Participation In Future Trials Research Articles

Participant experiences in a pilot study for methamphetamine withdrawal treatment: Implications for retention

IntroductionThere is little knowledge of the perspectives of people who use methamphetamine and have participated in clinical trials, and none for interventions not intended to address abstinence. A better understanding of these experiences could lead to more patient centred clinical trial design. This study seeks to understand the experiences of people who completed a clinical trial of lisdexamfetamine for the treatment of acute methamphetamine withdrawal. MethodsThematic analysis of open-ended, semi-structured interviews with eight people who participated in an inpatient clinical trial of lisdexamfetamine for acute methamphetamine withdrawal. Interviews were conducted between days 3 and 6 of admission to an inner-city Sydney hospital. ResultsParticipants described how research procedures, the research setting, and the investigational product affected their experiences while enrolled in a clinical trial. Of particular importance to participants were transparent and low burden trial procedures, a welcoming trial environment, trusting relationships and effective communication, which were linked with the participants’ subsequent decision to remain enrolled in the trial. DiscussionThe experiences of participants in this clinical trial can be distilled into four meta-themes: agency, caring-trust, safety, and communication. Participants spontaneously linked these experiences with a capacity to remain enrolled in the study. By considering the experiences of trial participants in clinical trial design, researchers can improve the experiences of future trial participants and facilitate their choice to remain enrolled in clinical trials.

Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU): Trial Satisfaction and Attitudes towards Future Clinical Trials.

Clinical trial satisfaction is increasingly important for future trial designs and is associated with treatment adherence and willingness to enroll in future research studies or to recommend trial participation. In this post-trial survey, we examined participant satisfaction and attitudes toward future clinical trials in the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU). We developed an anonymous, participant satisfaction survey tailored to participants enrolled in the DIAN-TU-001 double-blind clinical trial of solanezumab or gantenerumab and requested that all study sites share the survey with their trial participants. A total of 194 participants enrolled in the trial at 24 study sites. We utilized regression analysis to explore the link between participants' clinical trial experiences, their satisfaction, and their willingness to participate in upcoming trials. Survey responses were received over a sixteen-month window during 2020-2021 from 58 participants representing 15 study sites. Notably, 96.5% of the survey respondents expressed high levels of satisfaction with the trial, 91.4% would recommend trial participation, and 96.5% were willing to enroll again. Age, gender, and education did not influence satisfaction levels. Participants reported enhanced medical care (70.7%) and pride in contributing to the DIAN-TU trial (84.5%). Satisfaction with personnel and procedures was high (98.3%). Respondents had a mean age of 48.7 years, with most being from North America and Western Europe, matching the trial's demographic distribution. Participants' decisions to learn their genetic status increased during the trial, and most participants endorsed considering future trial participation regardless of the DIAN-TU-001 trial outcome. Results suggest that DIAN-TU-001 participants who responded to the survey exhibited high motivation to participate in research, overall satisfaction with the clinical trial, and willingness to participate in research in the future, despite a long trial duration of 4-7 years with detailed annual clinical, cognitive, PET, MRI, and lumbar puncture assessments. Implementation of features that alleviate barriers and challenges to trial participation is like to have a high impact on trial satisfaction and reduce participant burden.

Abstract 342: Willingness to Participate in an Active Pediatric Critical Care Interventional Trial Using Exception From Informed Consent

Introduction: Emergency interventional trials using Exception From Informed Consent (EFIC) are rare, but pooled survey data preceding 27 EFIC studies show that 73% of respondents were willing to be enrolled in the associated trial. However, given the hypothetical nature of these surveys, the actual rate of willingness to participate in an active EFIC trial and any associations with demographic characteristics are unknown. Aims: To 1) compare the actual rate of willingness to participate in an EFIC trial with that from previously published hypothetical surveys for the same trial; and 2) describe demographic characteristics associated with actual willingness rates. Hypothesis: We hypothesized that the actual rate of willingness to participate in an EFIC trial would be lower than the hypothetical survey rate. Methods: From April 13 to June 5, 2023, we attempted to notify all eligible patients/families of an active EFIC trial enrolling in our PICU and gave them the option to opt out from enrollment. Responses were recorded, and patient demographics were abstracted from the medical record. Major exclusion criteria were age over 25 years and state custody. Surveys were performed prior to trial initiation with a similar screening process. Likert scale responses for willingness to participate were dichotomized. Results: Of 207 families contacted, 149 (72%) were willing to participate in the trial which was similar to our pre-trial survey data (43/58 [74%]; p = 0.87). Willingness rates varied by race category (Asian 5/5, 100%; Black 8/18, 44%; Hispanic 22/33, 67%; White 66/84, 79%; Other 12/20 60%; Unknown 36/47, 77%; p = 0.03) but not patient age (willing, median 5 years [IQR 1, 13] vs not willing, median 7 years [IQR 1,4]; p=0.84). Conclusion: The actual rate of willingness to participate in an EFIC trial in the PICU was similar to the hypothetical rate reported in pre-trial survey data, suggesting surveys may reasonably reflect attitudes of potential participants. Willingness rates varied by race, though a significant proportion of data was missing. Reasons for racial differences in research engagement should be explored to better understand the consequences of long-standing structural racism in the US and the impact on future trial participation for these groups.

Preparing for future European efficacy trials of interventions to prevent HIV and other sexually transmitted infections: Lessons on willingness to participate and barriers to participation from ten German clinics serving behaviorally vulnerable men who have sex with men

Future efficacy testing of interventions to prevent HIV or other infections will require engagement of vulnerable populations. We characterized willingness to participate in a future HIV vaccine trial and barriers to participation among men who have sex with men in a 12-month German cohort study. Among 1015 participants at enrollment, 604 (60%) reported willingness, 60 (6%) were unwilling, 351 (35%) were unsure or refused to answer. Among those unwilling, the primary reason was fear of getting HIV. Among those willing, reasons included protection against HIV and furthering scientific knowledge. In a multivariable logistic regression model, higher odds of willingness to participate were seen among participants at the 12-month visit (aOR: 1.09, 95% CI: 1.04–1.15) and with prior knowledge of HIV vaccine research (aOR: 1.14, 95% CI: 1.06–1.23). Educating potential participants about vaccine research may facilitate recruitment and participation in future trials of HIV vaccine candidates and other prevention interventions.

Dose-finding based on feasibility and late-onset toxicity in adoptive cell therapy trials

ABSTRACT Cell therapies comprise one of the most important advances in oncology. One of the biggest challenges in the early development of cell therapies is to recommend safe and feasible doses to carry forward to middle development. The treatment involves extracting cells from a patient, expanding the cells and infusing the cells back into the patient. Each dose level being studied is defined by the number of cells infused into the trial participant. The manufacturing process may not generate enough cells for a given patient to receive their assigned dose level, making it infeasible to administer their intended dose. The primary design challenge is to efficiently use accumulated data from participants treated away from their assigned dose to efficiently allocate future trial participants and recommend a feasible maximum tolerated dose (FMTD) at the study conclusion. Currently, there are few available options for designing and implementing Phase I trials of cell therapies that can incorporate a dose feasibility endpoint. Moreover, the application of these designs is limited to a traditional dose-finding framework, where the dose-limiting toxicity (DLT) endpoint is observed in early cycles of therapy. This paper presents a novel phase I trial design for adoptive cell therapy that simultaneously accounts for dose feasibility and late-onset toxicities. We apply our design to a phase I dose-escalation trial of Rituximab-based bispecific activated T-cells combined with a fixed dose of Nivolumab. Our simulation results demonstrate that our proposed method can reduce trial duration without significantly hindering trial accuracy.

Structural MRI predicts clinical progression in presymptomatic genetic frontotemporal dementia: findings from the GENetic Frontotemporal dementia Initiative cohort.

Biomarkers that can predict disease progression in individuals with genetic frontotemporal dementia are urgently needed. We aimed to identify whether baseline MRI-based grey and white matter abnormalities are associated with different clinical progression profiles in presymptomatic mutation carriers in the GENetic Frontotemporal dementia Initiative. Three hundred eighty-seven mutation carriers were included (160 GRN, 160 C9orf72, 67 MAPT), together with 240 non-carrier cognitively normal controls. Cortical and subcortical grey matter volumes were generated using automated parcellation methods on volumetric 3T T1-weighted MRI scans, while white matter characteristics were estimated using diffusion tensor imaging. Mutation carriers were divided into two disease stages based on their global CDR®+NACC-FTLD score: presymptomatic (0 or 0.5) and fully symptomatic (1 or greater). The w-scores in each grey matter volumes and white matter diffusion measures were computed to quantify the degree of abnormality compared to controls for each presymptomatic carrier, adjusting for their age, sex, total intracranial volume, and scanner type. Presymptomatic carriers were classified as 'normal' or 'abnormal' based on whether their grey matter volume and white matter diffusion measure w-scores were above or below the cut point corresponding to the 10th percentile of the controls. We then compared the change in disease severity between baseline and one year later in both the 'normal' and 'abnormal' groups within each genetic subtype, as measured by the CDR®+NACC-FTLD sum-of-boxes score and revised Cambridge Behavioural Inventory total score. Overall, presymptomatic carriers with normal regional w-scores at baseline did not progress clinically as much as those with abnormal regional w-scores. Having abnormal grey or white matter measures at baseline was associated with a statistically significant increase in the CDR®+NACC-FTLD of up to 4 points in C9orf72 expansion carriers, and 5 points in the GRN group as well as a statistically significant increase in the revised Cambridge Behavioural Inventory of up to 11 points in MAPT, 10 points in GRN, and 8 points in C9orf72 mutation carriers. Baseline regional brain abnormalities on MRI in presymptomatic mutation carriers are associated with different profiles of clinical progression over time. These results may be helpful to inform stratification of participants in future trials.

Predicting Cognitive Decline in Older Adults Using Baseline Metrics of AD Pathologies, Cerebrovascular Disease, and Neurodegeneration.

Dementia is a growing socioeconomic challenge that requires early intervention. Identifying biomarkers that reliably predict clinical progression early in the disease process would better aid selection of individuals for future trial participation. Here, we compared the ability of baseline, single time-point biomarkers (CSF amyloid 1-42, CSF ptau-181, white matter hyperintensities (WMH), cerebral microbleeds, whole-brain volume, and hippocampal volume) to predict decline in cognitively normal individuals who later converted to mild cognitive impairment (MCI) (CNtoMCI) and those with MCI who later converted to an Alzheimer disease (AD) diagnosis (MCItoAD). Standardized baseline biomarker data from AD Neuroimaging Initiative 2 (ADNI2)/GO and longitudinal diagnostic data (including ADNI3) were used. Cox regression models assessed biomarkers in relation to time to change in clinical diagnosis using all follow-up time points available. Models were fit for biomarkers univariately and together in a multivariable model. Hazard ratios (HRs) were compared to evaluate biomarkers. Analyses were performed separately in CNtoMCI and MCItoAD groups. For CNtoMCI (n = 189), there was strong evidence that higher WMH volume (individual model: HR 1.79, p = 0.002; fully adjusted model: HR 1.98, p = 0.003) and lower hippocampal volume (individual: HR 0.54, p = 0.001; fully adjusted: HR 0.40, p < 0.001) were associated with conversion to MCI individually and independently. For MCItoAD (n = 345), lower hippocampal (individual model: HR 0.45, p < 0.001; fully adjusted model: HR 0.55, p < 0.001) and whole-brain volume (individual: HR 0.31, p < 0.001; fully adjusted: HR 0.48, p = 0.02), increased CSF ptau (individual: HR 1.88, p < 0.001; fully adjusted: HR 1.61, p < 0.001), and lower CSF amyloid (individual: HR 0.37, p < 0.001; fully adjusted: HR 0.62, p = 0.008) were most strongly associated with conversion to AD individually and independently. Lower hippocampal volume was a consistent predictor of clinical conversion to MCI and AD. CSF and brain volume biomarkers were predictive of conversion to AD from MCI, whereas WMH were predictive of conversion to MCI from cognitively normal. The predictive ability of WMH in the CNtoMCI group may be interpreted as some being on a different pathologic pathway, such as vascular cognitive impairment.

A systematic review and meta-analysis of weight loss in control group participants of lifestyle randomized trials

Randomized clinical trials (RCTs) of lifestyle modification have reported beneficial effects of interventions, compared to control. Whether participation in the control group has benefits is unknown. To determine whether control group participants experience weight loss during the course of RCTs. After prospective registration (PROSPERO CRD42021233070), we conducted searches in Medline, Scopus, Web of Science, Cochrane library and Clinicaltrials.gov databases from inception to May 2021 without language restriction to capture RCTs on dietary advice or physical activity interventions in adults with overweight, obesity or metabolic syndrome. Data extraction and study quality assessment was performed by two independent reviewers. Weight loss in the control group, i.e., the difference between baseline and post-intervention, was pooled using random effects model generating mean difference and 95% confidence interval (CI). Heterogeneity was assessed using the I2 statistical test. Subgroup meta-analysis was performed stratifying by follow-up period, type of control group protocols and high-quality studies. Among the 22 included studies (4032 participants), the risk of bias was low in 9 (40%) studies. Overall, the controls groups experienced weight loss of − 0.41 kg (95% CI − 0.53 to − 0.28; I2 = 73.5% p < 0.001). To identify a result that is an outlier, we inspected the forest plot for spread of the point estimates and the confidence intervals. The magnitude of the benefit was related to the duration of follow-up (− 0.51 kg, 95% CI − 0.68, − 0.3, for 1–4 months follow-up; − 0.32 kg, 95% CI − 0.58, − 0.07, 5–12 months; − 0.20 kg, 95% CI − 0.49, 0.10, ≥ 12 months). In high-quality studies we found an overall weight loss mean difference of − 0.16 (95% CI − 0.39, 0.09) with a considerable heterogeneity (I2 = 74%; p < 0.000). Among studies including control group in waiting lists and combining standard care, advice and material, no heterogeneity was found (I2 = 0%, p = 0.589) and (I2 = 0%, p = 0.438); and the mean difference was − 0.84 kg (95% CI − 2.47, 0.80) and − 0.65 kg (95% CI − 1.03, − 0.27) respectively. Participation in control groups of RCTs of lifestyle interventions had a benefit in terms of weight loss in meta-analysis with heterogeneity. These results should be used to interpret the benefits observed with respect to intervention effect in trials. That control groups accrue benefits should be included in patient information sheets to encourage participation in future trials among patients with overweight and obesity.

Development and validation of a multivariable prognostic model in de novo metastatic castrate sensitive prostate cancer.

Metastatic castrate sensitive prostate cancer (mCSPC) is a heterogeneous disease state with variable prognosis. Although several life-prolonging systemic agents are available, there is no robust multivariable model to predict prognosis and improve risk stratification in mCSPC. The objective of this study was to build and validate a multivariable prognostic model to predict overall survival (OS) in mCSPC. We used data from LATITUDE, a phase III randomized controlled trial in which men with de novo mCSPC were randomly allocated to either ADT plus abiraterone or ADT with placebo. Patients with non-missing data (n = 1,058) were randomly split in a 70:30 ratio to training (n = 743) and testing (n = 315) sets. Elastic net regression was used for variable selection. A multivariable Cox regression model for OS was then fitted using the selected variables. The predictive accuracy of the model was assessed on the testing set using the time-dependent area under curve (tAUC) with bootstrapped confidence intervals [CI] primarilyfor OS and secondarily forradiographic progression-free survival (rPFS). The 11 prognostic variables in the final model were performance status, number of skeletal metastases, Gleason score, presence of liver metastasis, worst pain score, albumin, lactate dehydrogenase, prostate-specific antigen, hemoglobin, and treatment regimen. The tAUC for predicting OS at 2- and 3-years was 0.74 (95%CI, 0.67-0.80) and 0.72 (95%CI, 0.65-0.77), respectively. The tAUC for rPFS at 2- and 3-years was 0.72 (95%CI, 0.65-0.77) and 0.77 (95%CI, 0.70-0.82), respectively. A prognostic model for men with de novo mCSPC was developed and validated in an independent testing set. Our model had high accuracy for predicting OS and rPFS. The model includes commonly used clinical and laboratory parameters and can guide risk stratification of these patients for participation in future trials.

The combination of transcatheter arterial chemoembolisation (TACE) and thermal ablation versus TACE alone for hepatocellular carcinoma.

Hepatocellular carcinoma is the sixth most common cancer worldwide. Hepatic resection is regarded as the curative therapy for hepatocellular carcinoma. However, only about 20% of people with hepatocellular carcinoma are candidates for resection, which highlights the importance of effective nonsurgical therapies. Until now, transcatheter arterial chemoembolisation (TACE) is the most common palliative therapy for hepatocellular carcinoma, but its clinical benefits remain unsatisfactory. During recent years, some studies have reported that the combination of TACE plus thermal ablation can confer a more favourable prognosis than TACE alone. However, clear and compelling evidence to prove the beneficial or harmful effects of the combination of TACE and thermal ablation therapy is lacking. To assess the beneficial and harmful effects of the combination of thermal ablation with TACE versus TACE alone in people with hepatocellular carcinoma. We performed searches in the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials in the Cochrane Library, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index-Science. We endeavoured to identify relevant randomised clinical trials also in the China National Knowledge Infrastructure (CNKI) and Wanfang databases. We searched trial registration websites for ongoing studies. We also handsearched grey literature sources. The date of last search was 22 December 2020. We planned to include all randomised clinical trials comparing the combination of TACE plus thermal ablation versus TACE alone for hepatocellular carcinoma, no matter the language, year of publication, publication status, and reported outcomes. We planned to use standard methodological procedures expected by Cochrane. We planned to calculate risk ratios (RRs) with the corresponding 95% confidence intervals (CIs). For time-to-event variables, we planned to use the methods of survival analysis and express the intervention effect as a hazard ratio (HR) with 95% Cl. If the log HR and the variance were not directly reported in reports, we planned to calculate them indirectly, following methods for incorporating summary time-to-event data into meta-analysis. We planned to assess the risk of bias of the included studies using the RoB 2 tool. We planned to assess the certainty of evidence with GRADE and present the evidence in a summary of findings table. Out of 2224 records retrieved with the searches, we considered 135 records eligible for full-text screening. We excluded 21 of these records because the interventions used were outside the scope of our review or the studies were not randomised clinical trials. We listed the remaining 114 records, reporting on 114 studies, under studies awaiting classification because we could not be sure that these were randomised clinical trials from the information in the study paper. We could not obtain information on the registration of the study protocol for any of the 114 studies. We could not obtain information on study approval by regional research ethics committees, either from the study authors or through our own searches of trial registries. Corresponding authors did not respond to our enquiries about the design and conduct of the studies, except for one from whom we did not receive a satisfactory response. We also raised awareness of our concerns to editors of the journals that published the 114 studies, and we did not hear back with useful information. Moreover, there seemed to be inappropriate inclusion of trial participants, based on cancer stage and severity of liver disease, who should have obtained other interventions according to guidelines from learned societies. Accordingly, we found no confirmed randomised clinical trials evaluating the combination of TACE plus thermal ablation versus TACE alone for people with hepatocellular carcinoma for inclusion in our review. We identified five ongoing trials, by handsearching in clinical trial websites. We could not find for inclusion any confirmed randomised clinical trials assessing the beneficial or harmful effects of the combination of TACE plus thermal ablation versus TACE alone in people with hepatocellular carcinoma. Therefore, our results did not show or reject the efficiency of the combination of TACE plus thermal ablation versus TACE alone for people with hepatocellular carcinoma. We need trials that compare the beneficial and harmful effects of the combination of TACE plus thermal ablation versus TACE alone in people with hepatocellular carcinoma, not eligible for treatments with curative intent (liver transplantation, ablation surgical resection) and who have sufficient liver reserve, as assessed by the Child Pugh score, and who do not have extrahepatic metastases. Therefore, future trial participants must be classified at Barcelona Clinic Liver Cancer Stage B (intermediate stage) (BCLC-B) or an equivalent, with other staging systems.

Trial readiness amongst EPAD longitudinal cohort study participants: Insights from the SPEAR study

AbstractBackgroundSPEAR (Study of Participant Experience of Alzheimer’s disease Research) was a sub‐study of work on the Ethical, Legal and Social Implications of the European Prevention of Alzheimer’s Dementia (EPAD) project. The EPAD Longitudinal Cohort Study (LCS) aimed to generate a detailed picture of biological and cognitive change over time, and to build a ‘readiness cohort’ to recruit eligible and willing participants into clinical trials. This poster presents findings about the willingness of cohort participants to participate in a future clinical trial.MethodA mixed‐method study was conducted with members of the EPAD Longitudinal Cohort Study (LCS) to explore motivations to participate, study experience and likely future participation in an Alzheimer’s prevention trial. A questionnaire was completed by 101 participants and 7 study partners from 4 EPAD sites across the UK. In‐depth qualitative interviews were conducted with 25 EPAD participants and study visits observed from the same 4 sites.ResultOver half of participants would consider participating in a clinical trial at the time of data collection. Almost none reported that they would “never” participate. The timing, location and duration of trials were important in how likely they would be to participate. The qualitative findings revealed a range of tentative attitudes towards the prospect of being recruited to a clinical trial, including feeling “morally obliged to continue” or indicating “I don’t want a drug,” should they agree to participate. Some said changes in their memory or cognition may also influence future decisions.ConclusionWhilst we saw high levels of willingness to participate in a clinical trial, these data highlight the importance of understanding how motivations, willingness, and expectations for trial participation may change over time. This supports the use of a staged consent model such as that adopted by EPAD. Qualitative research is needed to understand underlying reasons for participants’ trial readiness to identify any ethical issues in the recruitment of future trial participants.

Using self-determination theory to understand and improve recruitment for the Coaching for Healthy Ageing (CHAnGE) trial.

BackgroundIntervention trials promoting physical activity among older people frequently report low and unrepresentative recruitment. Better understanding of reasons for participation can help improve recruitment. This study explored why participants enrolled in the Coaching for Healthy Ageing (CHAnGE) trial, including how their decision was influenced by recruitment strategies. CHAnGE was a cluster randomised controlled trial testing the effectiveness of a healthy ageing program targeting inactivity and falls. Seventy-two groups of people aged 60+ were recruited from community organisations via informal presentations by the health coaches.MethodsWe conducted a secondary thematic analysis of interview data from our wider qualitative evaluation in which 32 purposively sampled trial participants took part in semi-structured interviews about their experiences of CHAnGE. Data relating to recruitment and participation were analysed inductively to identify themes, then a coding framework comprising the core constructs from self-determination theory—autonomy, competence and relatedness—was used to explore if and how this theory fit with and helped to explain our data.ResultsRecruitment presentations promoted the CHAnGE intervention well in terms of addressing value expectations of structured support, different forms of accountability, credibility, achievability and, for some, a potential to enhance social relationships. Participation was motivated by the desire for improved health and decelerated ageing, altruism and curiosity. These factors related strongly to self-determination concepts of autonomy, competence and relatedness, but the intervention’s demonstrated potential to support self-determination needs could be conveyed more effectively.ConclusionsFindings suggest that recruitment could have greater reach using: 1. Strengths-based messaging focusing on holistic gains, 2. Participant stories that highlight positive experiences, and 3. Peer support and information sharing to leverage altruism and curiosity. These theory-informed improvements will be used to increase participation in future trials, including people in hard-to-recruit groups. They may also inform other physical activity trials and community programs.

Lived time and the affordances of clinical research participation.

In this article, we address the problem of participation and the dominant focus on motivations in clinical research. We explore participation as a relational mode of 'being in time' in Alzheimer's dementia prevention-a field profoundly shaped by changing bodies through time, as well as promissory trends towards future-oriented preventative medicine. Analysis of interviews with older adults in a clinical trial platform demonstrates that what research 'does' or might (not) 'do' for participants emerges as temporalities of participants' everyday lives become entangled with the possibilities, constraints and demands of biomedical 'research time'. As well as consistent desires to help (future) others, we identify incidental possibilities for care that emerged from continued research participation. We argue that longitudinal research participation can productively be understood as a set of evolving affordances: whereby differing limits and possibilities for care and agency emerge in a world where dementia cannot be cured. Future trial participation is considered in terms of 'therapeutic affordances', which are likely to fluctuate as certain lived or imagined futures unfold. As such, we open up a conceptual space to think about why, how, and critically, when participation happens, as it emerges in relation to lived times of ageing and everyday life.

Greater Awareness and Knowledge of Clinical Research Increases Willingness to Participate in Future Vaccine TrialsAn Examination of the Enduring Impact of COVID-19 Pandemic

The devastating impact of COVID-19 pandemic, its fast-tracked vaccines and authorized treatments have led to more volunteers signing up to be part of clinical studies than any time in recent history. We sought to investigate the relationship between increased knowledge of vaccine clinical trials and willingness to participate in future vaccine trials. A convenience sample survey of the United States residents was conducted in May 2021. Over 1,100 adults completed questions about their knowledge of clinical vaccine trials and attitudes toward participation in future trials. A total of 1149 respondents completed the survey. The median age was 29. Amongst respondents, 47.9% were women. Over 85% had attended college. Most were married (60.1%). A significant proportion of respondents were of Hispanic origin (42.2%). Higher Knowledge Scores were observed for female respondents (p &lt;0.001);&gt;30 years-old respondents (p &lt;0.001) and respondents with a bachelors’ degree or higher (p &lt;0.05). Overall, the survey respondents felt that their COVID-19 pandemic experience had increased their knowledge of vaccine trials (807, 70.2%) and willingness to participate in future vaccine studies (677, 58.9%). In addition, over half of the respondents expressed willingness to sign up for a future vaccine study of any kind (51.5%) with another 38.0% willing to consider it. The findings from this survey confirms significant increased interest in clinical vaccine study participation in the midst of COVID-19 pandemic and provides actionable insights to improve outreach efforts with underrepresented populations in clinical research. Keywords: COVID-19; Clinical Trials Participat

Process study within a pilot cluster randomised trial in community pharmacy: An exploration of pharmacist readiness for research.

Community pharmacies have an increasingly prominent public health function. This includes addressing alcohol, but guidance on delivery of alcohol interventions in this setting is lacking. We have developed an intervention that integrates attention to alcohol within existing community pharmacy medicine review services. This paper examines the experiences of community pharmacists (CPs) in conducting a pilot trial of the intervention, including the acceptability of the trial patient recruitment procedures and the training and support provided by the research team. The pilot trial was conducted in 10 community pharmacies in Yorkshire, England. One CP from each pharmacy was recruited via a multi-stage process to assess motivation, commitment and capacity to participate. Each CP attended a research training day and received on-going research support to conduct the trial. Semi-structured audio-recorded face-to-face interviews (lasting 40-105min) were conducted with all the CPs at the end of the trial. Data were also available from three direct observations conducted during trial support visits. Data were analysed thematically. The CPs were supportive of research in community pharmacy but had little direct experiences of research themselves. They valued the training and support provided, which had quickly identified areas where CPs were deviating from the study recruitment protocol. In some instances, the boundaries between research and practice became blurred with CPs making changes to their usual routines and interactions with patients to accommodate the research. The trial procedures were acceptable to CPs, in part because of the training and support provided. There are also identifiable areas where CPs' readiness for research could be enhanced to facilitate participation in future trials in this setting.

Patient and healthcare professional experiences of the Salford Lung Studies: qualitative insights for future effectiveness trials

BackgroundRandomized controlled trials (RCTs) conducted in the routine care setting provide the opportunity to better understand the effectiveness of new medicines but can present recruitment difficulties. An improved understanding of the challenges/opportunities for patient and healthcare professional (HCP) engagement in clinical research is needed to enhance participation and trial experience. In this study, we explored patient and HCP drivers for, and experiences of, participation in the Salford Lung Studies (SLS), and their views on future trial participation and the overall value of such trials.MethodsThis was a qualitative study set in Salford, UK, comprising patient telephone interviews (N = 10) and HCP advisory boards (one with general practitioners [GPs], one with practice managers [PMs]); all individuals had participated in the SLS. Semi-structured telephone interviews were recorded, transcribed and analysed thematically. Advisory board meetings were analysed based on transcriptions of audio recordings and field notes.ResultsFor patients, key positive aspects of the SLS were the ease/convenience of study assessments and excellent relationships with study nurses. GPs and PMs considered the SLS to be well-organized and highlighted the value of research nurse support; they also described minor challenges relating to trial systems, initial financial strain on practices and staff turnover. All participants indicated that they were very likely to participate in future trials, citing a design closely aligned with routine care practice as essential. Several strategies to encourage trial participation were suggested, such as clearly communicating benefits to patients and ensuring flexible study assessments.ConclusionsPatients and HCPs had positive experiences of the SLS. The study design, closely aligned with routine care, was considered important to their high likelihood of participating in future trials. The experiences of patients and HCPs in the SLS provide valuable insights that will help inform future best practice in the design and conduct of future real-world effectiveness RCTs in primary care. The detailed first-hand experiences of HCPs will be of significant value to others considering engaging in clinical research and participating in effectiveness RCTs.

Clinical trials knowledge and attitudes of Vietnamese‐ and Anglo‐Australian cancer patients: A cross‐sectional study

Low participation in cancer clinical trials by culturally and linguistically diverse (CALD) patients limits access to cutting-edge treatments and generalizability of results. This is the first study exploring trials knowledge/attitudes and their association with trial participation in Vietnamese- and Anglo-Australian cancer patients. Eligible patients diagnosed with cancer in the past 10 years were invited to complete a self-report questionnaire comprising validated measures of: trials knowledge and attitudes, preferred information amount, preferred decision-making involvement, health literacy, and past and future (i.e. hypothetical) trial participation. Multivariable linear regression evaluated correlates of trials knowledge/attitudes. Multinomial logistic regression estimated the relationship between trials knowledge/attitudes and possible future trial participation. Vietnamese-Australian participants (n=50) had more negative attitudes regarding trials than Anglo-Australians (n=100; B=-9.28; 95% confidence interval [CI], -17.60 to -0.97; P=0.029), but similar knowledge (B=-0.91; 95% CI, -2.27 to 0.44; P=0.18). Future trial participation was associated with positive attitudes (odds ratio [OR]=1.08; 95% CI, 1.04-1.12; P<0.001) and greater knowledge (OR=1.30; 95% CI, 1.04-1.62; P=0.02), but not Vietnamese background (OR=0.95; 95% CI, 0.27-3.32; P=0.93). Despite poorer attitudes regarding trials in Vietnamese-Australians, Vietnamese background was not associated with less likely future trial participation, suggesting low trial participation by CALD patients may be more due to opportunity barriers. Improving knowledge and attitudes may increase trial participation generally.

Surgery for women with endometrioma prior to in vitro fertilisation: proposal for a feasible multicentre randomised clinical trial in the UK.

STUDY QUESTIONIs it feasible to undertake a randomised controlled trial to establish whether surgical removal of endometrioma or not, improves live birth rates from IVF?SUMMARY ANSWERA randomised controlled trial (RCT) comparing surgery versus no surgery to endometrioma prior to IVF is only feasible in UK if an adaptive rather than traditional study design is used; this would minimise resource wastage and complete the trial in an acceptable time frame.WHAT IS KNOWN ALREADYThere is wide variation in the management of endometriomas prior to IVF, with decisions about treatment being influenced by personal preferences.STUDY DESIGN, SIZE, AND DURATIONThis was a mixed-methods study consisting of an online survey of clinicians, a focus group and individual interviews with potential trial participants.PARTICIPANTS/MATERIALS, SETTING, METHODSEndometriosis and fertility experts across the UK were invited to participate in an online anonymised questionnaire. Potential future trial participants were recruited from a tertiary care fertility centre and invited to participate in either individual interviews or focus groups.MAIN RESULTS AND THE ROLE OF CHANCEClinicians and potential trial participants confirmed the need for an RCT to inform the management of an endometrioma prior to IVF. There were 126 clinicians who completed the survey, and the majority (70%) were willing to recruit to a trial. Half of those who responded indicated that they see at least 10 eligible women each year. The main barriers to recruitment were waiting lists for surgery and access to public funding for IVF. One focus group (n = 7) and five interviews were conducted with potential trial participants (n = 3) and their partners (n = 2). The findings from these discussions highlighted that recruitment and retention in a potential RCT could be improved by coordination between IVF and surgical services such that an operation does not delay IVF or affect access to public funding. Live birth was considered the most important outcome with an improvement of at least 10% considered the minimum acceptable by both patients and clinicians.LIMITATIONS, REASONS FOR CAUTIONThis feasibility study captured views of clinicians across the UK, but as patients were from a single Scottish centre, their views may not be representative of other areas with limited public funding for IVF.WIDER IMPLICATIONS OF THE FINDINGSThere is a need for an appropriately powered RCT to establish whether or not surgical treatment of endometrioma prior to IVF improves live birth rates. There are logistical issues to be considered due to limited number of participants, funding of IVF and waiting times. These could be overcome in a RCT by using an adaptive design which would include a prospectively planned opportunity for modification of specified aspects of the study design based on interim analysis of the data, coordination of IVF treatments and endometriosis surgeries and international collaboration. Similar principles could be used for other questions in fertility where a traditional approach for randomised trials is not feasible.STUDY FUNDING/COMPETING INTEREST(S)Funding was received from the NHS Grampian R&D pump priming fund (RG14437-12). S.B. is Editor-in-Chief of HROPEN, and A.W.H. is Deputy Editor of HROPEN. Neither was involved in the review of this manuscript. L.S. reports grants from CSO and NIHR to do endometriosis research, outside the submitted work. K.C. reports grants from NIHR/HTA and CSO during the conduct of the study. J.H.e., A.W.H., J.D., S.B.r., K.B., G.B., J.H.u. and K.G. report no conflict of interest.

Audience segmentation as a strategy for enhancing the use of research registries for recruiting patients into clinical trials

IntroductionHealth research registries have great potential to increase awareness of research opportunities among diverse patient populations and reduce disparities in clinical trial accrual. However, little research has focused on patients’ intentions to participate in clinical trials once they are enrolled in the registry and their intentions to remain in the registry over time. MethodsPatients (N = 312) enrolled in a university-based health research registry (i.e., Consent2Share) in the southeastern region of the US participated in an online survey. ResultsHealth research registry knowledge, perceived values, self-efficacy, trust, having chronic health concerns, and consent recall were positively correlated with intentions to remain enrolled in the research registry and participate in future clinical trials. Health research registry consent recall had significant positive associations with registry knowledge, perceived values, trust, registry retention, and participating in future trials. ConclusionThe process of consenting patients to the health research registry is important for recruitment, registry retention, and participation in future clinical trials. We identified key points of emphasis to expand participation in research registries as a strategy to increase clinical trial enrollment, such as deploying precision messages and tailored interventions.

Post-surgical opioid stewardship programs across Australia and New Zealand: Current situation and future directions.

Community harm associated with prescription opioids is causing global concern, and post-hospital discharge prescribing is contributing to the problem. We surveyed anaesthetists in Australia and New Zealand to determine which opioid stewardship measures are currently in place, and to gauge interest in participating in future health services research on introducing an opioid stewardship bundle of care. A total of 87 anaesthetists from 87 hospitals were invited to participate, and 45 (52%) responded. The extent of nine current opioid stewardship measures reported was highly variable. One respondent (2%) reported no measures introduced at their hospital; 12 (27%) one to two measures; 16 (36%) three or four measures; 13 (29%) five to seven measures; and 3 (7%), all nine measures were in place. Respondents were often interested in being contacted about future trial participation ( n = 33, 73%); however, concerns regarding feasibility of introducing an opioid stewardship bundle of care were widespread ( n = 22, 49%). It is possible that the variability in Australian and New Zealand opioid stewardship practice is due, in part, to the current limited evidence base for the individual measures, in addition to challenges in research translation. We have found that interest in further research on opioid stewardship is high. Comprehensive, locally adapted, evidence-based opioid stewardship measures may increase the safety of patients and the community following opioid therapy.