Research methods in medicine & health sciences最新文献

Two-step approaches for synthesizing proportions in a meta-analysis require first transforming the proportions to a scale where their distribution across studies can be approximated by a normal distribution. Commonly used transformations include the log, logit, arcsine, and Freeman-Tukey double-arcsine transformations. Alternatively, a generalized linear mixed model (GLMM) can be fit directly on the data using the exact binomial likelihood. Unlike popular two-step methods, this accounts for uncertainty in the within-study variances without a normal approximation and does not require an ad hoc correction for zero counts. However, GLMMs require choosing a link function; we illustrate how the AIC can be used to choose the best-fitting link when different link functions give different results. We also highlight how misspecification of the link function can introduce bias; using an empirical sandwich estimator for the standard error may not sufficiently avoid undercoverage due to link function misspecification. We demonstrate the application of GLMMs and choice of link function using data from a systematic review on the prevalence of fever in children with COVID-19.

Background: Over the last decade, there has been an increasing interest in risk-based monitoring (RBM) in clinical trials, resulting in a number of guidelines from regulators and its inclusion in ICH GCP. However, there is a lack of detail on how to approach RBM from a practical perspective, and insufficient understanding of best practice.

Purpose: We present a method for clinical trials units to track their metrics within clinical trials using descriptive statistics and visualisations.

Research design: We suggest descriptive statistics and visualisations within a SWAT methodology.

Study sample: We illustrate this method using the metrics from TEMPER, a monitoring study carried out in three trials at the MRC Clinical Trials Unit at UCL.

Data collection: The data collection for TEMPER is described in DOI: 10.1177/1740774518793379.

Results: We show the results and discuss a protocol for a Study-Within-A-Trial (SWAT 167) for those wishing to use the method.

Conclusions: The potential benefits metric tracking brings to clinical trials include enhanced assessment of sites for potential corrective action, improved evaluation and contextualisation of the influence of metrics and their thresholds, and the establishment of best practice in RBM. The standardisation of the collection of such monitoring data would benefit both individual trials and the clinical trials community.

Background: RCTs often face issues such as slow recruitment, poor intervention adherence and high attrition, however the 2020/2021 COVID-19 pandemic intensified these challenges. Strategies employed by the DISC trial to overcome pandemic-related barriers to recruitment, treatment delivery and retention may be useful to help overcome routine problems.

Methods: A structured survey and teleconference with sites was undertaken. Key performance indicators in relation to recruitment, treatment delivery and retention were compared descriptively before and after the pandemic started. This was situated also in relation to qualitative opinions of research staff.

Results: Prior to the pandemic, retention was 93.6%. Increased support from the central trial management team and remote data collection methods kept retention rates high at 81.2% in the first 6 months of the pandemic, rising to 89.8% in the subsequent 6 months. Advertising the study to patients resulted in 12.8 patients/month enquiring about participation, however only six were referred to recruiting sites. Sites reported increased support from junior doctors resolved research nurse capacity issues. One site avoided long delays by using theatre space in a private hospital.

Conclusions: Recruitment post-pandemic could be improved by identification of barriers, increased support from junior doctors through the NIHR associate PI scheme and advertising. Remote back-up options for data collection can keep retention high while reducing patient and site burden. To future proof studies against similar disruptions and provide more flexibility for participants, we recommend that RCTs have a back-up option of remote recruitment, a back-up location for surgeries and flexible approaches to collecting data.