Role of feasibility and pilot studies in randomised controlled trials: a cross-sectional study.

OBJECTIVES: To assess the value of pilot and feasibility studies to randomised controlled trials (RCTs) funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme. To explore the methodological components of pilot/feasibility studies and how they inform full RCTs. STUDY DESIGN: Cross-sectional study. SETTING: Both groups included NIHR HTA programme funded studies in the period 1 January 2010-31 December 2014 (decision date). Group 1: stand-alone pilot/feasibility studies published in the HTA Journal or accepted for publication. Group 2: all funded RCT applications funded by the HTA programme, including reference to an internal and/or external pilot/feasibility study. The methodological components were assessed using an adapted framework from a previous study. MAIN OUTCOME MEASURES: The proportion of stand-alone pilot and feasibility studies which recommended proceeding to full trial and what study elements were assessed. The proportion of 'HTA funded' trials which used internal and external pilot and feasibility studies to inform the design of the trial. RESULTS: Group 1 identified 15 stand-alone pilot/feasibility studies. Study elements most commonly assessed were testing recruitment (100% in both groups), feasibility (83%, 100%) and suggestions for further study/investigation (83%, 100%). Group 2 identified 161 'HTA funded' applications: 59 cited an external pilot/feasibility study where testing recruitment (50%, 73%) and feasibility (42%, 73%) were the most commonly reported study elements: 92 reported an internal pilot/feasibility study where testing recruitment (93%, 100%) and feasibility (44%, 92%) were the most common study elements reported. CONCLUSIONS: 'HTA funded' research which includes pilot and feasibility studies assesses a variety of study elements. Pilot and feasibility studies serve an important role when determining the most appropriate trial design. However, how they are reported and in what context requires caution when interpreting the findings and delivering a definitive trial.

MENOS4 trial: a multicentre randomised controlled trial (RCT) of a breast care nurse delivered cognitive behavioural therapy (CBT) intervention to reduce the impact of hot flushes in women with breast cancer: Study Protocol.

BACKGROUND: Women who have been treated for breast cancer may identify vasomotor symptoms, such as hot flushes and night sweats (HFNS), as a serious problem. HFNS are unpleasant to experience and can have a significant impact on daily life, potentially leading to reduced adherence to life saving adjuvant hormonal therapy. It is known that Cognitive Behavioural Therapy (CBT) is effective for the alleviation of hot flushes in both well women and women who have had breast cancer. Most women with breast cancer will see a breast care nurse and there is evidence that nurses can be trained to deliver psychological treatments to a satisfactory level, whilst also maintaining treatment fidelity. The research team will assess whether breast care nurses can effectively deliver a CBT intervention to alleviate hot flushes in women with breast cancer. METHODS: This study is a multi-centre phase III individually randomised controlled trial of group CBT versus usual care to reduce the impact of hot flushes in women with breast cancer. 120-160 women with primary breast cancer experiencing seven or more problematic HFNS a week will be randomised to receive either treatment as usual (TAU) or participation in the group CBT intervention plus TAU (CBT Group). A process evaluation using May's Normalisation Process Theory will be conducted, as well as practical and organisational issues relating to the implementation of the intervention. Fidelity of implementation of the intervention will be conducted by expert assessment. The cost effectiveness of the intervention will also be assessed. DISCUSSION: There is a need for studies that enable effective interventions to be implemented in practice. There is good evidence that CBT is helpful for women with breast cancer who experience HFNS, yet it is not widely available. It is not yet known whether the intervention can be effectively delivered by breast care nurses or implemented in practice. This study will provide information on both whether the intervention can effectively help women with hot flushes and whether and how it can be translated into routine clinical practice. TRIAL REGISTRATION: ISRCTN 12824632 . Registered 25-01-2017.

CONFIRM: a double-blind, placebo-controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial.

BACKGROUND: Mesothelioma is an incurable, apoptosis-resistant cancer caused in most cases by previous exposure to asbestos and is increasing in incidence. It represents a growing health burden but remains under-researched, with limited treatment options. Early promising signals of activity relating to both PD-L1- and PD-1-targeted treatment in mesothelioma implicate a dependency of mesothelioma on this immune checkpoint. There is a need to evaluate checkpoint inhibitors in patients with relapsed mesothelioma where treatment options are limited. METHODS: The addition of 12 months of nivolumab (anti-PD1 antibody) to standard practice will be conducted in the UK using a randomised, placebo-controlled phase III trial (the Cancer Research UK CONFIRM trial). A total of 336 patients with pleural or peritoneal mesothelioma who have received at least two prior lines of therapy will be recruited from UK secondary care sites. Patients will be randomised 2:1 (nivolumab:placebo), stratified according to epithelioid/non-epithelioid, to receive either 240 mg nivolumab monotherapy or saline placebo as a 30-min intravenous infusion. Treatment will be for up to 12 months. We will determine whether the use of nivolumab increases overall survival (the primary efficacy endpoint). Secondary endpoints will include progression-free survival, objective response rate, toxicity, quality of life and cost-effectiveness. Analysis will be performed according to the intention-to-treat principle using a Cox regression analysis for the primary endpoint (and for other time-to-event endpoints). DISCUSSION: The outcome of this trial will provide evidence of the potential benefit of the use of nivolumab in the treatment of relapsed mesothelioma. If found to be clinically effective, safe and cost-effective it is likely to become the new standard of care in the UK. TRIAL REGISTRATION: EudraCT Number: 2016-003111-35 (entered on 21 July 2016); ClinicalTrials.gov, ID: NCT03063450 . Registered on 24 February 2017.

The Tyneside Pegboard Test: development, validation, and observations in unilateral cerebral palsy.

AIM: The aims of this study were twofold: first, to develop and validate a timed test of unimanual and bimanual dexterity suitable for those with disability affecting hand function; second, to explore relationships between unimanual and bimanual completion times. METHOD: We developed the Tyneside Pegboard Test (TPT), an electronically timed test with three peg sizes, incorporating an asymmetrical bimanual task. Nine hundred and seventy-four participants (455 males, 519 females; age range 4-80y) provided normative data. Test-retest reliability and construct validity were assessed (50 adults: 14 males, 36 females; 15-73y) on two occasions 2 weeks apart. Bimanual and unimanual completion times were measured in 87 children (51 males, 36 females) with unilateral cerebral palsy (CP) and 498 individuals in a comparison group (238 males, 260 females; 5-15y). RESULTS: The comparison group showed an asymmetrical U-shaped relationship between completion times and age. Intraclass correlation coefficients ranged from 0.74 to 0.91, indicating moderate test-retest reliability. There was a negative relationship between average TPT bimanual times and Purdue pegboard bimanual scores (Spearman's rho -0.611, degrees of freedom 44, p<0.001). Children with unilateral CP had greater prolongation of bimanual than unimanual completion times compared with the comparison group (mean difference 20.31s, 95% confidence interval 18.13-22.49, p<0.001). INTERPRETATION: The TPT is accessible for those with impaired hand function. Children with unilateral CP demonstrated disproportionate bimanual deficits, even allowing for unimanual dexterity: this has implications for therapy. WHAT THIS PAPER ADDS: We developed an adapted, electronically timed 9-hole pegboard test. Our modifications facilitate use by those with disability affecting hand function. The test incorporates an asymmetrical bimanual task. Children with unilateral cerebral palsy showed disproportionate bimanual dexterity deficits even allowing for unimanual dexterity.

Correction to: Understanding Plain English Summaries: A Comparison of two Approaches to Improve the Quality of Plain English Summaries in Research.

[This corrects the article DOI: 10.1186/s40900-017-0064-0.].

Understanding Plain English summaries. A comparison of two approaches to improve the quality of Plain English summaries in research reports.

PLAIN ENGLISH SUMMARY: There is a need for the authors of research reports to be able to communicate their work clearly and effectively to readers who are not familiar with the research area. The National Institute for Health Research (NIHR), along with a number of other funding bodies and journals, require researchers to write short lay summaries, often termed plain English summaries (PESs), to make research accessible to the general public. Because many researchers write using technical, specialised language, particularly in scientific reports, writing PESs can be challenging. In this study we looked at how to improve the quality of PESs. We took PESs which had been submitted to the NIHR Journals Library and asked authors to rewrite them using new guidance. We also asked an independent medical writer to edit the summaries. We measured the quality of these three versions (original summary, rewritten summary and edited summary) in two ways. First, we asked a group of people who were not specialists in the subject area to read and rate how easy the summaries were to understand. Secondly, we used a well-known measure called the Flesch reading ease score to assess how easy the PESs were to read. We found that there was no difference in how easy people found the summaries to understand across the three versions. However, the PESs that were rewritten by the authors and that were edited by the independent medical writer were both easier to read than the originals. This shows that PESs can be improved and for organisations who feel that employing an independent writer to edit summaries, providing clear, practical guidance to authors may be a cost-effective alternative. BACKGROUND: Plain English summaries (PES) or lay summaries are often included as part of research reports and journal articles. These summaries are vital to ensure that research findings are accessible and available to non-specialist audiences, for example patients and members of the public. Writing a PES requires the adoption of a different style than is generally used in a traditional scientific report, and researchers can find this challenging. This study explored two possible ways to improve the quality of PESs in the NIHR Journals Library: 1) Providing enhanced guidance to authors and asking them to rewrite the PES and 2) Employing an independent medical writer to edit the PES. METHODS: We compared the three versions of the PES (original, author rewritten and independent writer edited) to assess 1) how easy they were to understand and 2) how easy they were to read. In order to establish how easy PESs were to understand, a group of 60 public reviewers read a set of summaries and rated them on a four point scale from "Did not understand" to "Understood all". The Flesch reading ease score was used to measure how easy the summaries were to read. RESULTS: Results indicated no significant difference across the three versions of the PES in terms of ease of understanding. However, both the author rewritten and independent writer edited versions were significantly easier to read than the original. There was no significant difference in ease of reading between these two versions. CONCLUSION: These findings suggest that employing independent medical writers to edit PESs and providing clear, practical guidance to authors are two ways in which the readability of PESs could be improved. Results have implications for journal editors and publishers seeking to enhance accessibility and availability of research findings.

Effect of parent-delivered action observation therapy on upper limb function in unilateral cerebral palsy: a randomized controlled trial.

AIM: To determine whether home-based, parent-delivered therapy comprising action observation (AO) and repeated practice (RP) improves upper limb function more than RP alone in children with unilateral cerebral palsy (UCP). DESIGN: single-blinded parallel-group randomized controlled trial with 1:1 allocation comparing AO+RP (intervention) with RP alone (control). RANDOMIZATION: computer-generated, with allocation concealment by opaque sequentially-numbered envelopes. SETTING: northern England, August 2011 to September 2013. PARTICIPANTS: 70 children with UCP; mean age 5.6 years (SD 2.1), 31 female. INTERVENTION: home-based activities were provided, tailored to interests and abilities. DURATION: 15 minutes/day, 5 days/week for 3 months. ASSESSMENTS: Assisting Hand Assessment (AHA; primary outcome measure), Melbourne Assessment 2 (MA2), and ABILHAND-Kids at baseline, 3 months, and 6 months. RESULTS: Outcome data was available at 3 months for 28 children in the AO+RP group and 31 controls, and at 6 months for 26 and 28 children respectively. There were no between-group differences in AHA, MA2, or ABILHAND-Kids at 3 or 6 months versus baseline (all p>0.05). Combined-group improvements (p<0.001), observed in AHA and MA2 at 3 months, were maintained at 6 months. ABILHAND-Kids also showed improvement at 3 months (p=0.003), maintained at 6 months. INTERPRETATION: Parent-delivered RP (with or without AO) improves upper limb function and could supplement therapist input.

Social media and anatomy education: Using twitter to enhance the student learning experience in anatomy.

Neuroanatomy is a difficult subject in medical education, with students often feeling worried and anxious before they have even started, potentially decreasing their engagement with the subject. At the University of Southampton, we incorporated the use of Twitter as a way of supporting students' learning on a neuroanatomy module to evaluate how it impacted upon their engagement and learning experience. The #nlm2soton hashtag was created and displayed (via a widget) on the university's virtual learning environment (VLE) for a cohort of 197 Year 2 medical students studying neuroanatomy. Student usage was tracked to measure levels of engagement throughout the course and frequency of hashtag use was compared to examination results. Student opinions on the use of Twitter were obtained during a focus group with eleven students and from qualitative questionnaires. The hashtag was used by 91% of the student cohort and, within this, more students chose to simply view the hashtag rather than make contributions. The completed questionnaire responses (n = 150) as well as focus group outcomes revealed the value of using Twitter. A negligible correlation was found between student examination scores and their viewing frequency of the hashtag however, no correlation was found between examination scores and contribution frequency. Despite this, Twitter facilitated communication, relieved anxieties and raised morale, which was valued highly by students and aided engagement with neuroanatomy. Twitter was successful in creating and providing a support network for students during a difficult module. Anat Sci Educ 9: 505-515. © 2016 American Association of Anatomists.

Bridging a yawning chasm: EEG investigations into the debate concerning the role of the human mirror neuron system in contagious yawning.

Ongoing debate in the literature concerns whether there is a link between contagious yawning and the human mirror neuron system (hMNS). One way of examining this issue is with the use of the electroencephalogram (EEG) to measure changes in mu activation during the observation of yawns. Mu oscillations are seen in the alpha bandwidth of the EEG (8-12 Hz) over sensorimotor areas. Previous work has shown that mu suppression is a useful index of hMNS activation and is sensitive to individual differences in empathy. In two experiments, we presented participants with videos of either people yawning or control stimuli. We found greater mu suppression for yawns than for controls over right motor and premotor areas, particularly for those scoring higher on traits of empathy. In a third experiment, auditory recordings of yawns were compared against electronically scrambled versions of the same yawns. We observed greater mu suppression for yawns than for the controls over right lateral premotor areas. Again, these findings were driven by those scoring highly on empathy. The results from these experiments support the notion that the hMNS is involved in contagious yawning, emphasise the link between contagious yawning and empathy, and stress the importance of good control stimuli.