Understanding potential barriers and enablers to a perioperative early phase cell therapy trial.

BACKGROUND AIMS: Early-phase cell therapy clinical trials depend on patient and physician involvement, yet barriers can impede their participation. METHODS: To optimize engagement for a planned cell therapy trial to prevent perioperative cardiac complications, the authors conducted semi-structured interviews with at-risk patients and physicians who could potentially be involved in the study. The authors used the theoretical domains framework to systematically identify potential barriers and enablers. RESULTS: Forty-one interviews were conducted to reach data saturation, and four overall potential barriers to participation (themes) were identified. Theme 1 emphasizes that patients and physicians need accessible information to better understand the benefits and risks of the novel therapy and trial procedures and to address misconceptions. Theme 2 underscores the need for clarity on whether the trial's primary purpose is safety or efficacy, as this may influence patient and physician decisions. Theme 3 recognizes the resource and logistic realities for patients (e.g., convenient follow-up appointments) and physicians (e.g., personnel to assist in trial procedures, competing priorities). Theme 4 describes the importance of social influences (e.g., physicians and family, peers/colleagues) that may affect decisions to participate and the importance of patient preferences (e.g., availability of physicians to discuss the trial, including caregivers in discussions). CONCLUSIONS: Prospectively addressing these issues may help optimize feasibility prior to conducting an expensive, resource-intensive trial.

Staff perspectives on barriers and enablers to implementing alternative source plasma eligibility criteria for gay, bisexual, and other men who have sex with men.

BACKGROUND: Canadian Blood Services introduced new eligibility criteria that allows some sexually active gay, bisexual, and other men who have sex with men (gbMSM) to donate source plasma, marking a significant change from time-based deferral criteria. We aimed to identify potential barriers and enablers to implementing the new criteria from the perspective of donor center staff. STUDY DESIGN AND METHODS: We conducted Theoretical Domains Framework-informed interviews with staff from two source plasma donation centers in Canada. RESULTS: We completed 28 interviews between June 2020 and April 2021. Three themes representing eight domains captured key tensions. Valuing inclusive eligibility criteria: staff support inclusive criteria; many were concerned the new criteria remained discriminatory. Investing in positive donor experiences: staff wished to foster positive donor experiences; however, they worried gbMSM donors would express anger and disappointment regarding the new criteria, staff would experience unease over using stigmatizing criteria and convey nonverbal cues of discomfort, and recurring plasma donors may behave inappropriately. Supporting education, training, and transparency of eligibility criteria: participants believed providing in-person training (i.e., to explain criteria rationale, address discomfort, practice responding to donor questions) and ensuring donors and the public were well-informed of the upcoming changes would improve implementation. DISCUSSION: Participant views emphasize the importance of supporting staff through training and transparent communication to optimize the delivery of world-class equitable care for a new cohort of donors who have previously been excluded from plasma donation. Findings inform which staff supports to consider to improve implementation as policies continue to shift internationally.

Addressing feasibility challenges to delivering intradialytic exercise interventions: a theory-informed qualitative study.

BACKGROUND: Intradialytic exercise (IDE) may improve physical function and health-related quality of life. However, incorporating IDE into standard hemodialysis care has been slow due to feasibility challenges. We conducted a multicenter qualitative feasibility study to identify potential barriers and enablers to IDE and generate potential solutions to these factors. METHODS: We conducted 43 semistructured interviews with healthcare providers and patients across 12 hospitals in Ontario, Canada. We used the Theoretical Domains Framework and directed content analysis to analyze the data. RESULTS: We identified eight relevant domains (knowledge, skills, beliefs about consequences, beliefs about capabilities, environmental context and resources, goals, social/professional role and identity, and social influences) represented by three overarching categories: knowledge, skills and expectations: lack of staff expertise to oversee exercise, uncertainty regarding exercise risks, benefits and patient interest, lack of knowledge regarding exercise eligibility; human, material and logistical resources: staff concerns regarding workload, perception that exercise professionals should supervise IDE, space, equipment and scheduling conflict concerns; and social dynamics of the unit: local champions and patient stories contribute to IDE sustainability. We developed a list of actionable solutions by mapping barriers and enablers to behavior change techniques. We also developed a feasibility checklist of 47 questions identifying key factors to address prior to IDE launch. CONCLUSIONS: Evidence-based solutions to identified barriers to and enablers of IDE and a feasibility checklist may help recruit and support units, staff and patients and address key challenges to the delivery of IDE in diverse clinical and research settings.

Building a Platform for Meaningful Patient Partnership to Accelerate "Bench-to-Bedside" Translation of Promising New Therapies.

Engaging patients as partners in the design and execution of early-phase clinical trials offers a unique opportunity to ensure patient perspectives are considered. Here we describe our experience partnering with four individuals with lived experience of blood cancer to co-develop documents and services to support participants of an early-phase trial. Through regular team meetings, patient partners co-developed a visual informed consent document and a non-technical summary of the informed consent document to facilitate participant understanding of trial procedures. Overall, patient partners highlighted important trial components that would not have been identified without their input.

So You Want to Give Stem Cells to Babies? Neonatologists and Parents' Views to Optimize Clinical Trials.

OBJECTIVE: To identify barriers and enablers that may influence parents' and neonatologists' participation in clinical trials of mesenchymal stromal cells for bronchopulmonary dysplasia. STUDY DESIGN: This qualitative study involved one-on-one semistructured interviews with parents of extremely preterm infants (n = 18) and neonatologists (n = 16). Interview guides and directed content analysis were framed using the theoretical domains framework, a tool specifically developed for implementation research to identify influences on behavior. RESULTS: Key barriers for parents included their lack of knowledge about clinical trial processes in general, stem cells, and concerns about their risks and side effects. Importantly, parents preferred to be approached for recruitment directly by a neonatologist, either before delivery or 1 or 2 weeks after birth. However, the majority of neonatologists felt that approaching parents was not part of their role. Neonatologists reported competing priorities, time commitment, costs, and lack of institutional support as significant barriers to their ability to recruit patients. CONCLUSIONS: By integrating stakeholders early into the development of a clinical trial of mesenchymal stromal cell therapy, we identified and can address important barriers to enrollment. Some identified barriers were unanticipated and could have compromised recruitment had they not been identified by this study. We suggest that this approach can be used more broadly for other early phase clinical trials in pediatrics.

Factors contributing to fidelity in a pilot trial of individualized resistant starches for pediatric inflammatory bowel disease: a fidelity study protocol.

BACKGROUND: The consumption of resistant starches is a promising adjuvant therapy for patients with inflammatory bowel disease. Rigorous evaluation of resistant starches in this setting depends on the intervention being delivered, received, and enacted as intended, that is, with fidelity. As part of a planned pilot trial, participants will be randomized to ingest resistant starches or a placebo. They will also be asked to collect stool samples and keep symptom and dose diaries to inform trial outcomes. We aim to identify potential factors impacting fidelity to the receipt and enactment of trial intervention and data collection activities from the perspective of patients and caregivers in the trial. Identifying fidelity barriers and enablers at the pilot trial phase of a clinical intervention may help to determine optimization processes when expanding to multiple sites in future trials. METHODS: We will conduct 15-30 semi-structured interviews with pilot trial participants (aged 8-17) and their caregivers. Trial participants will be approached for interviews approximately 6 months after the start of their trial participation. Personal projects analysis, a tool for understanding how individuals manage competing demands in their daily lives, will guide an in-depth exploration of how trial participants engage in activities related to intervention and data collection fidelity (ingesting resistant starches or placebo, collecting stool samples, keeping a symptom and dose diary) amidst the complexities of daily living. DISCUSSION: The present study will seek to explore and demonstrate how theory-informed fidelity assessments can be conducted alongside pilot trials to inform future multisite trials. Study results will clarify what factors may affect fidelity to trial intervention and data collection activities. Results may suggest what to modify to optimize the design and conduct, and ensure the integrity, of future multisite trials. Conducting process evaluations alongside clinical trials has the potential to improve our understanding of trial participant experiences. Results will provide a better understanding of how trial participants manage to engage in necessary trial activities along with other priorities.

Hematologists' barriers and enablers to screening and recruiting patients to a chimeric antigen receptor (CAR) T cell therapy trial: a theory-informed interview study.

BACKGROUND: Novel therapies often fail to reach the bedside due to low trial recruitment rates. Prior to conducting one of the first chimeric antigen receptor (CAR) T cell therapy trials in Canada, we used the Theoretical Domains Framework, a novel tool for identifying barriers and enablers to behavior change, to identify physician-related barriers and enablers to screening and recruiting patients for an early phase immunotherapy trial. METHODS: We conducted interviews with hematologists across Canada and used a directed content analysis to identify relevant domains reflecting the key factors that may affect screening and recruitment. RESULTS: In total, we interviewed 15 hematologists. Physicians expressed "cautious hope"; while expressing safety, feasibility, and screening criteria concerns, 14 out of 15 hematologists intended to screen for the trial (domains: knowledge, goals, beliefs about consequences, intentions). Physicians underscored the "challenging contexts," identifying resources, workload, forgetting, and patient wait times to receive CAR T cells as key practical barriers to screening (domains: environmental context and resources, memory, attention and decision-making, behavioral regulation). They also highlighted "variability in roles and procedures" that may lead to missed trial candidates (domain: social and professional role). Left unaddressed, these barriers may undermine trial recruitment. CONCLUSIONS: This study is among the first to use the Theoretical Domains Framework from the physician perspective to identify recruitment challenges to early phase trials and demonstrates the value of this approach for identifying barriers to screening and recruitment that may not otherwise have been elicited. This approach can optimize trial procedures and may serve to inform future promising early phase cancer therapy trials. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03765177 . Registered on December 5, 2018.

Navigating choice in the face of uncertainty: using a theory informed qualitative approach to identifying potential patient barriers and enablers to participating in an early phase chimeric antigen receptor T (CAR-T) cell therapy trial.

OBJECTIVES: Bench to bedside translation of groundbreaking treatments like chimeric antigen receptor T (CAR-T) cell therapy depends on patient participation in early phase trials. Unfortunately, many novel therapies fail to be adequately evaluated due to low recruitment rates, which slows patient access to emerging treatments. Using the Theoretical Domains Framework (TDF), we sought to identify potential patient barriers and enablers to participating in an early phase CAR-T cell therapy trial. DESIGN: We used qualitative semistructured interviews to identify potential barriers and enablers to patients' hypothetical participation in an early phase CAR-T cell therapy trial. We used the TDF and directed content analysis to identify relevant domains based on frequency, relevance and the presence of conflicting beliefs. PARTICIPANTS: Canadian adult patients diagnosed with haematological malignancies. RESULTS: In total, we interviewed 13 participants (8 women, 5 men). Participants ranged in age from 18 to 73 (median=56) and had been living with haematological cancer from a few months to several years. We found participants were unfamiliar with CAR-T cell therapy but wished to know more about treatment safety, efficacy and trial logistics (domains: knowledge, beliefs about consequences). They were motivated by altruistic considerations, though many prioritised personal health benefits despite recognising the goals (ie, establishing safety) of early phase clinical trials (domains: goals, intentions). Every participant valued receiving medical advice from their haematologists and oncologists, though some preferred impartial medical experts to inform their decision making (domain: social influences). Finally, participants indicated that improving access to financial and social supports would improve their trial participation experience (domain: environmental context and resources). CONCLUSION: Using the TDF allowed us to identify factors that might undermine participation to a CAR-T cell therapy trial and to optimise recruitment processes by considering patient perspectives to taking part in early phase trials.Trial regestration: NCT03765177; Pre-results.

Partnering with patients to get better outcomes with chimeric antigen receptor T-cell therapy: towards engagement of patients in early phase trials.

AIM: Though patient engagement in clinical research is growing, recent reports suggest few clinical trials report on such activities. To address this gap, we describe our approach to patient engagement in the development of a clinical trial protocol to assess a new immunotherapy for blood cancer (chimeric antigen receptor T-cell therapy, CAR-T cell therapy). METHODS: Our team developed a clinical trial protocol by working with patient partners from inception. Two patient partners with lived blood cancer experience were identified through referrals from our team's professional network and patient organization contacts. Our patient partners were onboarded to the team and engaged in several studies conducted to develop the clinical trial protocol, including a systematic review of the existing literature on the therapy, patient interviews and a survey to obtain perspectives on barriers and enablers to participating in the trial, an early economic analysis, and a retrospective cohort study. RESULTS: Engaging patient partners enhanced our research in ways that would not have otherwise occurred. By selecting patient important outcomes for data collection, our partners helped flag that quality of life and health utility measures have not been reported in previous CAR-T cell therapy trials for blood cancer. Our partners also co-developed a non-technical summary of the systematic review that summarized results in an accessible manner. Our patient partners reviewed interview and survey questions, to improve the language and appropriateness; provided recruitment suggestions; and provided a patient perspective on the results, thereby confirming the importance of findings. Input was also obtained on costs for the early economic analysis. Our patient partners identified costs that may be a burden to both patients and caregivers during a trial and helped to confirm that the overall structure of the economic model reflected the patient care pathway. Our patient partners also shared their diagnosis and treatment stories, which helped to provide the research team with insight into this experience. CONCLUSIONS: Contributions by our patient partners were invaluable to each component study, as well as the overall development of the trial protocol. We plan to use this approach in the future in order to meaningfully engage patients in the development of other clinical trials; we also hope that by reporting our methods this will help other research teams to do the same. TRIAL REGISTRATION: Affiliated with the development of NCT03765177.

What are potential barriers and enablers to patient and physician participation in Canadian cell therapy trials for stroke? A stakeholder interview study.

OBJECTIVES: Early phase cell therapy trials face many barriers to successful, timely completion. To optimise the conduct of a planned clinical trial of mesenchymal stem cell (MSC) therapy for chronic stroke, we sought patient and physician views on possible barriers and enablers that may influence their participation. DESIGN: Semistructured interview study. SETTING: Patients were recruited from three rehabilitation centres in Ontario, Canada; physicians were recruited from across Canada through snowball sampling. PARTICIPANTS: Thirteen chronic stroke patients (patients who had experienced a stroke at least 3 months prior; 10 male, 3 female) and 15 physicians (stroke physiatrists; 9 male, 6 female) participated in our interview study. Data adequacy was reached after 13 patient interviews and 13 physician interviews. METHODS: Interview guides and directed content analysis were based on the Theoretical Domains Framework (TDF). Interviews were coded, and relevant themes were identified. RESULTS: Most patients were optimistic about participating in an MSC therapy clinical trial, and many expressed interest in participating, even if it was a randomised controlled trial with the possibility of being allocated to a placebo group. However, the method of administration of cells (intravascular preferred to intracerebral) and goal of the trial (efficacy preferred to safety) may influence their intention to participate. All physicians expressed interest in screening for the trial, though many stated they were less motivated to contribute to a safety trial. Physicians also identified several time-related barriers and the need for resources to ensure feasibility. CONCLUSIONS: This novel application of the TDF helped identify key potential barriers and enablers prior to conducting a clinical trial of MSC therapy for stroke. This will be used to refine the design and conduct of our trial. A similar approach may be adopted by other investigators considering early phase cell therapy trials.