Elizabeth A Sweetman

Early enteral nutrition reduces mortality in trauma patients requiring intensive care: A meta-analysis of randomised controlled trials

INTRODUCTION To determine whether the provision of early standard enteral nutrition (EN) confers treatment benefits to adult trauma patients who require intensive care. MATERIALS AND METHODS MEDLINE and EMBASE were searched. Hand citation review of retrieved guidelines and systematic reviews was undertaken and academic and industry experts were contacted. Methodologically sound randomised controlled trials (RCTs) conducted in adult trauma patients requiring intensive care that compared the delivery of standard EN, provided within 24 h of injury, to standard care were included.The primary analysis was conducted on clinically meaningful patient-oriented outcomes, which included mortality, functional status and quality of life. Secondary analyses considered vomiting/regurgitation, pneumonia, bacteraemia, sepsis and multiple organ dysfunction syndrome. Meta-analysis was conducted using an analytical method known to minimise bias in the presence of sparse events. The impact of heterogeneity was assessed using the I2 metric. RESULTS Three RCTs with 126 participants were found to be free from major flaws and were included in the primary analysis. The provision of early EN was associated with a significant reduction in mortality(OR = 0.20, 95% confidence interval 0.04–0.91, I2 = 0). No other outcomes could be pooled. A sensitivity analysis and a confirmatory analysis conducted using a different analytical method confirmed the presence of a mortality reduction. CONCLUSION Although the detection of a statistically significant reduction in mortality is promising,overall trial quality was low and trial size was small. The results of this meta-analysis should be confirmed by the conduct of a large multi-center trial.

Failure to report protocol violations in clinical trials: a threat to internal validity?

BackgroundExcessive protocol violations (PV), which can be defined as preventable mistakes in study conduct, may result in patient harm and introduce errors into a clinical trials results leading to flawed trial conclusions.The purpose of this project was to gain a better understanding of reported PVs, to describe current practice with regards to the use of methods for the reduction of PVs and to investigate relationships between clinical trial characteristics and PVs.MethodsWe reviewed 80 clinical trials conducted across a broad range of medical specialties published in four major general medical journals (The Lancet, NEJM, JAMA, BMJ). Eligible papers were identified using a PubMed search. For each included trial, two authors independently abstracted information on trial characteristics, PV reporting and PV rates and interventions used to reduce PVs. PVs were categorised into one of five distinct types: enrolment, randomisation, study intervention, patient compliance and data collection errors. Associations between PVs and study characteristics were investigated using logistic regression.ResultsEighty clinical trials (20 from each journal) were identified from 101 consecutive PubMed abstracts. The median number of participants was 701 (range: 20 to 162, 367) and the median number of participating sites was 15 (range: 1 to 701). Nineteen percent (15/80) of included trials were single centre trials. The median study duration was 24 months (range: 5.81 - 127 months) and 74% (59/80) of included trials were primarily academic funded.Thirty two percent (26/80) of included trials failed to provide explicit reporting of any type of PV and none (0/80) of the trials provided explicit reporting of all five types of PVs. Larger clinical trials (more patients, more sites, longer duration, more complex management structure) were more likely to have more complete reporting of PVs.Only 9% (7/80) of trials reported the use of a specific study method to prevent PVs. Use of a run-in phase was the only method reported.ConclusionsPVs are under-reported. Although the CONSORT statement provides guidance on the reporting of PVs, reporting requirements are not explicit for all types of PVs. As a first step towards improved reporting by authors, we recommend the CONSORT statement highlight the importance of PVs by making reporting requirements more explicit.

A systematic review of techniques and interventions for improving adherence to inclusion and exclusion criteria during enrolment into randomised controlled trials.

BackgroundEnrolment of patients into a randomised controlled trial (RCT) in violation of key inclusion or exclusion criteria, may lead to excess avoidable harm. The purpose of this paper was to systematically identify and review techniques and interventions proven to prevent or avoid inappropriate enrolment of patients into RCTs.MethodsEMBASE, MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Methodology Register, online abstract repositories, and conference websites were searched. Experts were contacted and bibliographies of retrieved papers hand-searched. The search cut-off date was 31 August 2009.ResultsNo primary publications were found. We identified one study in the grey literature (conference abstracts and presentations) reporting the results of an evaluation of the effectiveness of an intervention designed to prevent or avoid inappropriate enrolment of patients into an RCT. In the context of a multicentre trial, use of a dummy enrolment run-in phase was shown to reduce enrolment errors significantly (P < 0.001), from 16.1% during the run-in phase to < 1% after trial initiation.ConclusionsOur systematic search yielded only one technique or intervention shown to improve adherence to eligibility criteria during enrolment into RCTs. Given the potential harm involved in recruiting patients into a clinical trial in violation of key eligibility criteria, future research is needed to better inform those conducting clinical trials of how best to prevent enrolment errors