Acceptability of adding a non-contrast abdominal CT scan to screen for kidney cancer and other abdominal pathology within a community-based CT screening programme for lung cancer: A qualitative study.

OBJECTIVES: The Yorkshire Kidney Screening Trial (YKST) is a feasibility study of adding non-contrast abdominal CT scanning to screen for kidney cancer and other abdominal malignancies to community-based CT screening for lung cancer within the Yorkshire Lung Screening Trial (YLST). This study explored the acceptability of the combined screening approach to participants and healthcare professionals (HCPs) involved in the trial. METHODS: We conducted semi-structured interviews with eight HCPs and 25 participants returning for the second round of scanning within YLST, 20 who had taken up the offer of the additional abdominal CT scan and five who had declined. Transcripts were analysed using thematic analysis, guided by the Theoretical Framework of Acceptability. RESULTS: Overall, combining the offer of a non-contrast abdominal CT scan alongside the low-dose thoracic CT was considered acceptable to participants, including those who had declined the abdominal scan. The offer of the additional scan made sense and fitted well within the process, and participants could see benefits in terms of efficiency, cost and convenience both for themselves as individuals and also more widely for the NHS. Almost all participants made an instant decision at the point of initial invitation based more on trust and emotions than the information provided. Despite this, there was a clear desire for more time to decide whether to accept the scan or not. HCPs also raised concerns about the burden on the study team and wider healthcare system arising from additional workload both within the screening process and downstream following findings on the abdominal CT scan. CONCLUSIONS: Adding a non-contrast abdominal CT scan to community-based CT screening for lung cancer is acceptable to both participants and healthcare professionals. Giving potential participants prior notice and having clear pathways for downstream management of findings will be important if it is to be offered more widely.

Understanding the Preferences and Considerations of the Public Towards Risk-Stratified Screening for Colorectal Cancer: Insights From Think-Aloud Interviews Based on a Discrete Choice Experiment.

CONTEXT: Risk stratification has been suggested as a strategy for improving cancer screening. Any changes to existing programmes must be acceptable to the public. OBJECTIVE: This study aimed to explore the preferences and considerations of individuals relating to the introduction of different risk-based strategies to determine eligibility for colorectal cancer (CRC) screening. STUDY DESIGN: Participants completed a discrete choice experiment (DCE) within online interviews. Nine conjoint-analysis tasks were created, each with two potential CRC screening programmes. The attributes included personal risk of CRC, screening invitation strategy and impact. Participants chose between programmes while thinking aloud and sharing their thoughts. Transcripts were analysed using codebook thematic analysis. PARTICIPANTS: Twenty participants based in England aged 40-79 years without previous cancer history or medical expertise. RESULTS: When choosing between programmes, participants first and primarily looked to prioritise saving lives. The harms associated with screening were viewed as a surprise but also felt by most to be inevitable; the benefits frequently outweighed, therefore, harms were considered less important. Risk stratification using individual characteristics was considered a nuanced approach to healthcare, which tended to be preferred over the age-alone model. Detailed personal risk information could be taken more seriously than non-personalised information to motivate behaviour change. Although it had minimal impact on decision-making, not diverting resources for screening from elsewhere was valued. Individuals who chose not to provide health information were considered irresponsible, while it was important that those with no information to provide should not lose out. CONCLUSION: Risk-stratified CRC screening is generally aligned with public preferences, with decisions between possible stratification strategies dominated by saving lives. Even if attributes including risk factors, risk stratification strategy and risk communication contributed less to the overall decision to select certain programmes, some levels more clearly fulfilled public values; therefore, all these factors should be taken into consideration when redesigning and communicating CRC screening programmes. PATIENT OR PUBLIC CONTRIBUTION: The primary data source for this study is interviews with 20 members of the public (current, past or future CRC screening invitees). Two public representatives contributed to planning this study, particularly the DCE.

Systematic review: risk prediction models for metachronous advanced colorectal neoplasia after polypectomy.

BACKGROUND AND AIM: Colorectal cancer (CRC) is the fourth leading cause of cancer death globally. CRC surveillance is a common indication for colonoscopy, representing a considerable burden for endoscopy services. Accurate identification of high-risk patients who would benefit from more intensive surveillance, as well as low-risk patients suitable for less frequent follow-up, could improve the effectiveness of surveillance protocols and resource use. Our aim was to identify and critically appraise published risk models for the occurrence of metachronous advanced colorectal neoplasia (ACN), defined here as CRC or advanced adenomas detected during surveillance colonoscopy. METHODS: We searched PubMed and EMBASE for primary research studies reporting the development and/or validation of multivariable models that predict metachronous ACN risk. Screening of studies for inclusion, data extraction, and risk of bias assessment were conducted by two researchers independently. RESULTS: We identified nine studies describing nine risk models. Six models were internally validated and two were externally validated. No model underwent both internal and external validation. Good model discrimination (concordance index > 0.7) was reported for two models during internal validation and for one model during external validation. Calibration was acceptable when assessed (n = 4). Methodological limitations and a high risk of bias were observed for all studies. CONCLUSIONS: Several published models predicting metachronous ACN risk showed some promise. However, adherence to methodological standards was limited, and only two models were externally validated. Head-to-head comparisons of existing models using populations independent from model development cohorts should be prioritized to identify models suitable for use in clinical practice.

Relationship between research activity and general practice performance: cross sectional and longitudinal analyses.

BACKGROUND: Research activity usually improves outcomes by being translated into practice. However, there is developing evidence that research activity itself may improve the overall performance of health care organisations. However, evidence that these relationships represent a causal impact of research activity is less clear. Additionally, the bulk of the existing evidence relates to hospital settings, and it is not known if those relationships would also be found in general practice, where most patient contacts occur. AIM: We sought to (a) test whether there were significant relationships between research activity in general practice and organisational performance (b) test whether those relationships were plausibly causal. DESIGN AND SETTING: We analysed national data between 2008 and 2019 using cross sectional and longitudinal analyses, on general practices in England. METHODS: We used cross-sectional, panel and instrumental variable analyses to explore relationships between research activity (including measures from the NIHR Clinical Research Network and the Royal College of General Practitioners) and practice performance (including clinical quality of care, patient reported experience of care, prescribing quality and hospital admissions) Results: In cross-sectional analyses, research activity was positively associated with several measures of practice performance, including clinical quality of care, patient reported experience of care, and reduced hospital admissions. The associations were generally modest in magnitude. However, longitudinal analyses did not support a reliable causal relationship. CONCLUSION: Similar to findings from hospital settings, research activity in general practice is associated with practice performance. There is less evidence that research is causing those improvements, although this may reflect the limited level of research activity in most practices. We identified no negative impacts, suggesting that research activity is a potential marker of quality and something that high quality practices can deliver alongside their core responsibilities.

Patient demographic characteristics and risk factors associated with sun protection behaviours in specialist melanoma clinics.

OBJECTIVE: We investigated the association between sun protection behaviours and demographic and melanoma risk characteristics of patients attending Australian melanoma specialist clinics. This may assist in targeting and tailoring melanoma prevention patient education for people at high-risk and specific population subgroups. METHODS: A cross-sectional analysis of questionnaire data collected from participants attending the dermatology clinics at two major melanoma centres in Sydney, Australia between February 2021 and September 2023. The primary outcome was Sun Protection Habits (SPH) index (a summary score measured as habitual past month use of sunscreen, hats, sunglasses, a shirt with sleeves that covers the shoulders, limiting midday sun exposure and seeking shade, using a Likert scale). The primary analysis considered the SPH index and its component items scored as continuous. RESULTS: Data from 883 people were analysed. Factors associated with less frequent sun protection behaviours overall included male gender, no personal history of melanoma, lower perceived risk, lower calculated 10-year risk of developing melanoma, and no private health insurance. People aged >61 years reported lower use of sunscreen but higher use of hats and sleeved-shirts compared with people in the younger age group. There was no difference in overall sun protection behaviours according to family history of melanoma, country of birth or by lifetime melanoma risk among people without a personal history of melanoma. CONCLUSIONS: These findings highlight the potential for targeting high-risk individuals with less frequent use of sun protection for patient education, public health messaging and ultimately improving sun protection behaviours.

The acceptability and clinical impact of using polygenic scores for risk-estimation of common cancers in primary care: a systematic review.

BACKGROUND: Polygenic scores (PGS) have been developed for cancer risk-estimation and show potential as tools to prompt earlier referral for high-risk individuals and aid risk-stratification within cancer screening programmes. This review explores the potential for using PGS to identify individuals at risk of the most common cancers seen in primary care. METHODS: Two electronic databases were searched up until November 2023 to identify quantitative, qualitative, and mixed methods studies that reported on the acceptability and clinical impact of using PGS to identify individuals at highest risk of breast, prostate, colorectal and lung cancer in primary care. The Mixed Methods Appraisal Tool (MMAT) was used to assess the quality of included studies and a narrative synthesis was used to analyse data. RESULTS: A total of 190 papers were identified, 18 of which were eligible for inclusion. A cancer risk-assessment tool incorporating PGS was acceptable to the general practice population and their healthcare providers but major challenges to implementation were identified, including lack of evidence for PGS in non-European ancestry and a need for healthcare provider education in genomic medicine. A PGS cancer risk-assessment had relatively limited impact on psychosocial outcomes and health behaviours. However, for prostate cancer, potential applications for its use in primary care were shown. CONCLUSIONS: Cancer risk assessment incorporating PGS in primary care is acceptable to patients and healthcare providers but there is a paucity of research exploring clinical impact. Few studies were identified, and more research is required before clinical implementation of PGS can be recommended.

Impact of research activity on performance of general practices: a qualitative study.

BACKGROUND: There is evidence that engaging in research is directly associated with better performance. If this relationship is to be strengthened, it is necessary to understand the mechanisms which might underlie that relationship. AIM: To explore the perspectives of staff and wider stakeholders about mechanisms by which research activity might impact on the performance of general practices. DESIGN & SETTING: Qualitative study using semi-structured interviews with general practice professionals and wider stakeholders in England. METHOD: Individual interviews with 41 purposively sampled staff in 'research ready' or 'research active' general practices and 21 other stakeholders. Interviews were independently coded by three researchers using a Framework approach. RESULTS: Participants described potential 'direct' and 'indirect' impacts on their work. 'Direct' impacts included research changing practice work (eg, additional records searches for particular conditions), bringing in additional resources (eg, access to investigations or staff) and improving relationships with patients. 'Indirect' impacts included job satisfaction (eg, perception of practice as a centre of excellence and innovation, and the variety afforded by research activity reducing burnout) and staff recruitment (increasing the attractiveness of the practice as a place to work). Respondents identified few negative impacts. CONCLUSIONS: Staff and stakeholders identified a range of potential impacts of research activity on practice performance, with impacts on their working lives most salient. Negative impacts were not generally raised. Nevertheless, respondents generally discussed potential impacts rather than providing specific examples of those impacts. This may reflect the type of research activity conducted in general practice, often led by external collaborators.

Implementation and external validation of the Cambridge Multimorbidity Score in the UK Biobank cohort.

BACKGROUND: Patients with multiple conditions present a growing challenge for healthcare provision. Measures of multimorbidity may support clinical management, healthcare resource allocation and accounting for the health of participants in purpose-designed cohorts. The recently developed Cambridge Multimorbidity scores (CMS) have the potential to achieve these aims using primary care records, however, they have not yet been validated outside of their development cohort. METHODS: The CMS, developed in the Clinical Research Practice Dataset (CPRD), were validated in UK Biobank participants whose data is not available in CPRD (the cohort used for CMS development) with available primary care records (n = 111,898). This required mapping of the 37 pre-existing conditions used in the CMS to the coding frameworks used by UK Biobank data providers. We used calibration plots and measures of discrimination to validate the CMS for two of the three outcomes used in the development study (death and primary care consultation rate) and explored variation by age and sex. We also examined the predictive ability of the CMS for the outcome of cancer diagnosis. The results were compared to an unweighted count score of the 37 pre-existing conditions. RESULTS: For all three outcomes considered, the CMS were poorly calibrated in UK Biobank. We observed a similar discriminative ability for the outcome of primary care consultation rate to that reported in the development study (C-index: 0.67 (95%CI:0.66-0.68) for both, 5-year follow-up); however, we report lower discrimination for the outcome of death than the development study (0.69 (0.68-0.70) and 0.89 (0.88-0.90) respectively). Discrimination for cancer diagnosis was adequate (0.64 (0.63-0.65)). The CMS performs favourably to the unweighted count score for death, but not for the outcomes of primary care consultation rate or cancer diagnosis. CONCLUSIONS: In the UK Biobank, CMS discriminates reasonably for the outcomes of death, primary care consultation rate and cancer diagnosis and may be a valuable resource for clinicians, public health professionals and data scientists. However, recalibration will be required to make accurate predictions when cohort composition and risk levels differ substantially from the development cohort. The generated resources (including codelists for the conditions and code for CMS implementation in UK Biobank) are available online.

Risk Prediction Models for Oral Cancer: A Systematic Review.

In the last 30 years, there has been an increasing incidence of oral cancer worldwide. Earlier detection of oral cancer has been shown to improve survival rates. However, given the relatively low prevalence of this disease, population-wide screening is likely to be inefficient. Risk prediction models could be used to target screening to those at highest risk or to select individuals for preventative interventions. This review (a) systematically identified published models that predict the development of oral cancer and are suitable for use in the general population and (b) described and compared the identified models, focusing on their development, including risk factors, performance and applicability to risk-stratified screening. A search was carried out in November 2022 in the Medline, Embase and Cochrane Library databases to identify primary research papers that report the development or validation of models predicting the risk of developing oral cancer (cancers of the oral cavity or oropharynx). The PROBAST tool was used to evaluate the risk of bias in the identified studies and the applicability of the models they describe. The search identified 11,222 articles, of which 14 studies (describing 23 models), satisfied the eligibility criteria of this review. The most commonly included risk factors were age (n = 20), alcohol consumption (n = 18) and smoking (n = 17). Six of the included models incorporated genetic information and three used biomarkers as predictors. Including information on human papillomavirus status was shown to improve model performance; however, this was only included in a small number of models. Most of the identified models (n = 13) showed good or excellent discrimination (AUROC > 0.7). Only fourteen models had been validated and only two of these validations were carried out in populations distinct from the model development population (external validation). Conclusions: Several risk prediction models have been identified that could be used to identify individuals at the highest risk of oral cancer within the context of screening programmes. However, external validation of these models in the target population is required, and, subsequently, an assessment of the feasibility of implementation with a risk-stratified screening programme for oral cancer.

Feasibility and acceptability of offering breast cancer risk assessment to general population women aged 30-39 years: a mixed-methods study protocol.

INTRODUCTION: Breast cancer incidence starts to increase exponentially when women reach 30-39 years, hence before they are eligible for breast cancer screening. The introduction of breast cancer risk assessment for this age group could lead to those at higher risk receiving benefits of earlier screening and preventive strategies. Currently, risk assessment is limited to women with a family history of breast cancer only. The Breast CANcer Risk Assessment in Younger women (BCAN-RAY) study is evaluating a comprehensive breast cancer risk assessment strategy for women aged 30-39 years incorporating a questionnaire of breast cancer risk factors, low-dose mammography to assess breast density and polygenic risk. This study will assess the feasibility and acceptability of the BCAN-RAY risk assessment strategy. METHODS AND ANALYSIS: This study involves women undergoing risk assessment as part of the BCAN-RAY case-control study (n=750). They will be aged 30-39 years without a strong family history of breast cancer and invited to participate via general practice. A comparison of uptake rates by socioeconomic status and ethnicity between women who participated in the BCAN-RAY study and women who declined participation will be conducted. All participants will be asked to complete self-report questionnaires to assess key potential harms including increased state anxiety (State Trait Anxiety Inventory), cancer worry (Lerman Cancer Worry Scale) and satisfaction with the decision to participate (Decision Regret Scale), alongside potential benefits such as feeling more informed about breast cancer risk. A subsample of approximately 24 women (12 at average risk and 12 at increased risk) will additionally participate in semistructured interviews to understand the acceptability of the risk assessment strategy and identify any changes needed to it to increase uptake. ETHICS AND DISSEMINATION: Ethical approval was granted by North West-Greater Manchester West Research Ethics Committee (reference: 22/NW/0268). Study results will be disseminated through peer-reviewed journals, conference presentations and charitable organisations. TRIAL REGISTRATION NUMBER: NCT05305963.

Evaluating the potential impact of lifestyle-based behavior change interventions delivered at the time of colorectal cancer screening.

PURPOSE: To analyze interventions implemented at the time of colorectal cancer (CRC) screening, or among individuals who have previously undergone investigation for CRC, focused on reducing CRC risk through promotion of lifestyle behavior change. Additionally, this review evaluated to what extent such interventions apply behavior change techniques (BCTs) to achieve their objectives. METHODS: Five databases were systematically searched to identify randomized control trials seeking to reduce CRC risk through behavior change. Outcomes were changes in health-related lifestyle behaviors associated with CRC risk, including changes in dietary habits, body mass index, smoking behaviors, alcohol consumption, and physical activity. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were pooled using random effects models. BCT's were coded from a published taxonomy of 93 techniques. RESULTS: Ten RCT's met the inclusion criteria. Greater increase in fruit/vegetable consumption in the intervention group were observed with respect to the control (SMD 0.13, 95% CI 0.08 to 0.18; p < 0.001). Across fiber, alcohol, fat, red meat, and multivitamin consumption, and smoking behaviors, similar positive outcomes were observed (SMD 0.09-0.57 for all, p < 0.01). However, among physical activity and body mass index, no difference between the intervention groups compared with controls were observed. A median of 7.5 BCTs were applied across included interventions. CONCLUSION: While magnitude of the observed effect sizes varied, they correspond to potentially important changes in lifestyle behaviors when considered on a population scale. Future interventions should identify avenues to maximize long-term engagement to promote sustained lifestyle behavior change.

Risk-stratified screening for the early detection of kidney cancer.

Earlier detection and screening for kidney cancer has been identified as a key research priority, however the low prevalence of the disease in unselected populations limits the cost-effectiveness of screening. Risk-stratified screening for kidney cancer may improve early detection by targeting high-risk individuals whilst limiting harms in low-risk individuals, potentially increasing the cost-effectiveness of screening. A number of models have been identified which estimate kidney cancer risk based on both phenotypic and genetic data, and while several of the former have been shown to identify individuals at high-risk of developing kidney cancer with reasonable accuracy, current evidence does not support including a genetic component. Combined screening for lung cancer and kidney cancer has been proposed, as the two malignancies share some common risk factors. A modelling study estimated that using lung cancer risk models (currently used for risk-stratified lung cancer screening) could capture 25% of patients with kidney cancer, which is only slightly lower than using the best performing kidney cancer-specific risk models based on phenotypic data (27%-33%). Additionally, risk-stratified screening for kidney cancer has been shown to be acceptable to the public. The following review summarises existing evidence regarding risk-stratified screening for kidney cancer, highlighting the risks and benefits, as well as exploring the management of potential harms and further research needs.

Risk factors for subsequent primary melanoma in patients with previous melanoma: a systematic review and meta-analysis.

BACKGROUND: Compared with the general population, people with a previous melanoma are at increased risk of developing another primary melanoma. Understanding the risk factors associated with multiple primary melanomas can inform patient education and tailored surveillance. OBJECTIVES: To examine the risk factors for subsequent primary melanoma in people with a previous melanoma, by conducting a systematic review and meta-analysis of the available data. METHODS: A systematic literature search was conducted in CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), Embase and MEDLINE. Studies that reported a risk estimate or raw frequencies and conducted between 1982 and August 2022 were included. Adjusted risk estimates were prioritized over univariable risk estimates. PRISMA reporting guidelines were followed. Random effects meta-analysis was conducted to derive pooled estimates. Quality assessment was conducted by two researchers using the Newcastle-Ottawa scale. GRADE was used to rate the certainty and quality of the evidence. RESULTS: Data from 27 studies involving 413 181 participants were pooled and analysed. Risk factors assessed included age and sex, environmental, lifestyle, phenotypic, genetic and histopathological factors, and there was wide variation in how they were categorized and analysed. Independent risk factors identified from pooled analyses included male sex [hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.40-1.53], increasing age per 10 years (HR 1.19, 95% CI 1.14-1.24), light skin colour (HR 1.44, 95% CI 1.23-1.70), family history [odds ratio (OR) 1.79, 95% CI 1.25-2.56], CDKN2A mutation (OR 5.29, 95% CI 2.70-10.37), a high or moderate naevus count [OR 2.63 (95% CI 1.61-4.30) and OR 1.64 (95% CI 1.07-2.51), respectively], one or more atypical naevi (OR 3.01, 95% CI 1.52-5.97), first lesions occurring on the head or neck, lentigo maligna subtype (HR 1.16, 95% CI 1.15-1.17), other subtype (HR 1.14, 95% CI 1.03-1.27) and inadequate sun protection (HR 1.85, 95% CI 0.98-3.50). Based on the GRADE criteria, there was high to very low confidence in the pooled effect estimates. CONCLUSIONS: This meta-analysis identified several consistent, independent risk factors for the development of subsequent primary melanoma. These findings will help stratify the risk of subsequent melanoma, tailor skin-check schedules and inform patient education.

Short-term psychosocial outcomes of adding a non-contrast abdominal computed tomography (CT) scan to the thoracic CT within lung cancer screening.

OBJECTIVES: To evaluate psychological, social, and financial outcomes amongst individuals undergoing a non-contrast abdominal computed tomography (CT) scan to screen for kidney cancer and other abdominal malignancies alongside the thoracic CT within lung cancer screening. SUBJECTS AND METHODS: The Yorkshire Kidney Screening Trial (YKST) is a feasibility study of adding a non-contrast abdominal CT scan to the thoracic CT within lung cancer screening. A total of 500 participants within the YKST, comprising all who had an abnormal CT scan and a random sample of one-third of those with a normal scan between 14/03/2022 and 24/08/2022 were sent a questionnaire at 3 and 6 months. Outcomes included the Psychological Consequences Questionnaire (PCQ), the short-form of the Spielberger State-Trait Anxiety Inventory, and the EuroQoL five Dimensions five Levels scale (EQ-5D-5L). Data were analysed using regression adjusting for participant age, sex, socioeconomic status, education, baseline quality of life (EQ-5D-5L), and ethnicity. RESULTS: A total of 380 (76%) participants returned questionnaires at 3 months and 328 (66%) at 6 months. There was no difference in any outcomes between participants with a normal scan and those with abnormal scans requiring no further action. Individuals requiring initial further investigations or referral had higher scores on the negative PCQ than those with normal scans at 3 months (standardised mean difference 0.28 sd, 95% confidence interval 0.01-0.54; P = 0.044). The difference was greater in those with anxiety or depression at baseline. No differences were seen at 6 months. CONCLUSION: Screening for kidney cancer and other abdominal malignancies using abdominal CT alongside the thoracic CT within lung cancer screening is unlikely to cause significant lasting psychosocial or financial harm to participants with incidental findings.

Phenotypes and rates of cancer-relevant symptoms and tests in the year before cancer diagnosis in UK Biobank and CPRD Gold.

Early diagnosis of cancer relies on accurate assessment of cancer risk in patients presenting with symptoms, when screening is not appropriate. But recorded symptoms in cancer patients pre-diagnosis may vary between different sources of electronic health records (EHRs), either genuinely or due to differential completeness of symptom recording. To assess possible differences, we analysed primary care EHRs in the year pre-diagnosis of cancer in UK Biobank and Clinical Practice Research Datalink (CPRD) populations linked to cancer registry data. We developed harmonised phenotypes in Read v2 and CTV3 coding systems for 21 symptoms and eight blood tests relevant to cancer diagnosis. Among 22,601 CPRD and 11,594 UK Biobank cancer patients, 54% and 36%, respectively, had at least one consultation for possible cancer symptoms recorded in the year before their diagnosis. Adjusted comparisons between datasets were made using multivariable Poisson models, comparing rates of symptoms/tests in CPRD against expected rates if cancer site-age-sex-deprivation associations were the same as in UK Biobank. UK Biobank cancer patients compared with those in CPRD had lower rates of consultation for possible cancer symptoms [RR: 0.61 (0.59-0.63)], and lower rates for any primary care consultation [RR: 0.86 (95%CI 0.85-0.87)]. Differences were larger for 'non-alarm' symptoms [RR: 0.54 (0.52-0.56)], and smaller for 'alarm' symptoms [RR: 0.80 (0.76-0.84)] and blood tests [RR: 0.93 (0.90-0.95)]. In the CPRD cohort, approximately representative of the UK population, half of cancer patients had recorded symptoms in the year before diagnosis. The frequency of non-specific presenting symptoms recorded in the year pre-diagnosis of cancer was substantially lower among UK Biobank participants. The degree to which results based on highly selected biobank cohorts are generalisable needs to be examined in disease-specific contexts.

A discrete choice experiment to understand public preferences and priorities for risk-stratified bowel cancer screening programmes in the UK.

OBJECTIVE: Public acceptability of bowel cancer screening programmes must be maintained, including if risk stratification is introduced. We aimed to describe and quantify preferences for different attributes of risk-stratified screening programmes amongst the UK population, focussing on who to invite for bowel screening. METHODS: We conducted a discrete choice experiment (DCE) including the following attributes: risk factors used to estimate bowel cancer risk (age plus/minus sex, lifestyle factors and genetics); personalisation of risk feedback; risk stratification strategy plus resource implications; default screening in the case of no risk information; number of deaths prevented by screening; and number experiencing physical harm from screening. We used the results of conditional logit regression models to estimate the importance of each attribute, willingness to trade-off between the attributes, and preferences for different programmes using contemporary risk scores and models. RESULTS: 1196 respondents completed the survey, generating 21,528 DCE observations. Deaths prevented was the most influential attribute on respondents' decision-making (contributing to 58.8% of the choice), followed by harms experienced (15.9%). For every three additional deaths prevented, respondents were willing to accept an additional screening harm per 100,000 people. Risk factors and risk stratification strategy contributed to just 11.1% and 3.6% of the choice, respectively. Although the influence on decision-making was small, respondents favoured more personalised feedback. CONCLUSIONS: Bowel cancer screening programmes that improve cancer outcomes, particularly by preventing more deaths amongst those screened, are most preferred by the public. Optimising risk prediction models, developing public communication, and readying infrastructure should be prioritised for implementation.

Prioritising cardiovascular disease risk assessment to high risk individuals based on primary care records.

OBJECTIVE: To provide quantitative evidence for systematically prioritising individuals for full formal cardiovascular disease (CVD) risk assessment using primary care records with a novel tool (eHEART) with age- and sex- specific risk thresholds. METHODS AND ANALYSIS: eHEART was derived using landmark Cox models for incident CVD with repeated measures of conventional CVD risk predictors in 1,642,498 individuals from the Clinical Practice Research Datalink. Using 119,137 individuals from UK Biobank, we modelled the implications of initiating guideline-recommended statin therapy using eHEART with age- and sex-specific prioritisation thresholds corresponding to 5% false negative rates to prioritise adults aged 40-69 years in a population in England for invitation to a formal CVD risk assessment. RESULTS: Formal CVD risk assessment on all adults would identify 76% and 49% of future CVD events amongst men and women respectively, and 93 (95% CI: 90, 95) men and 279 (95% CI: 259, 297) women would need to be screened (NNS) to prevent one CVD event. In contrast, if eHEART was first used to prioritise individuals for formal CVD risk assessment, we would identify 73% and 47% of future events amongst men and women respectively, and a NNS of 75 (95% CI: 72, 77) men and 162 (95% CI: 150, 172) women. Replacing the age- and sex-specific prioritisation thresholds with a 10% threshold identify around 10% less events. CONCLUSIONS: The use of prioritisation tools with age- and sex-specific thresholds could lead to more efficient CVD assessment programmes with only small reductions in effectiveness at preventing new CVD events.

Implementation of risk stratification within bowel cancer screening: a community jury study exploring public acceptability and communication needs.

BACKGROUND: Population-based cancer screening programmes are shifting away from age and/or sex-based screening criteria towards a risk-stratified approach. Any such changes must be acceptable to the public and communicated effectively. We aimed to explore the social and ethical considerations of implementing risk stratification at three different stages of the bowel cancer screening programme and to understand public requirements for communication. METHODS: We conducted two pairs of community juries, addressing risk stratification for screening eligibility or thresholds for referral to colonoscopy and screening interval. Using screening test results (where applicable), and lifestyle and genetic risk scores were suggested as potential stratification strategies. After being informed about the topic through a series of presentations and discussions including screening principles, ethical considerations and how risk stratification could be incorporated, participants deliberated over the research questions. They then reported their final verdicts on the acceptability of risk-stratified screening and what information should be shared about their preferred screening strategy. Transcripts were analysed using codebook thematic analysis. RESULTS: Risk stratification of bowel cancer screening was acceptable to the informed public. Using data within the current system (age, sex and screening results) was considered an obvious next step and collecting additional data for lifestyle and/or genetic risk assessment was also preferable to age-based screening. Participants acknowledged benefits to individuals and health services, as well as articulating concerns for people with low cancer risk, potential public misconceptions and additional complexity for the system. The need for clear and effective communication about changes to the screening programme and individual risk feedback was highlighted, including making a distinction between information that should be shared with everyone by default and additional details that are available elsewhere. CONCLUSIONS: From the perspective of public acceptability, risk stratification using current data could be implemented immediately, ahead of more complex strategies. Collecting additional data for lifestyle and/or genetic risk assessment was also considered acceptable but the practicalities of collecting such data and how the programme would be communicated require careful consideration.

Personalised colorectal cancer screening strategies: Information needs of the target population.

Prior faecal Hemoglobin (f-Hb) concentrations of a negative fecal immunochemical test (FIT) can be used for risk stratification in colorectal cancer (CRC) screening. Individuals with higher f-Hb concentrations may benefit from a shorter screening interval (1 year), whereas individuals with undetectable f-Hb concentrations could benefit from a longer screening interval (3 year). Individuals' views on personalised CRC screening and information needed to make a well-informed decision is unknown. We conducted three semi-structured focus groups among individuals eligible for CRC screening (i.e. men and women aged 55 to 75) in the Netherlands. Thematic analysis was used to analyse participants' information need on personalised CRC screening strategies. Fourteen individuals took part. The majority were positive about CRC screening and indicated that they would participate in personalised CRC screening. The rationale for a longer interval among those at lowest risk was, however, unclear for many. The preferred information on individual risk was variable: ranging from full information to only information on the personalised strategy without mentioning the risk. It was not possible to address everyone's need with a single approach. Additional communications, e.g. public media campaigns, billboards, videos on social media, were also suggested as necessary. This study showed that preferences on receiving information on individual CRC risk varied substantially and no consensus was reached. Introducing a personalised screening programme will require careful communication, particularly around the rationale for the strategy, and a layered approach to deliver information.

Using Polygenic Risk Scores for Prioritizing Individuals at Greatest Need of a Cardiovascular Disease Risk Assessment.

Background The aim of this study was to provide quantitative evidence of the use of polygenic risk scores for systematically identifying individuals for invitation for full formal cardiovascular disease (CVD) risk assessment. Methods and Results A total of 108 685 participants aged 40 to 69 years, with measured biomarkers, linked primary care records, and genetic data in UK Biobank were used for model derivation and population health modeling. Prioritization tools using age, polygenic risk scores for coronary artery disease and stroke, and conventional risk factors for CVD available within longitudinal primary care records were derived using sex-specific Cox models. We modeled the implications of initiating guideline-recommended statin therapy after prioritizing individuals for invitation to a formal CVD risk assessment. If primary care records were used to prioritize individuals for formal risk assessment using age- and sex-specific thresholds corresponding to 5% false-negative rates, then the numbers of men and women needed to be screened to prevent 1 CVD event are 149 and 280, respectively. In contrast, adding polygenic risk scores to both prioritization and formal assessments, and selecting thresholds to capture the same number of events, resulted in a number needed to screen of 116 for men and 180 for women. Conclusions Using both polygenic risk scores and primary care records to prioritize individuals at highest risk of a CVD event for a formal CVD risk assessment can efficiently prioritize those who need interventions the most than using primary care records alone. This could lead to better allocation of resources by reducing the number of risk assessments in primary care while still preventing the same number of CVD events.