Review
A systematic review of discontinued trials suggested that most reasons for recruitment failure were preventable

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Abstract

Objective

To collect and classify reported reasons for recruitment failure in discontinued randomized controlled trials (RCTs) and to assess reporting quality.

Methods

We systematically searched MEDLINE and EMBASE (2010–2014) and a previous cohort of RCTs for published RCTs reporting trial discontinuation due to poor recruitment. Teams of two investigators selected eligible RCTs working independently and extracted information using standardized forms. We used an iterative approach to classify reasons for poor recruitment.

Results

We included 172 RCTs discontinued due to poor recruitment (including 26 conference abstracts and 63 industry-funded RCTs). Of those, 131 (76%) reported one or more reasons for discontinuation due to poor recruitment. We identified 28 different reasons for recruitment failure; most frequently mentioned were overestimation of prevalence of eligible participants and prejudiced views of recruiters and participants on trial interventions. Few RCTs reported relevant details about the recruitment process such as how eligible participants were identified, the number of patients assessed for eligibility, and who actually recruited participants.

Conclusion

Our classification could serve as a checklist to assist investigators in the planning of RCTs. Most reasons for recruitment failure seem preventable with a pilot study that applies the planned informed consent procedure.

Introduction

One quarter of randomized controlled trials (RCTs) are prematurely discontinued [1]. RCT discontinuation represents a considerable waste of scarce research resources, in particular when the results and reasons for discontinuation are not published. The most common reason for RCT discontinuation is poor recruitment of participants [1]. Sharing the encountered recruitment difficulties with the scientific community is an important contribution to overcome similar problems in the future [2].

Qualitative and quantitative studies have already suggested various barriers and facilitators of recruitment [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17]. However, these studies were mostly restricted to specific countries or contexts; a current and comprehensive collection of recruitment barriers that led to the discontinuation of RCTs is still missing.

We conducted a qualitative systematic review of published RCTs discontinued due to poor recruitment to collect underlying reasons for recruitment failure as reported by trial investigators. We developed a comprehensive classification of reasons as orientation for investigators planning RCTs. A secondary objective of our study was to assess the reporting of recruitment in included RCT publications.

Section snippets

Eligibility criteria

We included RCT publications explicitly stating in their abstract that trials were discontinued due to poor recruitment of participants (i.e., the target sample size was not achieved). We did not impose any restrictions in terms of language of publications, RCT design, trial purpose (superiority/noninferiority/equivalence), or sample size. We did not consider interview studies, focus group studies, or surveys of trial participants or recruiting physicians independent of an actual RCT report.

Study selection

We

RCT characteristics

We identified a total of 172 eligible RCTs (148 through electronic search and 24 through the RCT cohort) that explicitly reported discontinuation due to poor recruitment in their abstract (Fig. 1). General characteristics of industry and non–industry-funded trials were very similar (Table 1).

Reporting quality

Of the 172 RCT publications, 76% reported one or more specific reasons for trial discontinuation due to poor recruitment. Most reports (83%) focused on results which were in 77% presented in sufficient

Discussion

We reviewed a total of 172 RCTs reporting trial discontinuation due to poor recruitment in their abstract. We identified a total of 28 different reasons for recruitment failure and categorized these in a way to provide orientation for trial investigators about common pitfalls. Investigators most frequently mentioned lack of eligible patients due to overestimated prevalence followed by prejudiced views of recruiters and participants on trial interventions; most reported reasons appeared

Conclusion

We identified 28 different reasons for poor recruitment leading to RCT discontinuation, most of which could be prevented. Our classification may serve as a checklist to remind investigators of crucial aspects. Detailed reporting of recruitment strategies, actual recruitment and retention rates, and publication of encountered recruitment difficulties would go a long way in helping other investigators in the planning of future RCTs and preventing the repetition of mistakes.

Acknowledgments

The authors would like to thank Christian Lengeler, Lars G. Hemkens, Mirjam Christ-Crain, Christiane Pauli-Magnus, Claudine A. Blum, Dominik Mertz, Jason W. Busse, and Gordon H. Guyatt for their valuable feedback on the classification of reasons for recruitment failure.

Ethical approval: For this type of study, formal consent is not required.

Authors' contributions: M.B., K.K.O., and S.S. conceived of the study, wrote the protocol, helped design the search strategy, collected data from included

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    Funding: This study was supported by the Swiss National Science Foundation (grant 320030_149496/1). The Swiss National Science Foundation had no role in the design and conduct of the study, analysis of the data, interpretation of the results, writing of the article, or the decision.

    Conflict of interest: None.

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