Patient and Caregiver Attitudes Towards Gene Therapy for Sickle Cell Disease: A Need for Partnership and Education

Background:

Fewer than 20% of patients with sickle cell disease (SCD) have access to curative matched sibling donor bone marrow transplantation (MSD-BMT). Development of novel therapies to ameliorate the serious morbidity and early mortality caused by SCD is a National Institute of Health research priority. Gene therapy for SCD has emerged as a promising approach in early-stage clinical trials approach with the potential to reach greater numbers of patients than MSD-BMT. Knowledge and attitudes of individuals with SCD towards this investigational new therapy and their willingness to participate in early-stage clinical trials have not been systematically described.

Methods:

Patients with SCD at least 13 years of age (n=66) and caregivers of children with SCD (n=38) were surveyed about knowledge, attitudes, and beliefs regarding gene therapy for SCD. Most questions utilized a 5-item Likert response scale while The Newest Vital Sign was used to assess health literacy. To explore attitudes around gene therapy in further detail, we identified a regionally diverse focus group comprised of 12 patients/caregivers with SCD from across the United States. We audio-recorded, transcribed verbatim, and analyzed five focus group discussions using thematic content analysis to identify salient themes related to attitudes towards gene therapy for SCD. Our goal was to identify the educational needs and preferences of this patient / caregiver stakeholder group.

Results:

Survey: Of the 104 survey respondents 96% identified as Black and 4% as Hispanic. Respondents were between 13-64 years (mean 29.6, Std Dev 11.9 years). HbSS and HbSC were the most common genotypes (61.5% and 24%, respectively). Only 4.8% of participants (N=5) felt "extremely knowledgeable" about gene therapy for SCD while most (63.4%) reported no/slight knowledge. We found no association between health literacy levels and gene therapy knowledge (p=0.361). Nearly 30% of participants reported that the risk of cancer as a potential side effect would "probably not prevent their enrollment" on a gene therapy trial while 48% said it "definitely/probably would preclude their participation". Most respondents had a neutral attitude regarding the safety of gene therapy for SCD and how good of a treatment it was (56.7% and 58.6%, respectively). Only a few respondents endorsed the idea that gene therapy was "unsafe" or "not a good treatment for SCD" (5.8% and 4.8% respectively). There was an association between increasing knowledge about gene therapy and agreement that it is safe (p=0.012) and a good treatment for SCD (p=0.031).

Focus Groups: Among the focus group participants, there was consensus that communication about gene therapy is suboptimal. Participants noted that clinicians frequently use medical jargon, do not tailor their approach to the individual patient/caregiver, and fail to adequately disclose important details. Focus group members desired more information about side effects and risks associated with conditioning chemotherapy, immunosuppression, risk of infertility, and hair loss. Participants, particularly parents of children with SCD, were worried about future unknown risks and described the enormity of the decision to enroll in an early-phase trial. Focus group members verbalized the need for inclusion of patients with SCD as partners during the informed consent/assent process and ideally, at the outset of the clinical trial design.

Conclusion:

Very few patients with SCD described feeling knowledgeable about gene therapy for SCD; a majority have neutral feelings about the safety and utility ("good treatment for SCD") of this new approach. Patient/caregiver-centered education about gene therapy in a manner that meets stakeholder informational needs is urgently needed. Given the temporary hold on lentiviral gene therapy trials for SCD (after some participants developed a myeloid neoplasm on an industry sponsored trial in February 2021) and the risk of cancer as a probable or definite barrier to enrollment in a gene therapy trial for many patients, transparency of information about these risks is essential. For the successful execution of novel trials in SCD, a community-based participatory research approach is vital.