Strategies to improve retention in randomised trials.

BACKGROUND: Poor retention of participants in randomised trials can lead to missing outcome data which can introduce bias and reduce study power, affecting the generalisability, validity and reliability of results. Many strategies are used to improve retention but few have been formally evaluated. OBJECTIVES: To quantify the effect of strategies to improve retention of participants in randomised trials and to investigate if the effect varied by trial setting. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Scopus, PsycINFO, CINAHL, Web of Science Core Collection (SCI-expanded, SSCI, CPSI-S, CPCI-SSH and ESCI) either directly with a specified search strategy or indirectly through the ORRCA database. We also searched the SWAT repository to identify ongoing or recently completed retention trials. We did our most recent searches in January 2020. SELECTION CRITERIA: We included eligible randomised or quasi-randomised trials of evaluations of strategies to increase retention that were embedded in 'host' randomised trials from all disease areas and healthcare settings. We excluded studies aiming to increase treatment compliance. DATA COLLECTION AND ANALYSIS: We extracted data on: the retention strategy being evaluated; location of study; host trial setting; method of randomisation; numbers and proportions in each intervention and comparator group. We used a risk difference (RD) and 95% confidence interval (CI) to estimate the effectiveness of the strategies to improve retention. We assessed heterogeneity between trials. We applied GRADE to determine the certainty of the evidence within each comparison. MAIN RESULTS: We identified 70 eligible papers that reported data from 81 retention trials. We included 69 studies with more than 100,000 participants in the final meta-analyses, of which 67 studies evaluated interventions aimed at trial participants and two evaluated interventions aimed at trial staff involved in retention. All studies were in health care and most aimed to improve postal questionnaire response. Interventions were categorised into broad comparison groups: Data collection; Participants; Sites and site staff; Central study management; and Study design. These intervention groups consisted of 52 comparisons, none of which were supported by high-certainty evidence as determined by GRADE assessment. There were four comparisons presenting moderate-certainty evidence, three supporting retention (self-sampling kits, monetary reward together with reminder or prenotification and giving a pen at recruitment) and one reducing retention (inclusion of a diary with usual follow-up compared to usual follow-up alone). Of the remaining studies, 20 presented GRADE low-certainty evidence and 28 presented very low-certainty evidence. Our findings do provide a priority list for future replication studies, especially with regard to comparisons that currently rely on a single study. AUTHORS' CONCLUSIONS: Most of the interventions we identified aimed to improve retention in the form of postal questionnaire response. There were few evaluations of ways to improve participants returning to trial sites for trial follow-up. None of the comparisons are supported by high-certainty evidence. Comparisons in the review where the evidence certainty could be improved with the addition of well-done studies should be the focus for future evaluations.

Measuring the impact of methodological research: a framework and methods to identify evidence of impact.

BACKGROUND: Providing evidence of impact highlights the benefits of medical research to society. Such evidence is increasingly requested by research funders and commonly relies on citation analysis. However, other indicators may be more informative. Although frameworks to demonstrate the impact of clinical research have been reported, no complementary framework exists for methodological research. Therefore, we assessed the impact of methodological research projects conducted or completed between 2009 and 2012 at the UK Medical Research Council Clinical Trials Unit Hub for Trials Methodology Research Hub, with a view to developing an appropriate framework. METHODS: Various approaches to the collection of data on research impact were employed. Citation rates were obtained using Web of Science (http://www.webofknowledge.com/) and analyzed descriptively. Semistructured interviews were conducted to obtain information on the rates of different types of research output that indicated impact for each project. Results were then pooled across all projects. Finally, email queries pertaining to methodology projects were collected retrospectively and their content analyzed. RESULTS: Simple citation analysis established the citation rates per year since publication for 74 methodological publications; however, further detailed analysis revealed more about the potential influence of these citations. Interviews that spanned 20 individual research projects demonstrated a variety of types of impact not otherwise collated, for example, applications and further developments of the research; release of software and provision of guidance materials to facilitate uptake; formation of new collaborations and broad dissemination. Finally, 194 email queries relating to 6 methodological projects were received from 170 individuals across 23 countries. They provided further evidence that the methodologies were impacting on research and research practice, both nationally and internationally. We have used the information gathered in this study to adapt an existing framework for impact of clinical research for use in methodological research. CONCLUSIONS: Gathering evidence on research impact of methodological research from a variety of sources has enabled us to obtain multiple indicators and thus to demonstrate broad impacts of methodological research. The adapted framework developed can be applied to future methodological research and thus provides a tool for methodologists to better assess and report research impacts.

Strategies to improve retention in randomised trials.

BACKGROUND: Loss to follow-up from randomised trials can introduce bias and reduce study power, affecting the generalisability, validity and reliability of results. Many strategies are used to reduce loss to follow-up and improve retention but few have been formally evaluated. OBJECTIVES: To quantify the effect of strategies to improve retention on the proportion of participants retained in randomised trials and to investigate if the effect varied by trial strategy and trial setting. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PreMEDLINE, EMBASE, PsycINFO, DARE, CINAHL, Campbell Collaboration's Social, Psychological, Educational and Criminological Trials Register, and ERIC. We handsearched conference proceedings and publication reference lists for eligible retention trials. We also surveyed all UK Clinical Trials Units to identify further studies. SELECTION CRITERIA: We included eligible retention trials of randomised or quasi-randomised evaluations of strategies to increase retention that were embedded in 'host' randomised trials from all disease areas and healthcare settings. We excluded studies aiming to increase treatment compliance. DATA COLLECTION AND ANALYSIS: We contacted authors to supplement or confirm data that we had extracted. For retention trials, we recorded data on the method of randomisation, type of strategy evaluated, comparator, primary outcome, planned sample size, numbers randomised and numbers retained. We used risk ratios (RR) to evaluate the effectiveness of the addition of strategies to improve retention. We assessed heterogeneity between trials using the Chi(2) and I(2) statistics. For main trials that hosted retention trials, we extracted data on disease area, intervention, population, healthcare setting, sequence generation and allocation concealment. MAIN RESULTS: We identified 38 eligible retention trials. Included trials evaluated six broad types of strategies to improve retention. These were incentives, communication strategies, new questionnaire format, participant case management, behavioural and methodological interventions. For 34 of the included trials, retention was response to postal and electronic questionnaires with or without medical test kits. For four trials, retention was the number of participants remaining in the trial. Included trials were conducted across a spectrum of disease areas, countries, healthcare and community settings. Strategies that improved trial retention were addition of monetary incentives compared with no incentive for return of trial-related postal questionnaires (RR 1.18; 95% CI 1.09 to 1.28, P value < 0.0001), addition of an offer of monetary incentive compared with no offer for return of electronic questionnaires (RR 1.25; 95% CI 1.14 to 1.38, P value < 0.00001) and an offer of a GBP20 voucher compared with GBP10 for return of postal questionnaires and biomedical test kits (RR 1.12; 95% CI 1.04 to 1.22, P value < 0.005). The evidence that shorter questionnaires are better than longer questionnaires was unclear (RR 1.04; 95% CI 1.00 to 1.08, P value = 0.07) and the evidence for questionnaires relevant to the disease/condition was also unclear (RR 1.07; 95% CI 1.01 to 1.14). Although each was based on the results of a single trial, recorded delivery of questionnaires seemed to be more effective than telephone reminders (RR 2.08; 95% CI 1.11 to 3.87, P value = 0.02) and a 'package' of postal communication strategies with reminder letters appeared to be better than standard procedures (RR 1.43; 95% CI 1.22 to 1.67, P value < 0.0001). An open trial design also appeared more effective than a blind trial design for return of questionnaires in one fracture prevention trial (RR 1.37; 95% CI 1.16 to 1.63, P value = 0.0003).There was no good evidence that the addition of a non-monetary incentive, an offer of a non-monetary incentive, 'enhanced' letters, letters delivered by priority post, additional reminders, or questionnaire question order either increased or decreased trial questionnaire response/retention. There was also no evidence that a telephone survey was either more or less effective than a monetary incentive and a questionnaire. As our analyses are based on single trials, the effect on questionnaire response of using offers of charity donations, sending reminders to trial sites and when a questionnaire is sent, may need further evaluation. Case management and behavioural strategies used for trial retention may also warrant further evaluation. AUTHORS' CONCLUSIONS: Most of the retention trials that we identified evaluated questionnaire response. There were few evaluations of ways to improve participants returning to trial sites for trial follow-up. Monetary incentives and offers of monetary incentives increased postal and electronic questionnaire response. Some other strategies evaluated in single trials looked promising but need further evaluation. Application of the findings of this review would depend on trial setting, population, disease area, data collection and follow-up procedures.