What is a pilot or feasibility study? A review of current practice and editorial policy

Background: In 2004, a review of pilot studies published in seven major medical journals during 2000-01 recommended that the statistical analysis of such studies should be either mainly descriptive or focus on sample size estimation, while results from hypothesis testing must be interpreted with caution. We revisited these journals to see whether the subsequent recommendations have changed the practice of reporting pilot studies. We also conducted a survey to identify the methodological components in registered research studies which are described as 'pilot' or 'feasibility' studies. We extended this survey to grant-awarding bodies and editors of medical journals to discover their policies regarding the function and reporting of pilot studies. Methods: Papers from 2007-08 in seven medical journals were screened to retrieve published pilot studies. Reports of registered and completed studies on the UK Clinical Research Network (UKCRN) Portfolio database were retrieved and scrutinized. Guidance on the conduct and reporting of pilot studies was retrieved from the websites of three grant giving bodies and seven journal editors were canvassed. Results: 54 pilot or feasibility studies published in 2007-8 were found, of which 26 (48%) were pilot studies of interventions and the remainder feasibility studies. The majority incorporated hypothesis-testing (81%), a control arm (69%) and a randomization procedure (62%). Most (81%) pointed towards the need for further research. Only 8 out of 90 pilot studies identified by the earlier review led to subsequent main studies. Twelve studies which were interventional pilot/feasibility studies and which included testing of some component of the research process were identified through the UKCRN Portfolio database. There was no clear distinction in use of the terms 'pilot' and 'feasibility'. Five journal editors replied to our entreaty. In general they were loathe to publish studies described as 'pilot'. Conclusion: Pilot studies are still poorly reported, with inappropriate emphasis on hypothesis-testing. Authors should be aware of the different requirements of pilot studies, feasibility studies and main studies and report them appropriately. Authors should be explicit as to the purpose of a pilot study. The definitions of feasibility and pilot studies vary and we make proposals here to clarify terminology

Are pilot trials useful for predicting randomisation and attrition rates in definitive studies: A review of publicly funded trials

BACKGROUND/AIMS: External pilot trials are recommended for testing the feasibility of main or confirmatory trials. However, there is little evidence that progress in external pilot trials actually predicts randomisation and attrition rates in the main trial. To assess the use of external pilot trials in trial design, we compared randomisation and attrition rates in publicly funded randomised controlled trials with rates in their pilots. METHODS: Randomised controlled trials for which there was an external pilot trial were identified from reports published between 2004 and 2013 in the Health Technology Assessment Journal. Data were extracted from published papers, protocols and reports. Bland-Altman plots and descriptive statistics were used to investigate the agreement of randomisation and attrition rates between the full and external pilot trials. RESULTS: Of 561 reports, 41 were randomised controlled trials with pilot trials and 16 met criteria for a pilot trial with sufficient data. Mean attrition and randomisation rates were 21.1% and 50.4%, respectively, in the pilot trials and 16.8% and 65.2% in the main. There was minimal bias in the pilot trial when predicting the main trial attrition and randomisation rate. However, the variation was large: the mean difference in the attrition rate between the pilot and main trial was -4.4% with limits of agreement of -37.1% to 28.2%. Limits of agreement for randomisation rates were -47.8% to 77.5%. CONCLUSION: Results from external pilot trials to estimate randomisation and attrition rates should be used with caution as comparison of the difference in the rates between pilots and their associated full trial demonstrates high variability. We suggest using internal pilot trials wherever appropriate

Variability in the functional composition of coral reef fish communities on submerged and emergent reefs in the central Great Barrier Reef, Australia

On coral reefs, depth and gradients related to depth (e.g. light and wave exposure) influence the composition of fish communities. However, most studies focus only on emergent reefs that break the sea surface in shallow waters (<10 m). On the Great Barrier Reef (GBR), submerged reefs (reefs that do not break the sea surface) occupy an area equivalent to all emergent reefs. However, submerged reefs have received comparatively little research attention, and fish communities associated with submerged reefs remain poorly quantified. Here, we quantify fish assemblages at each of three depths (10, 20 and 30 m) on eight submerged reefs (four mid-shelf and four outer-shelf) and two nearby emergent reefs in the central GBR where reef habitat extends from 0-~25 m depth. We examine how total fish abundance, the abundance of 13 functional groups, and the functional composition of fish communities varies among depths, reef types (submerged versus emergent reefs), and shelf position (mid-shelf versus outer-shelf). Overall fish abundance decreased sevenfold with depth, but declined less steeply (twofold) on outer-shelf submerged reefs than on both mid-shelf submerged reefs and emergent reefs. The functional composition of the fish assemblage also varied significantly among depths and reef types. Turnover in the functional composition of the fish community was also steeper on the mid-shelf, suggesting that shallow-affiliated groups extend further in deeper water on the outer-shelf. Ten of the 13 functional groups were more strongly associated with the shallowest depths (the upper reef slope of emergent reefs or the 'crests' of submerged reefs), two groups (soft coral/sponge feeders and mesopredators) were more abundant at the deepest sites. Our results confirm that submerged reefs in the central GBR support a wide range of coral reef fishes, and are an important component of the GBR ecosystem

Individual well-being and performance at work

This chapter addresses the conceptualization of individual well-being and performance in the work context, and discusses theoretical perspectives linking these concepts. It also discusses theoretical and empirical notions on the structure of well-being, after which the conceptualization of performance and the relations between individual well-being and performance. The chapter shows that many different conceptualizations of well-being exist, ranging from simple "affect only" approaches to complicate and sometimes idiosyncratic multidimensional frameworks that incorporate different aspects of human experience. The individual-level conceptualizations of well-being can conveniently be classified on two dimensions, namely whether they focus exclusively on affective well-being or employ a multidimensional approach, and whether they are context-free. The chapter focuses on individual-level perspectives on worker well-being and work performance. It also addresses higher-level perspectives, and the combination of individual-level and higher-level perspectives could yield additional perspectives on the role of well-being as an antecedent of performance

Novel cell types, neurosecretory cells, and body plan of the early-diverging metazoan Trichoplax adhaerens.

BACKGROUND: Trichoplax adhaerens is the best-known member of the phylum Placozoa, one of the earliest-diverging metazoan phyla. It is a small disk-shaped animal that glides on surfaces in warm oceans to feed on algae. Prior anatomical studies of Trichoplax revealed that it has a simple three-layered organization with four somatic cell types. RESULTS: We reinvestigate the cellular organization of Trichoplax using advanced freezing and microscopy techniques to identify localize and count cells. Six somatic cell types are deployed in stereotyped positions. A thick ventral plate, comprising the majority of the cells, includes ciliated epithelial cells, newly identified lipophil cells packed with large lipid granules, and gland cells. Lipophils project deep into the interior, where they alternate with regularly spaced fiber cells whose branches contact all other cell types, including cells of the dorsal and ventral epithelium. Crystal cells, each containing a birefringent crystal, are arrayed around the rim. Gland cells express several proteins typical of neurosecretory cells, and a subset of them, around the rim, also expresses an FMRFamide-like neuropeptide. CONCLUSIONS: Structural analysis of Trichoplax with significantly improved techniques provides an advance in understanding its cell types and their distributions. We find two previously undetected cell types, lipohil and crystal cells, and an organized body plan in which different cell types are arranged in distinct patterns. The composition of gland cells suggests that they are neurosecretory cells and could control locomotor and feeding behavior

Estimating the minimum important difference in the DEMQOL instrument in people with dementia

Purpose The Dementia-Related Quality of Life (DEMQOL) measure and the DEMQOL-Utility Score (DEMQOL-U) are validated tools for measuring quality of life (QOL) in people with dementia. What score changes translate to a clinically significant impact on patients’ lives was unknown. This study establishes the minimal important differences (MID) for these two instruments. Methods Anchor-based and distribution-based methods were used to estimate the MID scores from patients enrolled in a randomised controlled trial. For the anchor-based method, the global QOL (Q29) item from the DEMQOL was chosen as the anchor for DEMQOL and both Q29 and EQ-5D for DEMQOL-U. A one category difference in Q29, and a 0.07 point difference in EQ-5D score, were used to classify improvement and deterioration, and the MID scores were calculated for each category. These results were compared with scores obtained by the distribution-based methods. Results A total of 490 people with dementia had baseline DEMQOL data, of these 386 had 8-month data, and 344 had 12-month DEMQOL data. The absolute change in DEMQOL for a combined 1-point increase or decrease in the Q29 anchor was 5.2 at 8 months and 6.0 at 12 months. For the DEMQOL-U, the average absolute change at 8 and 12 months was 0.032 and 0.046 for the Q29 anchor and 0.020 and 0.024 for EQ-5D anchor. Conclusion We present MID scores for the DEMQOL and DEMQOL-U instruments obtained from a large cohort of patients with dementia. An anchored-based estimate of the MID for the DEMQOL is around 5 to 6 points; and 0.02 to 0.05 points for the DEMQOL-U. The results of this study can guide clinicians and researchers in the interpretation of these instruments comparisons between groups or within groups of people with dementia. Trial Registration Number and date of registration: ISRCTN17993825 on 11th October 2016

Use of MRI in the diagnosis of fetal brain abnormalities in utero (MERIDIAN): a multicentre, prospective cohort study.

BACKGROUND: In-utero MRI (iuMRI) has shown promise as an adjunct to ultrasound but the comparative diagnostic performance has been poorly defined. We aimed to assess whether the diagnostic accuracy and confidence of the prenatal diagnosis of fetal brain abnormalities is improved with iuMRI and assess the clinical impact and patient acceptability of iuMRI. METHODS: We did a multicentre, prospective, cohort study in the UK, at 16 fetal medicine centres, of pregnant women aged 16 years or older whose fetus had a brain abnormality detected by ultrasound at a gestational age of 18 weeks or more, had no contraindications to iuMRI, and consented to enter the study. Women carrying a fetus suspected of having a brain anomaly on ultrasound had iuMRI done within 14 days of ultrasound. The findings were reviewed by two independent panels and used to estimate diagnostic accuracy and confidence by comparison with outcome diagnoses. Changes in diagnosis, prognosis, and clinical management brought about by iuMRI and patient acceptability were assessed. FINDINGS: Participants were recruited between July 29, 2011, and Aug 31, 2014. The cohort was subdivided by gestation into the 18 weeks to less than 24 weeks fetus cohort (n=369) and into the 24 weeks or older fetus cohort (n=201). Diagnostic accuracy was improved by 23% (95% CI 18-27) in the 18 weeks to less than 24 weeks group and 29% (23-36) in the 24 weeks and older group (p<0·0001 for both groups). The overall diagnostic accuracy was 68% for ultrasound and 93% for iuMRI (difference 25%, 95% CI 21-29). Dominant diagnoses were reported with high confidence on ultrasound in 465 (82%) of 570 cases compared with 544 (95%) of 570 cases on iuMRI. IuMRI provided additional diagnostic information in 387 (49%) of 783 cases, changed prognostic information in at least 157 (20%), and led to changes in clinical management in more than one in three cases. IuMRI also had high patient acceptability with at least 95% of women saying they would have an iuMRI study if a future pregnancy were complicated by a fetal brain abnormality. INTERPRETATION: iuMRI improves diagnostic accuracy and confidence for fetal brain anomalies and leads to management changes in a high proportion of cases. This finding, along with the high patient acceptability, leads us to propose that any fetus with a suspected brain abnormality on ultrasound should have iuMRI to better inform counselling and management decisions. FUNDING: National Institute for Health Research Health Technology Assessment programme

An Investigation of the Shortcomings of the CONSORT 2010 Statement for the Reporting of Group Sequential Randomised Controlled Trials: A Methodological Systematic Review.

BACKGROUND: It can be argued that adaptive designs are underused in clinical research. We have explored concerns related to inadequate reporting of such trials, which may influence their uptake. Through a careful examination of the literature, we evaluated the standards of reporting of group sequential (GS) randomised controlled trials, one form of a confirmatory adaptive design. METHODS: We undertook a systematic review, by searching Ovid MEDLINE from the 1st January 2001 to 23rd September 2014, supplemented with trials from an audit study. We included parallel group, confirmatory, GS trials that were prospectively designed using a Frequentist approach. Eligible trials were examined for compliance in their reporting against the CONSORT 2010 checklist. In addition, as part of our evaluation, we developed a supplementary checklist to explicitly capture group sequential specific reporting aspects, and investigated how these are currently being reported. RESULTS: Of the 284 screened trials, 68(24%) were eligible. Most trials were published in "high impact" peer-reviewed journals. Examination of trials established that 46(68%) were stopped early, predominantly either for futility or efficacy. Suboptimal reporting compliance was found in general items relating to: access to full trials protocols; methods to generate randomisation list(s); details of randomisation concealment, and its implementation. Benchmarking against the supplementary checklist, GS aspects were largely inadequately reported. Only 3(7%) trials which stopped early reported use of statistical bias correction. Moreover, 52(76%) trials failed to disclose methods used to minimise the risk of operational bias, due to the knowledge or leakage of interim results. Occurrence of changes to trial methods and outcomes could not be determined in most trials, due to inaccessible protocols and amendments. DISCUSSION AND CONCLUSIONS: There are issues with the reporting of GS trials, particularly those specific to the conduct of interim analyses. Suboptimal reporting of bias correction methods could potentially imply most GS trials stopping early are giving biased results of treatment effects. As a result, research consumers may question credibility of findings to change practice when trials are stopped early. These issues could be alleviated through a CONSORT extension. Assurance of scientific rigour through transparent adequate reporting is paramount to the credibility of findings from adaptive trials. Our systematic literature search was restricted to one database due to resource constraints

Supersymmetry in carbon nanotubes in a transverse magnetic field

Electron properties of Carbon nanotubes in a transverse magnetic field are studied using a model of a massless Dirac particle on a cylinder. The problem possesses supersymmetry which protects low energy states and ensures stability of the metallic behavior in arbitrarily large fields. In metallic tubes we find suppression of the Fermi velocity at half-filling and enhancement of the density of states. In semiconducting tubes the energy gap is suppressed. These features qualitatively persist (although to a smaller degree) in the presence of electron interactions. The possibilities of experimental observation of these effects are discussed.Comment: A new section on electron interaction effects added and explanation on roles of supersymmetry expanded. Revtex4, 6 EPS figure file