Methods to improve recruitment to randomised controlled trials: Cochrane systematic review and meta-analysis
TL;DR: There are promising strategies for increasing recruitment to trials, but some methods, such as open-trial designs and opt-out strategies, must be considered carefully as their use may also present methodological or ethical challenges.
Abstract: Objective: To identify interventions designed to improve recruitment to randomised controlled trials, and to quantify their effect on trial participation. Design: Systematic review. Data sources: The Cochrane Methodology Review Group Specialised Register in the Cochrane Library, MEDLINE, EMBASE, ERIC, Science Citation Index, Social Sciences Citation Index, C2-SPECTR, the National Research Register and PubMed. Most searches were undertaken up to 2010; no language restrictions were applied. Study selection: Randomised and quasi-randomised controlled trials, including those recruiting to hypothetical studies. Studies on retention strategies, examining ways to increase questionnaire response or evaluating the use of incentives for clinicians were excluded. The study population included any potential trial participant (eg, patient, clinician and member of the public), or individual or group of individuals responsible for trial recruitment (eg, clinicians, researchers and recruitment sites). Two authors independently screened identified studies for eligibility. Results: 45 trials with over 43 000 participants were included. Some interventions were effective in increasing recruitment: telephone reminders to non-respondents (risk ratio (RR) 1.66, 95% CI 1.03 to 2.46; two studies, 1058 participants), use of opt-out rather than opt-in procedures for contacting potential participants (RR 1.39, 95% CI 1.06 to 1.84; one study, 152 participants) and open designs where participants know which treatment they are receiving in the trial (RR 1.22, 95% CI 1.09 to 1.36; two studies, 4833 participants). However, the effect of many other strategies is less clear, including the use of video to provide trial information and interventions aimed at recruiters.
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TL;DR: Overall, SNS interventions appeared to be effective in promoting changes in health-related behaviors, and further research regarding the application of these promising tools is warranted.
487 citations
TL;DR: It is argued that insufficient focus has been placed on the development and testing of recruitment and retention interventions, and adoption of innovative methods to develop, test, and implement recruitment interventions are required.
Abstract: Background: Despite significant investment in infrastructure many trials continue to face challenges in recruitment and retention. We argue that insufficient focus has been placed on the development and testing of recruitment and retention interventions. Methods: In this current paper, we summarize existing reviews about interventions to improve recruitment and retention. We report survey data from Clinical Trials Units in the United Kingdom to indicate the range of interventions used by these units to encourage recruitment and retention. We present the views of participants in a recent workshop and a priority list of recruitment interventions for evaluation (determined by voting among workshop participants). We also discuss wider issues concerning the testing of recruitment interventions. Results: Methods used to encourage recruitment and retention were categorized as: patient contact, patient convenience, support for recruiters, monitoring and systems, incentives, design, resources, and human factors. Interventions felt to merit investigation by respondents fell into three categories: training site staff, communication with patients, and incentives. Conclusions: Significant resources continue to be invested into clinical trials and other high quality studies, but recruitment remains a significant challenge. Adoption of innovative methods to develop, test, and implement recruitment interventions are required.
271 citations
TL;DR: The literature on interventions to improve recruitment to trials has plenty of variety but little depth, and only 3 of 72 comparisons are supported by high-certainty evidence according to GRADE.
Abstract: Background:
Recruiting participants to trials can be extremely difficult. Identifying strategies that improve trial recruitment would benefit both trialists and health research.
Objectives:
To quantify the effects of strategies for improving recruitment of participants to randomised trials. A secondary objective is to assess the evidence for the effect of the research setting (e.g. primary care versus secondary care) on recruitment.
Search methods:
We searched the Cochrane Methodology Review Group Specialised Register (CMR) in the Cochrane Library (July 2012, searched 11 February 2015); MEDLINE and MEDLINE In Process (OVID) (1946 to 10 February 2015); Embase (OVID) (1996 to 2015 Week 06); Science Citation Index & Social Science Citation Index (ISI) (2009 to 11 February 2015) and ERIC (EBSCO) (2009 to 11 February 2015).
Selection criteria:
Randomised and quasi-randomised trials of methods to increase recruitment to randomised trials. This includes non-healthcare studies and studies recruiting to hypothetical trials. We excluded studies aiming to increase response rates to questionnaires or trial retention and those evaluating incentives and disincentives for clinicians to recruit participants.
Data collection and analysis:
We extracted data on: the method evaluated; country in which the study was carried out; nature of the population; nature of the study setting; nature of the study to be recruited into; randomisation or quasi-randomisation method; and numbers and proportions in each intervention group. We used a risk difference to estimate the absolute improvement and the 95% confidence interval (CI) to describe the effect in individual trials. We assessed heterogeneity between trial results. We used GRADE to judge the certainty we had in the evidence coming from each comparison.
262 citations
TL;DR: Findings add weight to the case for PPI in clinical trials by indicating that it is likely to improve enrolment of participants, especially if it includes people with lived experience of the health condition under study.
Abstract: © Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to. Objective To investigate the impact of patient and public involvement (PPI) on rates of enrolment and retention in clinical trials and explore how this varies with the context and nature of PPI. Design Systematic review and meta-analysis. Data sources Ten electronic databases, including Medline, INVOLVE Evidence Library, and clinical trial registries. Eligibility criteria Experimental and observational studies quantitatively evaluating the impact of a PPI intervention, compared with no intervention or non-PPI intervention(s), on participant enrolment and/or retention rates in a clinical trial or trials. PPI interventions could include additional non-PPI components inseparable from the PPI (for example, other stakeholder involvement). Data extraction and analysis Two independent reviewers extracted data on enrolment and retention rates, as well as on the context and characteristics of PPI intervention, and assessed risk of bias. Random effects meta-analyses were used to determine the average effect of PPI interventions on enrolment and retention in clinical trials: main analysis including randomised studies only, secondary analysis adding non-randomised studies, and several exploratory subgroup and sensitivity analyses. Results 26 studies were included in the review; 19 were eligible for enrolment meta-analysis and five for retention meta-analysis. Various PPI interventions were identified with different degrees of involvement, different numbers and types of people involved, and input at different stages of the trial process. On average, PPI interventions modestly but significantly increased the odds of participant enrolment in the main analysis (odds ratio 1.16, 95% confidence interval and prediction interval 1.01 to 1.34). Non-PPI components of interventions may have contributed to this effect. In exploratory subgroup analyses, the involvement of people with lived experience of the condition under study was significantly associated with improved enrolment (odds ratio 3.14 v 1.07; P=0.02). The findings for retention were inconclusive owing to the paucity of eligible studies (odds ratio 1.16, 95% confidence interval 0.33 to 4.14), for main analysis). Conclusions These findings add weight to the case for PPI in clinical trials by indicating that it is likely to improve enrolment of participants, especially if it includes people with lived experience of the health condition under study. Further research is needed to assess which types of PPI work best in particular contexts, the cost effectiveness of PPI, the impact of PPI at earlier stages of trial design, and the impact of PPI interventions specifically targeting retention. Systematic review registration PROSPERO CRD42016043808.
260 citations
TL;DR: Suggestions to improve recruitment included reducing participant burden, providing support for individuals who do not speak English, and forming collaborations with primary care to improve the identification of, and access to, potentially eligible participants.
Abstract: Background
Recruiting the required number of participants is vital to the success of clinical research and yet many studies fail to achieve their expected recruitment rate. Increasing research participation is a key agenda within the NHS and elsewhere, but the optimal methods of improving recruitment to clinical research remain elusive. The aim of this study was to identify the factors that researchers perceive as influential in the recruitment of participants to clinically focused research.
220 citations
Cites background from "Methods to improve recruitment to r..."
...The recommendation to use an opt-out system, where patients are required to contact the research team if they do not wish to be invited to participate in clinical research, was made in a recent systematic review [3]....
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...© 2014 Newington and Metcalfe; licensee Bio Creative Commons Attribution License (http:/ distribution, and reproduction in any medium gaining interest and a recent systematic review of strategies aimed at improving recruitment to randomised controlled trials (RCTs) identified 45 relevant studies and categorised six types of intervention: trial design, obtaining consent, approach to participants, financial incentives, training for recruiters and trial coordination [3]....
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...Overall, the general strategies found to be effective in improving recruitment included: making telephone reminders to non-responders, having opt-out procedures where potential participants are required to contact the trial team if they do not want to be contacted about a trial, and having open rather than blinded trial designs [3]....
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References
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Book•
23 Sep 2019TL;DR: The Cochrane Handbook for Systematic Reviews of Interventions is the official document that describes in detail the process of preparing and maintaining Cochrane systematic reviews on the effects of healthcare interventions.
Abstract: The Cochrane Handbook for Systematic Reviews of Interventions is the official document that describes in detail the process of preparing and maintaining Cochrane systematic reviews on the effects of healthcare interventions.
21,235 citations
Journal Article•
17,222 citations
"Methods to improve recruitment to r..." refers methods in this paper
...Data synthesis Data were processed in accordance with the Cochrane handbook.(15) Trials were grouped according to the type of intervention evaluated (eg, monetary incentives, alternative forms of consent, etc), with intervention groupings based on similarities in form and content....
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...This was independently assessed by the same two reviewers, and summarised in line with Cochrane guidance (A, low risk; B, moderate risk and C, high risk).(15) Studies at a high risk of bias were not excluded, but results were interpreted in light of this....
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01 Jan 2013
9,769 citations
TL;DR: Empirical evidence is provided that inadequate methodological approaches in controlled trials, particularly those representing poor allocation concealment, are associated with bias.
Abstract: Objective. —To determine if inadequate approaches to randomized controlled trial design and execution are associated with evidence of bias in estimating treatment effects. Design. —An observational study in which we assessed the methodological quality of 250 controlled trials from 33 meta-analyses and then analyzed, using multiple logistic regression models, the associations between those assessments and estimated treatment effects. Data Sources. —Meta-analyses from the Cochrane Pregnancy and Childbirth Database. Main Outcome Measures. —The associations between estimates of treatment effects and inadequate allocation concealment, exclusions after randomization, and lack of double-blinding. Results. —Compared with trials in which authors reported adequately concealed treatment allocation, trials in which concealment was either inadequate or unclear (did not report or incompletely reported a concealment approach) yielded larger estimates of treatment effects ( P P =.01), with odds ratios being exaggerated by 17%. Conclusions. —This study provides empirical evidence that inadequate methodological approaches in controlled trials, particularly those representing poor allocation concealment, are associated with bias. Readers of trial reports should be wary of these pitfalls, and investigators must improve their design, execution, and reporting of trials. ( JAMA . 1995;273:408-412)
5,765 citations
"Methods to improve recruitment to r..." refers methods in this paper
...In addition, data on the method of randomisation, allocation concealment (adequate, clear and inadequate), blinding (full, partial and none), adequacy (objective, unclear and subjective) and reporting of outcome measures and level of follow-up were collected to allow the risk of bias in each study to be determined.(14) This was independently assessed by the same two reviewers, and summarised in line with Cochrane guidance (A, low risk; B, moderate risk and C, high risk)....
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TL;DR: A randomised controlled trials of methods to increase response to postal or electronic questionnaires found substantial heterogeneity among trial results in half of the strategies, which could improve the quality of health research.
Abstract: BACKGROUND: Postal and electronic questionnaires are widely used for data collection in epidemiological studies but non-response reduces the effective sample size and can introduce bias. Finding ways to increase response to postal and electronic questionnaires would improve the quality of health research. OBJECTIVES: To identify effective strategies to increase response to postal and electronic questionnaires. SEARCH STRATEGY: We searched 14 electronic databases to February 2008 and manually searched the reference lists of relevant trials and reviews, and all issues of two journals. We contacted the authors of all trials or reviews to ask about unpublished trials. Where necessary, we also contacted authors to confirm methods of allocation used and to clarify results presented. We assessed the eligibility of each trial using pre-defined criteria. SELECTION CRITERIA: Randomised controlled trials of methods to increase response to postal or electronic questionnaires. DATA COLLECTION AND ANALYSIS: We extracted data on the trial participants, the intervention, the number randomised to intervention and comparison groups and allocation concealment. For each strategy, we estimated pooled odds ratios (OR) and 95% confidence intervals (CI) in a random-effects model. We assessed evidence for selection bias using Egger's weighted regression method and Begg's rank correlation test and funnel plot. We assessed heterogeneity among trial odds ratios using a Chi(2) test and the degree of inconsistency between trial results was quantified using the I(2) statistic. MAIN RESULTS: PostalWe found 481 eligible trials. The trials evaluated 110 different ways of increasing response to postal questionnaires. We found substantial heterogeneity among trial results in half of the strategies. The odds of response were at least doubled using monetary incentives (odds ratio 1.87; 95% CI 1.73 to 2.04; heterogeneity P < 0.00001, I(2) = 84%), recorded delivery (1.76; 95% CI 1.43 to 2.18; P = 0.0001, I(2) = 71%), a teaser on the envelope - e.g. a comment suggesting to participants that they may benefit if they open it (3.08; 95% CI 1.27 to 7.44) and a more interesting questionnaire topic (2.00; 95% CI 1.32 to 3.04; P = 0.06, I(2) = 80%). The odds of response were substantially higher with pre-notification (1.45; 95% CI 1.29 to 1.63; P < 0.00001, I(2) = 89%), follow-up contact (1.35; 95% CI 1.18 to 1.55; P < 0.00001, I(2) = 76%), unconditional incentives (1.61; 1.36 to 1.89; P < 0.00001, I(2) = 88%), shorter questionnaires (1.64; 95% CI 1.43 to 1.87; P < 0.00001, I(2) = 91%), providing a second copy of the questionnaire at follow up (1.46; 95% CI 1.13 to 1.90; P < 0.00001, I(2) = 82%), mentioning an obligation to respond (1.61; 95% CI 1.16 to 2.22; P = 0.98, I(2) = 0%) and university sponsorship (1.32; 95% CI 1.13 to 1.54; P < 0.00001, I(2) = 83%). The odds of response were also increased with non-monetary incentives (1.15; 95% CI 1.08 to 1.22; P < 0.00001, I(2) = 79%), personalised questionnaires (1.14; 95% CI 1.07 to 1.22; P < 0.00001, I(2) = 63%), use of hand-written addresses (1.25; 95% CI 1.08 to 1.45; P = 0.32, I(2) = 14%), use of stamped return envelopes as opposed to franked return envelopes (1.24; 95% CI 1.14 to 1.35; P < 0.00001, I(2) = 69%), an assurance of confidentiality (1.33; 95% CI 1.24 to 1.42) and first class outward mailing (1.11; 95% CI 1.02 to 1.21; P = 0.78, I(2) = 0%). The odds of response were reduced when the questionnaire included questions of a sensitive nature (0.94; 95% CI 0.88 to 1.00; P = 0.51, I(2) = 0%).ElectronicWe found 32 eligible trials. The trials evaluated 27 different ways of increasing response to electronic questionnaires. We found substantial heterogeneity among trial results in half of the strategies. The odds of response were increased by more than a half using non-monetary incentives (1.72; 95% CI 1.09 to 2.72; heterogeneity P < 0.00001, I(2) = 95%), shorter e-questionnaires (1.73; 1.40 to 2.13; P = 0.08, I(2) = 68%), including a statement that others had responded (1.52; 95% CI 1.36 to 1.70), and a more interesting topic (1.85; 95% CI 1.52 to 2.26). The odds of response increased by a third using a lottery with immediate notification of results (1.37; 95% CI 1.13 to 1.65), an offer of survey results (1.36; 95% CI 1.15 to 1.61), and using a white background (1.31; 95% CI 1.10 to 1.56). The odds of response were also increased with personalised e-questionnaires (1.24; 95% CI 1.17 to 1.32; P = 0.07, I(2) = 41%), using a simple header (1.23; 95% CI 1.03 to 1.48), using textual representation of response categories (1.19; 95% CI 1.05 to 1.36), and giving a deadline (1.18; 95% CI 1.03 to 1.34). The odds of response tripled when a picture was included in an e-mail (3.05; 95% CI 1.84 to 5.06; P = 0.27, I(2) = 19%). The odds of response were reduced when "Survey" was mentioned in the e-mail subject line (0.81; 95% CI 0.67 to 0.97; P = 0.33, I(2) = 0%), and when the e-mail included a male signature (0.55; 95% CI 0.38 to 0.80; P = 0.96, I(2) = 0%). AUTHORS' CONCLUSIONS: Health researchers using postal and electronic questionnaires can increase response using the strategies shown to be effective in this systematic review.
1,312 citations