Protocol for a factorial randomised controlled trial, embedded within WHiTE 8 COPAL, of an Enhanced Trainee Principal Investigator Package and Additional Digital Nudge to increase recruitment rates

Introduction

Randomised controlled trials (RCTs) are considered the gold standard when evaluating the efficacy and effectiveness of health care interventions. Unfortunately, a significant number of well-designed RCTs struggle with the recruitment of participants and subsequently fail to reach their target sample size¹.

Several hypothetical and real-life studies on methods to improve participant recruitment to RCTs have been conducted with mixed results, with only a minority targeting recruiters to the trial^2–5. The results of a survey of clinical trials units in the UK concluded that priorities for evaluation included training site staff, methods of communication with patients and incentivising site staff⁶.

The aim of this real-life study is to assess the effects of targeting healthcare professional recruiters with an educational intervention with or without positive reinforcement on participant recruitment. This study within a trial (SWAT) will test two different methods of enhancing recruitment: introducing an enhanced trainee principal investigators (TPI) package, and personalised email nudges (see Extended data⁷) to healthcare professionals involved in patient recruitment. The SWAT will be implemented in a large, UK, multicentre orthopaedic RCT, the WHiTE 8 COPAL trial. The interventions have both been used in current orthopaedic trials, but their effects on recruitment have previously not been investigated.

Interventions

This will be a multicentre, 2×2 factorial RCT run between August 2018 and October 2019 with random allocation of the recruiting centre to one of four groups:

Full details of each intervention have been provided as Extended data⁷ and are summarised in Table 1. The consent to participate as a TPI and interventions will be implemented by the White 8 Research Fellow (author N.A.). Consent materials are also available as Extended data⁷.

Sample selection

As in many SWATs, a power calculation was not undertaken as the number of participating sites is fixed and driven by the needs of the host trial. All WHiTE centres planned to be recruiting to the WHiTE 8 trial will be included, except the centre in which N.A. is based. We anticipate a minimum of 20 centres being involved in recruiting. Trial interventions will only be discontinued if the host trial (WHiTE 8 Copal) is discontinued.

Randomisation

The WHiTE centres will be randomised by minimisation on a rolling basis as sites become activated to one of the four groups to balance key baseline characteristics. Self-reported site feasibility questionnaires completed by the recruitment centres will be used to collect the information required for the minimisation. Minimisation will be based on the following factors:

This randomisation will be performed using specialist computer software, MinimPy (Saghaei and Saghaei, 2011). This is an open trial and participating sites, the data analyst nor trial team will be blind to allocation.

Outcomes

The primary outcome is the total number of patients recruited in the first 6 months from a site opening to recruitment to the WHiTE 8 COPAL trial.

The secondary outcomes are: conversion rate from screened population collected monthly from the central recruitment database (coordinated by the Oxford Clinical Trials Research Unit); and the time taken to implement each intervention from commencing recruitment in each centre.

The trainee’s perspective of their role will be collected through the TPI survey (available as Extended data⁷ at the end of the SWAT in each centre. The Research Fellow will keep a record of the time taken delivering the TPI education intervention and a log of communication for peer-support during the period of the SWAT to inform future implementation.

Ethical issues

The University of York Health Sciences Ethics Committee has approved this study within a trial. Ethics Approval ID: HSRGC/2018/266/C. Substantive protocol amendments will be sought approval through then university ethics committee.

Trial registration

This SWAT is registered with ISRCTN (11600053) and is embedded in the WHITE 8 Copal trial (ISRCTN 15606075).

This SWAT is also registered to the SWAT repository store as part of the Northern Ireland Hub for Trials Methodology Research (SWAT 67).

Data analysis

Analysis will be conducted in STATA v15 on an intention-to-treat basis, including all sites in the group they were originally allocated to regardless of deviations based on non-compliance. Statistical significance will be assessed using logistic regression two-sided statistical tests at the 5% significance level. The trial will be reported to CONSORT guidelines, and a flow diagram will present the progression of sites through the trial.

Baseline data relating to the sites (including the minimisation factors) will be summarised for the four groups as randomised and as analysed to assess whether possible loss-to-follow-up has introduced selection bias. Continuous data will be presented using descriptive statistics (e.g., mean, standard deviation, median, minimum, maximum), while categorical data will be given as counts and percentages. No formal statistical comparison of baseline data will be undertaken between the four groups.

The number of participants recruited per site will be summarised. A Poisson regression model, containing the two interventions (Enhanced TPI and Email Nudge) and the minimisation factors (cluster size, and number recruited per month will be included in their continuous form) will be undertaken. Adjusted incidence rate ratios (IRRs) and associated 95% confidence intervals (CIs) will be obtained from this model. The presence of an interaction between the two interventions will also be tested by including an interaction term in the model.

Feasibility outcomes, such as the time required to run the education intervention and communication time and methods used for the peer support aspect of the intervention, will be reported descriptively.

A data monitoring committee will not be used as this a trial involving recruiters and patient safety will not be affected by conducting this trial. No formal auditing of trial procedure will take place.

Discussion

If successful, we would like to show that these can be feasibly implemented in future RCTs with additional benefit of reaching targeted sample sizes within the planned recruitment timeline due to increased recruitment rates.

Plans for dissemination

Results of this study will be form part of a PhD thesis, published in a peer-reviewed journal, presented at conferences and be shared with recruiting centres and clinical trials units.

Data availability