A comparison of methods for analyzing a binary composite endpoint with partially observed components in randomized controlled trials.

Composite endpoints are commonly used to define primary outcomes in randomized controlled trials. A participant may be classified as meeting the endpoint if they experience an event in one or several components (eg, a favorable outcome based on a composite of being alive and attaining negative culture results in trials assessing tuberculosis treatments). Partially observed components that are not missing simultaneously complicate the analysis of the composite endpoint. An intuitive strategy frequently used in practice for handling missing values in the components is to derive the values of the composite endpoint from observed components when possible, and exclude from analysis participants whose composite endpoint cannot be derived. Alternatively, complete record analysis (CRA) (excluding participants with any missing components) or multiple imputation (MI) can be used. We compare a set of methods for analyzing a composite endpoint with partially observed components mathematically and by simulation, and apply these methods in a reanalysis of a published trial (TOPPS). We show that the derived composite endpoint can be missing not at random even when the components are missing completely at random. Consequently, the treatment effect estimated from the derived endpoint is biased while CRA results without the derived endpoint are valid. Missing at random mechanisms require MI of the components. We conclude that, although superficially attractive, deriving the composite endpoint from observed components should generally be avoided. Despite the potential risk of imputation model mis-specification, MI of missing components is the preferred approach in this study setting.

Physiological, hyaluronan-selected intracytoplasmic sperm injection for infertility treatment (HABSelect): a parallel, two-group, randomised trial.

BACKGROUND: Sperm selection strategies aimed at improving success rates of intracytoplasmic sperm injection (ICSI) include binding to hyaluronic acid (herein termed hyaluronan). Hyaluronan-selected sperm have reduced levels of DNA damage and aneuploidy. Use of hyaluronan-based sperm selection for ICSI (so-called physiological ICSI [PICSI]) is reported to reduce the proportion of pregnancies that end in miscarriage. However, the effect of PICSI on livebirth rates is uncertain. We aimed to investigate the efficacy of PICSI versus standard ICSI for improving livebirth rates among couples undergoing fertility treatment. METHODS: This parallel, two-group, randomised trial included couples undergoing an ICSI procedure with fresh embryo transfer at 16 assisted conception units in the UK. Eligible women (aged 18-43 years) had a body-mass index of 19-35 kg/m2 and a follicle-stimulating hormone (FSH) concentration of 3·0-20·0 mIU/mL or, if no FSH measurement was available, an anti-müllerian hormone concentration of at least 1·5 pmol/L. Eligible men (aged 18-55 years) had not had a vasovasostomy or been treated for cancer in the 24 months before recruitment and were able, after at least 3 days of sexual abstinence, to produce freshly ejaculated sperm for the treatment cycle. Couples were randomly assigned (1:1) with an online system to receive either PICSI or a standard ICSI procedure. The primary outcome was full-term (≥37 weeks' gestational age) livebirth, which was assessed in all eligible couples who completed follow-up. This trial is registered, number ISRCTN99214271. FINDINGS: Between Feb 1, 2014, and Aug 31, 2016, 2772 couples were randomly assigned to receive PICSI (n=1387) or ICSI (n=1385), of whom 2752 (1381 in the PICSI group and 1371 in the ICSI group) were included in the primary analysis. The term livebirth rate did not differ significantly between PICSI (27·4% [379/1381]) and ICSI (25·2% [346/1371]) groups (odds ratio 1·12, 95% CI 0·95-1·34; p=0·18). There were 56 serious adverse events in total, including 31 in the PICSI group and 25 in the ICSI group; most were congenital abnormalities and none were attributed to treatment. INTERPRETATION: Compared with ICSI, PICSI does not significantly improve term livebirth rates. The wider use of PICSI, therefore, is not recommended at present. FUNDING: National Institute for Health Research Efficacy and Mechanism Evaluation Programme.

How to design a pre-specified statistical analysis approach to limit p-hacking in clinical trials: the Pre-SPEC framework.

Results from clinical trials can be susceptible to bias if investigators choose their analysis approach after seeing trial data, as this can allow them to perform multiple analyses and then choose the method that provides the most favourable result (commonly referred to as 'p-hacking'). Pre-specification of the planned analysis approach is essential to help reduce such bias, as it ensures analytical methods are chosen in advance of seeing the trial data. For this reason, guidelines such as SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) and ICH-E9 (International Conference for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) require the statistical methods for a trial's primary outcome be pre-specified in the trial protocol. However, pre-specification is only effective if done in a way that does not allow p-hacking. For example, investigators may pre-specify a certain statistical method such as multiple imputation, but give little detail on how it will be implemented. Because there are many different ways to perform multiple imputation, this approach to pre-specification is ineffective, as it still allows investigators to analyse the data in different ways before deciding on a final approach. In this article, we describe a five-point framework (the Pre-SPEC framework) for designing a pre-specified analysis approach that does not allow p-hacking. This framework was designed based on the principles in the SPIRIT and ICH-E9 guidelines and is intended to be used in conjunction with these guidelines to help investigators design the statistical analysis strategy for the trial's primary outcome in the trial protocol.

Evidence of unexplained discrepancies between planned and conducted statistical analyses: a review of randomised trials.

BACKGROUND: Choosing or altering the planned statistical analysis approach after examination of trial data (often referred to as 'p-hacking') can bias the results of randomised trials. However, the extent of this issue in practice is currently unclear. We conducted a review of published randomised trials to evaluate how often a pre-specified analysis approach is publicly available, and how often the planned analysis is changed. METHODS: A review of randomised trials published between January and April 2018 in six leading general medical journals. For each trial, we established whether a pre-specified analysis approach was publicly available in a protocol or statistical analysis plan and compared this to the trial publication. RESULTS: Overall, 89 of 101 eligible trials (88%) had a publicly available pre-specified analysis approach. Only 22/89 trials (25%) had no unexplained discrepancies between the pre-specified and conducted analysis. Fifty-four trials (61%) had one or more unexplained discrepancies, and in 13 trials (15%), it was impossible to ascertain whether any unexplained discrepancies occurred due to incomplete reporting of the statistical methods. Unexplained discrepancies were most common for the analysis model (n = 31, 35%) and analysis population (n = 28, 31%), followed by the use of covariates (n = 23, 26%) and the approach for handling missing data (n = 16, 18%). Many protocols or statistical analysis plans were dated after the trial had begun, so earlier discrepancies may have been missed. CONCLUSIONS: Unexplained discrepancies in the statistical methods of randomised trials are common. Increased transparency is required for proper evaluation of results.

The Impact of Preoperative Stoma Marking on Health-Related Quality of Life: A Comparison Cohort Study.

PURPOSE: The purpose of this study was to compare health-related quality of life (HRQOL) in patients receiving preoperative stoma marking by a certified wound, ostomy and continence nurse (CWOCN) to patients who did not receive preoperative marking. DESIGN: Quasi-experimental, nonrandomized comparison cohort study. SUBJECTS AND SETTING: The sample comprised 59 patients immediately following creation of a fecal stoma during an 18-month period between 2008 and 2010. The experimental group consisted of 35 patients with a mean age of 49.7 years who received preoperative stoma site marking by a CWOCN. Six of those 35 patients (17%) received preoperative ostomy education and stoma site marking. The control group consisted of 24 patients with a mean age of 60.1 years who did not receive preoperative stoma site marking or preoperative ostomy education. The study setting was a 500-bed Midwest Magnet-designated teaching hospital. METHODS: Data collection occurred at 2 points: within 72 hours before hospital discharge and 8 weeks after discharge. The Stoma Quality of Life (Stoma-QOL) instrument was used to measure HRQOL. Two CWOCNs and 3 RNs, all members of Memorial's Ostomy & Wound Services, administered the Stoma QOL within 72 hours before hospital discharge. The 2 CWOCNs followed a scripted message to collect functional lifestyle factors and administer the Stoma-QOL, for the second time at 8 weeks after discharge. RESULTS: Groups were compared using analysis of covariance to control for age; analysis demonstrated significantly higher HOQOL in the marked group compared to the unmarked group (F = 4.9, P = .031). CONCLUSION: Findings demonstrated that patients who underwent stoma site marking reported higher HRQOL than those who did not.

Evaluation of a Nurse-Driven Protocol to Remove Urinary Catheters: Nurses' Perceptions.

This article describes nurses' perceptions of the effect of a nurse-driven protocol in a Magnet-designated hospital. Post-protocol implementation data indicate improved job ease and positive patient feedback following protocol implementation. Younger or less-experienced nurses were likely to use the protocol.

Effects of Actissist, a digital health intervention for early psychosis: A randomized clinical trial.

Schizophrenia affects 24 million people worldwide. Digital health interventions drawing on psychological principles have been developed, but their effectiveness remains unclear. This parallel, assessor-blinded, randomized clinical trial aimed to investigate whether a cognitive behaviour therapy-informed digital health intervention (Actissist app) confers added benefit on psychotic symptoms over and above remote symptom monitoring (ClinTouch app). Participants recruited from UK community health services were randomized 1:1 to receive either Actissist plus treatment as usual (TAU) or ClinTouch plus TAU. Eligible participants were adults with schizophrenia-spectrum psychosis within five years of first episode onset meeting a criterion level of positive symptoms severity. The primary outcome was Positive and Negative Syndrome Scale (PANSS) symptoms total score at 12 weeks post-randomization. Intention-to-treat analysis included 172 participants, with 149 participants (86.6 %) providing primary outcome data. Actissist plus TAU was not associated with greater reduction than an active control remote symptom monitoring app (ClinTouch) in PANSS total score at post-randomization. There were no significant effects between groups across secondary measures. There were no serious adverse reactions. Both groups improved on the primary psychotic symptoms measure at primary end-point and on secondary measures over time. The Actissist app is safe but not superior to digital symptom monitoring.

The clinical utility of an SCN1A genetic diagnosis in infantile-onset epilepsy.

AIM: Genetic testing in the epilepsies is becoming an increasingly accessible clinical tool. Mutations in the sodium channel alpha 1 subunit (SCN1A) gene are most notably associated with Dravet syndrome. This is the first study to assess the impact of SCN1A testing on patient management from both carer and physician perspectives. METHOD: Participants were identified prospectively from referrals to the Epilepsy Genetics Service in Glasgow and contacted via their referring clinicians. Questionnaires exploring the consequences of SCN1A genetic testing for each case were sent to carers and physicians. RESULTS: Of the 244 individuals contacted, 182 (75%) carried a SCN1A mutation. Carers of 187 (77%) patients responded (90 females, 97 males; mean age at referral 4 y 10 mo; interquartile range 9 y 1 mo). Of those participants whose children tested positive for a mutation, 87% reported that genetic testing was helpful, leading to treatment changes resulting in fewer seizures and improved access to therapies and respite care. Out of 187 physicians, 163 responded (87%), of whom 48% reported that a positive test facilitated diagnosis earlier than with clinical and electroencephalography data alone. It prevented additional investigations in 67% of patients, altered treatment approach in 69%, influenced medication choice in 74%, and, through medication change, improved seizure control in 42%. INTERPRETATION: In addition to confirming a clinical diagnosis, a positive SCN1A test result influenced treatment choice and assisted in accessing additional therapies, especially in the very young.

How do autistic people fare in adult life and can we predict it from childhood?

This study describes social, mental health, and quality of life outcomes in early adulthood, and examines childhood predictors in the Special Needs and Autism Project (SNAP), a longitudinal population-based cohort. Young autistic adults face variable but often substantial challenges across many areas of life. Prediction of outcomes is important to set expectations and could lead to the development of targeted early intervention. Autistic children were enrolled at age 12 and parents reported outcomes 11 years later when their children were age 23 (n = 121). Thirty six percent of autistic adults were in competitive employment or education and 54% had frequent contact with friends. Only 5% of autistic adults were living independently, and 37% required overnight care. Moderate or severe anxiety and depression symptoms were found for 11% and 12% of young adults, respectively. Subjective quality of life was similar to UK averages except for social relationships. Using childhood IQ, autism traits and adaptive functioning meaningful predictions can be made of living situation, employment and education and physical health. Prediction was poor for friendships, mental health outcomes and other aspects of quality of life. Our results suggest that although young autistic adults face challenges across normative, social outcomes, they may be faring better in regard to mental health or quality of life. Childhood IQ, autism traits and adaptive functioning are most useful for predicting outcomes. After accounting for these factors, childhood measurements of behavioral and emotional problems and language offered little improvement in prediction of adult outcomes.

Fluid Optimisation in Emergency Laparotomy (FLO-ELA) Trial: study protocol for a multi-centre randomised trial of cardiac output-guided fluid therapy compared to usual care in patients undergoing major emergency gastrointestinal surgery.

INTRODUCTION: Postoperative morbidity and mortality in patients undergoing major emergency gastrointestinal surgery are a major burden on healthcare systems. Optimal management of perioperative intravenous fluids may reduce mortality rates and improve outcomes from surgery. Previous small trials of cardiac-output guided haemodynamic therapy algorithms in patients undergoing gastrointestinal surgery have suggested this intervention results in reduced complications and a modest reduction in mortality. However, this existing evidence is based mainly on elective (planned) surgery, with little evaluation in the emergency setting. There are fundamental clinical and pathophysiological differences between the planned and emergency surgical setting which may influence the effects of this intervention. A large definitive trial in emergency surgery is needed to confirm or refute the potential benefits observed in elective surgery and to inform widespread clinical practice. METHODS: The FLO-ELA trial is a multi-centre, parallel-group, open, randomised controlled trial. 3138 patients aged 50 and over undergoing major emergency gastrointestinal surgery will be randomly allocated in a 1:1 ratio using minimisation to minimally invasive cardiac output monitoring to guide protocolised administration of intra-venous fluid, or usual care without cardiac output monitoring. The trial intervention will be carried out during surgery and for up to 6 h postoperatively. The trial is funded through an efficient design call by the National Institute for Health and Care Research Health Technology Assessment (NIHR HTA) programme and uses existing routinely collected datasets for the majority of data collection. The primary outcome is the number of days alive and out of hospital within 90 days of randomisation. Participants and those delivering the intervention will not be blinded to treatment allocation. Participant recruitment started in September 2017 with a 1-year internal pilot phase and is ongoing at the time of publication. DISCUSSION: This will be the largest contemporary randomised trial examining the effectiveness of perioperative cardiac output-guided haemodynamic therapy in patients undergoing major emergency gastrointestinal surgery. The multi-centre design and broad inclusion criteria support the external validity of the trial. Although the clinical teams delivering the trial interventions will not be blinded, significant trial outcome measures are objective and not subject to detection bias. TRIAL REGISTRATION: ISRCTN 14729158. Registered on 02 May 2017.

Evaluating the impact of a nurse residency program for newly graduated registered nurses.

Nurse residency programs are designed to support graduate nurses as they assume the professional role. Evaluation of these programs has been inconsistent. The purpose of this descriptive research study was to evaluate a year-long nurse residency program using a nonexperimental, repeated measures design with qualitative questions. Results showed statistically significant differences in new nurse confidence, skills, and abilities at 12 months. Nursing turnover was one third of the national average. The metatheme that emerged from the data was "I see that I am not the only one."

Therapist-supported online cognitive therapy for post-traumatic stress disorder (PTSD) in young people: protocol for an early-stage, parallel-group, randomised controlled study (OPTYC trial).

INTRODUCTION: Post-traumatic stress disorder (PTSD) is a disabling psychiatric condition that affects a significant minority of young people exposed to traumatic events. Effective face-to-face psychological treatments for PTSD exist. However, most young people with PTSD do not receive evidence-based treatment. Remotely delivered digital interventions have potential to significantly improve treatment accessibility. Digital interventions have been successfully employed for young people with depression and anxiety, and for adults with PTSD. However, digital interventions to treat PTSD in young people have not been evaluated. The Online PTSD Treatment for Young People & Carers (OPTYC) trial will evaluate the feasibility, acceptability and initial indications of clinical efficacy of a novel internet-delivered Cognitive Therapy for treatment of PTSD in young people (iCT-PTSD-YP). METHODS AND ANALYSIS: This protocol describes a two-arm, parallel-groups, single-blind (outcome assessor), early-stage randomised controlled trial, comparing iCT-PTSD-YP with a waiting list (WL) comparator. N=34 adolescents (12-17 years old), whose primary problem is PTSD after exposure to a single traumatic event, will be recruited from 14 NHS Child and Adolescent Mental Health Services in London and southeast England, from secondary schools and primary care in the same region, or via self-referral from anywhere in the UK using the study website. Individual patient-level randomisation will allocate participants in a 1:1 ratio, randomised using minimisation according to sex and baseline symptom severity. The primary study outcomes are data on feasibility and acceptability, including recruitment, adherence, retention and adverse events (AEs). The primary clinical outcome is PTSD diagnosis 16 weeks post-randomisation. Secondary clinical outcomes include continuous measures of PTSD, anxiety and depression symptoms. Regression analyses will provide preliminary estimates of the effect of iCT-PTSD-YP on PTSD diagnosis, symptoms of PTSD, anxiety and depression relative to WL. Process-outcome evaluation will consider which mechanisms mediate recovery. Qualitative interviews with young people, families and therapists will evaluate acceptability. ETHICS AND DISSEMINATION: The study was approved by a UK Health Research Authority Research Ethics Committee (19/LO/1354). For participants aged under 16, informed consent will be provided by carers and the young person will be asked for their assent; participants aged 16 years or older can provide informed consent without their parent or caregiver's involvement. Findings will be disseminated broadly to participants, healthcare professionals, the public and other relevant groups. Study findings will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN16876240.

Relationships among individualism--collectivism, gender, and ingroup/outgroup status, and responses to conflict: a study in China and the United States.

Responses to conflict were studied in samples of college students from a highly collectivistic society (China, n = 207) and a highly individualistic society (United States n = 209). As predicted, the collectivistic society reported more conflict-reducing behaviors and less verbal or physical aggression. However, the effect of individualism/collectivism was moderated by both the ingroup/outgroup status of the target and gender of the participant. Chinese and US women did not differ on any measure. However, of the four groups, Chinese men reported the most conflict-reducing behaviors and the least physical aggression, whereas US men reported the fewest conflict-reducing behaviors and the greatest physical aggression. As predicted, conflict-reducing behaviors were more common in the ingroup condition and both verbal and physical aggression was more common in the outgroup condition. However, the latter were moderated by gender of the participant. US men reported greater physical aggression than any other group. Neither gender nor society had any effect on the level of indirect aggression. There were no gender or individualism/collectivism effects on indirect aggression. Observed gender effects were attributed to differences in how collectivistic and individualistic societies conceptualize masculinity. The effect sizes associated with the ingroup/outgroup condition were consistently and substantially larger than effect sizes associated with individualism/collectivism or gender.

Predicting Uncertain Multi-Dimensional Adulthood Outcomes From Childhood and Adolescent Data in People Referred to Autism Services.

INTRODUCTION: Autism spectrum disorder is a highly heterogeneous diagnosis. When a child is referred to autism services or receives a diagnosis of autism spectrum disorder it is not known what their potential adult outcomes could be. We consider the challenge of making predictions of an individual child's long-term multi-facetted adult outcome, focussing on which aspects are predictable and which are not. METHODS: We used data from 123 adults participating in the Autism Early Diagnosis Cohort. Participants were recruited from age 2 and followed up repeatedly through childhood and adolescence to adulthood. We predicted 14 adult outcome measures including cognitive, behavioral and well-being measures. Continuous outcomes were modeled using lasso regression and ordinal outcomes were modeled using proportional odds regression. Optimism corrected predictive performance was calculated using cross-validation or bootstrap. We also illustrated the prediction of an overall composite formed by weighting outcome measures by priorities elicited from parents. RESULTS: We found good predictive performance from age 9 for verbal and non-verbal IQ, and daily living skills. Predictions for symptom severity, hyperactivity and irritability improved with inclusion of behavioral data collected in adolescence but remained modest. For other outcomes covering well-being, depression, and positive and negative affect we found no ability to predict adult outcomes at any age. Predictions of composites based on parental priorities differed in magnitude and precision depending on which parts of the adult outcome were given more weight. CONCLUSION: Verbal and non-verbal IQ, and daily living skills can be predicted well from assessments made in childhood. For other adult outcomes, it is challenging to make meaningful predictions from assessments made in childhood and adolescence using the measures employed in this study. Future work should replicate and validate the present findings in different samples, investigate whether the availability of different measures in childhood and adolescence can improve predictions, and consider systematic differences in priorities.

Public availability and adherence to prespecified statistical analysis approaches was low in published randomized trials.

BACKGROUND AND OBJECTIVE: Prespecification of statistical methods in clinical trial protocols and statistical analysis plans can help to deter bias from p-hacking but is only effective if the prespecified approach is made available. STUDY DESIGN AND SETTING: For 100 randomized trials published in 2018 and indexed in PubMed, we evaluated how often a prespecified statistical analysis approach for the trial's primary outcome was publicly available. For each trial with an available prespecified analysis, we compared this with the trial publication to identify whether there were unexplained discrepancies. RESULTS: Only 12 of 100 trials (12%) had a publicly available prespecified analysis approach for their primary outcome; this document was dated before recruitment began for only two trials. Of the 12 trials with an available prespecified analysis approach, 11 (92%) had one or more unexplained discrepancies. Only 4 of 100 trials (4%) stated that the statistician was blinded until the SAP was signed off, and only 10 of 100 (10%) stated the statistician was blinded until the database was locked. CONCLUSION: For most published trials, there is insufficient information available to determine whether the results may be subject to p-hacking. Where information was available, there were often unexplained discrepancies between the prespecified and final analysis methods.

Process evaluation within pragmatic randomised controlled trials: what is it, why is it done, and can we find it?-a systematic review.

BACKGROUND: Process evaluations are increasingly conducted within pragmatic randomised controlled trials (RCTs) of health services interventions and provide vital information to enhance understanding of RCT findings. However, issues pertaining to process evaluation in this specific context have been little discussed. We aimed to describe the frequency, characteristics, labelling, value, practical conduct issues, and accessibility of published process evaluations within pragmatic RCTs in health services research. METHODS: We used a 2-phase systematic search process to (1) identify an index sample of journal articles reporting primary outcome results of pragmatic RCTs published in 2015 and then (2) identify all associated publications. We used an operational definition of process evaluation based on the Medical Research Council's process evaluation framework to identify both process evaluations reported separately and process data reported in the trial results papers. We extracted and analysed quantitative and qualitative data to answer review objectives. RESULTS: From an index sample of 31 pragmatic RCTs, we identified 17 separate process evaluation studies. These had varied characteristics and only three were labelled 'process evaluation'. Each of the 31 trial results papers also reported process data, with a median of five different process evaluation components per trial. Reported barriers and facilitators related to real-world collection of process data, recruitment of participants to process evaluations, and health services research regulations. We synthesised a wide range of reported benefits of process evaluations to interventions, trials, and wider knowledge. Visibility was often poor, with 13/17 process evaluations not mentioned in the trial results paper and 12/16 process evaluation journal articles not appearing in the trial registry. CONCLUSIONS: In our sample of reviewed pragmatic RCTs, the meaning of the label 'process evaluation' appears uncertain, and the scope and significance of the term warrant further research and clarification. Although there were many ways in which the process evaluations added value, they often had poor visibility. Our findings suggest approaches that could enhance the planning and utility of process evaluations in the context of pragmatic RCTs. TRIAL REGISTRATION: Not applicable for PROSPERO registration.

How pragmatic are the randomised trials used in recommendations for control of glycosylated haemoglobin levels in type 2 diabetic patients in general practice: an application of the PRECIS II tool.

BACKGROUND: Recommendations for good clinical practice have been reported to be difficult to apply in real life by primary care clinicians. This could be because the clinical trials at the origin of the guidelines are based on explanatory trials, conducted under ideal conditions not reflecting the reality of primary care, rather than pragmatic trials conducted under real-life conditions. The objective of this study was to evaluate how pragmatic are the clinical trials used to build the French High Authority of Health's recommendations on the management of type II diabetes. METHODS: Trials from the 2013 Cochrane meta-analysis that led to the 2013 French High Authority of Health's recommendations on the management of type II diabetes were selected. Each trial was analysed by applying the PRECIS-2 tool to evaluate whether the trial was pragmatic or explanatory, according to the nine domains of PRECIS-2. Each domain was scored between 1 (very explanatory) and 5 (very pragmatic) by two blinded researchers, and consensus was reached with a third researcher in case of discrepancy. Median scores were calculated for each of the nine domains. RESULTS: Twenty-three articles were analysed. Eight out of nine domains - namely eligibility, recruitment, setting, organisation, flexibility of delivery, flexibility of adherence, follow-up, and primary outcome - had a median score of less than 3, indicating a more explanatory design. Only the primary analysis domain had a score indicating a more pragmatic approach (median score of 4). In more than 25% of the articles, data to score the domains of recruitment, flexibility of delivery, flexibility of adherence, and primary analysis were missing. CONCLUSIONS: Trials used to build French recommendations for good clinical practice for the management of type 2 diabetes in primary care were more explanatory than pragmatic. Policy-makers should encourage the funding of pragmatic trials to evaluate the different strategies proposed for managing the patient's treatment according to HbA1C levels and give clinicians feasible recommendations.

MEMPHIS: a smartphone app using psychological approaches for women with chronic pelvic pain presenting to gynaecology clinics: a randomised feasibility trial.

OBJECTIVES: To evaluate the feasibility of a randomised trial of a modified, pre-existing, mindfulness meditation smartphone app for women with chronic pelvic pain. DESIGN: Three arm randomised feasibility trial. SETTING: Women were recruited at two gynaecology clinics in the UK. Interventions were delivered via smartphone or computer at a location of participants choosing. PARTICIPANTS: Women were eligible for the study if they were over 18, had been experiencing organic or non-organic chronic pelvic pain for 6 months or more, and had access to a computer or smartphone. 90 women were randomised. INTERVENTIONS: Daily mindfulness meditation delivered by smartphone app, an active control app which delivered muscle relaxation techniques, and usual care without app. Interventions were delivered over 60 days. PRIMARY AND SECONDARY OUTCOME MEASURES: Outcomes included length of recruitment, follow-up rates, adherence to the app interventions, and clinical outcomes measured at baseline, two, three and 6 months. RESULTS: The target sample size was recruited in 145 days. Adherence to the app interventions was extremely low (mean app use 1.8 days mindfulness meditation group, 7.0 days active control). Fifty-seven (63%) women completed 6-month follow-up, and 75 (83%) women completed at least one postrandomisation follow-up. The 95% CIs for clinical outcomes were consistent with no benefit from the mindfulness meditation app; for example, mean differences in pain acceptance scores at 60 days (higher scores are better) were -2.3 (mindfulness meditation vs usual care, 95% CI: -6.6 to 2.0) and -4.0 (mindfulness meditation vs active control, 95% CI: -8.1 to 0.1). CONCLUSIONS: Despite high recruitment and adequate follow-up rates, demonstrating feasibility, the extremely low adherence suggests a definitive randomised trial of the mindfulness meditation app used in this study is not warranted. Future research should focus on improving patient engagement. TRIAL REGISTRATION NUMBERS: NCT02721108; ISRCTN10925965; Results.

Relationships between individualism-collectivism, gender, and direct or indirect aggression: a study in China, Poland, and the US.

Direct and indirect aggression were studied in college students from China (women n=122; men n=97), a highly collectivistic culture; the US (women n=137; men n=136), a highly individualistic culture; and Poland (women n=105; men n=119), a culture with intermediate levels of collectivism and individualism. Consistent with a hypothesis derived from national differences in relative levels of collectivism and individualism, both direct and indirect aggression were higher in the US than in Poland and higher in Poland than in China. The theoretical implication of these results and directions for future research were discussed.

Improving the relevance of randomised trials to primary care: a qualitative study investigating views towards pragmatic trials and the PRECIS-2 tool.

BACKGROUND: Pragmatic trials have been suggested as a way to improve the relevance of clinical trial results to practice. PRECIS-2 (Pragmatic Explanatory Continuum Indicator Summary-2) is a trial design tool which considers how pragmatic a trial is across a number of domains. It is not known whether a pragmatic approach to all PRECIS-2 domains leads to results being more relevant to primary care. The aim of this study was to investigate the views of people with influence on primary care practice towards the design of randomised trials, pragmatic approaches to trial design, and the PRECIS-2 domains. METHODS: We carried out semi-structured interviews with people who influence practice in primary care in the UK. A thematic analysis was undertaken using the framework approach. RESULTS: We conducted individual or small group interviews involving an elite sample of 17 individuals. We found that an exclusively pragmatic approach to randomised trials may not always make the results of trials more applicable to primary care. For example, it may be better to have less flexibility in the way interventions are delivered in randomised trials than in practice. In addition, an appropriate balance needs to be struck when thinking about levels of resourcing and the intensity of steps needed to improve adherence in a trial. Across other aspects of a trial's design, for example the population and trial setting, a pragmatic approach was viewed as more appropriate. CONCLUSIONS: To maximize the relevance of research directed at primary care, trials should be conducted with the same populations and settings that are found in primary care. Across other aspects of trials it is not always necessary to match the conditions found in practice.