Strategies to improve retention in randomised trials: a Cochrane systematic review and meta-analysis

Objective: To quantify the effect of strategies to improve retention in randomised trials.<p></p> Design: Systematic review and meta-analysis.<p></p> Data sources Sources searched: MEDLINE, EMBASE, PsycINFO, DARE, CENTRAL, CINAHL, C2-SPECTR, ERIC, PreMEDLINE, Cochrane Methodology Register, Current Controlled Trials metaRegister, WHO trials platform, Society for Clinical Trials (SCT) conference proceedings and a survey of all UK clinical trial research units.<p></p> Review: methods Included trials were randomised evaluations of strategies to improve retention embedded within host randomised trials. The primary outcome was retention of trial participants. Data from trials were pooled using the fixed-effect model. Subgroup analyses were used to explore the heterogeneity and to determine whether there were any differences in effect by the type of strategy.<p></p> Results: 38 retention trials were identified. Six broad types of strategies were evaluated. Strategies that increased postal questionnaire responses were: adding, that is, giving a monetary incentive (RR 1.18; 95% CI 1.09 to 1.28) and higher valued incentives (RR 1.12; 95% CI 1.04 to 1.22). Offering a monetary incentive, that is, an incentive given on receipt of a completed questionnaire, also increased electronic questionnaire response (RR 1.25; 95% CI 1.14 to 1.38). The evidence for shorter questionnaires (RR 1.04; 95% CI 1.00 to 1.08) and questionnaires relevant to the disease/condition (RR 1.07; 95% CI 1.01 to 1.14) is less clear. On the basis of the results of single trials, the following strategies appeared effective at increasing questionnaire response: recorded delivery of questionnaires (RR 2.08; 95% CI 1.11 to 3.87); a ‘package’ of postal communication strategies (RR 1.43; 95% CI 1.22 to 1.67) and an open trial design (RR 1.37; 95% CI 1.16 to 1.63). There is no good evidence that the following strategies impact on trial response/retention: adding a non-monetary incentive (RR=1.00; 95% CI 0.98 to 1.02); offering a non-monetary incentive (RR=0.99; 95% CI 0.95 to 1.03); ‘enhanced’ letters (RR=1.01; 95% CI 0.97 to 1.05); monetary incentives compared with offering prize draw entry (RR=1.04; 95% CI 0.91 to 1.19); priority postal delivery (RR=1.02; 95% CI 0.95 to 1.09); behavioural motivational strategies (RR=1.08; 95% CI 0.93 to 1.24); additional reminders to participants (RR=1.03; 95% CI 0.99 to 1.06) and questionnaire question order (RR=1.00, 0.97 to 1.02). Also based on single trials, these strategies do not appear effective: a telephone survey compared with a monetary incentive plus questionnaire (RR=1.08; 95% CI 0.94 to 1.24); offering a charity donation (RR=1.02, 95% CI 0.78 to 1.32); sending sites reminders (RR=0.96; 95% CI 0.83 to 1.11); sending questionnaires early (RR=1.10; 95% CI 0.96 to 1.26); longer and clearer questionnaires (RR=1.01, 0.95 to 1.07) and participant case management by trial assistants (RR=1.00; 95% CI 0.97 to 1.04).<p></p> Conclusions: Most of the trials evaluated questionnaire response rather than ways to improve participants return to site for follow-up. Monetary incentives and offers of monetary incentives increase postal and electronic questionnaire response. Some strategies need further evaluation. Application of these results would depend on trial context and follow-up procedures.<p></p&gt

Use of strategies to improve retention in primary care randomised trials: a qualitative study with in-depth interviews

Objective To explore the strategies used to improve retention in primary care randomised trials.<p></p> Design Qualitative in-depth interviews and thematic analysis.<p></p> Participants 29 UK primary care chief and principal investigators, trial managers and research nurses.<p></p> Methods In-depth face-to-face interviews.<p></p> Results Primary care researchers use incentive and communication strategies to improve retention in trials, but were unsure of their effect. Small monetary incentives were used to increase response to postal questionnaires. Non-monetary incentives were used although there was scepticism about the impact of these on retention. Nurses routinely used telephone communication to encourage participants to return for trial follow-up. Trial managers used first class post, shorter questionnaires and improved questionnaire designs with the aim of improving questionnaire response. Interviewees thought an open trial design could lead to biased results and were negative about using behavioural strategies to improve retention. There was consensus among the interviewees that effective communication and rapport with participants, participant altruism, respect for participant's time, flexibility of trial personnel and appointment schedules and trial information improve retention. Interviewees noted particular challenges with retention in mental health trials and those involving teenagers.<p></p> Conclusions The findings of this qualitative study have allowed us to reflect on research practice around retention and highlight a gap between such practice and current evidence. Interviewees describe acting from experience without evidence from the literature, which supports the use of small monetary incentives to improve the questionnaire response. No such evidence exists for non-monetary incentives or first class post, use of which may need reconsideration. An exploration of barriers and facilitators to retention in other research contexts may be justified.<p></p&gt

Identifying additional studies for a systematic review of retention strategies in randomised controlled trials: making contact with trials units and trial methodologists

BACKGROUND: Search strategies for systematic reviews aim to identify all evidence relevant to the research question posed. Reports of methodological research can be difficult to find leading to biased results in systematic reviews of research methodology. Evidence suggests that contact with investigators can help to identify unpublished research. To identify additional eligible randomised controlled trials (RCTs) for a Cochrane systematic review of strategies to improve retention in RCTs, we conducted a survey of UK clinical trials units (CTUs) and made contact with RCT methodologists. METHODS: Key contacts for all UK CTUs were sent a personalised email with a short questionnaire and summary protocol of the Cochrane methodology review. The questionnaire asked whether a RCT evaluating strategies to improve retention embedded in a RCT had ever been conducted by the CTU. Questions about the stage of completion and publication of such RCTs were included. The summary protocol outlined the aims, eligibility criteria, examples of types of retention strategies, and the primary outcome for the systematic review. Personal communication with RCT methodologists and presentations of preliminary results of the review at conferences were also used to identify additional eligible RCTs. We checked the results of our standard searches to see if eligible studies identified through these additional methods were also found using our standard searches. RESULTS: We identified 14 of the 38 RCTs included in the Cochrane methodology review by contacting trials units and methodologists. Eleven of the 14 RCTs identified by these methods were either published in grey literature, in press or unpublished. Three remaining RCTs were fully published at the time. Six of the RCTs identified were not found through any other searches. The RCTs identified represented data for 6 of 14 RCTs of incentive strategies (52% of randomised participants included in the review), and 6 of 14 RCTs of communication strategies (52% of randomised participants included in the Cochrane review). Data were unavailable for two of the RCTs identified. CONCLUSIONS: Methodological evaluations embedded in RCTs may be unpublished, published in the grey literature or where published, poorly indexed in bibliographic databases. To identify such studies and minimise selection bias in systematic reviews of methodological evaluations, reviewers should consider contacting CTUs and trial methodologists

AXIS--a suitable case for treatment. UK Coordinating Committee on Cancer Research (UKCCCR) Colorectal Cancer Subcommittee.

Decisions about the role of adjuvant therapy in the management of colorectal cancer are rarely taken on the basis of sound scientific evidence. This is not because surgeons are capricious, but because sound scientific evidence is, unfortunately, a little thin on the ground. Since the first randomised trial in the UK was initiated some 15 years ago, less than 1% of the 26,000 cases of colorectal cancer each year have been entered into randomised clinical trials and a similar situation exists elsewhere. A recent overview of all of the published evidence worldwide from trials of radiotherapy in rectal cancer identified trials involving in total only some 5,000 patients. The individual trials were all too small to detect reliably (or refute reliably) any realistically moderate improvement in survival and, even when combined, their results are equivocal (Buyse et al., 1988). It is thus hardly surprising that surgeons are divided in their views of whether or not radiotherapy is a useful adjuvant treatment in this disease. A similar situation exists when considering the role of chemotherapy where, again, there is considerable uncertainty about whether adjuvant chemotherapy has any effect on mortality at all and, if it does have an effect, no consensus about the likely size of that effect. Recently, however, evidence that chemotherapy usually with 5-fluorouracil (5-FU) containing regimens - can moderately improve survival has been accumulating. The most promising treatments that have been examined are a 1-week post-operative infusion of 5-FU through the portal vein (Taylor et al., 1985), 18 months systemic administration of MOF (Fisher et al., 1988; Wolmark et al., 1988) and a year of systemic 5-FU given in conjunction with levamisole (Moertel et al., 1990). There is clearly a need for a more precise definition of the effect of adjuvant therapy on long term survival and so, in November 1989, the UKCCCR launched AXIS, an international randomised trial designed to be large enough to get definite evidence about any survival benefit of intraportal 5-FU and of perioperative radiotherapy. Even a moderate improvement in survival in this disease would be important because, since colorectal cancer is so common, an improvement of 'only' 5% in 5-year survival (say from 50% to 55%) could save many thousands of lives each year

Investigation of the role of morphology on the magnetic properties of Ca2Mn3O8 materials

Ca2Mn3O8 exhibits a complex layered structure comprised of Mn3O84- layers separated by Ca2+ ions. In contrast with the more traditional triangular Delafossite layered materials the Mn3O84- layers additionally exhibit an ordered vacancy which forms a 'bow-tie' like arrangement of the Mn4+ ions. We report a comprehensive study of the magnetic properties of a series of Ca2Mn3O8 materials with different morphologies. EXAFS and XANES analysis confirm no differences in either manganese environment or oxidation state between materials. Apparent differences in magnetic order from SQUID magnetometry can be rationalised by uncompensated surface spins arising as a result of changes to the surface:volume ratio between morphologies. Furthermore, these data suggest these materials are potentially frustrated in nature, due to the triangular connectivity of Mn4+ spins with a simple ‘spin-up/spin-down’ (↑↓) antiferromagnetic model unable to explain the data collected