methods vary. Methods for stakeholder involvement, especially consultation, need further development.

Using resource modelling to inform decision making and service planning: the case of colorectal cancer screening in Ireland.

BACKGROUND: Organised colorectal cancer screening is likely to be cost-effective, but cost-effectiveness results alone may not help policy makers to make decisions about programme feasibility or service providers to plan programme delivery. For these purposes, estimates of the impact on the health services of actually introducing screening in the target population would be helpful. However, these types of analyses are rarely reported. As an illustration of such an approach, we estimated annual health service resource requirements and health outcomes over the first decade of a population-based colorectal cancer screening programme in Ireland. METHODS: A Markov state-transition model of colorectal neoplasia natural history was used. Three core screening scenarios were considered: (a) flexible sigmoidoscopy (FSIG) once at age 60, (b) biennial guaiac-based faecal occult blood tests (gFOBT) at 55-74 years, and (c) biennial faecal immunochemical tests (FIT) at 55-74 years. Three alternative FIT roll-out scenarios were also investigated relating to age-restricted screening (55-64 years) and staggered age-based roll-out across the 55-74 age group. Parameter estimates were derived from literature review, existing screening programmes, and expert opinion. Results were expressed in relation to the 2008 population (4.4 million people, of whom 700,800 were aged 55-74). RESULTS: FIT-based screening would deliver the greatest health benefits, averting 164 colorectal cancer cases and 272 deaths in year 10 of the programme. Capacity would be required for 11,095-14,820 diagnostic and surveillance colonoscopies annually, compared to 381-1,053 with FSIG-based, and 967-1,300 with gFOBT-based, screening. With FIT, in year 10, these colonoscopies would result in 62 hospital admissions for abdominal bleeding, 27 bowel perforations and one death. Resource requirements for pathology, diagnostic radiology, radiotherapy and colorectal resection were highest for FIT. Estimates depended on screening uptake. Alternative FIT roll-out scenarios had lower resource requirements. CONCLUSIONS: While FIT-based screening would quite quickly generate attractive health outcomes, it has heavy resource requirements. These could impact on the feasibility of a programme based on this screening modality. Staggered age-based roll-out would allow time to increase endoscopy capacity to meet programme requirements. Resource modelling of this type complements conventional cost-effectiveness analyses and can help inform policy making and service planning.

The Multiple Sclerosis Risk Sharing Scheme Monitoring Study--early results and lessons for the future.

BACKGROUND: Risk sharing schemes represent an innovative and important approach to the problems of rationing and achieving cost-effectiveness in high cost or controversial health interventions. This study aimed to assess the feasibility of risk sharing schemes, looking at long term clinical outcomes, to determine the price at which high cost treatments would be acceptable to the NHS. METHODS: This case study of the first NHS risk sharing scheme, a long term prospective cohort study of beta interferon and glatiramer acetate in multiple sclerosis (MS) patients in 71 specialist MS centres in UK NHS hospitals, recruited adults with relapsing forms of MS, meeting Association of British Neurologists (ABN) criteria for disease modifying therapy. Outcome measures were: success of recruitment and follow up over the first three years, analysis of baseline and initial follow up data and the prospect of estimating the long term cost-effectiveness of these treatments. RESULTS: Centres consented 5560 patients. Of the 4240 patients who had been in the study for a least one year, annual review data were available for 3730 (88.0%). Of the patients who had been in the study for at least two years and three years, subsequent annual review data were available for 2055 (78.5%) and 265 (71.8%) patients respectively. Baseline characteristics and a small but statistically significant progression of disease were similar to those reported in previous pivotal studies. CONCLUSION: Successful recruitment, follow up and early data analysis suggest that risk sharing schemes should be able to deliver their objectives. However, important issues of analysis, and political and commercial conflicts of interest still need to be addressed.

Use of expert knowledge in evaluating costs and benefits of alternative service provisions: a case study.

OBJECTIVES: A treatment pathway model was developed to examine the costs and benefits of the current bowel cancer service in England and to evaluate potential alternatives in service provision. To use the pathway model, various parameters and probability distributions had to be specified. They could not all be determined from empirical evidence and, instead, expert opinion was elicited in the form of statistical quantities that gave the required information. The purpose of this study is to describe the procedures used to quantify expert opinion and note examples of good practice contained in the case study. METHODS: The required information was identified and preparatory discussion with four experts refined the questions they would be asked. In individual elicitation sessions they quantified their opinions, mainly in the form of point and interval estimates for specified variables. New methods have been developed for quantifying expert opinion and these were implemented in specialized software that uses interactive graphics. This software was used to elicit opinion about quantities related to measurable covariates. RESULTS: Assessments for thirty-four quantities were elicited and available checks supported their validity. Eight points of good practice in eliciting and using expert judgment were evident. Parameters and probability distributions needed for the pathway model were determined from the elicited assessments. Simulation results from the pathway model were used to inform policy on bowel cancer service provision. CONCLUSIONS: The study illustrates that quantifying and using expert judgment can be acceptable in real problems of practical importance. For full benefit to be gained from expert knowledge, elicitation must be conducted carefully and should be reported in detail.

Option appraisal of population-based colorectal cancer screening programmes in England.

OBJECTIVES: To estimate the effectiveness, cost-effectiveness and resource impact of faecal occult blood testing (FOBT) and flexible sigmoidoscopy (FSIG) screening options for colorectal cancer to inform the Department of Health's policy on bowel cancer screening in England. METHODS: We developed a state transition model to simulate the life experience of a cohort of individuals without polyps or cancer through to the development of adenomatous polyps and malignant carcinoma and subsequent death in the general population of England. The costs, effects and resource impact of five screening options were evaluated: (a) FOBT for individuals aged 50-69 (biennial screening); (b) FOBT for individuals aged 60-69 (biennial screening); (c) once-only FSIG for individuals aged 55; (d) once-only FSIG for individuals aged 60; and (e) once-only FSIG for individuals aged 60, followed by FOBT for individuals aged 61-70 (biennial screening). RESULTS: The model suggests that screening using FSIG with or without FOBT may be cost-saving and may produce additional benefits compared with a policy of no screening. The marginal cost-effectiveness of FOBT options compared to a policy of no screening is estimated to be below pound3000 per quality adjusted life year gained. CONCLUSIONS: Screening using FOBT and/or FSIG is potentially a cost-effective strategy for the early detection of colorectal cancer. However, the practical feasibility of alternative screening programmes is inevitably limited by current pressures on endoscopy services.