Describing the content of trial recruitment interventions using the TIDieR reporting checklist: a systematic methodology review.

BACKGROUND: Recruiting participants to clinical trials is an ongoing challenge, and relatively little is known about what recruitment strategies lead to better recruitment. Recruitment interventions can be considered complex interventions, often involving multiple components, targeting a variety of groups, and tailoring to different groups. We used the Template for Intervention Description and Replication (TIDieR) reporting checklist (which comprises 12 items recommended for reporting complex interventions) to guide the assessment of how recruitment interventions are described. We aimed to (1) examine to what extent we could identify information about each TIDieR item within recruitment intervention studies, and (2) observe additional detail for each item to describe useful variation among these studies. METHODS: We identified randomized, nested recruitment intervention studies providing recruitment or willingness to participate rates from two sources: a Cochrane review of trials evaluating strategies to improve recruitment to randomized trials, and the Online Resource for Research in Clinical triAls database. First, we assessed to what extent authors reported information about each TIDieR item. Second, we developed descriptive categorical variables for 7 TIDieR items and extracting relevant quotes for the other 5 items. RESULTS: We assessed 122 recruitment intervention studies. We were able to extract information relevant to most TIDieR items (e.g., brief rationale, materials, procedure) with the exception of a few items that were only rarely reported (e.g., tailoring, modifications, planned/actual fidelity). The descriptive variables provided a useful overview of study characteristics, with most studies using various forms of informational interventions (55%) delivered at a single time point (90%), often by a member of the research team (59%) in a clinical care setting (41%). CONCLUSIONS: Our TIDieR-based variables provide a useful description of the core elements of complex trial recruitment interventions. Recruitment intervention studies report core elements of complex interventions variably; some process elements (e.g., mode of delivery, location) are almost always described, while others (e.g., duration, fidelity) are reported infrequently, with little indication of a reason for their absence. Future research should explore whether these TIDieR-based variables can form the basis of an approach to better reporting of elements of successful recruitment interventions.

Methodological challenges in pragmatic trials in Alzheimer's disease and related dementias: Opportunities for improvement.

BACKGROUND AND AIMS: We need more pragmatic trials of interventions to improve care and outcomes for people living with Alzheimer's disease and related dementias. However, these trials present unique methodological challenges in their design, analysis, and reporting-often, due to the presence of one or more sources of clustering. Failure to account for clustering in the design and analysis can lead to increased risks of Type I and Type II errors. We conducted a review to describe key methodological characteristics and obtain a "baseline assessment" of methodological quality of pragmatic trials in dementia research, with a view to developing new methods and practical guidance to support investigators and methodologists conducting pragmatic trials in this field. METHODS: We used a published search filter in MEDLINE to identify trials more likely to be pragmatic and identified a subset that focused on people living with Alzheimer's disease or other dementias or included them as a defined subgroup. Pairs of reviewers extracted descriptive information and key methodological quality indicators from each trial. RESULTS: We identified N = 62 eligible primary trial reports published across 36 different journals. There were 15 (24%) individually randomized, 38 (61%) cluster randomized, and 9 (15%) individually randomized group treatment designs; 54 (87%) trials used repeated measures on the same individual and/or cluster over time and 17 (27%) had a multivariate primary outcome (e.g. due to measuring an outcome on both the patient and their caregiver). Of the 38 cluster randomized trials, 16 (42%) did not report sample size calculations accounting for the intracluster correlation and 13 (34%) did not account for intracluster correlation in the analysis. Of the 9 individually randomized group treatment trials, 6 (67%) did not report sample size calculations accounting for intracluster correlation and 8 (89%) did not account for it in the analysis. Of the 54 trials with repeated measurements, 45 (83%) did not report sample size calculations accounting for repeated measurements and 19 (35%) did not utilize at least some of the repeated measures in the analysis. No trials accounted for the multivariate nature of their primary outcomes in sample size calculation; only one did so in the analysis. CONCLUSION: There is a need and opportunity to improve the design, analysis, and reporting of pragmatic trials in dementia research. Investigators should pay attention to the potential presence of one or more sources of clustering. While methods for longitudinal and cluster randomized trials are well developed, accessible resources and new methods for dealing with multiple sources of clustering are required. Involvement of a statistician with expertise in longitudinal and clustered designs is recommended.

Informing the research agenda for optimizing audit and feedback interventions: results of a prioritization exercise.

BACKGROUND: Audit and feedback (A&F) interventions are one of the most common approaches for implementing evidence-based practices. A key barrier to more effective A&F interventions is the lack of a theory-guided approach to the accumulation of evidence. Recent interviews with theory experts identified 313 theory-informed hypotheses, spread across 30 themes, about how to create more effective A&F interventions. In the current survey, we sought to elicit from stakeholders which hypotheses were most likely to advance the field if studied further. METHODS: From the list of 313, three members of the research team identified 216 that were clear and distinguishable enough for prioritization. A web-based survey was then sent to 211 A&F intervention stakeholders asking them to choose up to 50 'priority' hypotheses following the header "A&F interventions will be more effective if…". Analyses included frequencies of endorsement of the individual hypotheses and themes into which they were grouped. RESULTS: 68 of the 211 invited participants responded to the survey. Seven hypotheses were chosen by > 50% of respondents, including A&F interventions will be more effective… "if feedback is provided by a trusted source"; "if recipients are involved in the design/development of the feedback intervention"; "if recommendations related to the feedback are based on good quality evidence"; "if the behaviour is under the control of the recipient"; "if it addresses barriers and facilitators (drivers) to behaviour change"; "if it suggests clear action plans"; and "if target/goal/optimal rates are clear and explicit". The most endorsed theme was Recipient Priorities (four hypotheses were chosen 92 times as a 'priority' hypotheses). CONCLUSIONS: This work determined a set of hypotheses thought by respondents to be to be most likely to advance the field through future A&F intervention research. This work can inform a coordinated research agenda that may more efficiently lead to more effective A&F interventions.

Informed consent in pragmatic trials: results from a survey of trials published 2014-2019.

OBJECTIVES: To describe reporting of informed consent in pragmatic trials, justifications for waivers of consent and reporting of alternative approaches to standard written consent. To identify factors associated with (1) not reporting and (2) not obtaining consent. METHODS: Survey of primary trial reports, published 2014-2019, identified using an electronic search filter for pragmatic trials implemented in MEDLINE, and registered in ClinicalTrials.gov. RESULTS: Among 1988 trials, 132 (6.6%) did not include a statement about participant consent, 1691 (85.0%) reported consent had been obtained, 139 (7.0%) reported a waiver and 26 (1.3%) reported consent for one aspect (eg, data collection) but a waiver for another (eg, intervention). Of the 165 trials reporting a waiver, 76 (46.1%) provided a justification. Few (53, 2.9%) explicitly reported use of alternative approaches to consent. In multivariable logistic regression analyses, lower journal impact factor (p=0.001) and cluster randomisation (p<0.0001) were significantly associated with not reporting on consent, while trial recency, cluster randomisation, higher-income country settings, health services research and explicit labelling as pragmatic were significantly associated with not obtaining consent (all p<0.0001). DISCUSSION: Not obtaining consent seems to be increasing and is associated with the use of cluster randomisation and pragmatic aims, but neither cluster randomisation nor pragmatism are currently accepted justifications for waivers of consent. Rather than considering either standard written informed consent or waivers of consent, researchers and research ethics committees could consider alternative consent approaches that may facilitate the conduct of pragmatic trials while preserving patient autonomy and the public's trust in research.

Cluster over individual randomization: are study design choices appropriately justified? Review of a random sample of trials.

BACKGROUND: Novel rationales for randomizing clusters rather than individuals appear to be emerging from the push for more pragmatic trials, for example, to facilitate trial recruitment, reduce the costs of research, and improve external validity. Such rationales may be driven by a mistaken perception that choosing cluster randomization lessens the need for informed consent. We reviewed a random sample of published cluster randomized trials involving only individual-level health care interventions to determine (a) the prevalence of reporting a rationale for the choice of cluster randomization; (b) the types of explicit, or if absent, apparent rationales for the use of cluster randomization; (c) the prevalence of reporting patient informed consent for study interventions; and (d) the types of justifications provided for waivers of consent. We considered cluster randomized trials for evaluating exclusively the individual-level health care interventions to focus on clinical trials where individual randomization is only theoretically possible and where there is a general expectation of informed consent. METHODS: A random sample of 40 cluster randomized trials were identified by implementing a validated electronic search filter in two electronic databases (Ovid MEDLINE and Embase), with two reviewers independently extracting information from each trial. Inclusion criteria were the following: primary report of a cluster randomized trial, evaluating exclusively an individual-level health care intervention, published between 2007 and 2016, and conducted in Canada, the United States, European Union, Australia, or low- and middle-income country settings. RESULTS: Twenty-five trials (62.5%, 95% confidence interval = 47.5%-77.5%) reported an explicit rationale for the use of cluster randomization. The most commonly reported rationales were those with logistical or administrative convenience (15 trials, 60%) and those that need to avoid contamination (13 trials, 52%); five trials (20%) were cited rationales related to the push for more pragmatic trials. Twenty-one trials (52.5%, 95% confidence interval = 37%-68%) reported written informed consent for the intervention, two (5%) reported verbal consent, and eight (20%) reported waivers of consent, while in nine trials (22.5%) consent was unclear or not mentioned. Reported justifications for waivers of consent included that study interventions were already used in clinical practice, patients were not randomized individually, and the need to facilitate the pragmatic nature of the trial. Only one trial reported an explicit and appropriate justification for waiver of consent based on minimum criteria in international research ethics guidelines, namely, infeasibility and minimal risk. CONCLUSION: Rationales for adopting cluster over individual randomization and for adopting consent waivers are emerging, related to the need to facilitate pragmatic trials. Greater attention to clear reporting of study design rationales, informed consent procedures, as well as justification for waivers is needed to ensure that such trials meet appropriate ethical standards.

Informed Consent Documents Used in Critical Care Trials Often Do Not Implement Recommendations.

OBJECTIVE: Informed consent documents are often poorly understood by research participants. In critical care, issues such as time pressure, patient capacity, and surrogate decision making complicate the consent process further. Recommendations exist for addressing critical care-specific consent issues; we examined how well existing practice implements these recommendations. DESIGN: We conducted a systematic search of the literature for recommendations specific to critical care informed consent and rated existing informed consent documents on their implementation of 1) 18 of these critical care recommendations and 2) 36 previously developed general informed consent recommendations. Four hundred twelve registered critical care trials were identified and a request sent to the principal investigators for an example of the informed consent document associated with the trial. Each consent document was rated on both set of recommendations. SETTING: We evaluated informed consent documents for trials conducted in English or French registered with clinicaltrials.gov. PATIENTS: Not applicable. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Independent coders rated implementation of each recommendation on a four-point scale. Of 412 requests, 137 informed consent documents were returned, for a response rate of 34.1%. Of these, 86 met inclusion criteria and were assessed. Overall agreement between raters was 90.6% (weighted κ = 0.79; 0.77-0.81). Implementation of the 18 critical care recommendations was highly variable, ranging between 2% and 96.5%. CONCLUSIONS: Critical care studies often do not provide the information recommended for those providing consent for research. These clear recommendations provide testable hypotheses about how to improve the consent process for patients and family members considering trial participation in the critical care setting.

Stakeholder views regarding ethical issues in the design and conduct of pragmatic trials: study protocol.

BACKGROUND: Randomized controlled trial (RCT) trial designs exist on an explanatory-pragmatic spectrum, depending on the degree to which a study aims to address a question of efficacy or effectiveness. As conceptualized by Schwartz and Lellouch in 1967, an explanatory approach to trial design emphasizes hypothesis testing about the mechanisms of action of treatments under ideal conditions (efficacy), whereas a pragmatic approach emphasizes testing effectiveness of two or more available treatments in real-world conditions. Interest in, and the number of, pragmatic trials has grown substantially in recent years, with increased recognition by funders and stakeholders worldwide of the need for credible evidence to inform clinical decision-making. This increase has been accompanied by the onset of learning healthcare systems, as well as an increasing focus on patient-oriented research. However, pragmatic trials have ethical challenges that have not yet been identified or adequately characterized. The present study aims to explore the views of key stakeholders with respect to ethical issues raised by the design and conduct of pragmatic trials. It is embedded within a large, four-year project that seeks to develop guidance for the ethical design and conduct of pragmatic trials. As a first step, this study will address important gaps in the current empirical literature with respect to identifying a comprehensive range of ethical issues arising from the design and conduct of pragmatic trials. By opening up a broad range of topics for consideration within our parallel ethical analysis, we will extend the current debate, which has largely emphasized issues of consent, to the range of ethical considerations that may flow from specific design choices. METHODS: Semi-structured interviews with key stakeholders (e.g. trialists, methodologists, lay members of study teams, bioethicists, and research ethics committee members), across multiple jurisdictions, identified based on their known experience and/or expertise with pragmatic trials. DISCUSSION: We expect that the study outputs will be of interest to a wide range of knowledge users including trialists, ethicists, research ethics committees, journal editors, regulators, healthcare policymakers, research funders and patient groups. All publications will adhere to the Tri-Agency Open Access Policy on Publications.

Practice Feedback Interventions: 15 Suggestions for Optimizing Effectiveness.

Electronic practice data are increasingly being used to provide feedback to encourage practice improvement. However, evidence suggests that despite decades of experience, the effects of such interventions vary greatly and are not improving over time. Guidance on providing more effective feedback does exist, but it is distributed across a wide range of disciplines and theoretical perspectives. Through expert interviews; systematic reviews; and experience with providing, evaluating, and receiving practice feedback, 15 suggestions that are believed to be associated with effective feedback interventions have been identified. These suggestions are intended to provide practical guidance to quality improvement professionals, information technology developers, educators, administrators, and practitioners who receive such interventions. Designing interventions with these suggestions in mind should improve their effect, and studying the mechanisms underlying these suggestions will advance a stagnant literature.

Impact of stated barriers on proposed warfarin prescription for atrial fibrillation: a survey of Canadian physicians.

BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia, and leading cause of ischemic stroke. Despite proven effectiveness, warfarin remains an under-used treatment in atrial fibrillation patients. We sought to study, across three physician specialties, a range of factors that have been argued to have a disproportionate effect on treatment decisions. METHODS: Cross-sectional survey of Canadian Family Doctors (FD: n = 500), Geriatricians (G: n = 149), and Internal Medicine specialists (IMS: n = 500). Of these, 1032 physicians were contactable, and 335 completed and usable responses were received. Survey questions and clinical vignettes asked about the frequency with which they see patients with atrial fibrillation, treatment practices, and barriers to the prescription of anticoagulants. RESULTS: Stated prescribing practices did not significantly differ between physician groups. Falls risk, bleeding risk and poor patient adherence were all highly cited barriers to prescribing warfarin. Fewer geriatricians indicated that history of patient falls would be a reason for not treating with warfarin (G: 47%; FD: 71%; IMS: 72%), and significantly fewer changed reported practice in the presence of falls risk (χ (2) (6) = 45.446, p < 0.01). Experience of a patient having a stroke whilst not on warfarin had a significant impact on vignette decisions; physicians who had had patients who experienced a stroke were more likely to prescribe warfarin (χ (2) (3) =10.7, p = 0.013). CONCLUSIONS: Barriers to treatment of atrial fibrillation with warfarin affect physician specialties to different extents. Prior experience of a patient suffering a stroke when not prescribed warfarin is positively associated with intention to prescribe warfarin, even in the presence of falls risk.

Health equity considerations in pragmatic trials in Alzheimer's and dementia disease: Results from a methodological review.

Introduction: To improve dementia care delivery for persons across all backgrounds, it is imperative that health equity is integrated into pragmatic trials. Methods: We reviewed 62 pragmatic trials of people with dementia published 2014 to 2019. We assessed health equity in the objectives; design, conduct, analysis; and reporting using PROGRESS-Plus which stands for Place of residence, Race/ethnicity, Occupation, Gender/sex, Religion, Education, Socioeconomic status, Social capital, and other factors such as age and disability. Results: Two (3.2%) trials incorporated equity considerations into their objectives; nine (14.5%) engaged with communities; 4 (6.5%) described steps to increase enrollment from equity-relevant groups. Almost all trials (59, 95.2%) assessed baseline balance for at least one PROGRESS-Plus characteristic, but only 10 (16.1%) presented subgroup analyses across such characteristics. Differential recruitment, attrition, implementation, adherence, and applicability across PROGRESS-Plus were seldom discussed. Discussion: Ongoing and future pragmatic trials should more rigorously integrate equity considerations in their design, conduct, and reporting. Highlights: Few pragmatic trials are explicitly designed to inform equity-relevant objectives.Few pragmatic trials take steps to increase enrollment from equity-relevant groups.Disaggregated results across equity-relevant groups are seldom reported.Adherence to existing tools (e.g., IMPACT Best Practices, CONSORT-Equity) is key.

Patient and public involvement in pragmatic trials: online survey of corresponding authors of published trials.

BACKGROUND: There are few data on patient and public involvement (PPI) in pragmatic trials. We aimed to describe the prevalence and nature of PPI within pragmatic trials, describe variation in prevalence of PPI by trial characteristics and compare prevalence of PPI reported by trial authors to that reported in trial publications. METHODS: We applied a search filter to identify pragmatic trials published from 2014 to 2019 in MEDLINE. We invited the corresponding authors of pragmatic trials to participate in an online survey about their specific trial. RESULTS: Of 3163 authors invited, 2585 invitations were delivered, 710 (27.5%) reported on 710 unique trials and completed the survey; 334 (47.0%) conducted PPI. Among those who conducted PPI, for many the aim was to increase the research relevance (86.3%) or quality (76.5%). Most PPI partners were engaged at protocol development stages (79.1%) and contributed to the co-design of interventions (70.9%) or recruitment or retention strategies (60.5%). Patient and public involvement was more common among trials involving children, trials conducted in the United Kingdom, cluster randomized trials, those explicitly labelled as "pragmatic" in the study manuscript, and more recent trials. Less than one-quarter of trials (22.8%) that reported PPI in the survey also reported PPI in the trial manuscript. INTERPRETATION: Nearly half of trialists in this survey reported conducting PPI and listed several benefits of doing so, but researchers who did not conduct PPI often cited a lack of requirement for it. Patient and public involvement appears to be significantly underreported in trial publications. Consistent and standardized reporting is needed to promote transparency about PPI methods, outcomes, challenges and benefits.

A review identified challenges distinguishing primary reports of randomized trials for meta-research: A proposal for improved reporting.

Meta-research is the discipline of studying research itself. A core investigative tool in meta-research is the use of systematic or scoping reviews to study the characteristics, methods and reporting of primary research studies. In the context of identifying eligible publications for methodological reviews of randomized controlled trials (RCTs), a challenge is to efficiently distinguish the primary trial report - which reports results for the primary outcome - from other types of reports, including design papers and secondary or supplementary analyses, or what we collectively refer to as non-primary reports. This may not be a straightforward task and may contribute to inefficiencies in the review process. Here, we draw on our recent methodological review of over 13,000 records to identify primary reports of pragmatic RCTs. We offer recommendations to improve the reporting of RCTs to facilitate more efficient identification of primary trial reports. We suggest that future updates to existing CONSORT guidelines include consideration of multiple trial reports and recommendations to clarify the primary or non-primary nature of each report. Our recommendations, together with improved adherence to inclusion of the trial registration number in the abstract and citation of a protocol or previously published primary report, would facilitate the conduct of methodological reviews.

Reporting of and explanations for under-recruitment and over-recruitment in pragmatic trials: a secondary analysis of a database of primary trial reports published from 2014 to 2019.

OBJECTIVES: To describe the extent to which pragmatic trials underachieved or overachieved their target sample sizes, examine explanations and identify characteristics associated with under-recruitment and over-recruitment. STUDY DESIGN AND SETTING: Secondary analysis of an existing database of primary trial reports published during 2014-2019, registered in ClinicalTrials.gov, self-labelled as pragmatic and with target and achieved sample sizes available. RESULTS: Of 372 eligible trials, the prevalence of under-recruitment (achieving <90% of target sample size) was 71 (19.1%) and of over-recruitment (>110% of target) was 87 (23.4%). Under-recruiting trials commonly acknowledged that they did not achieve their targets (51, 71.8%), with the majority providing an explanation, but only 11 (12.6%) over-recruiting trials acknowledged recruitment excess. The prevalence of under-recruitment in individually randomised versus cluster randomised trials was 41 (17.0%) and 30 (22.9%), respectively; prevalence of over-recruitment was 39 (16.2%) vs 48 (36.7%), respectively. Overall, 101 025 participants were recruited to trials that did not achieve at least 90% of their target sample size. When considering trials with over-recruitment, the total number of participants recruited in excess of the target was a median (Q1-Q3) 319 (75-1478) per trial for an overall total of 555 309 more participants than targeted. In multinomial logistic regression, cluster randomisation and lower journal impact factor were significantly associated with both under-recruitment and over-recruitment, while using exclusively routinely collected data and educational/behavioural interventions were significantly associated with over-recruitment; we were unable to detect significant associations with obtaining consent, publication year, country of recruitment or public engagement. CONCLUSIONS: A clear explanation for under-recruitment or over-recruitment in pragmatic trials should be provided to encourage transparency in research, and to inform recruitment to future trials with comparable designs. The issues and ethical implications of over-recruitment should be more widely recognised by trialists, particularly when designing cluster randomised trials.

Ethical considerations within pragmatic randomized controlled trials in dementia: Results from a literature survey.

Introduction: This review aims to describe the landscape of pragmatic randomized controlled trials (RCTs) in the context of Alzheimer's disease (AD) and related dementias with respect to ethical considerations. Methods: Searches of MEDLINE were performed from January 2014 until April 2019. Extracted information included: trial setting, interventions, data collection, study population, and ethical protections (including ethics approvals, capacity assessment, and informed consent). Results: We identified 62 eligible reports. More than two-thirds (69%) included caregivers or health-care professionals as research participants. Fifty-eight (94%) explicitly identified at least one vulnerable group. Two studies did not report ethics approval. Of 57 studies in which patients were participants, 55 (96%) reported that consent was obtained but in 37 studies (67%) no mention was made regarding assessment of the patients' capacity to consent to research participation. Discussion: Few studies reported protections implemented when vulnerable participants were included. Shortcomings remain when reporting consent approaches and capacity assessment.

Review of pragmatic trials found that multiple primary outcomes are common but so too are discrepancies between protocols and final reports.

OBJECTIVES: To describe prevalence of multiple primary outcomes, changes in primary outcomes and target sample sizes between protocols and final reports, and how issues of multiplicity are addressed in pragmatic trials. STUDY DESIGN AND SETTING: Individually randomized trials labeled as pragmatic, published 2014-2019 in MEDLINE and registered with ClinicalTrials.gov. RESULTS: We identified 262 final reports and located protocols for 159 (61%); primary outcomes were clearly reported in 145 (91%) protocols and 256 (98%) final reports. Thirty (19%) protocols and 38 (15%) final reports had multiple primary outcomes. Primary outcomes were present and identical in 128 (81%) matched protocol-final reports. Among 140 pairs with target sample sizes reported, 28 (20.0%) reduced their target sample size (mean 543 fewer participants per trial) and 16 (11.4%) increased it (mean 192 more participants per trial). Thirteen (29.5%) provided an explanation. Only 2 of 30 (7%) protocols and 4 of 38 (11%) final reports with co-primary outcomes explained how results would be interpreted in light of multiplicity; 21 of 30 (70%) protocols and 20 of 38 (53%) final reports accounted for co-primary outcomes in power calculations. CONCLUSION: Co-primary outcomes are common in pragmatic trials; improved transparency around design and analysis decisions involving co-primary outcomes is required.

An analysis of published trials found that current use of pragmatic trial labels is uninformative.

OBJECTIVES: Randomized trials labelled as "pragmatic" are attractive to funders, patients, and clinicians as the label implies that the results are directly applicable to clinical care. We examined how authors justify use of the label (e.g., by referring to one or more PRECIS [PRagmatic Explanatory Continuum Indicator Summary]-2 domains). STUDY DESIGN AND SETTING: We reviewed primary trial reports published 2014-2019, registered in ClinicalTrials.gov and using the pragmatic label anywhere in the report. RESULTS: Among 415 trials, the label was justified by reference to at least one design element in 282 (68.0%); of these, 240 (85.1%) referenced trial characteristics that can be mapped to one or more of the PRECIS-2 domains, most commonly eligibility (91, 32.3%), setting (90, 31.9%), flexibility delivery (89, 31.6%), and organization (75, 26.6%); 42 (14.9%) referenced characteristics that are not PRECIS-2 domains, most commonly type of intervention/comparator (48, 17%), recruitment without consent (22, 7.8%), routinely collected data (22, 7.8%), and cluster randomization (20, 7.1%). Most reports referenced only one or two design elements. Overall, 9/415 (2.2%) provided PRECIS wheels. CONCLUSION: Current use of pragmatic labels is uninformative. Authors should clarify the decision the trial is intended to support and include a PRECIS-2 table to make the design transparent.

Supporting Trial Participation in People with the Huntington's Gene: A Patient-Centered, Theory-Guided Survey of Barriers and Enablers.

BACKGROUND: Under-recruitment regularly impedes clinical trials, leading to wasted resources and opportunity costs. Methods for designing trial participation strategies rarely consider behavior change theory. OBJECTIVE: Informed by the Theoretical Domains Framework, we identified factors important to participating in Huntington's disease research and provide examples of how such a theory-informed approach can make specific suggestions about how to design targeted recruitment strategies. METHODS: We identified a range of trial participation barriers and enablers based on interviews of key informants and implemented an online survey of members of the Huntington's disease community, asking them to rate the extent to which different factors would affect likelihood to participate in a generic Huntington's disease trial. RESULTS: From 4,195 members, we received 323 responses and 243 completed surveys (323/4,195 or 8% participation, 243/323 or 75% completion). Respondents endorsed 9 barriers and 23 enablers relevant to trial participation. Most frequently endorsed barriers were travel to the study site (69%), worry about unknown side effects (65%), trial documents being difficult to understand (64%), and participation affecting other activities (49%). Enablers included optimism about likelihood of trial participation leading to a cure (98%), helping others (98%), contributing to science (97%), and having helpful people available to help with the participation decision (89%). CONCLUSION: Our theory-informed survey to identify barriers to and enablers of Huntington's disease trial participation identified 32 factors, from 13 theoretical domains relevant to trial participation, and suggests effective approaches for improving trial participation and patient experience.

Using behavioral theory and shared decision-making to understand clinical trial recruitment: interviews with trial recruiters.

BACKGROUND: Clinical trial recruitment is a continuing challenge for medical researchers. Previous efforts to improve study recruitment have rarely been informed by theories of human decision making and behavior change. We investigate the trial recruitment strategies reported by study recruiters, guided by two influential theoretical frameworks: shared decision-making (SDM) and the Theoretical Domains Framework (TDF) in order to explore the utility of these frameworks in trial recruitment. METHODS: We interviewed all nine active study recruiters from a multi-site, open-label pilot trial assessing the feasibility of a large-scale randomized trial. Recruiters were primarily nurses or master's-level research assistants with a range of 3 to 30 years of experience. The semi-structured interviews included questions about the typical recruitment encounter, questions concerning the main components of SDM (e.g. verifying understanding, directive vs. non-directive style), and questions investigating the barriers to and drivers of their recruitment activities, based on the TDF. We used directed content analysis to code quotations into TDF domains, followed by inductive thematic analysis to code quotations into sub-themes within domains and overarching themes across TDF domains. Responses to questions related to SDM were aggregated according to level of endorsement and informed the thematic analysis. RESULTS: The analysis helped to identify 28 sub-themes across 11 domains. The sub-themes were organized into six overarching themes: coordinating between people, providing guidance to recruiters about challenges, providing resources to recruiters, optimizing study flow, guiding the recruitment decision, and emphasizing the benefits to participation. The SDM analysis revealed recruiters were able to view recruitment interactions as successful even when enrollment did not proceed, and most recruiters took a non-directive (i.e. providing patients with balanced information on available options) or mixed approach over a directive approach (i.e. focus on enrolling patient in study). Most of the core SDM constructs were frequently endorsed. CONCLUSIONS: Identified sub-themes can be linked to TDF domains for which effective behavior change interventions are known, yielding interventions that can be evaluated as to whether they improve recruitment. Despite having no formal training in shared decision-making, study recruiters reported practices consistent with many elements of SDM. The development of SDM training materials specific to trial recruitment could improve the informed decision-making process for patients.

Results from a Theory-Guided Survey to Support Breast Cancer Trial Participation: Barriers, Enablers, and What to Do about them.

BACKGROUND: Ensuring adequate, informed, and timely participation in clinical trials is a multifactorial problem. We have previously developed a systematic, tailorable survey development approach that is informed by theory, can identify barriers and enablers to participation, and can suggest recruitment strategies to address these issues. In this study, we surveyed subscribers to the Canadian Breast Cancer Network (CBCN) in order to identify a comprehensive list of theory-informed barriers and enablers relevant to participation in a hypothetical breast cancer trial. METHODS: We developed and conducted an online survey of breast cancer patients informed by the Theoretical Domains Framework and designed to determine previous experience with clinical trials, knowledge about clinical trials, and importance of a comprehensive list of barriers and enablers to trial participation. Participants were contacted by email or through social media. RESULTS: From 2451 subscribers of the CBCN, we received 244 responses and 210 completed surveys (244/2451 or 9.9% participation, 210/244 or 86.1% completion). A total of 38% of respondents indicated experience in trial participation, but 83% indicated confidence in their knowledge about clinical trials. Those who had previously participated in clinical trials were more confident in their knowledge (χ2= 6.77, p = 0.009) and answered more knowledge questions (t = -3.90 p = 0.000). Endorsed barriers and enablers to participation included 39 factors across 12 of 14 domains relevant to behaviour change. Our approach identifies barriers that might be meaningfully addressed by careful knowledge provision ('If I would learn more about my condition'; 'If I find the trial documents hard to understand'), those that may require other theory-informed approaches to address ('my feelings about the quality of my drug plan'; 'my worry over unknown side effects'), and those that may require tailored approaches depending on participant differences such as previous experience in trials ('If there were patient-friendly decision-making tools to help you make your participation decision'). DISCUSSION: This work demonstrates that a comprehensive, theory-guided survey of barriers and enablers to participation in breast cancer clinical trials is feasible, can lead to detailed knowledge about the issues related to participation in specific trials, and most importantly, can lead to insights about evidence-based ways to better support patient participation.