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

Abstract

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.

Theory-guided interviews identified behavioral barriers and enablers to healthcare professionals recruiting participants to maternity trials

“…The results of this mapping exercise were then discussed with all members of the research team to ensure fidelity of the codebook. Similar to methods described in a recent study [13] , subthemes were compared across relevant domains in order to identify any relevant patterns…”

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

“…Though the TDF is used widely across implementation research to study health care provider behaviors and behavior change [13], application for the purposes of informing development of a clinical trial is relatively novel. Members of the authors' team have taken this approach to assess potential barriers to and enablers for trials in several different areas, including individualized temperature-reduced hemodialysis [14], MSC trials for bronchopulmonary dysplasia in neonates [15] and chronic stroke [16] and chimeric antigen receptor T-cell therapy for hematologic malignancies [21,22]. Similar to findings in the authors' current study, this approach has been successful in identifying modifiable factors to better align trials with patient needs and preferences (e.g., information needs, preferences on who to speak with about the trial, method of therapy administration) as well as potential barriers and resource needs for physicians (e.g., workload and time constraints, additional staff to assist).…”

“…The TDF is well established in implementation research, most typically to investigate implementation barriers and enablers, to inform the development of interventions and to develop process evaluations [13,17,18]. Recently, the authors' team and collaborators used the TDF to investigate barriers and enablers to patient participation and clinician involvement in early-phase clinical trials [15,16,21,22].…”

The Development of Theory-Informed Participant-Centred Interventions to Maximise Participant Retention in Randomised Controlled Trials

“…There are emerging examples in the literature of (components of) similar behavioural approaches being used to target trial recruitment to diagnose the problem but also some that extend to the development of theory-informed interventions, in this case targeting urologists to recruit from underserved populations in oncology [19][20][21][22]. Encouraging other trial teams to conceptualise trial problems as behaviours and develop behaviour change interventions targeting trial retention will allow the generation of a cumulative evidence base.…”