The Biomarker Toolkit - an evidence-based guideline to predict cancer biomarker success and guide development.

BACKGROUND: An increased number of resources are allocated on cancer biomarker discovery, but very few of these biomarkers are clinically adopted. To bridge the gap between Biomarker discovery and clinical use, we aim to generate the Biomarker Toolkit, a tool designed to identify clinically promising biomarkers and promote successful biomarker translation. METHODS: All features associated with a clinically useful biomarker were identified using mixed-methodology, including systematic literature search, semi-structured interviews, and an online two-stage Delphi-Survey. Validation of the checklist was achieved by independent systematic literature searches using keywords/subheadings related to clinically and non-clinically utilised breast and colorectal cancer biomarkers. Composite aggregated scores were generated for each selected publication based on the presence/absence of an attribute listed in the Biomarker Toolkit checklist. RESULTS: Systematic literature search identified 129 attributes associated with a clinically useful biomarker. These were grouped in four main categories including: rationale, clinical utility, analytical validity, and clinical validity. This checklist was subsequently developed using semi-structured interviews with biomarker experts (n=34); and 88.23% agreement was achieved regarding the identified attributes, via the Delphi survey (consensus level:75%, n=51). Quantitative validation was completed using clinically and non-clinically implemented breast and colorectal cancer biomarkers. Cox-regression analysis suggested that total score is a significant driver of biomarker success in both cancer types (BC: p>0.0001, 95.0% CI: 0.869-0.935, CRC: p>0.0001, 95.0% CI: 0.918-0.954). CONCLUSIONS: This novel study generated a validated checklist with literature-reported attributes linked with successful biomarker implementation. Ultimately, the application of this toolkit can be used to detect biomarkers with the highest clinical potential and shape how biomarker studies are designed/performed.

The development and evaluation of "Training the trainer" curriculum for surgical residents: Feasibility study.

BACKGROUND: Over the last decades, there has been greater emphasis on enhancing teaching skills and concepts of Train-The-Trainer (TTT) have been widely adopted across surgical training programs. Current TTT curricula, however, mostly address teaching generic principles without specific guidance on how to teach technical skills among residents. The aim of this proof-of-concept study was to design a bespoke TTT curriculum for surgical technical skills and evaluate its impact. MATERIAL AND METHODS: A bespoke TTT curriculum was developed to address key teaching surgical skills including a training framework, and performance enhancing feedback. The curriculum was delivered to 41 junior surgical residents in this feasibility study and focused on promoting a training framework including three domains; "set" involving pre-operative preparation, "dialogue" referring to teaching techniques and "closure" covering structured feedback. It was evaluated using Kirkpatrick's model: (i) course feedback; (ii) training quality assessment on a suturing simulated scenario using (a) Competency Assessment Tool (CAT) and a (b) Structured Training Trainer Assessment Report (STTAR) tool; (iii-iv) follow-up survey after one year. RESULTS: The TTT curriculum was well-perceived, with a median score of 4/5 ("agree") across all components of evaluation forms. The simulated training scenario demonstrated a significant reduction in suturing errors following delivery of training (pre-TTT [4.25; IQR:4.42]; post-TTT [2.34; IQR:2.38], p-value = 0.014). Improvement in teaching was also noted and reflected in 'Set' (pre-TTT [3.50; IQR: 3.00] and post-TTT [5.00; IQR: 0.00], p-value = 0.019) and 'Closure' (pre-TTT [4.75; IQR: 1.88] and post-TTT [5.00; IQR: 0.00], p value = 0.007). 25% of participants contributed to the long-term survey highlighting that most practiced skills within 6 months of the curriculum with positive feedback from their learners. CONCLUSION: This proof-of-concept study confirms the feasibility and acceptability of delivering a bespoke Train-The-Trainer curriculum to surgical residents. It provides a structured training framework that can enhance teaching technical skills.

Assessment of Technical Skills in Axillary Lymph Node Dissection.

OBJECTIVE: A simulator to enable safe practice and assessment of ALND has been designed, and face, content and construct validity has been investigated. SUMMARY AND BACKGROUND DATA: The reduction in the number of ALNDs conducted has led to decreased resident exposure and confidence. METHODS: A cross-sectional multicenter observational study was carried out between July 2017 and August 2018. Following model development, 30 surgeons of varying experience (n = "experts," n = 11 "senior residents," and n = 10 "junior residents") were asked to perform a simulated ALND. Face and content validity questionnaires were administered immediately after ALND. All ALND procedures were retrospectively assessed by 2 attending breast surgeons, blinded to operator identity, using a video-based assessment tool, and an end product assessment tool. RESULTS: Statistically significant differences between groups were observed across all operative subphases on the axillary clearance assessment tool (P < 0.001). Significant differences between groups were observed for overall procedure quality (P < 0.05) and total number of lymph nodes harvested (P < 0.001). However, operator grade could not be distinguished across other end product variables such as axillary vein damage (P = 0.864) and long thoracic nerve injury (P = 0.094). Overall, participants indicated that the simulator has good anatomical (median score >7) and procedural realism (median score >7). CONCLUSIONS: Video-based analysis demonstrates construct validity for ALND assessment. Given reduced ALND exposure, this simulation is a useful adjunct for both technical skills training and formative Deanery or Faculty administered assessments.

Development of a Reliable Surgical Quality Assurance System for 2-stage Esophagectomy in Randomized Controlled Trials.

OBJECTIVE: The aim was to develop a reliable surgical quality assurance system for 2-stage esophagectomy. This development was conducted during the pilot phase of the multicenter ROMIO trial, collaborating with international experts. SUMMARY OF BACKGROUND DATA: There is evidence that the quality of surgical performance in randomized controlled trials influences clinical outcomes, quality of lymphadenectomy and loco-regional recurrence. METHODS: Standardization of 2-stage esophagectomy was based on structured observations, semi-structured interviews, hierarchical task analysis, and a Delphi consensus process. This standardization provided the structure for the operation manual and video and photographic assessment tools. Reliability was examined using generalizability theory. RESULTS: Hierarchical task analysis for 2-stage esophagectomy comprised fifty-four steps. Consensus (75%) agreement was reached on thirty-nine steps, whereas fifteen steps had a majority decision. An operation manual and record were created. A thirty five-item video assessment tool was developed that assessed the process (safety and efficiency) and quality of the end product (anatomy exposed and lymphadenectomy performed) of the operation. The quality of the end product section was used as a twenty seven-item photographic assessment tool. Thirty-one videos and fifty-three photographic series were submitted from the ROMIO pilot phase for assessment. The overall G-coefficient for the video assessment tool was 0.744, and for the photographic assessment tool was 0.700. CONCLUSIONS: A reliable surgical quality assurance system for 2-stage esophagectomy has been developed for surgical oncology randomized controlled trials. ETHICAL APPROVAL: 11/NW/0895 and confirmed locally as appropriate, 12/SW/0161, 16/SW/0098.Trial registration number: ISRCTN59036820, ISRCTN10386621.

Challenges to quality assurance of surgical interventions in clinical oncology trials: A systematic review.

Where surgery forms the primary curative modality in surgical oncology trials the quality of this intervention has the potential to directly influence outcomes. Many trials however lack a robust framework to ensure surgical quality. We aim to report existing published challenges to quality assurance of surgical interventions within oncological trials. A systematic on-line literature search of Embase and Medline identified 34 relevant studies, including 19 RCTs, 11 further analyses of the primary RCTs, and 4 trial protocols. Inclusion criteria: oncological RCTs with a surgical intervention and/or associated publications relevant to the research question; 'Challenges to quality assurance of surgery in clinical oncology trials'. Selected articles were assessed by two reviewers to identify reported challenges to quality assurance of surgical intervention within these trials. Reported challenges to surgical quality could be classified as those affecting credentialing, standardisation and monitoring of surgical interventions. Constraints of using case volume for credentialing surgeons; inter-centre variation in the definition and execution of interventions; insufficient training, and monitoring of surgical quality, were the most commonly encountered challenges within each of these three domains. Findings confirmed an inadequacy in the implementation and reporting of effective surgical quality assurance measures. The surgical community should enable implementation of agreed upon mitigating strategies to overcome challenges to surgical quality in oncology trials.

The Trait Emotional Intelligence Questionnaire in Lebanon and the UK: A comparison of the psychometric properties in each country.

The aim of this study was to validate the Trait Emotional Intelligence Questionnaire (TEIQue v. 1.5) in a Lebanese sample and compare its factorial structure to that of a UK sample. There were similar gender and age distributions in both samples as well as satisfactory structural reliabilities at the global, factor, and facet levels. Results from exploratory factor analysis showed a four-factor structure similar to that originally obtained by the author of the questionnaire. There were strong correlations between the factor scores derived from the two datasets (≥.90). Tucker congruence supported the similarity between the Lebanese and UK factors. Independent-samples t tests showed that Lebanese participants scored higher on the Sociability factor and the facets of self-esteem, social awareness and emotion perception, whereas UK participants scored higher on the facets of stress management, optimism and relationships. Gender differences are also reported, and recommendations for future research discussed.

Surgical Quality Assurance in COLOR III: Standardization and Competency Assessment in a Randomized Controlled Trial.

OBJECTIVE: The aim of this study was to develop an objective and reliable surgical quality assurance system (SQA) for COLOR III, an international multicenter randomized controlled trial (RCT) comparing transanal total mesorectal excision (TaTME) with laparoscopic approach for rectal cancer. BACKGROUND OF SUMMARY DATA: SQA influences outcome measures in RCTs such as lymph nodes harvest, in-hospital mortality, and locoregional cancer recurrence. However, levels of SQA are variable. METHOD: Hierarchical task analysis of TaTME was performed. A 4-round Delphi methodology was applied for standardization of TaTME steps. Semistructured interviews were conducted in round 1 to identify key steps and tasks, which were rated as mandatory, optional, or prohibited in rounds 2 to 4 using questionnaires. Competency assessment tool (CAT) was developed and its content validity was examined by expert surgeons. Twenty unedited videos were assessed to test reliability using generalizability theory. RESULTS: Eighty-three of 101 surgical tasks identified reached 70% agreement (26 mandatory, 56 optional, and 1 prohibited). An operative guide of standardized TaTME was created. CAT is matrix of 9 steps and 4 performance qualities: exposure, execution, adverse event, and end-product. The overall G-coefficient was 0.883. Inter-rater and interitem reliability were 0.883 and 0.986. To enter COLOR III, 2 unedited TaTME and 1 laparoscopic TME videos were submitted and assessed by 2 independent assessors using CAT. CONCLUSION: We described an iterative approach to develop an objective SQA within multicenter RCT. This approach provided standardization, the development of reliable and valid CAT, and the criteria for trial entry and monitoring surgical performance during the trial.

The relative contribution of parenting practices in predicting trait emotional intelligence in an Italian adolescent sample.

This study examines the relationship between trait emotional intelligence (trait EI), support, and parental psychological control practices. Three hundred adolescents, between 11 and 13 years old, took part in the study (163 were males and 137 were females). Participants completed the Perceptions of Parents Scales for the parental support, the Dependency (DPC)- and Achievement (APC)-oriented Psychological Control Scales for the parental psychological control, and the Trait Emotional Intelligence Questionnaire-Child Form for the child's trait EI. Trait EI was related to parenting variables, and also, parental practices (both support and psychological control) predicted global trait EI in adolescents. Some gender-specific differences were found: both APC and DPC were negative predictors of trait EI in males, whereas only APC significantly predicted trait EI in females. Future longitudinal studies are needed to examine these results and to shed light on the processes involved in the development of trait EI. STATEMENT OF CONTRIBUTION: What is already known on the subject? There exists strong evidence of the interaction between parenting practices and emotional development in children and adolescents. Therefore, parental psychological control is negatively correlated with peer support and self-esteem, and positively related to anxiety and aggressive behaviour in children. However, there is paucity on research examining the relationship between parenting and trait EI in children. What does this study adds? This study extends earlier work in this field and investigates whether there is a relationship between trait EI and parenting practices (parental support and psychological control) and whether it depends on child and parent gender. This study, therefore, aims to investigate, for the first time, parental factors that may, in addition to those constitutional, be related to trait EI in children. Specifically, the objective of the present study was to investigate whether parenting practices would predict adolescents' trait EI and whether these relations depend on the gender.

Development of the Point-of-Care Key Evidence Tool (POCKET): a checklist for multi-dimensional evidence generation in point-of-care tests.

Background This study aimed to develop the Point-of-Care Key Evidence Tool (POCKET); a multi-dimensional checklist to guide the evaluation of point-of-care tests (POCTs) incorporating validity, utility, usability, cost-effectiveness and patient experience. The motivation for this was to improve the efficiency of evidence generation in POCTs and reduce the lead-time for the adoption of novel POCTs. Methods A mixed qualitative and quantitative approach was applied. Following a literature search, a three round Delphi process was undertaken incorporating a semi-structured interview study and two questionnaire rounds. Participants included clinicians, laboratory personnel, commissioners, regulators (including members of National Institute for Health and Care Excellence [NICE] committees), patients, industry representatives and methodologists. Qualitative data were analysed based on grounded theory. The final tool was revised at an expert stakeholder workshop. Results Forty-three participants were interviewed within the semi-structured interview study, 32 participated in the questionnaire rounds and nine stakeholders attended the expert workshop. The final version of the POCKET checklist contains 65 different evidence requirements grouped into seven themes. Face validity, content validity and usability has been demonstrated. There exists a shortfall in the evidence that industry and research methodologists believe should be generated regarding POCTs and what is actually required by policy and decision makers to promote implementation into current healthcare pathways. Conclusions This study has led to the development of POCKET, a checklist for evidence generation and synthesis in POCTs. This aims to guide industry and researchers to the evidence that is required by decision makers to facilitate POCT adoption so that the benefits they can bring to patients can be effectively realised.

What Attitudes and Values Are Incorporated Into Self as Part of Professional Identity Construction When Becoming a Surgeon?

PURPOSE: To make explicit the attitudes and values of a community of surgeons, with the aim of understanding professional identity construction within a specific group of residents. METHOD: Using a grounded theory method, the authors collected data from 16 postgraduate surgeons through interviews. They complemented these initial interview data with ethnographic observations and additional descriptive interviews to explore the attitudes and values learned by surgeons during residency training (2010-2013). The participants were attending surgeons and residents in a general surgical training program in a university teaching hospital in the United Kingdom. RESULTS: Participating surgeons described learning personal values or attitudes that they regarded as core to "becoming a surgeon" and key to professional identity construction. They described learning to be a perfectionist, to be accountable, and to self-manage and be resilient. They discussed learning to be self-critical, sometimes with the unintended consequence of seeming neurotic. They described learning effective teamwork as well as learning to take initiative and be innovative, which enabled them to demonstrate leadership and drive actions and agendas forward within the health care organization where they worked. CONCLUSIONS: To the authors' knowledge, this is the first study to systematically explore the learning of professional identity amongst postgraduate surgeons. The study contributes to the literature on professional identity construction within medical education. The authors conclude that the demise of the apprenticeship model and the rise of duty hours limitations may affect not only the acquisition of technical skills but, more important, the construction of surgeon professional identity.

Applied investigation of person-specific and context-specific factors on postoperative recovery and clinical outcomes of patients undergoing gastrointestinal cancer surgery: multicentre European study.

INTRODUCTION: Cancer treatments have greatly advanced over the past two decades causing survival improvements and reduced complications from cancer surgery. However, the cancer diagnosis and the effects of treatment modalities pose a major risk to patients' psychological well-being. Given current interest and emerging evidence about the importance of psychological and social factors on cancer survival and coping with cancer treatments, this study will build and expand research in order to identify key modifiable psychosocial variables that contribute to better physical and mental health following gastrointestinal cancer (GIC) surgery. OBJECTIVES: To elucidate the incidence of postoperative psychiatric morbidity within 6 months following GIC surgery. To identify key measurable modifiable preoperative psychological factors that can significantly affect postoperative psychiatric morbidity in patients undergoing surgery for GIC. To clarify the changes seen in a patient's psychological well-being during their treatment pathway for GIC. METHODS AND ANALYSIS: This multicentre study has an observational longitudinal study design. In total, 1000 patients will be screened with a multicomponent psychological questionnaire at four different time points: at diagnosis, preoperatively, 1 and 6 months after surgery. Data from this questionnaire will be linked to postoperative complications including psychiatric morbidity, length of hospital stay and recovery to normal activity. ETHICS AND DISSEMINATION: NHS Health Research Authority approval was gained on (REC reference 15.LO/1847) for the completion of this study. Multiple platforms will be used for the dissemination of the research data, including international clinical and patient group presentations and publication of research outputs in a high impact clinical journal.

COLOR III: a multicentre randomised clinical trial comparing transanal TME versus laparoscopic TME for mid and low rectal cancer.

INTRODUCTION: Total mesorectal excision (TME) is an essential component of surgical management of rectal cancer. Both open and laparoscopic TME have been proven to be oncologically safe. However, it remains a challenge to achieve complete TME with clear circumferential resections margin (CRM) with the conventional transabdominal approach, particularly in mid and low rectal tumours. Transanal TME (TaTME) was developed to improve oncological and functional outcomes of patients with mid and low rectal cancer. METHODS: An international, multicentre, superiority, randomised trial was designed to compare TaTME and conventional laparoscopic TME as the surgical treatment of mid and low rectal carcinomas. The primary endpoint is involved CRM. Secondary endpoints include completeness of mesorectum, residual mesorectum, morbidity and mortality, local recurrence, disease-free and overall survival, percentage of sphincter-saving procedures, functional outcome and quality of life. A Quality Assurance Protocol including centralised MRI review, histopathology re-evaluation, standardisation of surgical techniques, and monitoring and assessment of surgical quality will be conducted. DISCUSSION: The difference in involvement of CRM between the two treatment strategies is thought to be in favour of the TaTME. TaTME is therefore expected to be superior to laparoscopic TME in terms of oncological outcomes in case of mid and low rectal carcinomas.

A research protocol for developing a Point-Of-Care Key Evidence Tool 'POCKET': a checklist for multidimensional evidence reporting on point-of-care in vitro diagnostics.

INTRODUCTION: Point-of-care in vitro diagnostics (POC-IVD) are increasingly becoming widespread as an acceptable means of providing rapid diagnostic results to facilitate decision-making in many clinical pathways. Evidence in utility, usability and cost-effectiveness is currently provided in a fragmented and detached manner that is fraught with methodological challenges given the disruptive nature these tests have on the clinical pathway. The Point-of-care Key Evidence Tool (POCKET) checklist aims to provide an integrated evidence-based framework that incorporates all required evidence to guide the evaluation of POC-IVD to meet the needs of policy and decisionmakers in the National Health Service (NHS). METHODS AND ANALYSIS: A multimethod approach will be applied in order to develop the POCKET. A thorough literature review has formed the basis of a robust Delphi process and validation study. Semistructured interviews are being undertaken with POC-IVD stakeholders, including industry, regulators, commissioners, clinicians and patients to understand what evidence is required to facilitate decision-making. Emergent themes will be translated into a series of statements to form a survey questionnaire that aims to reach a consensus in each stakeholder group to what needs to be included in the tool. Results will be presented to a workshop to discuss the statements brought forward and the optimal format for the tool. Once assembled, the tool will be field-tested through case studies to ensure validity and usability and inform refinement, if required. The final version will be published online with a call for comments. Limitations include unpredictable sample representation, development of compromise position rather than consensus, and absence of blinding in validation exercise. ETHICS AND DISSEMINATION: The Imperial College Joint Research Compliance Office and the Imperial College Hospitals NHS Trust R&D department have approved the protocol. The checklist tool will be disseminated through a PhD thesis, a website, peer-reviewed publication, academic conferences and formal presentations.

Making meaning from sensory cues: a qualitative investigation of postgraduate learning in the operating room.

PURPOSE: The authors aimed to map and explicate what surgeons perceive they learn in the operating room. METHOD: The researchers used a grounded theory method in which data were iteratively collected through semistructured one-to-one interviews in 2010 and 2011 at four participating hospital sites. A four-person data analysis team from differing academic backgrounds qualitatively analyzed the content of the transcripts employing an immersion/crystallization approach. RESULTS: Participants were 22 UK surgeons, some of whom were in training at the time of the study and some of whom were attending surgeons. Major themes of learning in the operating room were perceived to be factual knowledge, motor skills, sensory semiosis, adaptive strategies, team working and management, and attitudes and behaviors. The analysis team classified 277 data points (short paragraphs or groups of sentences conveying meaning) under these major themes and subthemes. A key component of learning in the operating room that emerged from these data was sensory semiosis, defined as learning to make sense of visual and haptic cues. CONCLUSIONS: Although the authors found that learning in the operating room occurred across a wide range of domains, sensory semiosis was found to be an important theme that has not previously been fully acknowledged or discussed in the surgical literature. The discussion draws on the wider literature from the social sciences and cognitive psychology literature to examine how professionals learn to make meaning from "signs" making parallels with other medical specialties.

Residential mobility, neighbourhood deprivation and children's behaviour in the UK.

Using data from the first two waves (in 2001/02 and 2004) of the UK's Millennium Cohort Study (MCS), we attempted to separate the effect of residential mobility from the effect of neighbourhood deprivation on children's emotional and behavioural problems. Our sample was 23,162 children (aged 3-16 years) clustered in 12,692 families. We measured neighbourhood deprivation with the Index of Multiple Deprivation, a measure of neighbourhood-level socio-economic disadvantage, and residential mobility as household move between waves. Being in a lower deprivation neighbourhood at Wave 1 was related to lower scores of both emotional and behavioural problems 2 years later, even after adjustment for child's age and sex, family adversity, family structure and maternal psychological distress. However, children whose families subsequently moved-even within or between lower deprivation neighbourhoods-were at higher risk of emotional and behavioural problems. Adjusting for family socio-economic disadvantage at Wave 1 explained the association of residential mobility with emotional but not with behavioural problems, which remained significant even after accounting for change in family's socio-economic disadvantage between waves.

Adverse life events and emotional and behavioural problems in adolescence: the role of coping and emotion regulation.

We tested whether emotion regulation (cognitive reappraisal and expressive suppression) and coping (distraction, avoidance, support seeking and active coping) mediate or moderate the association between change in life stress (change in number of adverse life events) and change in adolescent problem behaviour. We used prospective and retrospective longitudinal data from a community sample. We measured change in problem behaviour as emotional and behavioural problems at Time 2 controlling for emotional and behavioural problems at Time 1, a year earlier. We measured change in life stress as life stress between Times 1 and 2, controlling for total previous life stress (before Time 1). Neither coping nor emotion regulation mediated the association between change in life stress and change in problem behaviour. Avoidance and expressive suppression were related to an increase in problem behaviour. Only cognitive reappraisal moderated the effect of increase in life stress on worsening of problem behaviour, suggesting that, as expected, cognitive reappraisal was a protective factor. In adolescents who reported they habitually reappraise, the association between change in life stress and change in emotional and behavioural problems was non-significant.

The role of general cognitive ability in moderating the relation of adverse life events to emotional and behavioural problems.

Previous studies have established the role of various measures of cognitive functioning in dampening the association between adverse life events ('life stress') and adolescents' emotional and behavioural problems. However, it is not yet clear if general cognitive ability ('intelligence') is a protective factor. In this study of 1,175 10- to 19-year-olds in five secondary schools in England, we explored this issue. We found that even after controlling for sex, age, family poverty, and special educational needs, the association of life stress with emotional, hyperactivity, and conduct problems was significant. General cognitive ability moderated the association between life stress and conduct problems; among adolescents with higher than average general cognitive ability, the association between life stress and conduct problems was non-significant.