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This study aims to (1) elucidate whether the Hawthorne effect exists, (2) explore under what conditions, and (3) estimate the size of any such effect. This systematic review summarizes and evaluates the strength of available evidence on the Hawthorne effect. An inclusive definition of any form of research artifact on behavior using this label, and without cointerventions, was adopted. Nineteen purposively designed studies were included, providing quantitative data on the size of the effect in eight randomized controlled trials, five quasiexperimental studies, and six observational evaluations of reporting on one's behavior by answering questions or being directly observed and being aware of being studied. Although all but one study was undertaken within health sciences, study methods, contexts, and findings were highly heterogeneous. Most studies reported some evidence of an effect, although significant biases are judged likely because of the complexity of the evaluation object. Consequences of research participation for behaviors being investigated do exist, although little can be securely known about the conditions under which they operate, their mechanisms of effects, or their magnitudes. New concepts are needed to guide empirical studies.

The Consolidated Standards of Reporting Trials (CONSORT) statement was developed to improve the reporting of randomised controlled trials. It was initially published in 1996 and focused on the reporting of parallel group randomised controlled trials. The statement was revised in 2001, with a further update in 2010. A separate CONSORT statement for the reporting of abstracts was published in 2008. In earlier papers we considered the implications of the 2001 version of the CONSORT statement for the reporting of cluster randomised trial. In this paper we provide updated and extended guidance, based on the 2010 version of the CONSORT statement and the 2008 CONSORT statement for the reporting of abstracts.

Adrian Grant pioneered methodological innovations in the randomised trials organised by the Perinatal Trials Service established at the national Perinatal Epidemiology Unit in Oxford, UK. This Commentary discusses these innovations, and shows the wide range of trials designed under his directorship.

AbstractImportanceThe protocol of a randomised trial is the foundation for study planning, conduct, reporting, and external review. However, trial protocols vary in their completeness and often do not address key elements of design and conduct. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement was first published in 2013 as guidance to improve the completeness of trial protocols. Periodic updates incorporating the latest evidence and best practices are needed to ensure that the guidance remains relevant to users.ObjectiveTo systematically update the SPIRIT recommendations for minimum items to address in the protocol of a randomised trial.DesignWe completed a scoping review and developed a project specific database of empirical and theoretical evidence to generate a list of potential changes to the SPIRIT 2013 checklist. The list was enriched with recommendations provided by lead authors of existing SPIRIT/CONSORT (Consolidated Standards of Reporting Trials) extensions (Harms, Outcomes, Non-pharmacological Treatment) and other reporting guidelines (TIDieR). The potential modifications were rated in a three-round Delphi survey followed by a consensus meeting.FindingsOverall, 317 individuals participated in the Delphi consensus process and 30 experts attended the consensus meeting. The process led to the addition of two new protocol items, revision to five items, deletion/merger of five items, and integration of key items from other relevant reporting guidelines. Notable changes include a new open science section, additional emphasis on the assessment of harms and description of interventions and comparators, and a new item on how patients and the public will be involved in trial design, conduct, and reporting. The updated SPIRIT 2025 statement consists of an evidence based checklist of 34 minimum items to address in a trial protocol, along with a diagram illustrating the schedule of enrolment, interventions, and assessments for trial participants. To facilitate implementation, we also developed an expanded version of the SPIRIT 2025 checklist and an accompanying explanation and elaboration document.Conclusions and relevanceWidespread endorsement and adherence to the updated SPIRIT 2025 statement have the potential to enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, funders, research ethics committees, journals, trial registries, policymakers, regulators, and other reviewers.

In this trial, critically ill children were randomly assigned to either tight glycemic control or conventional glycemic control. There was no significant between-group difference in major clinical outcomes, although hypoglycemia was more common with tight glycemic control. Hyperglycemia is a common complication in critical illness and is associated with adverse outcomes. 1 – 5 Single-center, randomized trials have shown that reduction of blood glucose to normal levels with the use of insulin reduces morbidity and mortality among adults in surgical intensive care units (ICUs), 6 with similar effects on morbidity but not on mortality among adults in nonsurgical ICUs. 7 However, two meta-analyses 8 , 9 have failed to show a benefit, and a large, international, multicenter trial showed that tight glycemic control increased mortality. 10 Data on tight glucose control with the use of insulin in critically ill children have been lacking. One . . .

Severe acute respiratory failure in adults causes high mortality despite improvements in ventilation techniques and other treatments (eg, steroids, prone positioning, bronchoscopy, and inhaled nitric oxide). We aimed to delineate the safety, clinical efficacy, and cost-effectiveness of extracorporeal membrane oxygenation (ECMO) compared with conventional ventilation support. In this UK-based multicentre trial, we used an independent central randomisation service to randomly assign 180 adults in a 1:1 ratio to receive continued conventional management or referral to consideration for treatment by ECMO. Eligible patients were aged 18–65 years and had severe (Murray score >3·0 or pH <7·20) but potentially reversible respiratory failure. Exclusion criteria were: high pressure (>30 cm H 2O of peak inspiratory pressure) or high FiO 2 (>0·8) ventilation for more than 7 days; intracranial bleeding; any other contraindication to limited heparinisation; or any contraindication to continuation of active treatment. The primary outcome was death or severe disability at 6 months after randomisation or before discharge from hospital. Primary analysis was by intention to treat. Only researchers who did the 6-month follow-up were masked to treatment assignment. Data about resource use and economic outcomes (quality-adjusted life-years) were collected. Studies of the key cost generating events were undertaken, and we did analyses of cost-utility at 6 months after randomisation and modelled lifetime cost-utility. This study is registered, number ISRCTN47279827. 766 patients were screened; 180 were enrolled and randomly allocated to consideration for treatment by ECMO (n=90 patients) or to receive conventional management (n=90). 68 (75%) patients actually received ECMO; 63% (57/90) of patients allocated to consideration for treatment by ECMO survived to 6 months without disability compared with 47% (41/87) of those allocated to conventional management (relative risk 0·69; 95% CI 0·05–0·97, p=0·03). Referral to consideration for treatment by ECMO treatment led to a gain of 0·03 quality-adjusted life-years (QALYs) at 6-month follow-up. A lifetime model predicted the cost per QALY of ECMO to be £19 252 (95% CI 7622–59 200) at a discount rate of 3·5%. We recommend transferring of adult patients with severe but potentially reversible respiratory failure, whose Murray score exceeds 3·0 or who have a pH of less than 7·20 on optimum conventional management, to a centre with an ECMO-based management protocol to significantly improve survival without severe disability. This strategy is also likely to be cost effective in settings with similar services to those in the UK. UK NHS Health Technology Assessment, English National Specialist Commissioning Advisory Group, Scottish Department of Health, and Welsh Department of Health.

Of 21 cluster trials identified in two major public health journals, only four (19%) had accounted for the clustering in the planning of the trial. 15 Similarly, in a review of physicians' patient care practices, 70% (38/54) of the identified studies had not appropriately accounted for the clustered nature of their study data in their analysis. 16 Of 16 cluster trials reviewed by Donner et al, only four provided any rationale for adopting a clustered design, only three accounted for clustering in the sample size calculations, and only eight accounted for clustering in the analysis. 17 Recent studies have shown continuing problems with the design and analysis of cluster trials; 42% (62/149) of trials of implementation research interventions did not account appropriately for the clustering in their design, 18 and 42% (10/24) of trials of clinical decision support systems did not appropriately account for clustering in their analysis (none accounted for clustering in their sample size calculations). Summary points Accurate reporting of trials is essential to ensure appropriate interpretation of results The CONSORT statement provides a framework for reporting individually randomised trials In some situations it is preferable to randomise groups of individuals (so called cluster randomised trials) Reports of cluster randomised trials require extra information on their special features The CONSORT statement has been extended to accommodate these features Inadequate methodological reporting of trials has been shown to be associated with bias in the estimate of treatment effects. 40 Use of the CONSORT statement for the reporting of two group parallel trials is associated with improved reporting quality. 41 42 43 We believe that the routine use of this proposed extension to the CONSORT statement will result in similar improvements for cluster trials.

High quality protocols facilitate proper planning, conduct, reporting, and external review of randomised trials, yet their completeness varies and key elements are often not considered. To strengthen good reporting of trial protocols, the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 statement has been updated to incorporate new evidence and emerging perspectives. This SPIRIT 2025 explanation and elaboration document provides users with exemplars of reporting in contemporary trial protocols, contextual elaboration, more detailed guidance on reporting, references to key empirical studies, an expanded checklist, and a link to a website for further information. The document is intended to be used in conjunction with the SPIRIT 2025 statement and serves as a resource for researchers planning a trial and for others interested in trial protocols.

Atrial Fibrillation After Cardiac Surgery (AFACS) occurs in about one in three patients following Coronary Artery Bypass Grafting (CABG). It is associated with increased short- and long-term morbidity, mortality and costs. To reduce AFACS incidence, efforts are often made to maintain serum potassium in the high-normal range (≥ 4.5mEq/L). However, there is no evidence that this strategy is efficacious. Furthermore, the approach is costly, often unpleasant for patients, and risks causing harm. We describe the protocol of a planned randomized non-inferiority trial to investigate the impact of intervening to maintain serum potassium ≥ 3.6 mEq/L vs ≥ 4.5 mEq/L on incidence of new-onset AFACS after isolated elective CABG. Patients undergoing isolated CABG at sites in the UK and Germany will be recruited, randomized 1:1 and stratified by site to protocols maintaining serum potassium at either ≥ 3.6 mEq/L or ≥ 4.5 mEq/L. Participants will not be blind to treatment allocation. The primary endpoint is AFACS, defined as an episode of atrial fibrillation, flutter or tachycardia lasting ≥ 30 seconds until hour 120 after surgery, which is both clinically detected and electrocardiographically confirmed. Assuming a 35% incidence of AFACS in the 'tight control group', and allowing for a 10% loss to follow-up, 1684 participants are required to provide 90% certainty that the upper limit of a one-sided 97.5% confidence interval (CI) will exclude a > 10% difference in favour of tight potassium control. Secondary endpoints include mortality, use of hospital resources and incidence of dysrhythmias not meeting the primary endpoint (detected using continuous heart rhythm monitoring). The Tight K Trial will assess whether a protocol to maintain serum potassium ≥ 3.6 mEq/L is non inferior to maintaining serum potassium ≥ 4.5 mEq/L in preventing new-onset AFACS after isolated CABG. ClinicalTrials.gov Identifier: NCT04053816. Registered on 13 August 2019. Last update 7 January 2021.

[This corrects the article DOI: 10.1371/journal.pone.0296525.].