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Abstract Background Although the challenges of recruiting to randomised controlled trials (RCTs) are well documented, few studies have focused on the impact that the communication between recruiters and patients has on patients’ participation decisions. Recruiters are thought to influence patient decision-making, but the mechanisms by which this occurs are unclear. The aim of this research was to investigate how patients interpret and use the information conveyed to them by healthcare professionals (HCPs) in trial participation decisions. Methods Three pragmatic UK-based multicentre RCTs were purposively sampled to provide contrasting clinical specialities. Data collection was integrated into each RCT, including audio-recordings of patient recruitment consultations and interviews with patients. Where possible, consultation audio-recordings were linked to interviews to explore how information communicated by recruiters was interpreted and used by patients during their decision-making. Data were analysed thematically, using the constant comparison approach. Results Twenty audio-recorded recruitment consultations were obtained across the 3 RCTs, combined with 42 interviews with patients who had consented to or declined RCT participation. Consultation and interview data were ‘linked’ for 17 individual patients. Throughout the patient’s clinical pathway, HCPs (both those involved in the RCT and not) influenced patients’ perceptions of treatment need and benefit by indicating that they preferred a particular treatment option for the patient as an individual. Whilst patients valued and were influenced by information conveyed by HCPs, they also drew on support from other sources and ultimately framed RCT participation decisions as their own. Patients’ willingness to be randomised hinged on perceptions of whether they stood to benefit from a particular treatment and the availability of those treatments outside of the trial. Conclusion This study supports the need for training and support for healthcare professionals involved throughout the clinical pathway of patients eligible for RCTs, as all healthcare professionals who interact with patients have the potential to influence their perceptions of treatments being compared in the trial. Trial registration OPTIMA ISRCTN42400492. Prospectively registered on 26 June 2012. Prepare for Kidney Care ISRCTN17133653. Prospectively registered on 31 May 2017. MARS 2 ISRCTN44351742. Retrospectively registered on 5 September 2018.

Abstract Background Screening men for prostate cancer using prostate-specific antigen (PSA) testing remains controversial. We aimed to estimate the likely budgetary impact on secondary care in England and Wales to inform screening decision makers. Methods The Cluster randomised triAl of PSA testing for Prostate cancer study (CAP) compared a single invitation to men aged 50–69 for a PSA test with usual care (no screening). Routinely collected hospital care data were obtained for all men in CAP, and NHS reference costs were mapped to each event via Healthcare Resource Group (HRG) codes. Secondary-care costs per man per year were calculated, and cost differences (and population-level estimates) between arms were derived annually for the first five years following randomisation. Results In the first year post-randomisation, secondary-care costs averaged across all men (irrespective of a prostate cancer diagnosis) in the intervention arm (n = 189279) were £44.80 (95% confidence interval: £18.30-£71.30) higher than for men in the control arm (n = 219357). Extrapolated to a population level, the introduction of a single PSA screening invitation could lead to additional secondary care costs of £314 million. Conclusions Introducing a single PSA screening test for men aged 50–69 across England and Wales could lead to very high initial secondary-care costs.

Summary: Background: Tumour-promoting inflammation is a “hallmark” of cancer and conventional epidemiological studies have reported links between various inflammatory markers and cancer risk. The causal nature of these relationships and, thus, the suitability of these markers as intervention targets for cancer prevention is unclear. Methods: We meta-analysed 6 genome-wide association studies of circulating inflammatory markers comprising 59,969 participants of European ancestry. We then used combined cis-Mendelian randomization and colocalisation analysis to evaluate the causal role of 66 circulating inflammatory markers in risk of 30 adult cancers in 338,294 cancer cases and up to 1,238,345 controls. Genetic instruments for inflammatory markers were constructed using genome-wide significant (P 70% was employed to indicate support for shared causal variants across inflammatory markers and cancer outcomes. Findings were replicated in the FinnGen study and then pooled using meta-analysis. Findings: We found strong evidence to support an association of genetically-proxied circulating pro-adrenomedullin concentrations with increased breast cancer risk (OR: 1.19, 95% CI: 1.10–1.29, q-value = 0.033, PPH4 = 84.3%) and suggestive evidence to support associations of interleukin-23 receptor concentrations with increased pancreatic cancer risk (OR: 1.42, 95% CI: 1.20–1.69, q-value = 0.055, PPH4 = 73.9%), prothrombin concentrations with decreased basal cell carcinoma risk (OR: 0.66, 95% CI: 0.53–0.81, q-value = 0.067, PPH4 = 81.8%), and interleukin-1 receptor-like 1 concentrations with decreased triple-negative breast cancer risk (OR: 0.92, 95% CI: 0.88–0.97, q-value = 0.15, PPH4 = 85.6%). These findings were replicated in pooled analyses with the FinnGen study. Though suggestive evidence was found to support an association of macrophage migration inhibitory factor concentrations with increased bladder cancer risk (OR: 2.46, 95% CI: 1.48–4.10, q-value = 0.072, PPH4 = 76.1%), this finding was not replicated when pooled with the FinnGen study. For 22 of 30 cancer outcomes examined, there was little evidence (q-value ≥0.20) that any of the 66 circulating inflammatory markers examined were associated with cancer risk. Interpretation: Our comprehensive joint Mendelian randomization and colocalisation analysis of the role of circulating inflammatory markers in cancer risk identified potential roles for 4 circulating inflammatory markers in risk of 4 site-specific cancers. Contrary to reports from some prior conventional epidemiological studies, we found little evidence of association of circulating inflammatory markers with the majority of site-specific cancers evaluated. Funding: Cancer Research UK (C68933/A28534, C18281/A29019, PPRCPJT∖100005), World Cancer Research Fund (IIG_FULL_2020_022), National Institute for Health Research (NIHR202411, BRC-1215-20011), Medical Research Council (MC_UU_00011/1, MC_UU_00011/3, MC_UU_00011/6, and MC_UU_00011/4), Academy of Finland Project 326291, European Union's Horizon 2020 grant agreement no. 848158 (EarlyCause), French National Cancer Institute (INCa SHSESP20, 2020-076), Versus Arthritis (21173, 21754, 21755), National Institutes of Health (U19 CA203654), National Cancer Institute (U19CA203654).

Abstract Background A quality improvement strategy (PReCePT) was used in a standard and enhanced format to scale up a clinical intervention (administering magnesium sulphate to women in preterm labour) across all maternity units in England to protect prematurely born infants from neurodevelopmental disabilities. Formal evaluations reported the effectiveness of the standard package alone in increasing the administration of magnesium sulphate. In this paper, we focus on the findings of the process evaluations, using normalisation process theory to explain how different implementation contexts generated the observed outcomes relating to normative and relational restructuring and sustainment. Methods Interviews were conducted with key individuals in implementation of leadership positions nationally and locally. Interviews were analysed initially using the framework method. We then engaged recursively with NPT constructs to generate generalisable insights with pragmatic applicability in other settings. Results In total, 72 interviews were conducted with good representation from units across England and staff from the National Academic Health Science Network. We found that all units irrespective of whether they received a standard or enhanced QI package were successful in the ‘normative restructuring’ of their setting to enable magnesium sulphate to be administered. This suggests that this implementation outcome is necessary to achieve improvements. However, it may not be sufficient to sustain the changes once additional resources have been withdrawn. Sustainment, our findings suggest, required ‘relational restructuring’ to accommodate altered workflows and facilitate the sharing of responsibilities and tasks in daily practice. Relational restructuring was more likely to have been achieved units receiving enhanced QI support but also happened in units with standard QI support, especially in those where perinatal team working was already well established. Conclusion Unlike other large QI-focused spread-and-scale programmes which failed to show any impact on outcomes, the PReCePT programme in both the enhanced and standard support packages led to improvements in the uptake of magnesium sulphate. The findings suggest that QI programmes interact with the enabling factors, such as strong interprofessional team working, already present in the setting. A standard package with minimal support was therefore sufficient in settings with enabling factors, but enhanced support was required in units where these were absent.

Abstract Background Recruiting patients to randomised controlled trials (RCTs) is often reported to be challenging, and the evidence base for effective interventions that could be used by staff (recruiters) undertaking recruitment is lacking. Although the experiences and perspectives of recruiters have been widely reported, an evidence synthesis is required in order to inform the development of future interventions. This paper aims to address this by systematically searching and synthesising the evidence on recruiters’ perspectives and experiences of recruiting patients into RCTs. Methods A qualitative evidence synthesis (QES) following Thomas and Harden’s approach to thematic synthesis was conducted. The Ovid MEDLINE, CINAHL, EMBASE, PsycInfo, Cochrane Central Register of Controlled Trials, ORRCA and Web of Science electronic databases were searched. Studies were sampled to ensure that the focus of the research was aligned with the phenomena of interest of the QES, their methodological relevance to the QES question, and to include variation across the clinical areas of the studies. The GRADE CERQual framework was used to assess confidence in the review findings. Results In total, 9316 studies were identified for screening, which resulted in 128 eligible papers. The application of the QES sampling strategy resulted in 30 papers being included in the final analysis. Five overlapping themes were identified which highlighted the complex manner in which recruiters experience RCT recruitment: (1) recruiting to RCTs in a clinical environment, (2) enthusiasm for the RCT, (3) making judgements about whether to approach a patient, (4) communication challenges, (5) interplay between recruiter and professional roles. Conclusions This QES identified factors which contribute to the complexities that recruiters can face in day-to-day clinical settings, and the influence recruiters and non-recruiting healthcare professionals have on opportunities afforded to patients for RCT participation. It has reinforced the importance of considering the clinical setting in its entirety when planning future RCTs and indicated the need to better normalise and support research if it is to become part of day-to-day practice. Trial registration PROSPERO CRD42020141297 (registered 11/02/2020).

Abstract Background Health optimisation programmes are increasingly popular and aim to support patients to lose weight or stop smoking ahead of surgery, yet there is little published evidence about their impact. This study aimed to assess the feasibility of evaluating a programme introduced by a National Health Service (NHS) clinical commissioning group offering support to smokers/obese patients in an extra 3 months prior to the elective hip/knee surgery pathway. Methods Feasibility study mapping routinely collected data sources, availability and completeness for 502 patients referred to the hip/knee pathway in February–July 2018. Results Data collation across seven sources was complex. Data completeness for smoking and ethnicity was poor. While 37% (184) of patients were eligible for health optimisation, only 28% of this comparatively deprived patient group accepted referral to the support offered. Patients who accepted referral to support and completed the programme had a larger median reduction in BMI than those who did not accept referral (− 1.8 BMI points vs. − 0.5). Forty-nine per cent of patients who accepted support were subsequently referred to surgery, compared to 61% who did not accept referral to support. Conclusions Use of routinely collected data to evaluate health optimisation programmes is feasible though demanding. Indications of the positive effects of health optimisation interventions from this study and existing literature suggest that the challenge of programme evaluation should be prioritised; longer-term evaluation of costs and outcomes is warranted to inform health optimisation policy development.

Abstract Background Many randomised controlled trials (RCTs) struggle to recruit, despite valiant efforts. The QRI (QuinteT Recruitment Intervention) uses innovative research methods to optimise recruitment by revealing previously hidden barriers related to the perceptions and experiences of recruiters and patients, and targeting remedial actions. It was designed to be integrated with RCTs anticipating difficulties at the outset. A new version of the intervention (QRI-Two) was developed for RCTs already underway with enrolment shortfalls. Methods QRIs in 12 RCTs with enrolment shortfalls during 2007–2017 were reviewed to document which of the research methods used could be rapidly applied to successfully identify recruitment barriers. These methods were then included in the new streamlined QRI-Two intervention which was applied in 20 RCTs in the USA and Europe during 2018–2019. The feasibility of the QRI-Two was investigated, recruitment barriers and proposed remedial actions were documented, and the QRI-Two protocol was finalised. Results The review of QRIs from 2007 to 2017 showed that previously unrecognised recruitment barriers could be identified but data collection for the full QRI required time and resources usually unavailable to ongoing RCTs. The streamlined QRI-Two focussed on analysis of screening/accrual data and RCT documents (protocol, patient-information), with discussion of newly diagnosed barriers and potential remedial actions in a workshop with the RCT team. Four RCTs confirmed the feasibility of the rapid application of the QRI-Two. When the QRI-Two was applied to 14 RCTs underway with enrolment shortfalls, an array of previously unknown/underestimated recruitment barriers related to issues such as equipoise, intervention preferences, or study presentation was identified, with new insights into losses of eligible patients along the recruitment pathway. The QRI-Two workshop enabled discussion of the newly diagnosed barriers and potential remedial actions to improve recruitment in collaboration with the RCT team. As expected, the QRI-Two performed less well in six RCTs at the start-up stage before commencing enrolment. Conclusions The QRI-Two can be applied rapidly, diagnose previously unrecognised recruitment barriers, and suggest remedial actions in RCTs underway with enrolment shortfalls, providing opportunities for RCT teams to develop targeted actions to improve recruitment. The effectiveness of the QRI-Two in improving recruitment requires further evaluation.

Background Health systems are under pressure to maintain services within limited resources. The Evidence-Based Interventions (EBI) programme published a first list of guidelines in 2019, which aimed to reduce inappropriate use of interventions within the NHS in England, reducing potential harm and optimising the use of limited resources. Seventeen procedures were selected in the first round, published in April 2019. Methods We evaluated changes in the trends for each procedure after its inclusion in the EBI’s first list of guidelines using interrupted time series analysis. We explored whether there was any evidence of spill-over effects onto related or substitute procedures, as well as exploring changes in geographical variation following the publication of national guidance. Results Most procedures were experiencing downward trends in the years prior to the launch of EBI. We found no evidence of a trend change in any of the 17 procedures following the introduction of the guidance. No evidence of spill-over increases in substitute or related procedures was found. Geographic variation in the number of procedures performed across English CCGs remained at similar levels before and after EBI. Conclusions The EBI programme had little success in its aim to further reduce the use of the 17 procedures it deemed inappropriate in all or certain circumstances. Most procedure rates were already decreasing before EBI and all continued with a similar trend afterwards. Geographical variation in the number of procedures remained at a similar level post EBI. De-adoption of inappropriate care is essential in maintaining health systems across the world. However, further research is needed to explore context specific enablers and barriers to effective identification and de-adoption of such inappropriate health care to support future de-adoption endeavours.

A key challenge for qualitative methods in applied health research is the fast pace that can characterize the public health and health and care service landscape, where there is a need for research informed by immediate pragmatic questions and relevant findings are required quickly to inform decision-making. The COVID-19 pandemic accelerated the pace at which evidence was needed to inform urgent public health and healthcare decision-making. This required qualitative researchers to step up to the challenge of conducting research at speed whilst maintaining rigor and ensuring the findings are credible. This article illustrates how working with multidisciplinary, collaborative teams and the tailoring of qualitative methods to be more pragmatic and efficient can provide timely and credible results. Using time-limited case studies of applied qualitative health research drawn from the work of the Behavioral and Qualitative Science Team from the National Institute for Health and Care Research Applied Research Collaboration West (NIHR ARC West), we illustrate our collaborative and intensive pragmatic qualitative (CLIP-Q) approach. CLIP-Q involves (i) collaboration at all stages of the design, conduct and implementation of projects and, where possible, co-production with people with lived experience, (ii) an intensive team-based approach to data collection and analysis at pace, and (iii) pragmatic study design and efficient strategies at each stage of the research process. The case studies include projects conducted pre COVID-19 and during the first wave of the pandemic, where urgent evidence was required in weeks rather than months to inform rapid public health and healthcare decision making.

A polygenic hazard score (PHS1) improves prostate cancer screening accuracy in European patients. Here, the authors test the performance of a version compatible with OncoArray genotypes (PHS2) in a multi-ethnic dataset and find that it risk-stratifies men for any, aggressive, and fatal prostate cancer.

Abstract Obesity is associated with an increased risk of advanced, recurrent and fatal prostate cancer. Adipokines may mediate this relationship. We conducted a systematic review and meta-analysis of associations of leptin and adiponectin with overall and aggressive prostate cancer. Bibliographic databases were systematically searched up to 1st April 2017. Log Odds Ratios (ORs) per 2.5 unit increase in adiponectin or leptin levels were derived and pooled. All analyses were stratified by study type (cross-sectional/prospective). 746 papers were retrieved, 34 eligible studies identified, 31 of these could be included in the meta-analysis. Leptin was not consistently associated with overall prostate cancer (pooled OR 1.00, 95%CI 0.98–1.02, per 2.5 ng/ml increase, prospective study OR 0.97, 95%CI 0.95–0.99, cross-sectional study OR 1.19, 95%CI 1.13–1.26) and there was weak evidence of a positive association with aggressive disease (OR 1.03, 95%CI 1.00–1.06). There was also weak evidence of a small inverse association of adiponectin with overall prostate cancer (OR 0.96, 95%CI 0.93–0.99, per 2.5 µg/ml increase), but less evidence of an association with aggressive disease (OR 0.98, 95%CI 0.94–1.01). The magnitude of any effects are small, therefore levels of circulating adiponectin or leptin alone are unlikely to be useful biomarkers of risk or prognosis.

Abstract Background The utility of patient screening logs and their impact on improving trial recruitment rates are unclear. We conducted a retrospective exploratory analysis of screening data collected within a multicentre randomised controlled trial investigating chemotherapy for upper tract urothelial carcinoma. Methods Participating centres maintained a record of patients meeting basic screening criteria stipulated in the trial protocol, submitting logs regularly to the clinical trial coordinating centre (CTC). Sites recorded the number of patients ineligible, not approached, declined and randomised. The CTC monitored proportions of eligible patients, approach rate (proportion of eligible patients approached) and acceptance rate (proportion recruited of those approached). Data were retrospectively analysed to identify patterns of screening activity and correlation with recruitment. Results Data were collected between May 2012 and August 2016, during which time 71 sites were activated—a recruitment period of 2768 centre months. A total of 1138 patients were reported on screening logs, with 2300 requests for logs sent by the CTC and 47% of expected logs received. A total of 758 patients were reported as ineligible, 36 eligible patients were not approached and 207 declined trial participation. The approach rate was 91% (344/380), and the acceptance rate was 40% (137/344); these rates remained consistent throughout the data collection. The main reason patients provided for declining (99/207, 48%) was not wanting to receive chemotherapy. There was a moderately strong correlation (r = 0.47) between the number reported on screening logs and the number recruited per site. Considerable variation in data between centres was observed, and 54/191 trial participants (28%) enrolled during this period were not reported on logs. Conclusions Central collection of screening logs can identify reasons for patients declining trial participation and help monitor trial activity at sites; however, obtaining complete data can be challenging. There was a correlation between the number of patients reported on logs and recruitment; however, this was likely confounded by sites’ available patient population. The use of screening logs may not be appropriate for all trials, and their use should be carefully considered in relation to the associated workload. No evidence was found that central collection of screening logs improved recruitment rates in this study, and their continued use warrants further investigation. Trial registration ISRCTN98387754 . Registered on 31 January 2012

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Abstract Background Recruitment to randomised controlled trials (RCTs) is challenging. Pre-trial qualitative research provides insights into the feasibility and acceptability of proposed trial designs and delivery; however, this is rarely conducted. This paper reports on work undertaken in advance of the Prepare for Kidney Care trial (formerly PrepareME), which compares preparing for dialysis with preparing for conservative care for patients with chronic kidney disease. The paper describes how the findings refined plans for the forthcoming trial. Methods Semi-structured interviews were undertaken with health-care professionals involved in delivering or recruiting to the trial. Interview findings were considered in relation to observations of a patient advisory group workshop and introductory site visits, which were set up to present the trial to professionals involved in the internal pilot phase of the RCT. The use of findings and input from multiple sources was intended to support suggested refinements to the forthcoming trial. The findings were fed back to the trial management group and other expert stakeholders. Results Sixteen health-care professionals were interviewed, and one patient advisory group workshop and six introductory visits to sites involved in the internal pilot were observed. The professionals interviewed included renal consultants, nurses and renal social workers. Key themes identified from the interviews, supported by the observations, were concerns around the eligibility criteria, the feasibility of the trial intervention, imbalances in the presentation of the trial arms, and anticipated recruitment issues arising from patients’ and clinicians’ preferences for one arm or the other. Changes to the design were made in response, including to the content of the intervention, the presentation of the trial arms and the name of the RCT. Conclusions This study highlights the value of carrying out pre-trial work with health-care professionals to identify issues with delivering the proposed trial. This work can be particularly valuable in trials of new interventions, for which the barriers to their integration into routine care are unknown. This work has important implications for facilitating the identification of further obstacles in the main RCT. We suggest that pre-trial qualitative work is undertaken to address design issues early on, in addition to ongoing qualitative research to monitor the emergence of obstacles affecting recruitment.

The original version of this Article contained an error in the spelling of the author Manuela Gago-Dominguez, which was incorrectly given as Manuela G. Dominguez. This has now been corrected in both the PDF and HTML versions of the Article.

Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.

Chromosome 8q24 is known to be a major susceptibility region for prostate cancer risk. Here the authors analyze genetic data across the 8q24 region from 71,535 prostate cancer patients identifying 12 risk loci, three previously unreported, highlighting the contribution of germline variation at this locus.

Prostate cancer (PrCa) involves a large heritable genetic component. Here, the authors perform multivariate fine-mapping of known PrCa GWAS loci, identifying variants enriched for biological function, explaining more familial relative risk, and with potential application in clinical risk profiling.

Abstract Background Research has shown that recruitment to trials is a process that stretches from identifying potentially eligible patients, through eligibility assessment, to obtaining informed consent. The length and complexity of this pathway means that many patients do not have the opportunity to consider participation. This article presents the development of a simple framework to document, understand and improve the process of trial recruitment. Methods Eight RCTs integrated a QuinteT Recruitment Intervention (QRI) into the main trial, feasibility or pilot study. Part of the QRI required mapping the patient recruitment pathway using trial-specific screening and recruitment logs. A content analysis compared the logs to identify aspects of the recruitment pathway and process that were useful in monitoring and improving recruitment. Findings were synthesised to develop an optimised simple framework that can be used in a wide range of RCTs. Results The eight trials recorded basic information about patients screened for trial participation and randomisation outcome. Three trials systematically recorded reasons why an individual was not enrolled in the trial, and further details why they were not eligible or approached, or declined randomisation. A framework to facilitate clearer recording of the recruitment process and reasons for non-participation was developed: SEAR – Screening, to identify potentially eligible trial participants; Eligibility, assessed against the trial protocol inclusion/exclusion criteria; Approach, the provision of oral and written information and invitation to participate in the trial, and Randomised or not, with the outcome of randomisation or treatment received. Conclusions The SEAR framework encourages the collection of information to identify recruitment obstacles and facilitate improvements to the recruitment process. SEAR can be adapted to monitor recruitment to most RCTs, but is likely to add most value in trials where recruitment problems are anticipated or evident. Further work to test it more widely is recommended.

Abstract Background There is ongoing debate about the harms and benefits of a national prostate cancer screening programme. Several model-based cost-effectiveness analyses have been developed to determine whether the benefits of prostate cancer screening outweigh the costs and harms caused by over-detection and over-treatment, and the different approaches may impact results. Methods To identify models of prostate cancer used to assess the cost-effectiveness of prostate cancer screening strategies, a systematic review of articles published since 2006 was conducted using the NHS Economic Evaluation Database, Medline, EMBASE and HTA databases. The NICE website, UK National Screening website, reference lists from relevant studies were also searched and experts contacted. Key model features, inputs, and cost-effectiveness recommendations were extracted. Results Ten studies were included. Four of the studies identified some screening strategies to be potentially cost-effective at a PSA threshold of 3.0 ng/ml, including single screen at 55 years, annual or two yearly screens starting at 55 years old, and delayed radical treatment. Prostate cancer screening was modelled using both individual and cohort level models. Model pathways to reflect cancer progression varied widely, Gleason grade was not always considered and clinical verification was rarely outlined. Where quality of life was considered, the methods used did not follow recommended practice and key issues of overdiagnosis and overtreatment were not addressed by all studies. Conclusion The cost-effectiveness of prostate cancer screening is unclear. There was no consensus on the optimal model type or approach to model prostate cancer progression. Due to limited data availability, individual patient-level modelling is unlikely to increase the accuracy of cost-effectiveness results compared with cohort-level modelling, but is more suitable when assessing adaptive screening strategies. Modelling prostate cancer is challenging and the justification for the data used and the approach to modelling natural disease progression was lacking. Country-specific data are required and recommended methods used to incorporate quality of life. Influence of data inputs on cost-effectiveness results need to be comprehensively assessed and the model structure and assumptions verified by clinical experts.

Abstract Background Surgical site infections (SSIs) are common, occurring in up to 25% of > 4 million operations performed in England each year. Previous trials of the effect of wound dressings on the risk of developing a SSI are of poor quality and underpowered. Methods/Design This study is a feasibility and pilot trial to examine the feasibility of a full trial that will compare simple dressings, no dressing and tissue-glue as a dressing. It is examining the overall acceptability of trial participation, identifying opportunities for refinement, testing the feasibility of and validating new outcome tools to assess SSI, wound management issues and patients’ wound symptom experiences. It is also exploring methods for avoiding performance bias and blinding outcome assessors by testing the feasibility of collecting wound photographs taken in theatre immediately after wound closure and, at 4–8 weeks after surgery, taken by participants themselves or their carers. Finally, it is identifying the main cost drivers for an economic evaluation of dressing types. Integrated qualitative research is exploring acceptability and reasons for non-adherence to allocation. Adults undergoing primary elective or unplanned abdominal general surgery or Caesarean section are eligible. The main exclusion criteria are abdominal or other major surgery less than three months before the index operation or contraindication to dressing allocation. The trial is scheduled to recruit for nine months. The findings will be used to inform the design of a main trial. Discussion This pilot trial is the first pragmatic study to randomise participants to no dressing or tissue-glue as a dressing versus a simple dressing. Early evidence from the ongoing pilot shows that recruitment is proceeding well and that the interventions are acceptable to participants. Combined with the qualitative findings, the findings will inform whether a main, large trial is feasible and, if so, how it should be designed. Trial registration ISRCTN49328913 . Registered on 20 October 2015.

Abstract Background Informed consent (IC) is an ethical and legal prerequisite for trial participation, yet current approaches evaluating participant understanding for IC during recruitment lack consistency. No validated measure has been identified that evaluates participant understanding for IC based on their contributions during consent interactions. This paper outlines the development and formative evaluation of the Participatory and Informed Consent (PIC) measure for application to recorded recruitment appointments. The PIC allows the evaluation of recruiter information provision and evidence of participant understanding. Methods Published guidelines for IC were reviewed to identify potential items for inclusion. Seventeen purposively sampled trial recruitment appointments from three diverse trials were reviewed to identify the presence of items relevant to IC. A developmental version of the measure (DevPICv1) was drafted and applied to six further recruitment appointments from three further diverse trials to evaluate feasibility, validity, stability and inter-rater reliability. Findings guided revision of the measure (DevPICv2) which was applied to six further recruitment appointments as above. Results DevPICv1 assessed recruiter information provision (detail and clarity assessed separately) and participant talk (detail and understanding assessed separately) over 20 parameters (or 23 parameters for three-arm trials). Initial application of the measure to six diverse recruitment appointments demonstrated promising stability and inter-rater reliability but a need to simplify the measure to shorten time for completion. The revised measure (DevPICv2) combined assessment of detail and clarity of recruiter information and detail and evidence of participant understanding into two single scales for application to 22 parameters or 25 parameters for three-arm trials. Application of DevPICv2 to six further diverse recruitment appointments showed considerable improvements in feasibility (e.g. time to complete) with good levels of stability (i.e. test-retest reliability) and inter-rater reliability maintained. Conclusions The DevPICv2 provides a measure for application to trial recruitment appointments to evaluate quality of recruiter information provision and evidence of patient understanding and participation during IC discussions. Initial evaluation shows promising feasibility, validity, reliability and ability to discriminate across a range of recruiter practice and evidence of participant understanding. More validation work is needed in new clinical trials to evaluate and refine the measure further.

Abstract Background A research register (Reach West) has been established to facilitate recruitment of people and patients to health-related research. We conducted a prospective feasibility study to investigate the practicality of recruiting through outpatient clinics. Methods Patients over 18 years of age attending dental, eye or oncology outpatient clinics in an acute hospital in the West of England were provided with the opportunity to participate in Reach West. In Phase I, recruitment packs were handed to clinic attendees who could place completed consent forms in secure drop-box or return them later on-line or by post. In Phase II, recruitment packs were posted directly to patients with consent forms to be returned by post or on-line. Response rates by age, sex, postcode (for level of deprivation), and clinic type were recorded for those agreeing to participate on paper or on-line. Results In Phase I, 2,314 of 4,500 (51.4%) of recruitment packs were handed out to clinic attendees, and 114 (5%) consented to join Reach West. In Phase II, 7,173 of 9000 packs were posted (79.7%), and 387 (5.4%) consented to participate. The overall consent rate was 6% (580), with the majority doing so on paper (87%) rather than on-line. The sample was balanced by sex, but mostly comprised people over 50 years located in less deprived postcodes. Non-staff costs for postal recruitment were lower than hand-outs in clinic (£6.84 compared with £8.05 per participant). Conclusions Recruiting participants to the Reach West register was feasible among those with oncology, dental or eye outpatient appointments by post or with packs given out in the clinic. Response rates were similar to those achieved for other registers. Recruitment of participants can be achieved through outpatient clinics but other strategies will also be required to attract large numbers of participants and more diverse populations.

Abstract Background Consent remains a crucial, yet challenging, cornerstone of clinical practice. The ethical, legal and professional understandings of this construct have evolved away from a doctor-centred act to a patient-centred process that encompasses the patient’s values, beliefs and goals. This alignment of consent with the philosophy of shared decision-making was affirmed in a recent high-profile Supreme Court ruling in England. The communication of information is central to this model of health care delivery but it can be difficult for doctors to gauge the information needs of the individual patient. The aim of this paper is to describe ‘core information sets’ which are defined as a minimum set of consensus-derived information about a given procedure to be discussed with all patients. Importantly, they are intended to catalyse discussion of subjective importance to individuals. Main body The model described in this paper applies health services research and Delphi consensus-building methods to an idea orginally proposed 30 years ago. The hypothesis is that, first, large amounts of potentially-important information are distilled down to discrete information domains. These are then, secondly, rated by key stakeholders in multiple iterations, so that core information of agreed importance can be defined. We argue that this scientific approach is key to identifying information important to all stakeholders, which may otherwise be communicated poorly or omitted from discussions entirely. Our methods apply systematic review, qualitative, survey and consensus-building techniques to define this ‘core information’. We propose that such information addresses the ‘reasonable patient’ standard for information disclosure but, more importantly, can serve as a spring board for high-value discussion of importance to the individual patient. Conclusion The application of established research methods can define information of core importance to informed consent. Further work will establish how best to incorporate this model in routine practice.

Over one hundred loci have been identified to be associated with the familial risk of prostate cancer but the functional effects are poorly understood. Here the authors use single-nucleotide variant and epigentic data to show an underlying genetic architecture marked by histone modification.

International government guidance recommends patient and public involvement (PPI) to improve the relevance and quality of research. PPI is defined as research being carried out ‘with’ or ‘by’ patients and members of the public rather than ‘to’, ‘about’ or ‘for’ them (http://www.invo.org.uk/). Patient involvement is different from collecting data from patients as participants. Ethical considerations also differ. PPI is about patients actively contributing through discussion to decisions about research design, acceptability, relevance, conduct and governance from study conception to dissemination. Occasionally patients lead or do research. The research methods of PPI range from informal discussions to partnership research approaches such as action research, co-production and co-learning. This article discusses how researchers can involve patients when they are applying for research funding and considers some opportunities and pitfalls. It reviews research funder requirements, draws on the literature and our collective experiences as clinicians, patients, academics and members of UK funding panels.

International government guidance recommends patient and public involvement (PPI) to improve the relevance and quality of research. PPI is defined as research being carried out ‘with’ or ‘by’ patients and members of the public rather than ‘to’, ‘about’ or ‘for’ them ( http://www.invo.org.uk/). Patient involvement is different from collecting data from patients as participants. Ethical considerations also differ. PPI is about patients actively contributing through discussion to decisions about research design, acceptability, relevance, conduct and governance from study conception to dissemination. Occasionally patients lead or do research. The research methods of PPI range from informal discussions to partnership research approaches such as action research, co-production and co-learning. This article discusses how researchers can involve patients when they are applying for research funding and considers some opportunities and pitfalls. It reviews research funder requirements, draws on the literature and our collective experiences as clinicians, patients, academics and members of UK funding panels.