Dignity during work-integrated learning: Piloting an online learning resource for placement students and supervisors.

What was the educational challenge?Medical student abuse within work-integrated learning (WIL) is well-reported, with negative consequences for wellbeing, motivation, and learning. Conversely, workplace dignity, described as respecting the worth of others and self, has positive impacts on wellbeing, learning, and relationships for WIL students and supervisors. Stakeholders often struggle to articulate what workplace dignity means, and can downplay or do nothing in the face of WIL indignities.What was the solution and how was this implemented?We created an innovative research-informed online learning resource about WIL dignity to improve stakeholders' understandings and help them get the best from WIL placements ensuring these are dignified, safe, and educationally productive. The resource included three topics: (a) workplace dignity and why it matters; (b) upholding dignity; and (c) strengthening dignity.What lessons were learned?We conducted a pilot qualitative evaluation involving 13 semi-structured interviews with students and supervisors to elicit their views and experiences of the resource. Our key findings across three overarching categories were: (1) perceived benefits (motivations to complete the resource; content of the resource; online pedagogies); (2) potential applications of learning (reinforcing existing knowledge; developing new knowledge; promoting reflection; changing workplace practices); and (3) suggested improvements (barriers to resource use; resource content; online pedagogies; timing of resource implementation; embedding the resource in broader learning).What are the next steps?Although we identified numerous perceived benefits, and applications of learning, the findings suggested opportunities for further development, especially improving the resource's social interactivity. We recommend that further resource implementation includes student-educator and student-peer interactivity to maximise learning, and longitudinal evaluation of the resource.

Factors influencing decision-making processes for intensive care therapy goals: A systematic integrative review.

BACKGROUND: Delivering intensive care therapies concordant with patients' values and preferences is considered gold standard care. To achieve this, healthcare professionals must better understand decision-making processes and factors influencing them. AIM: The aim of this study was to explore factors influencing decision-making processes about implementing and limiting intensive care therapies. DESIGN: Systematic integrative review, synthesising quantitative, qualitative, and mixed-methods studies. METHODS: Five databases were searched (Medline, The Cochrane central register of controlled trials, Embase, PsycINFO, and CINAHL plus) for peer-reviewed, primary research published in English from 2010 to Oct 2022. Quantitative, qualitative, or mixed-methods studies focussing on intensive care decision-making were included for appraisal. Full-text review and quality screening included the Critical Appraisal Skills Program tool for qualitative and mixed methods and the Medical Education Research Quality Instrument for quantitative studies. Papers were reviewed by two authors independently, and a third author resolved disagreements. The primary author developed a thematic coding framework and performed coding and pattern identification using NVivo, with regular group discussions. RESULTS: Of the 83 studies, 44 were qualitative, 32 quantitative, and seven mixed-methods studies. Seven key themes were identified: what the decision is about; who is making the decision; characteristics of the decision-maker; factors influencing medical prognostication; clinician-patient/surrogate communication; factors affecting decisional concordance; and how interactions affect decisional concordance. Substantial thematic overlaps existed. The most reported decision was whether to withhold therapies, and the most common decision-maker was the clinician. Whether a treatment recommendation was concordant was influenced by multiple factors including institutional cultures and clinician continuity. CONCLUSION: Decision-making relating to intensive care unit therapy goals is complicated. The current review identifies that breadth of decision-makers, and the complexity of intersecting factors has not previously been incorporated into interventions or considered within a single review. Its findings provide a basis for future research and training to improve decisional concordance between clinicians and patients/surrogates with regards to intensive care unit therapies.

A roadmap to realist interviews in health professions education research: Recommendations based on a critical analysis.

CONTEXT: Realist evaluation is increasingly employed in health professions education research (HPER) because it can unpack the extent to which complex educational interventions work (or not), for whom under what circumstances and how. While realist evaluation is not wedded to particular methods, realist interviews are commonly the primary, if not only, data collection method in realist evaluations. While qualitative interviewing from an interpretivist standpoint has been well-articulated in the HPER literature, realist interviewing differs substantially. The former elicits participants' views and experiences of a topic of inquiry, whereas realist interviewing focuses on building, testing and/or refining programme theory. Therefore, this article aims to help readers better understand, conduct, report and critique realist interviews as part of realist evaluations. METHODS: In this paper, we describe what realist approaches are, what realist interviewing is and why realist interviewing matters. We outline five stages to realist interviewing (developing initial programme theory, realist sampling/samples, the interview itself, realist analysis and reporting realist interviews), drawing on two illustrative cases from our own realist evaluations employing interviewing to bring theory to life. We provide a critical analysis of 12 realist evaluations employing interviewing in the HPER literature. Alongside reporting standards, and our own realist interviewing experiences, this critical analysis of published articles serves to foreground our recommendations for realist interviewing. CONCLUSIONS: We encourage HPE researchers to consider realist interviews as part of realist evaluations of complex interventions. Our critical analysis reveals that realist interviews can provide unique insights into HPE, but authors now need to report their sampling approach, type of interviewing and interview questions more explicitly. Studies should also more explicitly draw on existing realist interviewing literature and follow reporting guidelines for realist evaluations. We hope this paper provides a useful roadmap to conducting, reporting and critically appraising realist interviews in HPER.

Unpacking economic programme theory for supervision training: Preliminary steps towards realist economic evaluation.

INTRODUCTION: Cost studies are increasingly popular given resource constraints. While scholars stress the context-dependent nature of cost, and the importance of theory, cost studies remain context-blind and atheoretical. However, realist economic evaluation (REE) privileges context and the testing/refinement of economic programme theory. This preliminary REE serves to test and refine economic programme theory for supervision training programmes of different durations to better inform future programme design/implementation. METHODS: Our preliminary REE unpacked how short (half-day) and extended (12 week) supervision training programmes in Victoria, Australia, produced costs and outcomes. We employed mixed methods: qualitative realist and quantitative cost methods. Economically optimised programme models were developed guided by identified cost-sensitive mechanisms and contexts. RESULTS: As part of identified context-mechanism-outcome configurations (CMOCs) for both training programmes, we found a wider diversity of positive outcomes but greater costs for the extended programme (11 outcomes; AU$3069/learner) compared with the short programme (7 outcomes; $385/learner). We identified four shared cost-sensitive mechanisms for both programmes (training duration, learner protected time, learner engagement, and facilitator competence) and one shared cost-sensitive context (learners' supervisory experience). We developed two economically optimised programme models: (1) short programme for experienced supervisors facilitated by senior educators ($406/learner); and (2) extended programme for inexperienced supervisors facilitated by junior educators ($2104/learner). DISCUSSION: Our initial economic programme theory was somewhat supported, refuted and refined. Results were partly consistent with previous research, but also extended it through unpacking cost-sensitive mechanisms and contexts. Although our preliminary REE fills a pressing gap in the methodology literature, conducting REE was challenging given our desire to integrate economic and realist analyses fully, and remain faithful to realist principles. Attention to training duration and experience levels of the facilitator-learner dyad may help to balance the cost and outcomes of training programmes.

Balancing the effectiveness and cost of online education: A preliminary realist economic evaluation.

PURPOSE: While online learning for faculty development has grown substantially over recent decades, it has been further accelerated in the face of the worldwide pandemic. The effectiveness of online learning has been repeatedly established through systematic reviews and meta-analyses, yet questions remain about its cost-effectiveness. This study evaluates how synchronous online supervision training workshops and their cost-effectiveness might work, and in what contexts. METHODS: We conducted preliminary realist economic evaluation including qualitative (13 realist interviews), and quantitative approaches (cost Ingredients method). We developed a cost-optimised model based on identified costs and cost-sensitive mechanisms. RESULTS: We identified 14 recurring patterns (so-called demi-regularities) illustrating multiple online workshop outcomes (e.g. satisfaction, engagement, knowledge), generated by various mechanisms (e.g. online technology, mixed pedagogies involving didactic and active/experiential learning, peer learning), and triggered by two contexts (supervisor experience levels, and workplace location). Each workshop cost $302.92 per learner, but the optimised model including senior facilitators cost $305.70. CONCLUSIONS: Our initial realist program theories were largely supported and refined. Although findings were largely concordant with previous literature, we illustrate how online workshop costs compare favourably with face-to-face alternatives. We encourage program developers to consider synchronous online learning for faculty development especially for remote learners, and in resource-constrained environments.

The applicability of generalisability and bias to health professions education's research.

CONTEXT: Research in health professions education (HPE) spans an array of topics and draws from a diversity of research domains , which brings richness to our understanding of complex phenomena and challenges us to appreciate different approaches to studying them. To fully appreciate and benefit from this diversity, scholars in HPE must be savvy to the hallmarks of rigour that differ across research approaches. In the absence of such recognition, the valuable contributions of many high-quality studies risk being undermined. METHODS: In this article, we delve into two constructs---generalisability and bias--that are commonly invoked in discussions of rigour in health professions education research. We inspect the meaning and applicability of these constructs to research conducted from different paradigms (i.e., positivist and constructivist) and orientations (i.e., objectivist and subjectivist) and then describe how scholars can demonstrate rigour when these constructs do not align with the assumptions underpinning their research. CONCLUSIONS: A one-size-fits-all approach to evaluating the rigour of HPE research disadvantages some approaches and threatens to reduce the diversity of research in our field. Generalisability and bias are two examples of problematic constructs within paradigms that embrace subjectivity; others are equally problematic. As a way forward, we encourage HPE scholars to inspect their assumptions about the nature and purpose of research-both to defend research rigour in their own studies and to ensure they apply standards of rigour that align with research they read and review.

Materials matter: Understanding the importance of sociomaterial assemblages for OSCE candidate performance.

INTRODUCTION: The OSCE is a sociomaterial assemblage-a meshing together of human and material components producing multiple effects. Materials matter because they shape candidate performance, with potentially calamitous career consequences if materials influence performance unjustly. Although the OSCE literature refers to materials, few papers study the sociomateriality of OSCEs. Therefore, we explored OSCE stakeholders' talk about sociomaterial assemblages to better understand their importance for candidate performance. METHODS: We conducted 15 focus groups with OSCE candidates (n = 42), examiners (n = 20) and simulated patients (n = 17) after an Australian postgraduate nursing OSCE. Sociomateriality informed our team-based framework analysis of data. RESULTS: Participants identified a multiplicity of OSCE materials (objects, technologies and spaces) thought to matter for candidate performance. Candidates' unfamiliarity with materials and missing or malfunctioning materials were reported to yield numerous negative impacts (eg cognitive overload, negative affect, time-wasting), thereby adversely affecting candidate performance. Both examiners and candidates made micro-adjustments to sociomaterial assemblages during the OSCE in order to make it work (eg candidates saying what they would do rather than doing it). Sometimes, such tinkering extended so far that sociomaterial assemblages were ruptured (eg examiners ignoring rubrics to help pass candidates), potentially influencing OSCE standardisation. DISCUSSION: Our novel empirical study extends previous conceptual work by illustrating wide-ranging sociomaterial assemblages influencing OSCE candidate performance. Further research is now needed employing sociomaterial approaches to further elucidate sociomaterial entanglements in diverse OSCEs. We encourage OSCE stakeholders to become more attuned to the productive nature of materials within all stages of OSCE design and implementation.

Exploring health care graduates' conceptualisations of preparedness for practice: A longitudinal qualitative research study.

INTRODUCTION: Although preparedness for practice (P4P) has been variously described, little shared understanding exists about what P4P is across the health professions. How P4P is conceptualised matters, because this shapes how stakeholders think, talk about and act towards it. Further, multiple understandings can result in diverse expectations for graduate performance. This study therefore explores health care learners' solicited and unsolicited conceptualisations of P4P over their early graduate transition. METHODS: We conducted longitudinal qualitative research including individual and group entrance interviews (phase 1: n = 35), longitudinal audio-diaries (phase 2: n = 30), and individual and group exit interviews (phase 3: n = 22) with learners from four disciplines (dietetics, medicine, nursing and pharmacy). We employed framework analysis to interrogate data cross-sectionally and longitudinally. RESULTS: We found 13 conceptualisations of P4P (eg knowledge, confidence), broadly similar across the disciplines. We found some conceptualisations dominant in both solicited and unsolicited talk (eg skills), some dominant only in solicited talk (eg competence) and others dominant only in unsolicited talk (eg experience). Although most conceptualisations appeared relatively stable across time, some appeared to dominate at certain time points only (eg employability and skills in phases 1 and 2, and competence in phase 3). DISCUSSION: This novel study extends previous uniprofessional work by illustrating a broader array of conceptualisations, differences between professions, solicited versus unsolicited talk and longitudinal cohort patterns. We encourage health care educators to discuss these different P4P understandings in graduate transition interventions. Further research is needed to explore other stakeholders' conceptualisations, and over a duration beyond the early graduate transition.

Exploring the impact of education on preclinical medical students' tolerance of uncertainty: a qualitative longitudinal study.

Tolerance of uncertainty, a construct describing individuals' responses to perceived uncertainty, has relevancy across healthcare systems, yet little work explores the impact of education on medical students' tolerance of uncertainty. While debate remains as to whether tolerance of uncertainty is changeable or static, the prevailing conceptual healthcare tolerance of uncertainty model (Hillen et al. in Soc Sci Med 180:62-75, 2017) suggests that individuals' tolerance of uncertainty is influenced by so-called moderators. Evidence regarding education's role as a moderator of tolerance of uncertainty is, however, lacking. Preliminary work exploring medical students' professional identity formation within anatomy learning identified tolerance of uncertainty as a theme warranting further exploration. Extending from this work, our research question was: How does the anatomy education learning environment impact medical students' tolerance of uncertainty? To address this question, qualitative data were collected longitudinally across two successive cohorts through online discussion forums during semester and end of semester interviews. Framework analysis identified five stimuli of uncertainty, four moderators of uncertainty, and cognitive, emotional and behavioral responses to uncertainty with variable valency (positive and/or negative). Longitudinal data analyses indicated changes in stimuli, moderators and responses to uncertainty over time, suggesting that tolerance of uncertainty is changeable rather than static. While our findings support the Hillen et al. (Soc Sci Med 180:62-75, 2017) model in parts, our data extend this model and the previous literature. Although further research is needed about students' development of tolerance of uncertainty in the clinical learning environment, we encourage medical educators to incorporate aspects of tolerance of uncertainty into curricular and learning environments.

Doctors' identity transitions: Choosing to occupy a state of 'betwixt and between'.

CONTEXT: During transitions, doctors engage in identity work to adapt to changes in multiple domains. Accompanied by this are dynamic 'liminal' phases. Definitions of liminality denote a state of being 'betwixt and between' identities. From a social constructionist perspective, being betwixt and between professional identities may either involve a sense of disrupted self, requiring identity work to move through and out of being betwixt and between (ie, temporary liminality), or refer to the experiences of temporary workers (eg, locum doctors) or those in dual roles (eg, clinician-managers) who find themselves perpetually betwixt and between professional identities (ie, perpetual liminality) and use identity work to make themselves contextually relevant. In the health care literature, liminality is conceptualised as a linear process, but this does not align with current notions of transitions that are depicted as multiple, complex and non-linear. METHODS: We undertook a longitudinal narrative inquiry study using audio-diaries to explore how doctors experience liminality during trainee-to-trained transitions. In three phases, we: (a) interviewed 20 doctors about his or her trainee-to-trained transitions; (b) collected longitudinal audio-diaries from 17 doctors for 6-9 months, and (c) undertook exit interviews with these 17 doctors. Data were analysed thematically, both cross-sectionally and longitudinally, using identity work theory as an analytical lens. RESULTS: All participants experienced liminality. Our analysis enabled us to identify temporary and perpetual liminal experiences. Furthermore, fine-grained analysis of participants' identity talk enabled us to identify points in participants' journeys at which he or she rejected identity grants associated with his or her trained status and instead preferred to remain in and thus occupy liminality (ie, neither trainee nor trained doctor). CONCLUSIONS: This paper is the first to explore longitudinally doctors' liminal experiences through trainee-to-trained transitions. Our findings also make conceptual contributions to the health care literature, as well as the wider interdisciplinary liminality literature, by adding further layers to conceptualisations and introducing the notion of occupying liminality.

Female victims and female perpetrators: medical students' narratives of gender dynamics and professionalism dilemmas.

Medicine is a gendered discipline, in which women, both as patients and practitioners, have often held subordinate positions. The reproduction of dominant gender biases in the medical setting can negatively impact the professional development of medical students and the wellbeing of patients. In this analysis of medical students' narratives of professionalism dilemmas, we explore students' experiences of gender bias in hospital settings. Seventy-one students participated in 12 group interviews, where they discussed witnessing or participating in various activities that they thought were professionalism lapses. Within the dataset, 21 narratives had a distinctly gendered component broadly pertaining to patient dignity and safety dilemmas, informed consent issues, and female student abuse. Interestingly, perpetrators of such acts were commonly female healthcare professionals and educators. Although students recognized such acts as professionalism lapses and often expressed concern for patient wellbeing, students did not intervene or report such acts due to hierarchical cultural contexts, and at times even reproduced the discriminatory behavior they were criticizing. This raises concerns about medical students' professionalism development and the extent to which gender bias is ingrained within particular medical systems. The normalization of disrespectful and abusive treatment of female patients poses immediate and future consequences to the wellbeing and safety of women. Furthermore, the same socio-cultural values that sustain these acts may account for perpetrators often being women themselves as they strive to overcome their subordinate position within medicine.

Student dignity during work-integrated learning: a qualitative study exploring student and supervisors' perspectives.

While University students increasingly participate in work-integrated learning (WIL), their dignity is often violated during WIL. The current literature is limited in so far as it typically focuses on student perspectives within healthcare contexts and does not use the concept of 'dignity'. Instead, this study explored student and supervisor perspectives on student dignity during WIL across healthcare and non-healthcare disciplines. Research questions included: What are: (1) types of student dignity experiences and patterns by groups; (2) factors contributing to experiences; (3) consequences of experiences? Sixty-five semi-structured interviews were conducted using narrative interviewing techniques with 30 supervisors and 46 students from healthcare (medicine, nursing and counselling) and non-healthcare (business, law and education) disciplines. Data were analyzed using framework analysis. Nine common narrative types were identified within 344 stories: verbal abuse, right for learning opportunities, care, inclusion, reasonable expectations, right for appropriate feedback, equality, trust, and right to be informed. Factors contributing to dignity experiences and consequences were often at the individual level (e.g. student/supervisor characteristics). We found some salient differences in perceptions of experiences between students and supervisors, but few differences between healthcare and non-healthcare disciplines. This study extends WIL research based on student perspectives in healthcare, and provides practice and further research guidance to enhance student dignity during WIL.

Supervision training in healthcare: a realist synthesis.

Supervision matters: it serves educational, supportive and management functions. Despite a plethora of evidence on the effectiveness of supervision, scant evidence for the impact of supervision training exists. While three previous literature reviews have begun to examine the effectiveness of supervision training, they fail to explore the extent to which supervision training works, for whom, and why. We adopted a realist approach to answer the question: to what extent do supervision training interventions work (or not), for whom and in what circumstances, and why? We conducted a team-based realist synthesis of the supervision training literature focusing on Pawson's five stages: (1) clarifying the scope; (2) determining the search strategy; (3) study selection; (4) data extraction; and (5) data synthesis. We extracted contexts (C), mechanisms (M) and outcomes (O) and CMO configurations from 29 outputs including short (n = 19) and extended-duration (n = 10) supervision training interventions. Irrespective of duration, interventions including mixed pedagogies involving active and/or experiential learning, social learning and protected time served as mechanisms triggering multiple positive supervisor outcomes. Short-duration interventions also led to positive outcomes through mechanisms such as supervisor characteristics, whereas facilitator characteristics was a key mechanism triggering positive and negative outcomes for extended-duration interventions. Disciplinary and organisational contexts were not especially influential. While our realist synthesis builds on previous non-realist literature reviews, our findings extend previous work considerably. Our realist synthesis presents a broader array of outcomes and mechanisms than have been previously identified, and provides novel insights into the causal pathways in which short and extended-duration supervision training interventions produce their effects. Future realist evaluation should explore further any differences between short and extended-duration interventions. Educators are encouraged to prioritize mixed pedagogies, social learning and protected time to maximize the positive supervisor outcomes from training.

An international study of trainee-trained transitions: Introducing the transition-to-trained-doctor (T3D) model.

Background: Throughout their careers, doctors and other healthcare professionals experience numerous transitions. When supporting transitions, opportunities for development and learning should be maximized, while stressors having negative impacts on well-being should be minimized. Building on our international data, this study aimed to develop a conceptual model of the trainee-trained transition (i.e. the significant transitions experienced by doctors as they complete postgraduate training moving from trainee/resident status to medical specialist roles).Methods: Employing Multiple and Multidimensional Transitions (MMT) theory and current conceptualizations of clinical context, this study undertook secondary analysis of 55 interviews with doctors from three countries (Netherlands, Cananda and the UK) undergoing trainee-trained transitions.Results: Through this analysis, the Transition-To-Trained-Doctor (T3D) conceptual model has been developed. This model takes into consideration the multiple contexts and multiple domains in which transitions take place.Discussion: This model is significant in that it has several uses and is applicable across countries: to remind doctors, managers and medical educators of the complexity of transitions; to frame and facilitate supportive conversations; and as a basis to teach about transitions.

Student and clinician identities: how are identities constructed in interprofessional narratives?

CONTEXT: Although the literature on professional identity formation in medical education is increasing, it is scant by comparison on student and clinician identities within interprofessional contexts. We therefore adopt a novel discursive approach to identities to explore how soon-to-become graduates and workplace-based clinicians construct their own and others' identities in interprofessional student-clinician (IPSC) interaction narratives. METHODS: We conducted a qualitative narrative interview study with 38 students and 23 clinicians representing the fields of medicine, midwifery, nursing, occupational therapy, paramedicine and physiotherapy. Through framework analysis, we identified the breadth of student and clinician identity constructions across 208 IPSC interaction narratives, and explored how common constructions differed by narrative and narrator. Through in-depth positioning analysis, we explored how student and clinician identities are discursively positioned within two selected IPSC interaction narratives. RESULTS: We identified 11 common constructions of student identities and eight common constructions of clinician identities across all 208 narratives. We found differences in identity constructions across positively versus negatively evaluated narratives, and student versus clinician narrators, highlighting the rhetorical nature of narratives. Our in-depth positioning analysis of two narratives illustrates how one student and one clinician discursively positioned theirs and others' identities during interprofessional interactions, and how identities vary depending on narrators' evaluations of their stories. Although both positioning analyses illustrate how the narrators' language serves to reproduce the common societal discourse of interprofessional conflict, the clinician narrative also draws on the competing discourse of interprofessional collaboration. CONCLUSIONS: Although some of the identities support previous uniprofessional research, our findings illustrate greater breadth and depth in terms of student and clinician identities within interprofessional contexts. We encourage educators to embed identities curricula into existing workplace learning for students and clinicians to help them make sense of their developing professional and interprofessional identities. Workplace educators should facilitate meaningful IPSC interactions to promote interprofessional learning and collaboration.

Setting priorities for health education research: A mixed methods study.

Introduction: Identifying priority research topics that meet the needs of multiple stakeholders should maximize research investment. Aim: To identify priorities for health education research. Methods: A three-stage sequential mixed methods study was conducted. Priorities for health education research were identified through a qualitative survey with 104 students, patients, academics, and clinicians across five health sciences and 12 professions (stage 1). These findings were analyzed using framework analysis and transposed into a quantitative survey whereby 780 stakeholders rated and ranked the identified priorities. Descriptive statistics identified priorities, exploratory factor analysis grouped priorities and differences between stakeholders were determined using Mann-Whitney U tests (stage 2). Six individual or group interviews with 16 participants (stage 3) further explicated the results from previous stages. Results: Of 30 priorities identified, the top were: how best to ensure students develop the required skills for work; how to promote resiliency and well-being in students; and ensuring the curriculum prepares students for work. For the majority of priorities, no significant differences were found between different stakeholder groups. Conclusions: These findings will be used to inform health educational research strategy both locally and nationally. Further research should explore if setting priorities can be translated effectively into education research policy and practice.

3 versus 6 months of adjuvant oxaliplatin-fluoropyrimidine combination therapy for colorectal cancer (SCOT): an international, randomised, phase 3, non-inferiority trial.

BACKGROUND: 6 months of oxaliplatin-containing chemotherapy is usually given as adjuvant treatment for stage 3 colorectal cancer. We investigated whether 3 months of oxaliplatin-containing chemotherapy would be non-inferior to the usual 6 months of treatment. METHODS: The SCOT study was an international, randomised, phase 3, non-inferiority trial done at 244 centres. Patients aged 18 years or older with high-risk stage II and stage III colorectal cancer underwent central randomisation with minimisation for centre, choice of regimen, sex, disease site, N stage, T stage, and the starting dose of capecitabine. Patients were assigned (1:1) to receive 3 months or 6 months of adjuvant oxaliplatin-containing chemotherapy. The chemotherapy regimens could consist of CAPOX (capecitabine and oxaliplatin) or FOLFOX (bolus and infused fluorouracil with oxaliplatin). The regimen was selected before randomisation in accordance with choices of the patient and treating physician. The primary study endpoint was disease-free survival and the non-inferiority margin was a hazard ratio of 1·13. The primary analysis was done in the intention-to-treat population and safety was assessed in patients who started study treatment. This trial is registered with ISRCTN, number ISRCTN59757862, and follow-up is continuing. FINDINGS: 6088 patients underwent randomisation between March 27, 2008, and Nov 29, 2013. The intended treatment was FOLFOX in 1981 patients and CAPOX in 4107 patients. 3044 patients were assigned to 3 month group and 3044 were assigned to 6 month group. Nine patients in the 3 month group and 14 patients in the 6 month group did not consent for their data to be used, leaving 3035 patients in the 3 month group and 3030 patients in the 6 month group for the intention-to-treat analyses. At the cutoff date for analysis, there had been 1482 disease-free survival events, with 740 in the 3 month group and 742 in the 6 month group. 3 year disease-free survival was 76·7% (95% CI 75·1-78·2) for the 3 month group and 77·1% (75·6-78·6) for the 6 month group, giving a hazard ratio of 1·006 (0·909-1·114, test for non-inferiority p=0·012), significantly below the non-inferiority margin. Peripheral neuropathy of grade 2 or worse was more common in the 6 month group (237 [58%] of 409 patients for the subset with safety data) than in the 3 month group (103 [25%] of 420) and was long-lasting and associated with worse quality of life. 1098 serious adverse events were reported (492 reports in the 3 month group and 606 reports in the 6 month group) and 32 treatment-related deaths occurred (16 in each group). INTERPRETATION: In the whole study population, 3 months of oxaliplatin-containing adjuvant chemotherapy was non-inferior to 6 months of the same therapy for patients with high-risk stage II and stage III colorectal cancer and was associated with reduced toxicity and improved quality of life. Despite the fact the study was underpowered, these data suggest that a shorter duration leads to similar survival outcomes with better quality of life and thus might represent a new standard of care. FUNDING: Medical Research Council, Swedish Cancer Society, NETSCC, and Cancer Research UK.

Circulating biomarkers during treatment in patients with advanced biliary tract cancer receiving cediranib in the UK ABC-03 trial.

BACKGROUND: Advanced biliary tract cancer (ABC) has a poor prognosis. Cediranib, in addition to cisplatin/gemcitabine [CisGem], improved the response rate, but did not improve the progression-free survival (PFS) in the ABC-03 study. Minimally invasive biomarkers predictive of cediranib benefit may improve patient outcomes. METHODS: Changes in 15 circulating plasma angiogenesis or inflammatory-related proteins and cytokeratin-18 (CK18), measured at baseline and during therapy until disease progression, were correlated with overall survival (OS) using time-varying covariate Cox models (TVC). RESULTS: Samples were available from n = 117/124 (94%) patients. Circulating Ang1&2, FGFb, PDGFbb, VEGFC, VEGFR1 and CK18 decreased as a result of the therapy, independent of treatment with cediranib. Circulating VEGFR2 and Tie2 were preferentially reduced by cediranib. Patients with increasing levels of VEGFA at any time had a worse PFS and OS; this detrimental effect was attenuated in patients receiving cediranib. TVC analysis revealed CK18 and VEGFR2 increases correlated with poorer OS in all patients (P < 0.001 and P = 0.02, respectively). CONCLUSIONS: Rising circulating VEGFA levels in patients with ABC, treated with CisGem, are associated with worse PFS and OS, not seen in patients receiving cediranib. Rising levels of markers of tumour burden (CK18) and potential resistance (VEGFR2) are associated with worse outcomes and warrant validation.

SCOT: a comparison of cost-effectiveness from a large randomised phase III trial of two durations of adjuvant Oxaliplatin combination chemotherapy for colorectal cancer.

BACKGROUND: The Short Course Oncology Therapy (SCOT) study is an international, multicentre, non-inferiority randomised controlled trial assessing the efficacy, toxicity, and cost-effectiveness of 3 months (3 M) versus the usually given 6 months (6 M) of adjuvant chemotherapy in colorectal cancer. METHODS: In total, 6088 patients with fully resected high-risk stage II or stage III colorectal cancer were randomised and followed up for 3-8 years. The within-trial cost-effectiveness analysis from a UK health-care perspective is presented using the resource use data, quality of life (EQ-5D-3L), time on treatment (ToT), disease-free survival after treatment (DFS) and overall survival (OS) data. Quality-adjusted partitioned survival analysis and Kaplan-Meier Sample Average Estimator estimated QALYs and costs. Probabilistic sensitivity and subgroup analysis was undertaken. RESULTS: The 3 M arm is less costly (-£4881; 95% CI: -£6269; -£3492) and entails (non-significant) QALY gains (0.08; 95% CI: -0.086; 0.230) due to a better significant quality of life. The net monetary benefit was significantly higher in 3 M under a wide range of monetary values of a QALY. The subgroup analysis found similar results for patients in the CAPOX regimen. However, for the FOLFOX regimen, 3 M had lower QALYs than 6 M (not statistically significant). CONCLUSIONS: Overall, 3 M dominates 6 M with no significant detrimental impact on QALYs. The results provide the economic case that a 3 M treatment strategy should be considered a new standard of care.