Centre selection for clinical trials and the generalisability of results: a mixed methods study.

BACKGROUND: The rationale for centre selection in randomised controlled trials (RCTs) is often unclear but may have important implications for the generalisability of trial results. The aims of this study were to evaluate the factors which currently influence centre selection in RCTs and consider how generalisability considerations inform current and optimal practice. METHODS AND FINDINGS: Mixed methods approach consisting of a systematic review and meta-summary of centre selection criteria reported in RCT protocols funded by the UK National Institute of Health Research (NIHR) initiated between January 2005-January 2012; and an online survey on the topic of current and optimal centre selection, distributed to professionals in the 48 UK Clinical Trials Units and 10 NIHR Research Design Services. The survey design was informed by the systematic review and by two focus groups conducted with trialists at the Birmingham Centre for Clinical Trials. 129 trial protocols were included in the systematic review, with a total target sample size in excess of 317,000 participants. The meta-summary identified 53 unique centre selection criteria. 78 protocols (60%) provided at least one criterion for centre selection, but only 31 (24%) protocols explicitly acknowledged generalisability. This is consistent with the survey findings (n = 70), where less than a third of participants reported generalisability as a key driver of centre selection in current practice. This contrasts with trialists' views on optimal practice, where generalisability in terms of clinical practice, population characteristics and economic results were prime considerations for 60% (n = 42), 57% (n = 40) and 46% (n = 32) of respondents, respectively. CONCLUSIONS: Centres are rarely enrolled in RCTs with an explicit view to external validity, although trialists acknowledge that incorporating generalisability in centre selection should ideally be more prominent. There is a need to operationalize 'generalisability' and incorporate it at the design stage of RCTs so that results are readily transferable to 'real world' practice

A Complete Redesign of the Cardiopulmonary Resuscitation (CPR) and Automated External Defibrillator (AED) Learning Experience

Survival following sudden cardiac arrest in the community can be framed as a complex systems problem for which systems thinking and design methodologies may be applied. Focusing on the subsystem of the learning experience of cardiopulmonary resuscitation and use of an automated external defibrillator (CPR/AED), we used a systems approach to understand the current state of learning and a design methodology to identify improvements. A systems diagnosis identified six elements within the learning experience - need for training, opportunity for training, training class characteristics, perceived competence, anticipated event characteristics, and perceived readiness to act – each of which had positive and negative meanings and outcomes. As the elements are interactive and complex, the expected central property of learning – likelihood to act - may not be realized because of significant conflicts and obstructions. Design methodology identified 250 elements for an ideal CPR/AED learning experience which could be arranged as a containing system with eight interactive categories. Based on a system thinking and design methodology approach we suggested ten changes to improve the current state of the CPR/AED learning experience

Peer expectations about outstanding competencies of men and women medical students

Men and women enrolled in a combined premedical-medical school programme were asked as they began their clinical training to rate their anticipated competence on sixteen criteria relevant to medical practice. Competence dimensions tapped scientific/technical skills, dedication/commitment, and interpersonal skills. Students then were asked to nominate one classmate whom they expected might be‘the best’in each area. Self-ratings revealed few differences among men and women. Peer nominations, however, revealed a preponderance of male nominees in ten competence areas. Women dominated nominations only in the category of sensitivity to patients. Patterns persisted when peer nominations were controlled for students’academic standing and self-ratings on parallel dimensions. The data suggest that medical school peer groups share expectations about competencies of men and women as physicians which are consistent with generalized sex stereotypes and career patterns of men and women physicians.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74843/1/1467-9566.ep11340055.pd

Staff understanding of recovery-orientated mental health practice: a systematic review and narrative synthesis

Background: Mental health policy is for staff to transform their practice towards a recovery orientation. Staff understanding of recovery-orientated practice will influence the implementation of this policy. The aim of this study was to conduct a systematic review and narrative synthesis of empirical studies identifying clinician and manager conceptualisations of recovery-orientated practice. Methods: A systematic review of empirical primary research was conducted. Data sources were online databases (n = 8), journal table of contents (n = 5), internet, expert consultation (n = 13), reference lists of included studies and references to included studies. Narrative synthesis was used to integrate the findings. Results: A total of 10,125 studies were screened, 245 full papers were retrieved, and 22 were included (participants, n = 1163). The following three conceptualisations of recovery-orientated practice were identified: clinical recovery, personal recovery and service-defined recovery. Service-defined recovery is a new conceptualisation which translates recovery into practice according to the goals and financial needs of the organisation. Conclusions: Organisational priorities influence staff understanding of recovery support. This influence is leading to the emergence of an additional meaning of recovery. The impact of service-led approaches to operationalising recovery-orientated practice has not been evaluated. Trial Registration: The protocol for the review was pre-registered (PROSPERO 2013: CRD42013005942)

Making sense of the evolving nature of depression narratives and their inherent conflicts

Originally a psychiatric diagnosis fashioned by Western psychiatry in the 20th Century, depression evolved to encompass varying lineages of discourse and care. This article elucidates some of the current challenges – as well as emerging discourses – influencing the category of depression. Depression-like experiences are shaped by (at times conflicting) subjectivities, claims to knowledge, material realities, social contexts and access to resources. With no unified understanding of the category of ‘depression’ available, lay people, social and neuro scientists, GPs, psychiatrists, talking therapists and pharmaceutical companies all attempt to shape narratives of depression. The current paper focuses on patient narratives about depression – in the context of these wider debates – to better elucidate the ways in which depression discourses are publically developing along varying lines. In conclusion, the paper suggests that we could better conceptualise the resulting ‘depression(s)’ with concepts such as ‘society of mind’ and notions of subjectivity unbounded by individuals

Treatment effects may remain the same even when trial participants differed from the target population

Objective RCTs have been criticised for lacking external validity. We assessed whether a trial in people with type I diabetes mellitus (T1DM) mirrored the wider population, and applied sample-weighting methods to assess the impact of differences on our trial's findings. Study design and setting The REPOSE trial was nested within a large UK cohort capturing demographic, clinical and quality of life (QoL) data for people with T1DM undergoing structured diabetes-specific education. We firstly assessed whether our RCT participants were comparable to this cohort using propensity score modelling. Following this we re-weighted the trial population to better match the wider cohort and re-estimated the treatment effect. Results Trial participants differed from the cohort in regards to sex, weight, HbA1c and also QoL and satisfaction with current treatment. Nevertheless, the treatment effects derived from alternative model weightings were similar to that of the original RCT. Conclusions Our RCT participants differed in composition to the wider population but the original findings were unaffected by sampling adjustments. We encourage investigators take steps to address criticisms of generalisability, but doing so is problematic: external data, even if available, may contain limited information and analyses can be susceptible to model misspecification