Retention Of Participants In Trials Research Articles

SWAT 84: effects of same-day consent vs delayed consent on the recruitment and retention of trial participants—an observational SWAT

Background and aimThe recruitment process in a randomized trial can be challenging. Poor recruitment can have a negative impact on the allocated budget and estimated completion date of the study and may result in an underpowered study. We aimed to perform a Study Within A Trial (SWAT) to evaluate the impact of same-day consent or delayed consent on recruitment and retention in the host trial.MethodsThis SWAT is designed as a prospective cohort design. The host trial was a randomized controlled trial evaluating the effectiveness of an intensive lifestyle modification programme in participants with peripheral arterial disease. Researchers screened the participants for inclusion and exclusion criteria. Informed consents were obtained from the participants who were willing to participate in the study on a standardized consent form. Participants were given the option to consent on the same day or to delay their consent. Following the consent, the participants were allocated to two groups (same-day consent vs. delayed consent) based on pre-determined criteria for SWAT. One hundred sixteen participants were consented to take part in the host trial. Seventy-five participants were randomized to the host trial. The primary outcome was the proportion of participants who withdrew consent at the recruitment phase. Secondary outcomes were reasons for consent withdrawal and dropout, attrition rate, and adherence with the host trial intervention.ResultsThere was a significantly lower consent-withdrawal rate in same-day consent (17.4%, n = 8/46), compared to the delayed consent group (47.1%, n = 33/70), p = 0.001. There was a significantly lower dropout rate in participants randomized following same-day consent (10.5%, n = 4/38), compared to those randomized after delayed consent (29.7%, n = 11/37), p = 0.038. Transport was the main reason mentioned for consent withdrawal and dropout. In participants randomized to the host trial intervention arm, there was a significant difference in adherence (percentage of the 12-week programme completed) between same-day consent (96.7% ± 4.9) and delayed consent participants (86.4% ± 11.2), p = 0.003, as well as number of weeks completed (mean difference = − 1.547, 95% confidence intervals (− 2.237 to − 0.85)), p = 0.02.ConclusionThis SWAT found evidence that participants who gave consent on the same day seemed to have better adherence and fewer-withdrawal and dropout rates.SWAT registrationThe SWAT was registered on the Northern Ireland Network for Trials Methodology Research, SWAT 84.

Recruitment interventions for trials involving adults lacking capacity to consent: methodological and ethical considerations for designing Studies Within a Trial (SWATs)

BackgroundThe number of interventions to improve recruitment and retention of participants in trials is rising, with a corresponding growth in randomised Studies Within Trials (SWATs) to evaluate their (cost-)effectiveness. Despite recognised challenges in conducting trials involving adults who lack capacity to consent, until now, no individual-level recruitment interventions have focused on this population. Following the development of a decision aid for family members making non-emergency trial participation decisions on behalf of people with impaired capacity, we have designed a SWAT to evaluate the decision aid in a number of host trials (CONSULT). Unlike in recruitment SWATs to date, the CONSULT intervention is aimed at a ‘proxy’ decision-maker (a family member) who is not a participant in the host trial and does not receive the trial intervention. This commentary explores the methodological and ethical considerations encountered when designing such SWATs, using the CONSULT SWAT as a case example. Potential solutions to address these issues are also presented.DiscussionWe encountered practical issues around informed consent, data collection, and follow-up which involves linking the intervention receiver (the proxy) with recruitment and retention data from the host trial, as well as issues around randomisation level, resource use, and maintaining the integrity of the host trial. Unless addressed, methodological uncertainty about differential recruitment and heterogeneity between trial populations could potentially limit the scope for drawing robust inferences and harmonising data from different SWAT host trials. Proxy consent is itself ethically complex, and so when conducting a SWAT which aims to disrupt and enhance proxy consent decisions, there are additional ethical issues to be considered.ConclusionsDesigning a SWAT to evaluate a recruitment intervention for non-emergency trials with adults lacking capacity to consent has raised a number of methodological and ethical considerations. Explicating these challenges, and some potential ways to address them, creates a starting point for discussions about conducting these potentially more challenging SWATs. Increasing the evidence base for the conduct of trials involving adults lacking capacity to consent is intended to improve both the ability to conduct these trials and their quality, and so help build research capacity for this under-served population.

The development of theory-informed participant-centred interventions to maximise participant retention in randomised controlled trials

BackgroundA failure of clinical trials to retain participants can influence the trial findings and significantly impact the potential of the trial to influence clinical practice. Retention of participants involves people, often the trial participants themselves, performing a behaviour (e.g. returning a questionnaire or attending a follow-up clinic as part of the research). Most existing interventions that aim to improve the retention of trial participants fail to describe any theoretical basis for the potential effect (on behaviour) and also whether there was any patient and/or participant input during development. The aim of this study was to address these two problems by developing theory- informed, participant-centred, interventions to improve trial retention.MethodsThis study was informed by the Theoretical Domains Framework and Behaviour Change Techniques Taxonomy to match participant reported determinants of trial retention to theoretically informed behaviour change strategies. The prototype interventions were described and developed in a co-design workshop with trial participants. Acceptability and feasibility (guided by (by the Theoretical Framework of Acceptability) of two prioritised retention interventions was explored during a focus group involving a range of trial stakeholders (e.g. trial participants, trial managers, research nurses, trialists, research ethics committee members). Following focus group discussions stakeholders completed an intervention acceptability questionnaire.ResultsEight trial participants contributed to the co-design of the retention interventions. Four behaviour change interventions were designed: (1) incentives and rewards for follow-up clinic attendance, (2) goal setting for improving questionnaire return, (3) participant self-monitoring to improve questionnaire return and/or clinic attendance, and (4) motivational information to improve questionnaire return and clinic attendance. Eighteen trial stakeholders discussed the two prioritised interventions. The motivational information intervention was deemed acceptable and considered straightforward to implement whilst the goal setting intervention was viewed as less clear and less acceptable.ConclusionsThis is the first study to develop interventions to improve trial retention that are based on the accounts of trial participants and also conceptualised and developed as behaviour change interventions (to encourage attendance at trial research visit or return a trial questionnaire). Further testing of these interventions is required to assess effectiveness.

Monitoring strategies for clinical intervention studies.

Monitoring strategies for clinical intervention studies.

Behavioral and social science research to support development of educational materials for clinical trials of broadly neutralizing antibodies for HIV treatment and prevention.

Early integration of behavioral and social sciences research into clinical trials can improve trial conduct and facilitate future implementation of biomedical interventions. We sought to examine participants' experiences in clinical trials with broadly neutralizing antibodies and describe the development of educational materials for use in future broadly neutralizing antibody research. We conducted semi-structured interviews with trial participants in phase 1 trials evaluating safety and efficacy of broadly neutralizing antibodies for HIV prevention and treatment and key informants (i.e. trial staff involved in broadly neutralizing antibody research). Semi-structured interviews were transcribed and analyzed thematically. Based on findings from the interviews, we developed educational materials addressing concerns and misconceptions identified among trial participants with input from community and research stakeholders. Educational materials were used in subsequent clinical trials with broadly neutralizing antibodies. We evaluated trial staff's experiences with newly developed educational materials in follow-up key informant interviews. Although most participants were concerned about long-term harms related to the investigational product upon enrollment, absence of severe side effects in the trial led to an underestimation of risks related to the study during trial participation. Participants showed a poor understanding of what broadly neutralizing antibodies are and the differences between broadly neutralizing antibodies and other HIV prevention and treatment products, such as antiretrovirals. Many trial participants overestimated the possible public health impact of the broadly neutralizing antibody trials in which they were enrolled, associating broadly neutralizing antibody research with the development of vaccine or cure for HIV in the near future. Based on these concerns and misconceptions among trial participants, we developed a frequently asked questions document and adapted an existing educational video about broadly neutralizing antibodies. In follow-up interviews, key informants reported that materials helped address trial participants' concerns and questions related to the trial. Key informants reported using the educational materials not only during informed consent but also throughout trial participation, which contributed to making informed consent an "ongoing" process. Integration of behavioral research into clinical trials with broadly neutralizing antibodies is key to identify and address key concerns among trial participants. Behavioral and social sciences research promotes communication between trial participants and biomedical researchers, facilitates engagement of participants and trial staff, and strengthens trial conduct. Development of educational materials collaboratively by behavioral and clinical scientists, trial staff, and community stakeholders is feasible and may help to address trial participants' concerns and misconceptions. Future research should evaluate the impact of educational materials in recruitment and retention of trial participants.

VP55 Trial Recruitment & Retention Using Digital Tools: A Qualitative Study

IntroductionRecruitment of participants and their retention in randomized controlled trials (RCTs) is key for research efficiency. However, for many trials, recruiting and retaining participants meeting the eligible criteria is extremely challenging. Digital tools are increasingly being used to identify, recruit and retain participants. While these tools are being used, there is a lack of quality evidence to determine their value in trial recruitment.MethodsThe aim of the main study was to identify the benefits and characteristics of innovative digital recruitment and retention tools for more efficient conduct of RCTs. Here we report on the qualitative data collected on the characteristics of digital tools required by trialists, research participants, primary care staff, research funders and Clinical Trials Units (CTUs) to judge them useful. A purposive sampling strategy was used to identify 16 participants from five stakeholder groups. A theoretical framework was informed from results of a survey with UKCRC registered CTUs. Semi-structured interviews were conducted and analysed using an inductive approach. A content and thematic analysis was used to explore the stakeholder's viewpoint and the value of digital tools.ResultsThe content analysis revealed that ‘barriers / challenges ‘ and ‘awareness of evidence’ were the most commonly discussed areas. Three key emergent themes were present across all groups: ‘security and legitimacy of information’, ‘inclusivity’, and ‘availability of human interaction’. Other themes focused on the engagement of stakeholders in their use and adoption of digital technology to enhance the recruitment/retention process. We also noted some interesting similarities and differences between practitioner and participant groups.ConclusionsThe key emergent themes clearly demonstrate the use of digital technology in the recruitment and retention of participants in trials. The challenge, however, is using these existing tools without sufficient evidence to support the usefulness compared to traditional techniques. This raises important questions around the potential value for future research.

A feasibility study of a randomised controlled trial to examine the impact of the ABCDE bundle on quality of life in ICU survivors

BackgroundEarly rehabilitation has been found to prevent delirium and weakness that can hamper the recovery of intensive care unit (ICU) survivors. Integrated clinical practice guidelines for managing patient pain, agitation and delirium (PAD) have been developed. The Awakening and Breathing Coordination, Delirium monitoring/management, and Early exercise/mobility (ABCDE) bundle provides a strategy to implement PAD guidelines into everyday clinical practice. However, there is limited evidence on the effectiveness of the ABCDE bundle in the literature.The purpose of this study was to evaluate the feasibility of conducting a full-scale randomised controlled trial comparing the ABCDE bundle to standard care in an ICU. Trial feasibility was defined as the successful recruitment and retention of trial participants, adherence to the intervention, identification of barriers to the intervention, and the rigorous collection of outcome data.MethodsA prospective, single-centre, randomised controlled feasibility study was conducted. Thirty adult mechanically ventilated participants were recruited from an eight-bed ICU in south east Queensland, Australia, between April 2015 and December 2015. Participants were randomised to receive either the ABCDE bundle or standard routine management. The ABCDE bundle integrated prescribed awakening and breathing trials, delirium monitoring and management, and prescribed exercise and mobility regimes. Feasibility outcomes measured included recruitment and retention rates, intervention fidelity, and the feasibility of participant outcome data collection. Outcome measurement assessors were blinded to participant assignment. It was not possible to blind the research team or the participant to group assignment.ResultsIn total, 30 (81.1%) of 37 eligible participants consented and were randomised to the intervention group (n = 15) or the control group (n = 15). Of these, 23 (76.6%) participants successfully completed the 90-day post discharge assessment. A lengthy recruitment period of 8 months was related to overly stringent inclusion and exclusion criteria. Intervention adherence exceeded defined success rates with participation in awakening and breathing trials, delirium monitoring and exercise interventions performed on 80.2, 97.4 and 90.2% of ventilated days respectively. Outcome assessments were successfully and accurately performed at ICU and hospital discharge and 90-day post hospital discharge. Intervention participants were deemed to be delirious on 39.6% of mechanically ventilated days indicating a requirement for a scripted regime to prevent delirium.ConclusionsWith minor adjustment of inclusion and exclusion criteria, the inclusion of delirium management protocols, and encouragement of family engagement and involvement, a large-scale definitive randomised controlled trial to test the impact of the ABCDEF bundle will be feasible.Trial registrationAustralian New Zealand Clinical Trials Registry 12614000763640 Date registered 17/08/2014

“To have, to hold, from this day forward”: understanding current practice regarding the retention of trial participants

Findings Clear and cohesive definitions of retention were given. However, there was less agreement about the concept of ‘withdrawal’ from a trial. More experienced trialists emphasised different levels of withdrawal and were happy to negotiate with participants in order to at least collect primary outcome data. Novice trialists presumed the participants wanted to withdraw from all aspects of the trial and made no further contact with them. Research Nurses used their interpersonal skills to motivate participants to remain in their trials. This required time not routinely acknowledged within the funding of trials. Participants described proactive and reactive approaches to retention. Proactive approaches involved anticipated and considered strategies, both formal and informal, to maintain retention. Conversely, reactive approaches were typified by unanticipated and spontaneous strategies, some formalised others informal, developed in response to retention problems during the trial.

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

ObjectiveTo quantify the effect of strategies to improve retention in randomised trials.DesignSystematic review and meta-analysis.Data sourcesSources searched: MEDLINE, EMBASE, PsycINFO, DARE, CENTRAL, CINAHL, C2-SPECTR, ERIC, PreMEDLINE, Cochrane Methodology Register, Current...

Participants as community-based peer educators: Impact on a clinical trial site in KwaZulu-Natal

Participant recruitment, retention and product adherence are necessary to measure the efficacy or effectiveness of an intervention in a clinical trial. As part of a Phase III HIV prevention trial in a rural area in Kwazulu-Natal, South Africa, a peer educator programme was initiated to aid in recruitment and retention of trial participants from the community. Enrolled trial participants who had completed at least 6 months of trial participation and who had honoured all of their scheduled trial visits within that period were approached to be peer educators. Following additional selection criteria, 24 participants were eligible to be trained as peer educators. Training topics included HIV/AIDS, sexually transmitted infections, nutrition, antiretrovirals, clinical trials, and methods of disseminating this information to the community. The role of peer educators was to bring interested women from their community to the trial site for comprehensive education and information about the trial and possibly trial participation. A total of 1879 women were educated by peer educators between July 2004 and December 2006. Of these, 553 women visited the trial site for further education and screening for participation in the trial. Peer educators provided continuous education and support to women enrolled in the trial which also promoted retention, ultimately contributing to the site’s 94% retention rate. Recruitment and retention efforts of trial participants are likely to be enhanced by involving trial participants as peer educators. Such trial participants are in a better position to understand cultural dynamics and hence capable of engaging the community with appropriate HIV prevention and trial-related messaging.

Inclusion of South African adolescents in HIV vaccine trials.

South Africa has more people living with HIV than any other nation. The HIV epidemic in South Africa is being driven by new infections among adolescents. Inclusion of adolescents in HIV vaccine trials is essential for successful vaccine development, however, recruitment and retention of at-risk South African adolescents into these trials poses a number of legal, ethical and operational challenges. This article discusses the South African ethico-legal context in which future adolescent HIV vaccine trials would be conducted followed by a review of available data regarding strategies for recruitment into these trials and retention of trial participants.

Novel strategies implemented to ensure high participant retention rates in a community based HIV prevention effectiveness trial in South Africa and Zimbabwe

Background The identification of new HIV prevention methods that women can initiate themselves are urgently needed, particularly in high prevalence settings. HIV prevention trials must be designed with large sample sizes and/or substantial follow-up periods to ensure enough statistical power to measure product effectiveness. This paper describes the attendance rates of the Methods for Improving Reproductive Health in Africa (MIRA) trial, reasons for missed visits, and strategies used to retain participants; and examines demographic and behavioural predictors of retaining women. Methods HIV negative, sexually active females were enrolled into the MIRA trial in Zimbabwe and South Africa. Once enrolled, women were expected to visit the clinic at 2 weeks and quarterly thereafter for 12 to 24 months. Tabulations of visit-specific retention rates are presented, along with a descriptive summary of retention strategies established prior to and in response to challenges incurred during implementation. Both univariate and multivariate logistic regression models were created in STATA to examine predictors of being retained vs. lost-to-follow-up. Results At the three sites, the final retention rates were 94%, 93% and 89% for Zimbabwe, Durban and Johannesburg, respectively. This was achievable through intensive outreach efforts toward the latter part of the trial and a commitment from all staff. Each site implemented several retention strategies. Conclusion The high retention rates were achievable in this trial through added staff efforts and resources. Community involvement was also crucial to achieve these rates. Retention of trial participants should be considered during trial design and implemented from the onset.