Developing a survey of barriers and facilitators to recruitment in randomized controlled trials

The survey has been designed as an online questionnaire to be completed by study teams involved with recruitment to a trial. The process of developing the questionnaire is presented in Figure 1. The survey is divided into four main sections to collect information about the site and study role of the responders, the perceived facilitators and barriers to recruitment, strategies applied to overcome the problems and suggestions for changes in organization of future trials.

Free-text space is provided for participants to enter information on their site or center of recruitment, their role in the study, whether they opened to recruitment, and their duration and period of involvement if they were not involved for the whole trial recruitment period. It is possible to add questions for collecting further information on the estimated number of eligible patients, the numbers expected to be randomized, and the hospital policy on recruitment to the study. Skip logic can be applied to direct questions selectively to responders depending on their response to previous questions so that they may skip questions that do not apply to them. The second section provides the survey participants with preformed lists of potential factors affecting recruitment that could act as facilitators or barriers to recruitment.

A list of potential facilitators and barriers affecting recruitment to randomized controlled trials was made from a review of existing literature on the subject. A literature search on Medline using the search terms ‘recruitment’, ‘enrolment’ combined with the AND connector to search terms for ‘clinical trials’ and ‘randomised controlled trials’ identified the major reviews on the subject that were used to develop the list of factors.

The reviews used to design the survey questionnaire are briefly described below. The process of selecting and classifying the factors for inclusion in the survey questionnaire is presented in Table 1. The Health Technology Assessment (HTA) report, ‘Factors that limit the quality, number and progress of randomized controlled trials’ by Prescott et al. [37] reported patient and clinician barriers to participation in randomized controlled trials. The authors of that report conducted a systematic review of studies that reported problems related to recruitment of clinicians and patients to clinical trials and identified the important barriers.

The HTA report ‘Recruitment to randomised trials: strategies for trial enrolment and participation study: The STEPS study’ aimed to identify the factors associated with good and poor recruitment to multicenter trials (38). They conducted an epidemiological review (The STEPS study Part A) of a cohort of trials funded by the Medical Research Council (MRC) and the National Health Service Health Technology Assessment (NHS HTA) program between January 1994 and December 2002. They tested hypotheses of factors for association with recruitment success in the cohort of multicenter randomized controlled trials included in the review, described patterns of recruitment and reported trialists’ perceptions of factors associated with good or poor recruitment. The study also reported the reasons for delay in recruitment and early and late participant recruitment problems in the included cohort of trials based on the trialists’ reports submitted to the funding bodies. The STEPS study (Part B) reported case studies of trials that recruited successfully and had particularly interesting lessons for recruitment. This aim of this part of the study was to gain role specific and location specific insights to the four included trials by interviewing 45 individuals in total across the four trials with different internal perspectives. Four key stages of a trial that may affect recruitment were identified: 1) foundation work involving engagement of collaborators, establishing scientific rigor, funding and financial considerations, 2) recruitment processes, 3) delivery of care and 4) delivery of research. Common factors in the success of the included trials were reported based on analysis of themes identified in the four key stages and from the responses of the interviewees. Toerien et al. [39] reviewed the recruitment and retention rates in randomized controlled trials published in six major journals between July and December 2004 and investigated the association of these rates with trial characteristics such as study size, number of arms, single/multicenter, treatment focus (drug/surgery/allied/others), active/placebo control, time to assessment and type of funding. The Cochrane systematic review on strategies to improve recruitment to randomized controlled trials [2] identified 45 randomized and quasi-randomized controlled trials of interventions directed at potential participants or clinicians, which aimed to improve recruitment of participants to clinical trials. These interventions were divided into six categories: design change, modification to the consent form or process, modification to the approach made to potential participants, financial incentives for participants, modification of training given to recruiters and greater contact between trial coordinator and trial sites. The systematic review of strategies for increasing recruitment to randomized controlled trials by Caldwell et al. [40] looked at the effect of recruitment interventions such as novel trial designs, recruiter differences, incentives and different methods of providing trial information on recruitment success in randomized clinical trials.

From the facilitators and barriers reported in the above studies (37,38) and the potential factors and interventions tested for association with recruitment success (2,38-40), a list of potential factors affecting recruitment was generated by classifying the facilitators and barriers into various categories. This process is presented in Table 1. The factors that were generic and expected to operate commonly at all sites were classified as ‘trial level factors’. These included factors such as funding for the trial, trial design, choice of patient inclusion criteria, type of intervention, previous pilot/feasibility assessment, perception of clinical equipoise, publicity about the trial, trial management, etcetera The factors which could operate differentially between sites were classified as ‘site level factors’ and included factors such as time to open up site, recruitment target, local clinical arrangements, number and availability of trained staff, competing research projects and local research culture to list a few. We excluded factors for which objective information is available such as delays in ethical clearance, research and development delays, and problems with supply of investigational drug/placebo etcetera The various facilitators and barriers relating to patients’ and clinicians’ participation in clinical trials, as described in the above studies were listed under ‘patient related and clinical team related factors’. The factors related to providing information to patients and seeking consent such as amount and complexity of trial information, clarity in presentation of trial information, time and setting of consent seeking and role and seniority of person seeking consent were categorized separately as ‘information and consent related factors’. Lastly, the study team factors such as motivation and research experience of study team, communication and coordination between research teams were presented. Each category formed a separate question in the survey questionnaire to help the participants think through the issues arising during recruitment to the trial.

This section of the survey could be designed to elicit only barriers, only facilitators, or both barriers and facilitators to recruitment. In order to decrease the length of the survey and capture information on both facilitators and barriers in a common question, the factors were reworded such that they could apply both as a facilitator or barrier depending on whether they boosted or hindered recruitment respectively. The questions in this section were designed to obtain graded responses from ‘-3’ to ‘+3’ depending on whether the factor was perceived to be a strong (−3), intermediate (−2) or weak barrier (−1), 0 if thought to be not applicable and weak (+1), intermediate (+2), or strong facilitator (+3).

Open-type questions were provided to obtain information on the various strategies applied to overcome the problems and for participants to express their reflective experiences and views on how trials could be organized differently in the future to improve recruitment.

The paper version of the questionnaire was sent for piloting to a small sample of five people. Three out of the five people (60%) responded. The initial version had separate lists of facilitators and barriers and participants were asked to identify the top five in each list. Two out of the three respondents found the questionnaire lengthy, difficult to complete and it took them 35 to 40 minutes to do so. Some questions were thought to be ambiguous and there was a suggestion for use of computers to enhance the presentation and make it easier to complete.

After the pilot, the questionnaire was modified. The length of the questionnaire was reduced by combining the facilitators and barriers into a single list of factors that could be graded as either in the same question. Efforts were made to provide an evidence-based list of factors affecting recruitment while taking measures to keep the length of the survey and time of completion within reasonable limits. Factors for which objective information was believed to be available from other sources, such as delays in ethical or research and development approval or problems with supply of investigational drug/placebo were excluded from the questionnaire. However, free text space for additional comments was provided at the end for responders to note any issues not covered in the survey.

The factors were reworded so that they were simpler and clearer. An online version was created by using survey software (http://​www.​surveygizmo.​com). The questions were arranged such that they had a logical flow. Each category of factors was arranged as small separate sections on a webpage for better presentation and ease of completion. The participants could easily navigate forward and backward to revisit a section if they needed to and the completion time was reduced to 10 to 15 minutes. The survey instrument (Additional file 1: Figure S1) has been used to investigate the recruitment experience of clinical teams in a large multicenter randomized controlled trial with children in the United Kingdom (MAGNETIC trial). The response rates are presented here, but the results of the survey for identified facilitators and barriers, the strategies applied to overcome these barriers and the suggestions for better organization of trials to improve recruitment, will be published separately. The MAGNETIC trial was a large multicenter, randomized, double-blind placebo-controlled trial evaluating the role of nebulized magnesium in acute severe asthma in children. It recruited over 500 children over a period of 26 months from 30 sites across the United Kingdom. The recruitment experience varied across sites and the opportunity to gather information about this study was believed to be important. There were three other sites that had opened to recruitment but did not recruit any patients and four others where efforts were made to set up the trial but did not open to recruitment. The survey was sent to all 37 sites as recruitment problems and perspectives of clinical teams were envisaged to be different at different sites. The names and contact email addresses of the potential responders were obtained from the delegation logs. This included all clinical team members including the Principal Investigators (PIs), research nurses (RNs),medical practitioners, nursing staff and nurse practitioners, who were delegated to be involved with recruitment to the trial. The survey was emailed to 522 contacts at all 37 sites. Since contact email addresses were expected to change over the course of the trial, especially for the various clinical staff, we selectively pursued responses from the Principal Investigator and at least one research nurse at each site.

The first section was designed to collect information about the responder’s study role, site of recruitment and period and duration of his or her involvement in the trial. Personal information such as name was not collected; instead, each survey participant was assigned a unique identification code for purposes of data collection and analysis. Information on sites and study role was also used to examine representation in responses.

The second section provided a comprehensive list of factors affecting recruitment and the survey participants were asked to rate each factor from ‘-3’ to ‘+3’ as described. Each factor could be assigned only one score. This question was designed in this format to enable us to deduce the most commonly identified strong barriers and facilitators and also to enable us to calculate average scores for each factor. The last section had open-ended questions to gain information on the interventions applied and to collate reflective experiences and suggestions of the study team to improve recruitment with space for additional comments.

The project team sent initial invitations that described the aims and objectives of the survey, provided information about the survey, and requested participation in the survey to the potential participants. The email provided the link to the online questionnaire, stated that participation in the survey was voluntary, and that consent would be assumed by the person completing the questionnaire. The responders were reassured that no personal information such as names would be collected, no site will be identified in any publication and confidentiality of data will be maintained.

A total of 169 complete responses were obtained. We achieved a PI and one research nurse response per site from 86% and 94% of sites respectively. The response rates for PIs and RNs (one per site) are summarized in Table 2.

One hundred percent of the responders completed all questions ranking the factors affecting recruitment as facilitators or barriers. Of those responders 108 of 169 (64%) responded to the open question on interventions or strategies applied to overcome the barriers identified. Free-text suggestions were obtained from 115 of the 169 (68%) respondents on future reorganization of the trial to improve recruitment.