Patient and public perspectives on cell and gene therapies: a systematic review

Cell and gene therapies hold immense promise for treating and potentially curing diseases by restoring function. However, these therapies are not without risks and present complex logistical, economic, ethical, and social challenges. Public and patient understanding and acceptance are crucial for successful implementation. This study addresses a significant gap in knowledge by systematically reviewing existing evidence on patient and public perspectives on cell and gene therapies to inform future research, education, and awareness-raising initiatives. The researchers aimed to understand the current level of public and patient knowledge, their acceptance of these therapies, their understanding of associated risks and benefits, and their information needs and sources. This understanding is vital for stakeholders, including potential funders and future recipients of these therapies, to engage in informed discussions and contribute to policy decisions.

The review screened over 10,000 titles and abstracts, ultimately selecting 35 publications for in-depth analysis. These publications encompassed a range of study designs and methodologies, including qualitative and quantitative approaches, investigating the perspectives of patients with various conditions (e.g., ischemic stroke, cystic fibrosis, sickle cell anemia, HIV), carers, and members of the general public. The literature review served as a foundation for identifying key themes and sub-themes related to patient and public understanding and acceptance of cell and gene therapies.

The researchers followed a systematic review methodology registered with PROSPERO (CRD42019138131) and adhered to PRISMA guidelines. They conducted a comprehensive search across multiple databases (Medline, Embase, CINAHL, PsycINFO, Cochrane Library, DARE, and others) using the SIGN patient issues filter. The search was limited to studies published since 2005. Studies were included if they focused on cell and gene therapies in clinical applications or trials and involved patients, carers, or the general public. Excluded studies included those focused solely on healthcare professionals or scientists, those solely on embryonic stem cell or germline therapy, and those focused on hematopoietic stem cell transplants. Two reviewers independently screened titles and abstracts, and full texts were evaluated. A narrative synthesis of findings was conducted due to the heterogeneity of included studies. Critical appraisal of included studies considered response rates, sample sizes, participant characteristics, study methods, and funding sources. Data extraction included participant demographics, health status, type of therapy, and study conclusions. The researchers did not conduct a meta-analysis or meta-synthesis due to the significant heterogeneity of the studies.

The review revealed four major themes: 1. **Knowledge and Understanding:** Patient knowledge of cell and gene therapies varied widely. Patients with specific conditions often had limited prior knowledge. Higher education and male gender were associated with greater knowledge. Patients often lacked understanding of cell sources, viral vectors, infection risks, and the distinction between research and clinical applications. They struggled to grasp the timeframes for research translation to clinical practice. 2. **Acceptance:** Acceptance of cell and gene therapies generally increased after information provision. Factors associated with greater acceptance included male gender, older age, higher education, longer disease duration, greater severity, and increased risk of death. Some patients focused on potential benefits, while others expressed concerns about uncertainties and risks. Parents of young children expressed more risk concerns than adults. Cost was a significant barrier; many patients considered a price far below the actual cost to be reasonable. 3. **Understanding of Risks and Benefits:** Patients often overestimated the benefits and underestimated the risks. Concerns about chemotherapy's side effects in conjunction with gene therapy were also prevalent. Patients consistently indicated a need for more information on potential benefits, risks, and logistical aspects of trial participation to inform benefit-risk assessments. 4. **Information Needs and Sources:** Patients desired more information regardless of demographics. They favored information from large, long-term studies with explicit risk and side effect reporting. They also desired more personalized information and clearer explanations of study eligibility. Television and other media were primary information sources, while physicians were considered most trustworthy, although patients often hesitated to discuss concerns directly with their doctors.

The findings highlight significant gaps in patient and public knowledge and understanding of cell and gene therapies. Therapeutic misconceptions and overestimation of benefits were common, potentially due to unbalanced media reporting. While physicians are seen as the most trustworthy information source, better communication strategies are needed to facilitate open discussions between patients and their physicians. Public trust in scientists and medical researchers is higher than in other groups. The ethical considerations of cell and gene therapies, particularly those involving embryonic cells and gene editing, are actively debated. High costs and access issues pose further challenges. Comparisons with oncology trials reveal similar patterns of therapeutic misestimation. The review also notes the influence of patient advocacy groups and public opinion on policy and funding decisions.

This review underscores the critical need for high-quality patient and public education on cell and gene therapies. Future research should focus on addressing knowledge gaps, improving risk communication, and exploring the experiences of patients who have undergone these therapies. Co-designing future research and educational materials with patient organizations is essential. Addressing the ethical, cost, and access challenges associated with these therapies is crucial for ensuring equitable access and successful implementation.

The review's findings are limited by the quality and heterogeneity of the included studies. Methodological issues, such as variable response rates, sample sizes, and reporting of participant characteristics, affect the generalizability of the findings. The absence of studies on the experiences of patients who have received these therapies also represents a gap in the evidence base. The relative lack of studies on gene therapy compared to cell therapy may also limit the comprehensive scope of this review.