Original Article
Development of a complex intervention improved randomization and informed consent in a randomized controlled trial

https://doi.org/10.1016/j.jclinepi.2008.02.010Get rights and content

Abstract

Objective

Multicenter randomized trials are required for pragmatic evaluations of health care interventions, but recruitment is difficult. Systematic reviews failed to identify robust strategies to improve recruitment. We developed and evaluated a complex intervention to increase levels of randomization and informed consent.

Study Design and Setting

The ProtecT (Prostate testing for cancer and Treatment) trial compares radical surgery, radical conformal radiotherapy, and active monitoring for men aged 50–69 years with localized prostate cancer. The intervention was developed using qualitative research methods (content, thematic and conversation analysis). Rates of randomization and immediate acceptance of allocation were measured every 6 months to evaluate the impact of the intervention.

Results

The complex intervention comprised reviews of centers falling below study targets, training programmes, documents and individually tailored feedback. Over 65% of eligible participants consented to randomization. Trial participants became increasingly well informed as immediate acceptance of allocation rose from 65% to 81% between 2001 and 2005.

Conclusion

This complex intervention resulted in high levels of randomization and informed consent in a difficult trial. The generic aspects of the intervention could be applied to other trials to maximize randomization and informed consent, and allow the mounting of trials previously considered too difficult.

Section snippets

Background

Pragmatic multicenter randomized controlled trials are widely acknowledged as the design of choice for evaluating the effectiveness of health care interventions in a range of settings applicable to real-life health systems. Recruitment difficulties have been identified as a major cause of trials failing to start, being abandoned, or requiring additional support to reach (often revised) target sample sizes [1], [2], [3], but strategies to improve recruitment to trials remain few and of limited

The ProtecT study

The ProtecT (Prostate testing for cancer and Treatment) trial compares radical surgery, radical conformal radiotherapy, and active monitoring in men aged 50–69 years with localized prostate cancer in nine clinical centers in the UK [9]. Ethical approval was obtained from a multicenter research ethics committee. A feasibility study was undertaken in three centers in 1999–2001 with a nested trial of recruitment strategies [7] and integrated qualitative research [9]. The qualitative research

Results

The timing and constituents of the complex intervention are shown with the rates of randomization and immediate acceptance of allocation calculated each year from 2001 to 2007 (Fig. 1). The rate of immediate acceptance of allocation rose from 66% in 2002 to 71% in 2003, following center reviews, training and publication of document one (Fig. 1). This rise continued and increased to 78% in 2005, following intensified training and the publication of document two, in 2004. The rate of

Discussion

Multicenter trials are complex to mount and require considerable investment, but they often fail to recruit at the speed and to the level originally anticipated [1], [2], [3], [4], [5], [8]. Systematic reviews have identified many barriers but few robust interventions to improve recruitment [1], [4], [5], [6], [8]. The implementation of the complex intervention in the ProtecT study led to a marked increase in the rate of immediate acceptance of allocation over time (from 65% to 81%) with the

Acknowledgments

Contributions: F.C.H., J.L.D. and D.E.N. are PIs of the ProtecT trial; J.A.L. is the ProtecT trial co-ordinator; E.S. provided support and training for nurse-recruiters; D.G., P.P. and P.B. are lead clinical center investigators; T.P. is the lead statistician. J.L.D. devised the idea for this paper, led and carried out the qualitative research with L.B. and the Quartet team (see below). All authors contributed to the writing of the paper. J.L.D. is the guarantor.

Funding: The ProtecT study is

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