Estimating the Cost of 3 Risk Prediction Strategies for Potential Use in the United Kingdom National Breast Screening Program.

Background: Economic evaluations have suggested that risk-stratified breast cancer screening may be cost-effective but have used assumptions to estimate the cost of risk prediction. The aim of this study was to identify and quantify the resource use and associated costs required to introduce a breast cancer risk-stratification approach into the English national breast screening program. Methods: A micro-costing study, conducted alongside a cohort-based prospective trial (BC-PREDICT), identified the resource use and cost per individual (£; 2021 price year) of providing a risk-stratification strategy at a woman's first mammography. Costs were calculated for 3 risk-stratification approaches: Tyrer-Cuzick survey, Tyrer-Cuzick with Volpara breast-density measurement, and Tyrer-Cuzick with Volpara breast-density measurement and testing for 142 single nucleotide polymorphisms (SNP). Costs were determined for the intervention as implemented in the trial and in the health service. Results: The cost of providing the risk-stratification strategy was calculated to be £16.45 for the Tyrer-Cuzick survey approach, £21.82 for the Tyrer-Cuzick with Volpara breast-density measurement, and £102.22 for the Tyrer-Cuzick with Volpara breast-density measurement and SNP testing. Limitations: This study did not use formal expert elicitation methods to synthesize estimates. Conclusion: The costs of risk prediction using a survey and breast density measurement were low, but adding SNP testing substantially increases costs. Implementation issues present in the trial may also significantly increase the cost of risk prediction. Implications: This is the first study to robustly estimate the cost of risk-stratification for breast cancer screening. The cost of risk prediction using questionnaires and automated breast density measurement was low, but full economic evaluations including accurate costs are required to provide evidence of the cost-effectiveness of risk-stratified breast cancer screening. Highlights: Economic evaluations have suggested that risk-stratified breast cancer screening may be a cost-effective use of resources in the United Kingdom.Current estimates of the cost of risk stratification are based on pragmatic assumptions.This study provides estimates of the cost of risk stratification using 3 strategies and when these strategies are implemented perfectly and imperfectly in the health system.The cost of risk stratification is relatively low unless single nucleotide polymorphisms are included in the strategy.

Reasons for using indoor tanning devices: A systematic review of qualitative evidence.

PURPOSE: Despite the established causal links to skin cancer, skin ageing and eye inflammation, people continue to use indoor tanning devices (hereafter 'sunbeds'). Understanding the reasons underlying the use of sunbeds is essential for developing effective interventions. The purpose of this study was to collate all existing evidence from qualitative papers published to date that had assessed motivations for using sunbeds. METHODS: Six databases were searched from inception to February 2020 for qualitative studies that explored adults' experiences of using sunbeds. Sixteen studies met the inclusion criteria, and a narrative evidence synthesis was used to collate findings from each primary study. RESULTS: Users of sunbeds were motivated primarily by aesthetic concerns but also by perceived psychological benefits (well-being, confidence and 'fitting in') and physical benefits (improvement in skin conditions such as acne, acquiring vitamin D and preventing sunburn). People also chose indoor tanning over alternatives such as fake tans because they considered the alternatives unacceptable and did not consider indoor tanning a serious health risk. To date, no studies have explored alternatives to meeting non-aesthetic needs related to the use of sunbeds. CONCLUSIONS: This comprehensive explanation for the practice of indoor tanning provides the basis for development of complex interventions to reduce the harm caused by using sunbeds. Effective interventions should include promotion of alternatives, such as different methods of relaxing, to satisfy underlying motivations, changing social norms and correcting misperceptions about health benefits.

RadBone: bone toxicity following pelvic radiotherapy - a prospective randomised controlled feasibility study evaluating a musculoskeletal health package in women with gynaecological cancers undergoing pelvic radiotherapy.

INTRODUCTION: Patients receiving radiotherapy are at risk of developing radiotherapy-related insufficiency fractures, which are associated with increased morbidity and pose a significant burden to patients' quality of life and to the health system. Therefore, effective preventive techniques are urgently required. The RadBone randomised controlled trial (RCT) aims to determine the feasibility and acceptability of a musculoskeletal health package (MHP) intervention in women undergoing pelvic radiotherapy for gynaecological malignancies and to preliminary explore clinical effectiveness of the intervention. METHODS AND ANALYSIS: The RadBone RCT will evaluate the addition to standard care of an MHP consisting of a physical assessment of the musculoskeletal health, a 3-month prehabilitation personalised exercise package, as well as an evaluation of the fracture risk and if required the prescription of appropriate bone treatment including calcium, vitamin D and-for high-risk individuals-bisphosphonates. Forty participants will be randomised in each group (MHP or observation) and will be followed for 18 months. The primary outcome of this RCT will be feasibility, including the eligibility, screening and recruitment rate, intervention fidelity and attrition rates; acceptability and health economics. Clinical effectiveness and bone turnover markers will be evaluated as secondary outcomes. ETHICS AND DISSEMINATION: This study has been approved by the Greater Manchester East Research Ethics Committee (Reference: 20/NW/0410, November 2020). The results will be published in peer-reviewed journals, will be presented in national and international conferences and will be communicated to relevant stakeholders. Moreover, a plain English report will be shared with the study participants, patients' organisations and media. TRIAL REGISTRATION NUMBER: NCT04555317.

Nailfold capillaroscopy: a survey of current UK practice and 'next steps' to increase uptake among rheumatologists.

OBJECTIVES: To identify barriers to the use of nailfold capillaroscopy as a diagnostic tool for patients presenting with Raynaud's phenomenon in UK rheumatology centres and to obtain rheumatologists' views on a proposed internet-based standardized system for clinical reporting of nailfold capillaroscopy images. METHODS: An online survey was developed using expert opinion from clinicians, scientists and health service researchers. The survey was piloted and sent to UK-based rheumatologists using established electronic mailing lists between October 2020 and March 2021. Survey data were analysed using descriptive statistics. RESULTS: A total of 104 rheumatologists representing rheumatology centres across the UK responded to the survey. Wide variations in terms of workloads and practices were described. Thirty-four (33%) respondents reported using nailfold capillaroscopy only at their own centre, 33 (32%) referred to other centres, 9 (9%) did both and 28 (27%) did not use capillaroscopy at all. Of the 43 respondents using capillaroscopy on site, 25 (58%) used either a dermatoscope or universal serial bus microscope and 9 (21%) used videocapillaroscopy. Among the 61 respondents not undertaking capillaroscopy on site, barriers included lack of equipment (85%), lack of experience in acquiring images (69%) and lack of expertise in interpreting images (67%). Sixty-six respondents (63%) expressed interest in an internet-based, standardized automated system for reporting images. CONCLUSION: Most UK rheumatologists currently do not perform nailfold capillaroscopy on site. An internet-based nailfold capillaroscopy system for use with low-cost microscopes as well as with videocapillaroscopy could help increase uptake of capillaroscopy and thereby facilitate early diagnosis of SSc across the UK.

Cost-effectiveness of a policy-based intervention to reduce melanoma and other skin cancers associated with indoor tanning.

BACKGROUND: The use of indoor tanning devices causes melanoma and other skin cancers with resulting morbidity, mortality and increased healthcare costs. Policymakers require robust economic evidence to inform decisions about a possible ban of such devices to mitigate these burdens. OBJECTIVES: To assess the health costs and consequences of introducing a policy-based intervention across England to ban commercial indoor tanning with an accompanying public information campaign. METHODS: A cost-effectiveness analysis, adopting a healthcare system perspective, was conducted using a decision model to track a national cohort of 18-year-olds over a lifetime time horizon. A nationwide ban on commercial indoor tanning combined with a public information campaign (the policy-based intervention) was compared with the status quo of availability of commercial indoor tanning. The expected costs (currency, GBP; price year, 2019) and quality-adjusted life-years (QALYs) were calculated. Net monetary benefit (NMB) (net benefit measured in cost compared with an accepted threshold) and net health benefit (NHB) (net gain in QALYs compared with an accepted threshold) of implementation were calculated. A probabilistic sensitivity analysis was used to calculate the probability that the intervention was cost-effective. RESULTS: Compared with the current situation, a ban on commercial indoor tanning combined with a public information campaign would result in 1206 avoided cases of melanoma, 207 fewer melanoma deaths and 3987 averted cases of keratinocyte cancers over the lifetime of all 18-year-olds (n = 618 873) living in England in 2019. An additional 497 QALYs would be realized along with healthcare cost-savings of £697 858. This intervention would result in an NMB of £10.6m and an NHB of 530 QALYS. Multiple sensitivity analyses confirmed the robustness of the findings. At a cost-effectiveness threshold of £20 000, there is a 99% likelihood of this policy-based intervention being cost-effective. CONCLUSIONS: The implementation of a ban on commercial indoor tanning across England with an accompanying public information campaign would be an effective use of healthcare resources.

Sunbed Use among 11- to 17-Year-Olds and Estimated Number of Commercial Sunbeds in England with Implications for a 'Buy-Back' Scheme.

Prior to 2011 legislation prohibiting children from using commercial sunbeds, the prevalence of sunbed use in 15- to 17-year-olds in some areas in England was as high as 50%. Despite significant decreases since 2011, children today still practice indoor tanning. We estimated current sunbed use in 11- to 17-year-olds in England, the number of available commercial sunbed units, and the associated cost of a 'buy-back' scheme to remove commercial sunbeds under a potential future policy to ban sunbeds. We undertook a calibration approach based on published prevalence rates in English adults and other sources. Internet searches were undertaken to estimate the number of sunbed providers in Greater Manchester, then we extrapolated this to England. Estimated mean prevalence of sunbed use was 0.6% for 11- to 14-year-olds and 2.5% for 15- to 17-year-olds, equating to 62,130 children using sunbeds in England. A predicted 2958 premises and 17,865 sunbeds exist nationally and a 'buy-back' scheme would cost approximately GBP 21.7 million. Public health concerns remain greatest for 11- to 17-year-olds who are particularly vulnerable to developing skin cancers after high ultraviolet exposure.

The effect on work presenteeism of job retention vocational rehabilitation compared to a written self-help work advice pack for employed people with inflammatory arthritis: protocol for a multi-centre randomised controlled trial (the WORKWELL trial).

BACKGROUND: Work problems are common in people with inflammatory arthritis. Up to 50% stop work within 10 years due to their condition and up to 67% report presenteeism (i.e. reduced work productivity), even amongst those with low disease activity. Job retention vocational rehabilitation (JRVR) may help prevent or postpone job loss and reduce presenteeism through work assessment, work-related rehabilitation and enabling job accommodations. This aims to create a better match between the person's abilities and their job demands. The objectives of the Workwell trial are to test the overall effectiveness and cost-effectiveness of JRVR (WORKWELL) provided by additionally trained National Health Service (NHS) occupational therapists compared to a control group who receive self-help information both in addition to usual care. METHODS: Based on the learning from a feasibility trial (the WORK-IA trial: ISRCTN76777720 ), the WORKWELL trial is a multi-centre, pragmatic, individually-randomised parallel group superiority trial, including economic evaluation, contextual factors analysis and process evaluation. Two hundred forty employed adults with rheumatoid arthritis, undifferentiated inflammatory arthritis or psoriatic arthritis (in secondary care), aged 18 years or older with work instability will be randomised to one of two groups: a self-help written work advice pack plus usual care (control intervention); or WORKWELL JRVR plus a self-help written work advice pack and usual care. WORKWELL will be delivered by occupational therapists provided with additional JRVR training from the research team. The primary outcome is presenteeism as measured using the Work Limitations Questionnaire-25. A comprehensive range of secondary outcomes of work, health, contextual factors and health resource use are included. Outcomes are measured at 6- and 12- months (with 12-months as the primary end-point). A multi-perspective within-trial cost-effectiveness analyses will also be conducted. DISCUSSION: This trial will contribute to the evidence base for provision of JRVR to people with inflammatory arthritis. If JRVR is found to be effective in enabling people to keep working, the findings will support decision-making about provision of JRVR by rheumatology teams, therapy services and healthcare commissioners, and providing evidence of the effectiveness of JRVR and the economic impact of its implementation. TRIAL REGISTRATION: Clinical Trials.Gov: NCT03942783 . Registered 08/05/2019 ( https://clinicaltrials.gov/ct2/show/NCT03942783 ); ISRCTN Registry: ISRCTN61762297 . Registered:13/05/2019 ( http://www.isrctn.com/ISRCTN61762297 ). Retrospectively registered.

Randomised clinical trial of a gastrointestinal care bundle to reduce symptoms in patients with pelvic cancer undergoing chemoradiotherapy.

OBJECTIVE: Pelvic radiotherapy is used to treat 17 000 people in the UK each year. Eight in 10 develop difficult bowel problems during pelvic treatment, especially diarrhoea, urgency and incontinence. Some cannot complete treatment, reducing the chance of cancer cure. Undertaking gastroenterologist-led investigation and management during pelvic radiotherapy has never been evaluated. In this study, we aimed to assess whether patients could successfully receive a novel gastrointestinal (GI) care bundle during chemoradiotherapy (feasibility aim) and would experience reduced symptom severity (clinical impact aim). DESIGN: This randomised controlled trial recruited patients with cervical and bladder cancers undergoing radical chemoradiotherapy. Participants were randomised to intervention or control groups. Questionnaire and anthropometric data were collected. All intervention group patients received individualised dietary counselling weekly throughout treatment, and if bowel symptoms developed they were offered rapid-access investigation and treatment for any identified pathology: lactose intolerance, bacterial overgrowth or bile acid malabsorption. RESULTS: Feasibility: 50 participants were recruited, 24 were randomised to the intervention group and 26 to the control group. All completed 20 fractions of external beam pelvic radiotherapy. It was possible to perform 57/72 (79%) of proposed intervention tests with no disruption of oncological management. CLINICAL IMPACT: All participants developed GI symptoms during radiotherapy. The median symptom score for each group increased from baseline at 6 weeks. This was from 0.156 (0.000-0.333) to 0.600 (0.250-1.286) in the control group, and from 0.00 (0.000-0.300) to 0.402 (0.000-0.667) in the intervention group. CONCLUSION: It was feasible to recruit to and deliver a randomised controlled trial of interventions in patients undergoing pelvic chemoradiotherapy. Lower median bowel scores were reported in the intervention group at 6 weeks, with fewer patients experiencing symptoms overall. TRIAL REGISTRATION NUMBER: ISRCTN783488.

Critical points for an accurate human genome analysis.

Next-generation sequencing is radically changing how DNA diagnostic laboratories operate. What started as a single-gene profession is now developing into gene panel sequencing and whole-exome and whole-genome sequencing (WES/WGS) analyses. With further advances in sequencing technology and concomitant price reductions, WGS will soon become the standard and be routinely offered. Here, we focus on the critical steps involved in performing WGS, with a particular emphasis on points where WGS differs from WES, the important variables that should be taken into account, and the quality control measures that can be taken to monitor the process. The points discussed here, combined with recent publications on guidelines for reporting variants, will facilitate the routine implementation of WGS into a diagnostic setting.

What are colorectal cancer survivors' preferences for dietary advice? A best-worst discrete choice experiment.

PURPOSE: Studies on healthy lifestyle interventions in survivors of colorectal cancer have been disappointing, demonstrating only modest changes. This study aims to quantify people's preferences for different aspects of dietary intervention. METHOD: A best-worst discrete choice experiment was designed and incorporated into a questionnaire including participants' characteristics and a self-assessment of lifestyle. RESULTS: The response rate was 68% and 179 questionnaires were analysed. When analysing aggregate preferences, the modes of information provision selected as the most preferred were "face-to-face" (willingness to pay (WTP) £63.97, p ≤ 0.001) and "telephone" (WTP £62.36, p < 0.001) discussions whereas group discussions were preferred least (WTP -£118.96, p ≤ 0.001). Scenarios that included hospitals were most preferred (WTP £17.94, p = 0.031), and the favoured provider was bowel cancer nurses (WTP £75.11, p ≤ 0.001). When investigating preference heterogeneity, three sub-groups were identified: Firstly, "technophiles" preferring email (WTP £239.60, p ≤ 0.001) were male, were younger and had fewer risk factors. Secondly, a "one-to-one" group had strong preference for interventions over the telephone or at their local doctors and were older (WTP £642.13, p ≤ 0.001). Finally, a "person-centred" group preferred face-to-face individual or group sessions (WTP £358.79, p < 0.001) and had a high risk lifestyle. CONCLUSION: For survivors of colorectal cancer, there is not one approach that suits all when it comes to providing dietary advice. IMPLICATIONS FOR CANCER SURVIVORS: This is important information to consider when planning healthy lifestyle interventions which include dietary advice for survivors of colorectal cancer. Aligning services to individuals' preferences has the potential to improve patient experience and outcomes by increasing uptake of healthy lifestyle advice services and promoting a more tailored approach to dietary modifications, acknowledging sub-groups of people within the total population of colorectal cancer survivors.

Exploring the feasibility of delivering standardized genomic care using ophthalmology as an example.

PURPOSE: Broadening access to genomic testing and counseling will be necessary to realize the benefits of personalized health care. This study aimed to assess the feasibility of delivering a standardized genomic care model for inherited retinal dystrophy (IRD) and of using selected measures to quantify its impact on patients. METHODS: A pre-/post- prospective cohort study recruited 98 patients affected by IRD to receive standardized multidisciplinary care. A checklist was used to assess the fidelity of the care process. Three patient-reported outcome measures-the Genetic Counselling Outcome Scale (GCOS-24), the ICEpop CAPability measure for Adults (ICECAP-A), and the EuroQol 5-dimension questionnaire (EQ-5D)-and a resource-use questionnaire were administered to investigate rates of missingness, ceiling effects, and changes over time. RESULTS: The care model was delivered consistently. Higher rates of missingness were found for the genetic-specific measure (GCOS-24). Considerable ceiling effects were observed for the generic measure (EQ-5D). The ICECAP-A yielded less missing data without significant ceiling effects. It was feasible to use telephone interviews for follow-up data collection. CONCLUSION: The study highlighted challenges and solutions associated with efforts to standardize genomic care for IRD. The study identified appropriate methods for a future definitive study to assess the clinical effectiveness and cost-effectiveness of the care model.Genet Med advance online publication 02 March 2017.

Toward health technology assessment of whole-genome sequencing diagnostic tests: challenges and solutions.

Whole-genome sequencing (WGS) is being applied within research settings across Europe to develop genomic WGS-based diagnostic tests. The focus of this perspective paper is to describe if, and how, current approaches of health technology assessment could be applied to WGS-based diagnostic tests. This perspective draws on the collective view from a trans-European multidisciplinary consortium of methodologists, clinicians and scientists. Specific challenges can be described by using the PICO (population, intervention, comparator, outcome) framework to inform health technology assessment. Practical solutions are suggested which require joined-up, multidisciplinary working across healthcare systems using existing expert networks so that emergent issues for the health technology assessment of WGS can be met in a timely fashion.

Valuing Preferences for the Process and Outcomes of Clinical Genetics Services: A Pilot Study.

BACKGROUND: Understanding preferences for the process and outcomes of clinical genetics services (CGS) is a first step to developing these services appropriately. AIM: The aim of this study was to quantify the relative importance of attributes defining the process of service delivery and the patient outcomes of CGS. METHODS: An online hybrid conjoint analysis discrete choice experiment (CA-DCE) was piloted in a purposive sample (n = 37) of CGS patients and non-patients to identify (i) service attributes (n = 13) perceived to facilitate informed decision making; (ii) relative preferences for six attributes (5 process, 1 outcome: ability to make an informed decision). A three-step approach was taken to link the data from the CA-DCE using hierarchical information integration and ordered logit and multinomial logit models. Marginal willingness-to-pay (WTP) values were calculated. RESULTS: Services that facilitate informed decision making, with shorter waiting times and involving pre-consultation contact were preferred. Estimated WTP values were: service location (£3170; 95% CI -391 to 15,098); waiting time (-£1080; 95% CI -3659 to -603); pre-consultation contact (£7765; 95% CI 2542-33,937); improved informed decision making (£2254; 95% CI 775-9866). CONCLUSION: This study suggests that hybrid stated preference experiments offer a practical solution to understanding preferences for how CGS services are delivered.

Variation in healthcare services for specialist genetic testing and implications for planning genetic services: the example of inherited retinal dystrophy in the English NHS.

This study aims to identify and quantify the extent of current variation in service provision of a genetic testing service for dominant and X-linked retinal dystrophies in the English National Health Service (NHS). National audit data (all test requests and results (n = 1839) issued between 2003 and 2011) and survey of English regional genetic testing services were used. Age- and gender-adjusted standardised testing rates were calculated using indirect standardisation, and survey responses were transcribed verbatim and data collated and summarised. The cumulative incidence rate of testing in England was 4.5 per 100,000 population for males and 2.6 per 100,000 population for females. The standardised testing rate (STR) varied widely between regions of England, being particularly low in the North-east (STR 0.485), with half as many tests as expected based on the size and demographic distribution of the population and high in the South-east (STR 1.355), with 36 % more tests than expected. Substantial and significantly different rates of testing were found between regional populations. Specific policy mechanisms to promote, monitor and evaluate the regional distribution of access to genetic and genomic testing are required. However, commissioners will require information on the scope and role of genetic services and the population at risk of the conditions for which patients are tested.

Cost effectiveness of a pharmacist-led information technology intervention for reducing rates of clinically important errors in medicines management in general practices (PINCER).

BACKGROUND AND OBJECTIVE: We recently showed that a pharmacist-led information technology-based intervention (PINCER) was significantly more effective in reducing medication errors in general practices than providing simple feedback on errors, with cost per error avoided at £79 (US$131). We aimed to estimate cost effectiveness of the PINCER intervention by combining effectiveness in error reduction and intervention costs with the effect of the individual errors on patient outcomes and healthcare costs, to estimate the effect on costs and QALYs. METHODS: We developed Markov models for each of six medication errors targeted by PINCER. Clinical event probability, treatment pathway, resource use and costs were extracted from literature and costing tariffs. A composite probabilistic model combined patient-level error models with practice-level error rates and intervention costs from the trial. Cost per extra QALY and cost-effectiveness acceptability curves were generated from the perspective of NHS England, with a 5-year time horizon. RESULTS: The PINCER intervention generated £2,679 less cost and 0.81 more QALYs per practice [incremental cost-effectiveness ratio (ICER): -£3,037 per QALY] in the deterministic analysis. In the probabilistic analysis, PINCER generated 0.001 extra QALYs per practice compared with simple feedback, at £4.20 less per practice. Despite this extremely small set of differences in costs and outcomes, PINCER dominated simple feedback with a mean ICER of -£3,936 (standard error £2,970). At a ceiling 'willingness-to-pay' of £20,000/QALY, PINCER reaches 59 % probability of being cost effective. CONCLUSIONS: PINCER produced marginal health gain at slightly reduced overall cost. Results are uncertain due to the poor quality of data to inform the effect of avoiding errors.

Valuing the benefits of genetic testing for retinitis pigmentosa: a pilot application of the contingent valuation method.

BACKGROUND: Technological advances present an opportunity for more people with, or at risk of, developing retinitis pigmentosa (RP) to be offered genetic testing. Valuation of these tests using current evaluative frameworks is problematic since benefits may be derived from diagnostic information rather than improvements in health. This pilot study aimed to explore if contingent valuation method (CVM) can be used to value the benefits of genetic testing for RP. METHODS: CVM was used to elicit willingness-to-pay (WTP) values for (1) genetic counselling and (2) genetic counselling with genetic testing. Telephone and face-to-face interviews with a purposive sample of individuals with (n=25), and without (n=27), prior experience of RP were used to explore the feasibility and validity of CVM in this context. RESULTS: Faced with a hypothetical scenario, the majority of participants stated that they would seek genetic counselling and testing in the context of RP. Between participant groups, respondents offered similar justifications for stated WTP values. Overall stated WTP was higher for genetic counselling plus testing (median=£524.00) compared with counselling alone (median=£224.50). Between-group differences in stated WTP were statistically significant; participants with prior knowledge of the condition were willing to pay more for genetic ophthalmology services. CONCLUSIONS: Participants were able to attach a monetary value to the perceived potential benefit that genetic testing offered regardless of prior experience of the condition. This exploratory work represents an important step towards evaluating these services using formal cost-benefit analysis.