Utility of polygenic risk scores in UK cancer screening: a modelling analysis.

BACKGROUND: It is proposed that, through restriction to individuals delineated as high risk, polygenic risk scores (PRSs) might enable more efficient targeting of existing cancer screening programmes and enable extension into new age ranges and disease types. To address this proposition, we present an overview of the performance of PRS tools (ie, models and sets of single nucleotide polymorphisms) alongside harms and benefits of PRS-stratified cancer screening for eight example cancers (breast, prostate, colorectal, pancreas, ovary, kidney, lung, and testicular cancer). METHODS: For this modelling analysis, we used age-stratified cancer incidences for the UK population from the National Cancer Registration Dataset (2016-18) and published estimates of the area under the receiver operating characteristic curve for current, future, and optimised PRS for each of the eight cancer types. For each of five PRS-defined high-risk quantiles (ie, the top 50%, 20%, 10%, 5%, and 1%) and according to each of the three PRS tools (ie, current, future, and optimised) for the eight cancers, we calculated the relative proportion of cancers arising, the odds ratios of a cancer arising compared with the UK population average, and the lifetime cancer risk. We examined maximal attainable rates of cancer detection by age stratum from combining PRS-based stratification with cancer screening tools and modelled the maximal impact on cancer-specific survival of hypothetical new UK programmes of PRS-stratified screening. FINDINGS: The PRS-defined high-risk quintile (20%) of the population was estimated to capture 37% of breast cancer cases, 46% of prostate cancer cases, 34% of colorectal cancer cases, 29% of pancreatic cancer cases, 26% of ovarian cancer cases, 22% of renal cancer cases, 26% of lung cancer cases, and 47% of testicular cancer cases. Extending UK screening programmes to a PRS-defined high-risk quintile including people aged 40-49 years for breast cancer, 50-59 years for colorectal cancer, and 60-69 years for prostate cancer has the potential to avert, respectively, a maximum of 102, 188, and 158 deaths annually. Unstratified screening of the full population aged 48-49 years for breast cancer, 58-59 years for colorectal cancer, and 68-69 years for prostate cancer would use equivalent resources and avert, respectively, an estimated maximum of 80, 155, and 95 deaths annually. These maximal modelled numbers will be substantially attenuated by incomplete population uptake of PRS profiling and cancer screening, interval cancers, non-European ancestry, and other factors. INTERPRETATION: Under favourable assumptions, our modelling suggests modest potential efficiency gain in cancer case detection and deaths averted for hypothetical new PRS-stratified screening programmes for breast, prostate, and colorectal cancer. Restriction of screening to high-risk quantiles means many or most incident cancers will arise in those assigned as being low-risk. To quantify real-world clinical impact, costs, and harms, UK-specific cluster-randomised trials are required. FUNDING: The Wellcome Trust.

'You feel like you've been duped': is the current system for health professionals declaring potential conflicts of interest in the UK fit for purpose? A mixed methods study.

OBJECTIVE: To understand: if professionals, citizens and patients can locate UK healthcare professionals' statements of declarations of interests, and what citizens understand by these. DESIGN: The study sample included two groups of participants in three phases. First, healthcare professionals working in the public domain (health professional participants, HPP) were invited to participate. Their conflicts and declarations of interest were searched for in publicly available data, which the HPP checked and confirmed as the 'gold standard'. In the second phase, laypeople, other healthcare professionals and healthcare students were invited to complete three online tasks. The first task was a questionnaire about their own demographics. The second task was questions about doctors' conflicts of interest in clinical vignette scenarios. The third task was a request for each participant to locate and describe the declarations of interest of one of the named healthcare professionals identified in the first phase, randomly assigned. At the end of this task, all lay participants were asked to indicate willingness to be interviewed at a later date. In the third phase, each lay respondent who was willing to be contacted was invited to a qualitative interview to obtain their views on the conflicts and declaration of interest they found and their meaning. SETTING: Online, based in the UK. PARTICIPANTS: 13 public-facing health professionals, 379 participants (healthcare professionals, students and laypeople), 21 lay interviewees. OUTCOME MEASURES: (1) Participants' level of trust in professionals with variable conflicts of interest, as expressed in vignettes, (2) participants' ability to locate the declarations of interest of a given well-known healthcare professional and (3) laypeoples' understanding of healthcare professionals declarations and conflicts of interest. RESULTS: In the first phase, 13 health professionals (HPP) participated and agreed on a 'gold standard' of their declarations. In the second phase, 379 citizens, patients, other healthcare professionals and students participated. Not all completed all aspects of the research. 85% of participants thought that knowing about professional declarations was definitely or probably important, but 76.8% were not confident they had found all relevant information after searching. As conflicts of interest increased in the vignettes, participants trusted doctors less. Least trust was associated with doctors who had not disclosed their conflicts of interest. 297 participants agreed to search for the HPP 'gold standard' declaration of interest, and 169 reported some data. Of those reporting any findings, 61 (36%) located a relevant link to some information deemed fit for purpose, and 5 (3%) participants found all the information contained in the 'gold standard'. In the third phase, qualitative interviews with 21 participants highlighted the importance of transparency but raised serious concerns about how useful declarations were in their current format, and whether they could improve patient care. Unintended consequences, such as the burden for patients and professionals to use declarations were identified, with participants additionally expressing concerns about professional bias and a lack of insight over conflicts. Suggestions for improvements included better regulation and organisation, but also second opinions and independent advice where conflicts of interest were suspected. CONCLUSION: Declarations of interest are important and conflicts of interest concern patients and professionals, particularly in regard to trust in decision-making. If declarations, as currently made, are intended to improve transparency, they do not achieve this, due to difficulties in locating and interpreting them. Unintended consequences may arise if transparency alone is assumed to provide management of conflicts. Increased trust resulting from transparency may be misplaced, given the evidence on the hazards associated with conflicts of interest. Clarity about the purposes of transparency is required. Future policies may be more successful if focused on reducing the potential for negative impacts of conflicts of interest, rather than relying on individuals to locate declarations and interpret them. TRIAL REGISTRATION NUMBER: The protocol was pre-registered at https://osf.io/e7gtq.

Investigation into financial conflicts of interest and screening for atrial fibrillation in the UK: a cross-sectional study.

OBJECTIVE: To understand the relationship between financial conflicts of interest and recommendations for atrial fibrillation (AF) screening in the UK, via examining (1) if the UK media recommend for or against screening for AF, and (2) the financial conflicts of interests of AF screening commentators. DESIGN: Cross-sectional study. SETTING/PARTICIPANTS: References in UK mainstream media, Twitter, the UK's National Health Service (NHS), patient information websites and major UK heart-related charities regarding screening for AF between1 January 2018 and 31 July 2021. OUTCOME MEASURES: Proportion of references advocating for, against and presenting balanced/neutral views on screening. Proportion of references citing commentators with financial conflicts of interest. RESULTS: 217 media stories were identified, containing 284 comments about screening for AF. 185/217 (85.3%) of articles were in favour, 9 (4.1%) were against and 23 (10.6%) were balanced. Quotations within were located from 194 commentators; 44 were quoted more than once. 41/44 (93.2%) were in favour of screening. Of these 41, 37 (90.2%) had a direct or indirect financial conflict of interest, including that due to a work role. Two were balanced and one was negative. 2553 tweets using 3 hashtags promoting screening were analysed. 2119 (83%) of the most impactful tweets promoting AF screening were by industry or organisations with industry funding. Of 23 NHS organisations holding information about funding and promoting AF screening online, 22 (96%) had industry funding. 9 (90%) of the top 10 patient information websites promoting AF screening had industry funding. Four main UK patient charities in this sector promoting screening received industry funding. CONCLUSIONS: The vast majority of UK media promotes screening for AF, in contrast to the position of the independent UK National Screening Committee, which recommends against screening. Most commentators, internal NHS organisations and UK charities promoting screening had a direct or indirect financial conflict of interest. Independent information was rare. The reasons for this are unknown. Readers should consider the potential for the impact of financial conflicts on recommendations to screen.

Policies on doctors' declaration of interests in medical organisations: a thematic analysis.

OBJECTIVES: There has been growing concern about doctors' conflicts of interests (COIs) but it is unclear what processes and tools exist to enable the consistent declaration and management of such interests. This study mapped existing policies across a variety of organisations and settings to better understand the degree of variation and identify opportunities for improvement. DESIGN: Thematic analysis. SETTING: We studied the COI policies of 31 UK and international organisations which set or influence professional standards or engage doctors in healthcare commissioning and provision settings. PARTICIPANTS: 31 UK and international organisations. MAIN OUTCOME MEASURES: Organisational policy similarities and differences. RESULTS: Most policies (29/31) referred to the need for individuals to apply judgement when deciding whether an interest is a conflict, with just over half (18/31) advocating a low threshold. Policies differed on the perception of frequency of COI, the timings of declarations, the type of interests that needed to be declared, and how COI and policy breaches should be managed. Just 14/31 policies stated a duty to report concerns in relation to COI. Only 18/31 policies advised COI would be published, while three stated that any disclosures would remain confidential. CONCLUSIONS: The analysis of organisational policies revealed wide variation in what interests should be declared, when and how. This variation suggests that the current system may not be adequate to maintain a high level of professional integrity in all settings and that there is a need for better standardisation that reduces the risk of errors while addressing the needs of doctors, organisations and the public.

How are declarations of interest working? A cross-sectional study in declarations of interest in healthcare practice in Scotland and England in 2020/2021.

OBJECTIVE: To understand arrangements for healthcare organisations' declarations of staff interest in Scotland and England in the context of current recommendations. DESIGN: Cross-sectional study of a random selection of National Health Service (NHS) hospital registers of interest by two independent observers in England, all NHS Boards in Scotland and a random selection of Clinical Commissioning Groups (CCGs) in England. SETTING: NHS Trusts in England (NHSE), NHS Boards in Scotland, CCGs in England, and private healthcare organisations. PARTICIPANTS: Registers of declarations of interest published in a random sample of 67 of 217 NHS Trusts, a random sample of 15 CCGs of in England, registers held by all 14 NHS Scotland Boards and a purposeful selection of private hospitals/clinics in the UK. MAIN OUTCOME MEASURES: Adherence to NHSE guidelines on declarations of interests, and comparison in Scotland. RESULTS: 76% of registers published by Trusts did not routinely include all declaration of interest categories recommended by NHS England. In NHS Scotland only 14% of Boards published staff registers of interest. Of these employee registers (most obtained under Freedom of Information), 27% contained substantial retractions. In England, 96% of CCGs published a Gifts and Hospitality register, with 67% of CCG staff declaration templates and 53% of governor registers containing full standard NHS England declaration categories. Single organisations often held multiple registers lacking enough information to interpret them. Only 35% of NHS Trust registers were organised to enable searching. None of the private sector organisations studied published a comparable declarations of interest register. CONCLUSION: Despite efforts, the current system of declarations frequently lacks ability to meaningfully obtain complete healthcare professionals' declaration of interests.