Real-time monitoring and feedback to improve shared decision-making for surgery (the ALPACA Study): protocol for a mixed-methods study to inform co-development of an inclusive intervention.

INTRODUCTION: High-quality shared decision-making (SDM) is a priority of health services, but only achieved in a minority of surgical consultations. Improving SDM for surgical patients may lead to more effective care and moderate the impact of treatment consequences. There is a need to establish effective ways to achieve sustained and large-scale improvements in SDM for all patients whatever their background. The ALPACA Study aims to develop, pilot and evaluate a decision support intervention that uses real-time feedback of patients' experience of SDM to change patients' and healthcare professionals' decision-making processes before adult elective surgery and to improve patient and health service outcomes. METHODS AND ANALYSIS: This protocol outlines a mixed-methods study, involving diverse stakeholders (adult patients, healthcare professionals, members of the community) and three National Health Service (NHS) trusts in England. Detailed methods for the assessment of the feasibility, usability and stakeholder views of implementing a novel system to monitor the SDM process for surgery automatically and in real time are described. The study will measure the SDM process using validated instruments (CollaboRATE, SDM-Q-9, SHARED-Q10) and will conduct semi-structured interviews and focus groups to examine (1) the feasibility of automated data collection, (2) the usability of the novel system and (3) the views of diverse stakeholders to inform the use of the system to improve SDM. Future phases of this work will complete the development and evaluation of the intervention. ETHICS AND DISSEMINATION: Ethical approval was granted by the NHS Health Research Authority North West-Liverpool Central Research Ethics Committee (reference: 21/PR/0345). Approval was also granted by North Bristol NHS Trust to undertake quality improvement work (reference: Q80008) overseen by the Consent and SDM Programme Board and reporting to an Executive Assurance Committee. TRIAL REGISTRATION NUMBER: ISRCTN17951423; Pre-results.

A systematic scoping review protocol to summarise and appraise the use of artificial intelligence in the analysis of digital videos of invasive general surgical procedures.

Background: Intraoperative video recordings are a valuable addition to operative written documentation. However, the review of these videos often requires surgical expertise and takes considerable time. While a large amount of work has been undertaken to understand the role of artificial intelligence (AI) in healthcare more generally, the application of these techniques to automate the analysis of surgical videos is currently unclear. In this systematic scoping review, we sought to give a contemporary overview of the use of AI research in the analysis of digital videos of invasive general surgical procedures. We will describe and summarise the study characteristics, purpose of the applications and stage of development, to ascertain how these techniques might be applied in future research and to identify gaps in current knowledge (e.g. uncertainties about the study methods). Methods: Systematic searches will be conducted in OVID Medline and Embase, using terms related to 'artificial intelligence', 'surgery' and 'video' to identify all potentially relevant studies published since 1st January 2012. All primary studies where AI has been applied to the analysis of videos (recorded by conventional digital cameras or laparoscopic or robotic-assisted technology) of general surgical procedures will be included. Data extraction will include study characteristics, governance, details of video datasets and AI models, measures of accuracy, validation and any reported limitations. Ethics and dissemination: No ethical approval is required as primary data will not be collected. The results will be disseminated at relevant conferences, on social media and published in a peer-reviewed journal.

Remote assessment of surgical site infection (SSI) using patient-taken wound images: Development and evaluation of a method for research and routine practice.

BACKGROUND/AIM: Clinical assessment of wounds for surgical site infection (SSI) after hospital discharge is challenging and resource intensive. Remote assessment using digital images may be feasible and expedite SSI diagnosis. Acceptable and accurate methods for this process are needed. This study developed and evaluated the feasibility, acceptability and usability of a method for patients to capture standardised wound images for remote wound assessment to detect SSI. MATERIALS AND METHODS: The work was conducted in two phases. Phase I involved: i) a review of literature to identify key components of photography relevant to taking wound images, ii) development of wound photography instructions for patients and a secure process for transmission of images using electronic survey software and iii) pre-testing of the photography instructions and processing method with a sample of 16 patients using cognitive interviews and observations. Phase II involved a prospective cohort study of 89 patients to evaluate the feasibility, acceptability and usability of the remote method following discharge from hospital after surgery. Quality of the images was assessed by three independent clinical reviewers. RESULTS: Some 21 key components for photographing wounds were identified from 11 documents. Of these, 16 were relevant to include in instructions for patients to photograph their wounds. Pre-testing and subsequent iterations improved understanding and ease of use of the instructions and the process for transmitting images. Fifty-two of 89 (58.4%) patients testing the method remotely took an image of their wound(s) and 46/52 (88.5%) successfully transmitted images. When it was possible to ascertain a reason for not taking/transmitting images, this was primarily health problems (n = 7) or lack of time/poor engagement with the study (n = 4) rather than problems relating to technology/competency (n = 2) or practical issues relating to the wound itself (n = 2). Eighty-seven (85.3%) of the 102 images received were evaluated to be of high quality and sufficient to remotely assess SSI by at least two independent reviewers. CONCLUSION: A simple, standardised and acceptable method for patients to take and transmit wound images suitable for remote assessment of SSI has been developed and tested and is now available for use in routine clinical care and research.

A standardized measurement instrument was recommended for evaluating operator experience in complex healthcare interventions.

OBJECTIVE: During development of complex surgical innovations, modifications occur to optimize safety and efficacy. Operators' experiences (how professionals feel undertaking the innovation) drive this process but comprehensive overviews of measures of this concept are lacking. This study identified and appraised measures to assess operators' experience of surgical innovation. STUDY DESIGN AND SETTING: There were three phases: (1) Literature reviews identified measures of operators' experience and concepts measured were extracted and grouped into domains. (2) Quality appraisal was conducted to assess content validity of identified instruments and was supported by COnsensus-based Standards for the selection of health Measurement Instruments methodology. Self-reported measurement instruments that had underdone formal development were eligible. Content validity was assessed using COnsensus-based Standards for the selection of health Measurement Instruments criteria for good content validity (rated sufficient/insufficient/indeterminate/inconsistent), informed by standards for measurement development and domains identified in phase 1. (3) Instruments determined suitable and of sufficient quality underwent supplemental appraisal in interviews with international multidisciplinary professionals and a focus group. RESULTS: Literature reviews identified 16 measurement instruments from 243 studies. Most assessed 'psychological' experiences and 'usability'. No instrument was specifically validated for innovative surgery. Three instruments were rated 'sufficient' (Surgery Task Load Index [SURG-TLX]) or 'indeterminate' (Spielberger State-Trait Anxiety Inventory, Imperial Stress Assessment Tool). Twenty professionals were interviewed (seven female; 15 specialties; six countries) and the focus group included 10 participants (four professionals, six researchers). The SURG-TLX was considered the most relevant, comprehensive, and comprehensible instrument. CONCLUSION: The SURG-TLX is preliminarily recommended to measure operators' experiences of innovation. Further work exploring its role and impact on surgical innovation is required.

Identification of outcomes to inform the development of a core outcome set for surgical innovation: a targeted review of case studies of novel surgical devices.

OBJECTIVE: Outcome selection and reporting in studies of novel surgical procedures and devices lacks standardisation, hindering safe and effective evaluation. A core outcome set (COS) to measure and report in all studies of surgical innovation is needed. We explored outcomes in a specific sample of innovative surgical device case studies to identify outcome domains specifically relevant to innovation to inform the development of a COS. DESIGN: A targeted review of 11 purposive selected case studies of innovative surgical devices. METHODS: Electronic database searches in PubMed (July 2018) identified publications reporting the introduction and evaluation of each device. Outcomes were extracted and categorised into domains until no new domains were conceptualised. Outcomes specifically relevant to evaluating innovation were further scrutinised. RESULTS: 112 relevant publications were identified, and 5926 outcomes extracted. Heterogeneity in study type, outcome selection and reporting was observed across surgical devices. Categorisation of outcomes was performed for 2689 (45.4%) outcomes into five broad outcome domains. Outcomes considered key to the evaluation of innovation (n=66; 2.5%) were further categorised as surgeon/operator experience (n=40; 1.5%), unanticipated events (n=15, 0.6%) and modifications (n=11; 0.4%). CONCLUSION: Outcome domains unique to evaluating innovative surgical devices have been identified. Findings have been combined with multiple other data sources relevant to the evaluation of surgical innovation to inform the development of a COS to measure and report in all studies evaluating novel surgical procedures/devices.

Artificial intelligence as a diagnostic aid in cross-sectional radiological imaging of the abdominopelvic cavity: a protocol for a systematic review.

INTRODUCTION: The application of artificial intelligence (AI) technologies as a diagnostic aid in healthcare is increasing. Benefits include applications to improve health systems, such as rapid and accurate interpretation of medical images. This may improve the performance of diagnostic, prognostic and management decisions. While a large amount of work has been undertaken discussing the role of AI little is understood regarding the performance of such applications in the clinical setting. This systematic review aims to critically appraise the diagnostic performance of AI algorithms to identify disease from cross-sectional radiological images of the abdominopelvic cavity, to identify current limitations and inform future research. METHODS AND ANALYSIS: A systematic search will be conducted on Medline, EMBASE and the Cochrane Central Register of Controlled Trials to identify relevant studies. Primary studies where AI-based technologies have been used as a diagnostic aid in cross-sectional radiological images of the abdominopelvic cavity will be included. Diagnostic accuracy of AI models, including reported sensitivity, specificity, predictive values, likelihood ratios and the area under the receiver operating characteristic curve will be examined and compared with standard practice. Risk of bias of included studies will be assessed using the QUADAS-2 tool. Findings will be reported according to the Synthesis Without Meta-analysis guidelines. ETHICS AND DISSEMINATION: No ethical approval is required as primary data will not be collected. The results will inform further research studies in this field. Findings will be disseminated at relevant conferences, on social media and published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021237249.

Three wound-dressing strategies to reduce surgical site infection after abdominal surgery: the Bluebelle feasibility study and pilot RCT.

BACKGROUND: Surgical site infection (SSI) affects up to 20% of people with a primary closed wound after surgery. Wound dressings may reduce SSI. OBJECTIVE: To assess the feasibility of a multicentre randomised controlled trial (RCT) to evaluate the effectiveness and cost-effectiveness of dressing types or no dressing to reduce SSI in primary surgical wounds. DESIGN: Phase A - semistructured interviews, outcome measure development, practice survey, literature reviews and value-of-information analysis. Phase B - pilot RCT with qualitative research and questionnaire validation. Patients and the public were involved. SETTING: Usual NHS care. PARTICIPANTS: Patients undergoing elective/non-elective abdominal surgery, including caesarean section. INTERVENTIONS: Phase A - none. Phase B - simple dressing, glue-as-a-dressing (tissue adhesive) or 'no dressing'. MAIN OUTCOME MEASURES: Phase A - pilot RCT design; SSI, patient experience and wound management questionnaires; dressing practices; and value-of-information of a RCT. Phase B - participants screened, proportions consented/randomised; acceptability of interventions; adherence; retention; validity and reliability of SSI measure; and cost drivers. DATA SOURCES: Phase A - interviews with patients and health-care professionals (HCPs), narrative data from published RCTs and data about dressing practices. Phase B - participants and HCPs in five hospitals. RESULTS: Phase A - we interviewed 102 participants. HCPs interpreted 'dressing' variably and reported using available products. HCPs suggested practical/clinical reasons for dressing use, acknowledged the weak evidence base and felt that a RCT including a 'no dressing' group was acceptable. A survey showed that 68% of 1769 wounds (727 participants) had simple dressings and 27% had glue-as-a-dressing. Dressings were used similarly in elective and non-elective surgery. The SSI questionnaire was developed from a content analysis of existing SSI tools and interviews, yielding 19 domains and 16 items. A main RCT would be valuable to the NHS at a willingness to pay of £20,000 per quality-adjusted life-year. Phase B - from 4 March 2016 to 30 November 2016, we approached 862 patients for the pilot RCT; 81.1% were eligible, 59.4% consented and 394 were randomised (simple, n = 133; glue, n = 129; no dressing, n = 132); non-adherence was 3 out of 133, 8 out of 129 and 20 out of 132, respectively. SSI occurred in 51 out of 281 participants. We interviewed 55 participants. All dressing strategies were acceptable to stakeholders, with no indication that adherence was problematic. Adherence aids and patients' understanding of their allocated dressing appeared to be key. The SSI questionnaire response rate overall was 67.2%. Items in the SSI questionnaire fitted a single scale, which had good reliability (test-retest and Cronbach's alpha of > 0.7) and diagnostic accuracy (c-statistic = 0.906). The key cost drivers were hospital appointments, dressings and redressings, use of new medicines and primary care appointments. LIMITATIONS: Multiple activities, often in parallel, were challenging to co-ordinate. An amendment took 4 months, restricting recruitment to the pilot RCT. Only 67% of participants completed the SSI questionnaire. We could not implement photography in theatres. CONCLUSIONS: A main RCT of dressing strategies is feasible and would be valuable to the NHS. The SSI questionnaire is sufficiently accurate to be used as the primary outcome. A main trial with three groups (as in the pilot) would be valuable to the NHS, using a primary outcome of SSI at discharge and patient-reported SSI symptoms at 4-8 weeks. TRIAL REGISTRATION: Phase A - Current Controlled Trials ISRCTN06792113; Phase B - Current Controlled Trials ISRCTN49328913. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 39. See the NIHR Journals Library website for further project information. Funding was also provided by the Medical Research Council ConDuCT-II Hub (reference number MR/K025643/1).

Wound infections are common after surgery. Some are cured with simple treatment, but others may lead to serious problems. Reducing the risk of a wound infection is important. We do not know if the type of dressing, or not using a dressing, influences the risk of infection. A study that allocated patients to receive different dressings (or no dressing) would answer this question. We did preliminary research to explore whether or not such a study is possible. We interviewed doctors, nurses and patients about their views on dressings and a future study. We also described dressings currently being used in the NHS and found that simple dressings and tissue adhesive (glue) 'as-a-dressing' are used most frequently. We studied existing evidence and interviewed experts to develop a questionnaire, completed by patients, to identify wound infections after patients leave hospital and tested its accuracy. We also explored taking photographs of wounds. We investigated whether or not a major study would be worth the cost and designed a pilot study to test its feasibility. The pilot study recruited 394 patients undergoing abdominal operations in five NHS hospitals. These patients were allocated to have a simple dressing, glue-as-a-dressing or no dressing, and 92% received the allocated dressing method. Patients and their doctors and nurses found the dressing methods to be acceptable. We showed that the new patient questionnaire accurately identified infections. Patients or their carers also found it acceptable to photograph their wounds. Our research suggests that a future large study would be worth the investment and is possible.

Development of a single, practical measure of surgical site infection (SSI) for patient report or observer completion.

BACKGROUND: Surgical site infections (SSIs) are the third most common hospital-associated infection and can lead to significant patient morbidity and healthcare costs. Identification of SSIs is key to surveillance and research but reliable assessment is challenging, particularly after hospital discharge when most SSIs present. Existing SSI measurement tools have limitations and their suitability for post-discharge surveillance is uncertain. AIMS: This study aimed to develop a single measure to identify SSI after hospital discharge, suitable for patient or observer completion. METHODS: A three-phase mixed methods study was undertaken: Phase 1, an analysis of existing tools and semi-structured interviews with patients and professionals to establish the content of the measure; Phase 2, development of questionnaire items suitable for patients and professionals; Phase 3, pre-testing the single measure to assess acceptability and understanding to both stakeholder groups. Interviews and pre-testing took place over 12 months in 2014-2015 with patients and professionals from five specialties recruited from two UK hospital Trusts. FINDINGS: Analyses of existing tools and interviews identified 19 important domains for assessing SSIs. Domains were developed into provisional questionnaire items. Pre-testing and iterative revision resulted in a final version with 16 items that were understood and easily completed by patients and observers (healthcare professionals). CONCLUSION: A single patient and observer measure for post-discharge SSI assessment has been developed. Further testing of the validity, reliability and accuracy of the measure is underway.

A mixed-methods feasibility and external pilot study to inform a large pragmatic randomised controlled trial of the effects of surgical wound dressing strategies on surgical site infections (Bluebelle Phase B): study protocol for a randomised controlled trial.

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.

Three nested randomized controlled trials of peer-only or multiple stakeholder group feedback within Delphi surveys during core outcome and information set development.

BACKGROUND: Methods for developing a core outcome or information set require involvement of key stakeholders to prioritise many items and achieve agreement as to the core set. The Delphi technique requires participants to rate the importance of items in sequential questionnaires (or rounds) with feedback provided in each subsequent round such that participants are able to consider the views of others. This study examines the impact of receiving feedback from different stakeholder groups, on the subsequent rating of items and the level of agreement between stakeholders. METHODS: Randomized controlled trials were nested within the development of three core sets each including a Delphi process with two rounds of questionnaires, completed by patients and health professionals. Participants rated items from 1 (not essential) to 9 (absolutely essential). For round 2, participants were randomized to receive feedback from their peer stakeholder group only (peer) or both stakeholder groups separately (multiple). Decisions as to which items to retain following each round were determined by pre-specified criteria. RESULTS: Whilst type of feedback did not impact on the percentage of items for which a participant subsequently changed their rating, or the magnitude of change, it did impact on items retained at the end of round 2. Each core set contained discordant items retained by one feedback group but not the other (3-22 % discordant items). Consensus between patients and professionals in items to retain was greater amongst those receiving multiple group feedback in each core set (65-82 % agreement for peer-only feedback versus 74-94 % for multiple feedback). In addition, differences in round 2 scores were smaller between stakeholder groups receiving multiple feedback than between those receiving peer group feedback only. Variability in item scores across stakeholders was reduced following any feedback but this reduction was consistently greater amongst the multiple feedback group. CONCLUSIONS: In the development of a core outcome or information set, providing feedback within Delphi questionnaires from all stakeholder groups separately may influence the final core set and improve consensus between the groups. Further work is needed to better understand how participants rate and re-rate items within a Delphi process. TRIAL REGISTRATION: The three randomized controlled trials reported here were each nested within the development of a core information or outcome set to investigate processes in core outcome and information set development. Outcomes were not health-related and therefore trial registration was not applicable.

'Trial Exegesis': Methods for Synthesizing Clinical and Patient Reported Outcome (PRO) Data in Trials to Inform Clinical Practice. A Systematic Review.

PURPOSE: The CONSORT extension for patient reported outcomes (PROs) aims to improve reporting, but guidance on the optimal integration with clinical data is lacking. This study examines in detail the reporting of PROs and clinical data from randomized controlled trials (RCTs) in gastro-intestinal cancer to inform design and reporting of combined PRO and clinical data from trials to improve the 'take home' message for clinicians to use in practice. MATERIALS AND METHODS: The case study was undertaken in gastro-intestinal cancer trials. Well-conducted RCTs reporting PROs with validated instruments were identified and categorized into those combining PRO and clinical data in a single paper, or those separating data into linked primary and supplemental papers. Qualitative methods were developed to examine reporting of the critical interpretation of the trial results (trial exegesis) in the papers in relation of the PRO and clinical outcomes and applied to each publication category. Results were used to inform recommendations for practice. RESULTS: From 1917 screened abstracts, 49 high quality RCTs were identified reported in 36 combined and 15 linked primary and supplemental papers. In-depth analysis of manuscript text identified three categories for understanding trial exegesis: where authors reported a "detailed", "general", or absent PRO rationale and integrated interpretation of clinical and PRO results. A total of 11 (30%) and 6 (16%) combined papers reported "detailed" PRO rationale and integrated interpretation of results although only 2 (14%) and 1 (7%) primary papers achieved the same standard respectively. Supplemental papers provide better information with 11 (73%) and 3 (20%) achieving "detailed" rationale and integrated interpretation of results. Supplemental papers, however, were published a median of 20 months after the primary RCT data in lower impact factor journals (median 16.8 versus 5.2). CONCLUSION: It is recommended that single papers, with detailed PRO rationale and integrated PRO and clinical data are published to optimize trial exegesis. Further work to examine whether this improves the use of PRO data to inform practice is needed.

A Systematic Review of Patient-reported Outcomes in Randomized Controlled Trials of Unplanned General Surgery.

Unplanned general surgery represents a major workload and requires comprehensive evaluation with appropriate outcomes. This study aimed to summarize current reporting of patient-reported outcomes (PROs) in randomized clinical trials (RCTs) in unplanned general surgery. A systematic review identified RCTs reporting PROs in the commonest six areas of unplanned general surgery. Details of the PRO measures were examined using the CONSORT extension for PRO reporting in RCTs. Extracted information about each PRO domain included the reporting of baseline PROs, rationale for PRO selection and whether PRO findings were used in conjunction with clinical outcomes to inform treatment recommendations. The internal validity of included studies was assessed using the Cochrane risk of bias tool. 12,519 abstracts were screened and 20 RCTs containing data from 2037 patients included. Included studies used 14 separate PRO measures covering 35 different health domains. A visual analogue assessment of pain was most frequently reported (n = 13). Reporting of baseline PRO data was uncommon (11/35 PRO domains). The rationale for PRO data collection and a PRO-specific hypothesis were provided for 9 (25.7 %) and 5 (14.3 %) domains, respectively. Seventeen RCTs (85.0 %) used the PRO data alongside clinical outcomes to inform treatment recommendations. Of the 116 risk of bias assessments, 77 (66.0 %) were judged as high or unclear. There is a lack of well designed, and conducted RCTs in unplanned general surgery that include PROs. Future work to define relevant PROs and methods for optimal assessment are needed to inform health care decision-making.

Developing core outcomes sets: methods for identifying and including patient-reported outcomes (PROs).

BACKGROUND: Synthesis of patient-reported outcome (PRO) data is hindered by the range of available PRO measures (PROMs) composed of multiple scales and single items with differing terminology and content. The use of core outcome sets, an agreed minimum set of outcomes to be measured and reported in all trials of a specific condition, may improve this issue but methods to select core PRO domains from the many available PROMs are lacking. This study examines existing PROMs and describes methods to identify health domains to inform the development of a core outcome set, illustrated with an example. METHODS: Systematic literature searches identified validated PROMs from studies evaluating radical treatment for oesophageal cancer. PROM scale/single item names were recorded verbatim and the frequency of similar names/scales documented. PROM contents (scale components/single items) were examined for conceptual meaning by an expert clinician and methodologist and categorised into health domains. A patient advocate independently checked this categorisation. RESULTS: Searches identified 21 generic and disease-specific PROMs containing 116 scales and 32 single items with 94 different verbatim names. Identical names for scales were repeatedly used (for example, 'physical function' in six different measures) and others were similar (overlapping face validity) although component items were not always comparable. Based on methodological, clinical and patient expertise, 606 individual items were categorised into 32 health domains. CONCLUSION: This study outlines a methodology for identifying candidate PRO domains from existing PROMs to inform a core outcome set to use in clinical trials.

Selecting and measuring optimal outcomes for randomised controlled trials in surgery.

BACKGROUND: Randomised controlled trials (RCTs) in surgery are complex to design and conduct and face unique challenges compared to trials in other specialties. The appropriate selection, measurement and reporting of outcomes are one aspect that requires attention. Outcomes in surgical RCTs are often ill-defined, inconsistent and at high risk of bias in their assessment and historically, there has been an undue focus on short-term outcomes and adverse events meaning the value of trial results for clinical practice and decision-making is limited. PURPOSE: This review addresses three key problems with surgical trial outcomes­choosing the right outcomes for the trial design and purpose, selecting relevant outcomes to measure from the range of possible outcomes, and measuring outcomes with minimal risk of bias. Each obstacle is discussed in turn, highlighting some suggested solutions and current initiatives working towards improvements in these areas. Some examples of good practice in this field are also discussed. CONCLUSIONS: Many of the historical problems with surgical trial outcomes may be overcome with an increased understanding of the trial design and purpose and recognition that pragmatic trials require assessments of outcomes that are patient-centred in addition to measurement of short-term outcomes. The use of core outcome sets developed for specific surgical interventions and the application of novel methods to blind outcome assessors will also improve outcome measurement and reporting. It is recommended that surgeons work together with trial methodologists to integrate these approaches into RCTs in surgery. This will facilitate the appropriate evaluation of surgical interventions with informative outcomes so that results from trials can be useful for clinical practice.

Psychological impact of prostate biopsy: physical symptoms, anxiety, and depression.

PURPOSE: To investigate the psychological impact of prostate biopsy, including relationships between physical biopsy-related symptoms and anxiety and depression. PATIENTS AND METHODS: A prospective cohort of 1,147 men, nested within the Prostate Testing for Cancer and Treatment trial and recommended to receive prostate biopsy, completed questionnaires assessing physical and psychological harms after biopsy in the Prostate Biopsy Effects study. Psychological impact was measured using the Hospital Anxiety and Depression Scale, and scores were compared according to experiences of biopsy-related symptoms at biopsy, and at 7 and 35 days afterward, and in relation to biopsy results. RESULTS: A total of 1,144 men (99.7%) returned questionnaires at biopsy, with 1,090 (95.0%) and 1,016 (88.6%) responding at 7 and 35 days postbiopsy. Most men experienced biopsy-related symptoms as no problem or a minor problem, and overall levels of anxiety and depression were low and similar to normative levels. Of men receiving a negative biopsy result (n = 471), anxiety was greater in those experiencing problematic biopsy-related symptoms compared with those experiencing nonproblematic symptoms at 7 days for the following symptoms: pain (P < .001), shivers, (P = .020), hematuria (P < .001), hematochezia (P < .001), and hemoejaculate (P < .001). Anxiety was reduced, although symptoms were not, after 35 days. Overall levels of anxiety were low across all time points except at the 35-day assessment among men who had received a cancer diagnosis. CONCLUSION: Problematic postbiopsy symptoms can lead to increased anxiety, distinct from distress related to diagnosis of prostate cancer. Men and doctors need to consider these additional potential harms of biopsy when deciding whether to initiate prostate-specific antigen testing.

A systematic review of on-site monitoring methods for health-care randomised controlled trials.

BACKGROUND: Monitoring the conduct of clinical trials is recommended by International Conference of Harmonisation Good Clinical Practice (ICH GCP) guidelines and is integral to trial quality assurance. On-site monitoring, that is, visiting trial sites, is one part of this process but little is known about the procedures that are performed in practice. PURPOSE: To examine and summarise published on-site monitoring methods for health-care clinical trials, including evaluations of their benefits and costs to trials. METHODS: A systematic literature review identified all articles reporting the methods and practices of on-site monitoring of randomised controlled trials (RCTs). Articles were categorised into (1) reports from research groups and organisations, (2) reports from individual RCTs, (3) randomised trials of on-site monitoring interventions, (4) cost simulations, or (5) surveys of trial staff and monitors. Data were extracted on the characteristics of the trials and groups reporting on-site monitoring (e.g., geographical origin, sponsor, and trial focus). Information from articles in categories (1)-(3) was summarised on the frequency and scope of site monitoring visits, monitoring team size and composition, activities during site visits, and reporting structures. Evaluations of the benefits and disadvantages of on-site monitoring were examined for all included articles. RESULTS: In total, 57 articles were identified, comprising 21 articles about the on-site monitoring practices of 16 research groups, 30 articles from 26 RCTs, 1 on-site monitoring intervention RCT, 2 cost simulations, and 3 surveys. Publications in categories (1)-(3), mostly originated from the United States (33/52, 63%) or Europe (15/52, 29%), were predominantly describing non-commercial organisations or trials (45/52, 87%), with heart disease (9/26, 35%) or cancer (5/26, 19%) the commonest focus of individual RCTs. The frequency of visits ranged from every 6-8 weeks up to once every 3 years, with mostly all trial sites visited. The number of monitors visiting a site varied between 1 and 8. The most common on-site monitoring activity was verifying source data and consent forms, with a focus on data accuracy. Only six articles evaluated their on-site monitoring process, with improvements observed in recruitment rates and protocol adherence but with direct costs and staff time viewed as the major disadvantages. The on-site monitoring RCT ended prematurely so preventing full assessment. LIMITATIONS: Trialists and organisations may utilise additional unpublished on-site monitoring systems. The varied terminology used to describe monitoring may have limited identification of some relevant articles. CONCLUSIONS: This review demonstrated that on-site monitoring is utilised in trials worldwide but systems vary considerably with little evidence to support practice. These on-site monitoring practices need to be evaluated empirically, including costs, to provide robust evidence for the contribution of site visits to trial performance and quality.

Systematic review reveals limitations of studies evaluating health-related quality of life after potentially curative treatment for esophageal cancer.

PURPOSE: To (1) assess the quality of studies evaluating Health-Related Quality of Life (HRQL) after potentially curative treatment for esophageal cancer, and (2) to identify high-quality studies that provide robust HRQL results. METHODS: A systematic literature search is to identify studies evaluating HRQL with a validated multidimensional patient-reported outcome measure. Study quality focused on study design, risk of bias, HRQL outcome reporting, and additional issues of reporting and methodology. A study was deemed high-quality if criteria for robust study methodology and robust HRQL outcome reporting were met. RESULTS: Six RCTs, 12 cohort studies, 13 case-series, and 31 cross-sectional studies were identified. Overall risk of bias was high. Reporting of HRQL concept (e.g., a priori hypothesis), methodology (e.g., reasons for missing data), and interpretation (e.g., clinical significance) was often absent or unclear. Additional issues of reporting (e.g., unclear treatment descriptions) and methodology (e.g., no control for multiple testing) were identified. Four studies (6%) met the criteria for robust study methodology, and 26 studies (42%) met the criteria for robust HRQL outcome reporting. We identified three high-quality studies (5%)--two RCTs and one case-series--capable of providing robust results. CONCLUSIONS: Current evidence is restricted in its ability to inform practice on HRQL after potentially curative treatment for esophageal cancer.

Do the risk factors of age, family history of prostate cancer or a higher prostate specific antigen level raise anxiety at prostate biopsy?

To date, little is known of the impact knowledge of personal risk factors has on anxiety in men undergoing biopsy tests for prostate cancer. This analysis explores anxiety scores of men at higher risk due to age, family history of prostate cancer and a higher prostate specific antigen (PSA) level when proceeding from PSA test to prostate biopsy. A prospective cohort of 4198 men aged 50-69 years with a PSA result of >3ng/ml was studied, recruited for the Prostate testing for cancer and Treatment study (ProtecT). Anxiety scores at the time of biopsy were lower in older men (p<0.001). No age group showed an increase in anxiety as the men proceeded from PSA testing to biopsy, although older men did not show the same level of decrease in anxiety as younger men (p=0.035). There was no difference in anxiety scores at biopsy between men with or without a family history of prostate cancer (p=0.68), or between those with a raised PSA of 10-<20ng/ml compared to a PSA result of 3-<10ng/ml (p=0.46). Change in scores since the initial PSA test appeared unaffected by family history (p=0.995) or by PSA result (p=0.76). Within the context of a research study, the increased risk of prostate cancer through older age, having a family history of prostate cancer, or having a significantly elevated PSA level appears to have no detrimental effect on men's anxiety level when proceeding to biopsy.