Key messages
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Telling people what treatment they will receive – rather than them not being told – improves recruitment.
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Telephoning people who don't respond to an initial postal invitation to join a trial improves recruitment when the initial recruitment rate is low.
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Tailored, user-tested information leaflets, sending letters about the importance of research, or providing a link to videos make little or no difference to recruitment.
What are research trials?
Research trials compare different approaches, such as treatments, programmes, or ways of delivering services. In health care, trials are essential to test new medicines and devices on human volunteers (‘trial participants’) to make sure they are safe and effective. However, finding and keeping trial participants is challenging. About half of all trials fail to recruit the number of people they need on time. Strategies to boost recruitment include changing trial methods and improving information for potential participants and how they are invited to take part.
What did we want to find out?
We wanted to find out which strategies encouraged more people to join research trials, and whether they:
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were good value for money (cost-effective);
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made any difference to whether people stayed in the trial until the end (retention); and
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had any effect on the diversity of the people and places involved.
What did we do?
We searched for studies that tested different recruitment strategies embedded within research trials. Potential participants were chosen by chance to receive different recruitment approaches, and the studies measured how many people joined the trial.
We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as methods and the number of people participating.
What did we find?
We found 91 studies, each involving between 37 and 30,000 participants, mostly conducted in the UK (46 studies) and USA (23 studies). All were in healthcare trials. Nearly all (99%) were carried out in high-income countries. Most studies gave little information about the people they recruited.
The studies tested 65 different recruitment strategies ranging from changes to trial methods to how people were approached and informed about taking part. Participants had different health concerns (e.g. cancer, surgery).
We are confident in the evidence for only 5 of the 65 strategies investigated, and we focus on these below.
Main results
Trial procedures
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Potential participants are more likely to join an ‘open-label’ trial, where they know their treatment, than a ‘blinded’ trial, where they do not know which treatment they will receive (3 trials, 9004 participants).
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For every 100 people invited, an open-label trial recruits 10 more participants.
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The trials involved mostly women in the UK and Estonia.
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There was no information about cost-effectiveness and retention.
Telephone reminders
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Telephoning people who have not responded to a postal invite improves recruitment (2 trials, 1450 people).
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Six more people take part if 100 people are called.
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Participants were aged 58 years on average and lived in Canada and Norway.
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There was no information on cost-effectiveness or retention.
Letters about the importance of research
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Sending letters about the importance of research before the trial invitation does not significantly improve recruitment (2 trials, 5376 participants).
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One more person joins if 100 people are sent a letter.
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This small gain was not good value, costing 2.08 pounds sterling (GBP) per additional participant recruited.
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The trials involved mostly older white people in the UK and Ireland.
QR code or link to videos alongside printed information leaflets
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Providing a QR code or link to videos alongside a printed information leaflet makes no difference to recruitment (7 trials, 11,612 participants) or retention (5 trials, 7403 participants).
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There is zero change per 100 people.
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This strategy was not cost-effective (GBP 0.78 more).
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The trials involved people in the UK.
Information leaflets
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Information leaflets developed with input from people similar to those being recruited make no difference compared to standard leaflets (6 trials, 27,805 participants).
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Both types of leaflet result in 7 in 100 people joining the trial.
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The trials involved people in the UK, mostly older women in one trial.
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There was no information on cost-effectiveness or retention.
What are the limitations of the evidence?
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Our confidence in all but the five strategies above is limited because they were tested in only one trial, the trials testing them had problems with their methods, or the results were very uncertain.
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We found cost information for only 8 strategies, and retention information for only 15 trials.
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Few trials reported information about participants' age, sex, gender, education level, and income level, so we are not sure how effective the strategies would be for different people.
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Most trials (75%) were carried out in the UK or USA, so our findings may not apply to healthcare systems in other parts of the world. We screened all non-English studies, none were eligible.
How up to date is this evidence?
This review updates our 2018 review. The evidence is current to February 2023.
Read the full abstract
Background
Recruiting participants to randomised controlled trials (RCTs) is challenging. Identifying effective recruitment strategies would benefit health research: poor recruitment leads to underpowered trials, reducing the reliability of findings and increasing the risk of wasted resources, ethical concerns, and trial failure. Evidence to inform recruitment strategies is increasingly generated through Studies Within A Trial (SWATs), which are methodological studies embedded within host RCTs. This is an update of a review last published in 2018.
Objectives
Primary: to quantify the effects of strategies to improve recruitment of participants to RCTs.
Secondary: to evaluate recruitment strategies' cost-effectiveness and impact on retention, and the equity, diversity, and inclusion (EDI) characteristics of recruited participants.
Search strategy
We used MEDLINE, Embase, and six other databases to identify the studies included in the review. We also sought unpublished recruitment SWATs through social media and targeted email dissemination to trial methodology networks. The latest search date was 16 February 2023.
Selection criteria
We included randomised SWATs evaluating trial recruitment strategies embedded in healthcare and non-healthcare trials. We excluded quasi-randomised, hypothetical, questionnaire-only, retention-only, or clinician incentive studies.
Data collection and analysis
Primary outcome: proportion of eligible participants or centres recruited.
Secondary outcomes: cost-effectiveness, retention rates, and EDI characteristics of included participants.
We conducted random-effects meta-analysis for strategies evaluated in at least two studies; otherwise, we synthesised results narratively. We reported effects as risk differences (RDs) with 95% confidence intervals (CIs), and assessed between-trial heterogeneity. We used GRADE to assess the certainty of evidence for the primary outcome. We expressed cost-effectiveness as the incremental cost per additional participant recruited in pounds sterling (GBP).
Main results
We identified 91 eligible studies (53 new to this update), providing 94 comparisons and involving at least 176,747 participants. Eighty-one studies involved strategies aimed at trial participants, while 10 evaluated strategies aimed at recruiters. All were healthcare studies.
We found 65 recruitment strategies; 49 were evaluated in a single study. Only five strategies were supported by high-certainty evidence according to GRADE criteria, and we focus on these strategies in the summary below.
Open-label trials versus blinded, placebo trials. Open-label trials recruited more participants than blinded trials (RD 10%, 95% CI 8% to 12%; 3 studies, 9004 participants), corresponding to approximately 10 additional participants per 100 approached. The studies involved mostly women in the UK and Estonia. No cost or retention data were reported.
Telephone reminder versus no telephone reminder. Telephone reminders to people who did not respond to an initial postal invitation boosted recruitment by 6% (95% CI 3% to 9%; 2 studies, 1450 participants), in trials with low underlying recruitment (we are less certain for trials with over 10% recruitment). The studies involved people with a mean age of 58 years in Canada and Norway. No cost or retention data were reported.
Recruitment primer letter versus no letter. Pre-recruitment letters and leaflets designed to encourage participation made little or no difference to recruitment (absolute improvement 1%, 95% CI −1% to 2%; 2 studies, 5376 participants), and were associated with increased costs compared to not sending a primer (incremental cost: GBP 2.08). The studies involved mostly older white people in the UK and Ireland.
Multimedia information via a digital link/QR code plus paper participant information leaflet (PIL) versus paper PIL alone. This made little or no difference to recruitment (absolute improvement 0%, 95% CI −1% to 1%; 7 studies, 11,612 participants) and retention (absolute improvement 0%, 95% CI −2% to 3%; 5 studies, 7403 participants), and increased costs compared to not including multimedia information (incremental cost: GBP 0.78). The studies involved people in the UK.
Optimised, user-tested PIL versus standard PIL. Optimising participant information leaflets (e.g. through user-testing the leaflet with the target population to shape its content, format, and appearance) made little or no difference to recruitment: absolute improvement was 0% (95% CI 0% to 1%; 6 studies, 27,805 participants). The studies involved people in the UK. Only one study reported EDI data; participants were mostly older women. No cost or retention data were reported.
We had moderate-certainty evidence for 13 other strategies; confidence was often reduced because the results came from single studies. Seven strategies involved changes to how potential participants received information; four involved changes to trial conduct; one targeted the recruiter or recruitment site; and one tested non-monetary incentives.
We had much less confidence in the other 47 comparisons because the studies had design flaws, were single studies, or had very uncertain results.
Costs were reported in only 17 of 91 studies. Strategy impact on retention was reported in 15 studies. All but one study (99%) were from high-income countries. The most reported demographics were age (49 studies), sex (32 studies), gender (27 studies), and education level (16 studies).
Authors' conclusions
The evidence on strategies to improve trial recruitment remains broad but lacks depth. Of 65 strategies evaluated, only five were supported by high-certainty evidence. Open-label trial designs and telephone reminders to non-responders increased recruitment, while optimised participant information leaflets, recruitment primer letters, and multimedia information provided alongside a paper participant information leaflet had little or no effect. Reporting of participant characteristics was poor, limiting assessment of equity, diversity, and inclusion across most studies.
Evidence is heavily skewed toward high-income countries. Future research must prioritise evaluations in low-to-middle-income settings and consistently report cost, retention, and EDI outcomes.
We strongly urge the methodology research community to strengthen the evidence base by prioritising replications of existing strategies over the development and testing of new ones.
Funding
National Institute for Health and Care Research (Advanced Fellowship, Adwoa Parker, reference:NIHR302256).
Health Research Board, Republic of Ireland, Evidence Synthesis Ireland (grant ESI-2021-001)
Registration
This review updates an earlier Cochrane review, which was first published in 2002 and subsequently updated in 2007, 2010, and 2018. Previous versions of the review and their protocols are available at:
https://doi.org/10.1002/14651858.MR000013.pub2
https://doi.org/10.1002/14651858.MR000013.pub3
https://doi.org/10.1002/14651858.MR000013.pub4
https://doi.org/10.1002/14651858.MR000013.pub5
https://doi.org/10.1002/14651858.MR000013.pub6
