Characterizing People with Sickle Cell Disease Who Share Attitudes Regarding Clinical Trial Participation: Findings from the Global LISTEN Survey

Background: Recruiting a sufficiently large and diverse pool of participants is critical to the success and global generalizability of clinical trials for sickle cell disease (SCD). The Learning and Insights into Sickle Cell Trial Experiences (LISTEN) Survey was a large international survey that investigated the global attitudes of people with SCD toward clinical trial participation. The survey identified several motivators and barriers that may affect a person's decision to participate in a clinical trial and highlighted the importance of individualized communication to improve access and recruitment. To understand survey responses, participants with similar attitudes were grouped into five distinct groups (archetypes) defined by their responses to questions about motivators and barriers to trial participation (James J et al. Blood 2023;142[Suppl 1]:2498).

Aim: To further characterize the five patient archetypes identified from the LISTEN Survey, to understand how a person's situation, impact of SCD on their lives and relationship with the healthcare system may affect their attitudes to clinical research participation.

Methods: Between October 2022 and August 2023, people with SCD (≥18 years old) from 17 countries completed the global LISTEN Survey. The survey included general background questions and assessed the perceived importance of factors that affect decisions to participate in a clinical trial. A hierarchical cluster analysis was used to identify patterns in responses to survey questions and organize into archetypes of people with SCD who shared similar attitudes. Five archetypes were identified and based on the responses could be described as treatment motivated (TM, primarily motivated by the opportunity to try a new treatment and less concerned about most barriers), practical minded (PM, primarily motivated by potential to better manage symptoms but concerned about practical barriers), care motivated (CM, primarily motivated by access to SCD specialists and investigational treatment after the trial), uncertain (UN, concerned about most barriers, in particular the risk that trial treatment may be inferior), and risk averse (RA, highly concerned about the risk of side effects). These archetypes were further characterized according to respondent demographics, regional distribution and treatment received. Differences in the distribution across the archetypes were assessed using a chi-squared test.

Results: A total of 1,145 adults with SCD (58% female) with a median age of 30 years completed the survey. Of these, 980 could be defined in an archetype: 22% TM, 14% PM, 6% CM, 23% UN and 20% RA.

Demographically, the five archetypes were well balanced for mean age (30-33 years), proportion living in rural areas (15-18%), burden of SCD (13-19% with high burden) and education level (33-37% completing higher education). Differences across the archetypes were observed for household income (65% TM, 64% PM, 78% CM, 53% UN and 53% RA had income in the lowest three brackets per country; p<0.05) and gender (61% TM, 63% PM, 45% CM, 61% UN and 53% RA were female; p<0.05).

The distribution of archetypes differed across geographical regions. Each archetype was represented in every region and no single archetype was dominant in a specific region. The archetype distributions by region were as follows: North America (n=222) 31% TM, 17% PM, 2% CM, 23% UN and 27% RA; South America (n=113) 25% TM, 19% PM, 7% CM, 33% UN and 16% RA; Europe (n=213) 23% TM, 12% PM, 4% CM, 34% UN and 28% RA; Sub-Saharan Africa (n=262) 25% TM, 20% PM, 10% CM, 28% UN and 17% RA; India (n=58) 43% TM, 16% PM, 3% CM, 2% UN and 36% RA; Middle East and North Africa (n=112) 16% TM, 15% PM, 15% CM, 32% UN and 21% RA.

The archetypes were well balanced for trust in healthcare professionals (60-66%) and whether respondents received blood transfusions (27-40%) or no treatment at all (1-4%). The proportion of respondents who received treatment to reduce or alleviate SCD symptoms differed across archetypes (64% TM, 73% PM, 82% CM, 68% UN and 67% RA; p<0.05).

Conclusions: Few differences in demographic and other characteristics were observed between groups of people with SCD defined by shared attitudes to clinical trial participation. This suggests that determining a person's attitude is complex and underscores the importance of adopting personalized approaches to understand what factors may motivate or discourage an individual to participate in a clinical trial.

Mahlangu:BioMarin: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novo Nordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Honoraria, Research Funding, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Spark: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. James:Novo Nordisk: Consultancy; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Vertex: Honoraria, Membership on an entity's Board of Directors or advisory committees. Andemariam:Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Fulcrum Therapeutics: Other: Data Safety Monitoring Board / Adjudication Committee; Hemanext: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; American Society of Hematology: Research Funding; Health Resources and Services Administration: Research Funding; bluebird bio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi Genzyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Vertex: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Global Blood Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Editas: Other: Data Safety Monitoring Board / Adjudication Committee; Connecticut Department of Public Health: Research Funding; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding; Afimmune: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Accordant: Consultancy, Membership on an entity's Board of Directors or advisory committees. Waller:Novo Nordisk Health Care A/G: Current Employment. Al-Behaisi:Novo Nordisk Health Care A/G: Current Employment. Morrell:Novo Nordisk: Consultancy, Research Funding. Colombatti:Vertex/Addmedica: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; Forma Therapeutics: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees. Trimnell:Agios Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Graphite Bio: Consultancy; Novo Nordisk: Consultancy; Pfizer: Consultancy; Bluebird Bio: Membership on an entity's Board of Directors or advisory committees; Vertex Pharmaceuticals: Consultancy; Sickle Cell Disease Committee - NHLBI: Membership on an entity's Board of Directors or advisory committees; Sickle Cell 101: Current Employment.