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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.

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.

Patients want personalized information before surgery; most do not receive personalized risk estimates. Inadequate information contributes to poor experience and medicolegal complaints. We hypothesized that exposure to the Personalized Risk Evaluation and Decision Making in Preoperative Clinical Assessment (PREDICT) app, a personalized risk communication tool, would improve patient knowledge and satisfaction after anesthesiology consultations compared with standard care. We conducted a prospective clinical study (before-after design) and used patient-reported data to calculate personalized risks of morbidity, mortality, and expected length of stay using a locally calibrated National Surgical Quality Improvement Program risk calculator embedded in the PREDICT app. In the standard care (before) phase, the application’s materials and output were not available to participants; in the PREDICT app (after) phase, personalized risks were communicated. Our primary outcome was knowledge score after the anesthesiology consultation. Secondary outcomes included patient satisfaction, anxiety, feasibility, and acceptability. We included 183 participants (90 before; 93 after). Compared with standard care phase, the PREDICT app phase had higher post-consultation: knowledge of risks (14.3% higher; 95% confidence interval [CI], 6.5 to 22.0; P < 0.001) and satisfaction (0.8 points; 95% CI, 0.1 to 1.4; P = 0.03). Anxiety was unchanged (− 1.9%; 95% CI, − 4.2 to 0.5; P = 0.13). Acceptability was high for patients and anesthesiologists. Exposure to a patient-facing, personalized risk communication app improved knowledge of personalized risk and increased satisfaction for adults before elective inpatient surgery. www.clinicaltrials.gov (NCT03422133); registered 5 February 2018.

IntroductionChimeric antigen receptor T-cell (CAR-T) therapy is a class of immunotherapy. An economic evaluation conducted at an early stage of development of CAR-T therapy for treatment of adult relapsed or refractory acute lymphoblastic leukaemia could provide insight into factors contributing to the cost of treatment, the potential clinical benefits, and what the health system can afford. Traditionally, stakeholders are engaged in certain parts of health technology assessment processes, such as in the identification and selection of technologies, formulation of recommendations, and implementation of recommendations; however, little is known about processes for stakeholder engagement during the conduct of the assessment. This is especially the case for economic evaluations. Stakeholders, such as clinicians, policy-makers, patients, and their support networks, have insight into factors that can enhance the validity of an economic evaluation model. This research outlines a specific methodology for stakeholder engagement and represents an avenue to enhance health economic evaluations and support the use of these models to inform decision making for resource allocation. This protocol may inform a tailored framework for stakeholder engagement processes in future economic evaluation model development.Methods and analysisWe will involve clinicians, healthcare researchers, payers, and policy-makers, as well as patients and their support networks in the conduct and verification of an early economic evaluation of a novel health technology to incorporate stakeholder-generated knowledge. Three stakeholder-specific focus groups will be conducted using an online adaptation of the nominal group technique to elicit considerations from each. This study will use CAR-T therapy for adults with relapsed or refractory B-cell acute lymphoblastic leukaemia as a basis for investigating broader stakeholder engagement processes.Ethics and disseminationThis study received ethics approval from the Ottawa Hospital Research Institute Research Ethics Board (REB 20200320-01HT) and the results will be shared via conference presentations, peer-reviewed publications, and ongoing stakeholder engagement.

ObjectivesBench 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.DesignWe 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.ParticipantsCanadian adult patients diagnosed with haematological malignancies.ResultsIn 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).ConclusionUsing 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.

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.

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 for 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, 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

Patients want personalized information before surgery; most do not receive personalized risk estimates. Inadequate information contributes to poor experience and medicolegal complaints. We hypothesized that exposure to the Personalized Risk Evaluation and Decision Making in Preoperative Clinical Assessment (PREDICT) app, a personalized risk communication tool, would improve patient knowledge and satisfaction after anesthesiology consultations compared with standard care.We conducted a prospective clinical study (before-after design) and used patient-reported data to calculate personalized risks of morbidity, mortality, and expected length of stay using a locally calibrated National Surgical Quality Improvement Program risk calculator embedded in the PREDICT app. In the standard care (before) phase, the application's materials and output were not available to participants; in the PREDICT app (after) phase, personalized risks were communicated. Our primary outcome was knowledge score after the anesthesiology consultation. Secondary outcomes included patient satisfaction, anxiety, feasibility, and acceptability.We included 183 participants (90 before; 93 after). Compared with standard care phase, the PREDICT app phase had higher post-consultation: knowledge of risks (14.3% higher; 95% confidence interval [CI], 6.5 to 22.0; P0.001) and satisfaction (0.8 points; 95% CI, 0.1 to 1.4; P = 0.03). Anxiety was unchanged (- 1.9%; 95% CI, - 4.2 to 0.5; P = 0.13). Acceptability was high for patients and anesthesiologists.Exposure to a patient-facing, personalized risk communication app improved knowledge of personalized risk and increased satisfaction for adults before elective inpatient surgery.www.clinicaltrials.gov (NCT03422133); registered 5 February 2018.RéSUMé: OBJECTIF: Les patients veulent disposer d’informations personnalisées avant leur chirurgie, mais la plupart d’entre eux ne reçoivent pas d’estimations de leur risque personnalisées. Des informations inadéquates contribuent à une mauvaise expérience et à des plaintes médicolégales. Nous avons émis l’hypothèse qu’une exposition à l’application PREDICT (Personalized Risk Evaluation and Decision Making in Preoperative Clinical Assessment), un outil de communication du risque personnalisé, améliorerait les connaissances et la satisfaction des patients après leurs consultations en anesthésiologie comparativement à des soins standard. MéTHODE: Nous avons réalisé une étude clinique prospective (de type avant-après) et utilisé les données rapportées par les patients afin de calculer leur risque personnalisé de morbidité et de mortalité, ainsi que la durée de séjour anticipée à l’aide d’un calculateur de risque tiré du Programme national d’amélioration de la qualité chirurgicale que nous avons calibré localement et intégré à l’application PREDICT. Dans la phase de soins standard (avant), le contenu et les résultats de l’application n’étaient pas divulgués aux participants; dans la phase comportant l’application PREDICT (après), les risques personnalisés étaient communiqués. Notre critère d’évaluation principal était le score des connaissances des patients après la consultation en anesthésiologie. Les critères d’évaluation secondaires comprenaient la satisfaction des patients et leur niveau d’anxiété ainsi que la faisabilité et l’acceptabilité d’une telle approche. RéSULTATS: Nous avons inclus 183 participants (90 avant; 93 après). Comparativement à la phase de soins standard, la phase avec l’application PREDICT a démontré un niveau plus élevé de connaissances des risques post consultation (14,3 % plus élevé; intervalle de confiance [IC] 95 %, 6,5 à 22,0; P0,001) et de satisfaction (0,8 point; IC 95 %, 0,1 à 1,4; P = 0,03). L’anxiété est demeurée inchangée (− 1,9 %; IC 95 %, − 4,2 à 0,5; P = 0,13). L’acceptabilité était élevée, tant chez les patients que chez les anesthésiologistes. CONCLUSION: L’exposition des patients à une application de communication du risque personnalisé a amélioré leurs connaissances de leur risque personnalisé et augmenté la satisfaction des adultes avant une chirurgie non urgente et non ambulatoire. ENREGISTREMENT DE L’éTUDE: www.clinicaltrials.gov (NCT03422133); enregistrée le 5 février 2018.