Hopes, Expectations, Misconceptions: Adolescents and Parents Reflect On Gene Therapy Research

Background and Purpose: Duchenne muscular dystrophy (DMD) is a degenerative disease with no cure, affecting boys causing progressive muscle deterioration leading to early death (early 20s). Gene transfer is an experimental approach to treating DMD raising complex ethical issues related to risks, benefits, and decision making. For example, early phase clinical trials are not designed to benefit participants, yet participation may have risks. What factors other than clinical benefit are relevant to parents and adolescents? Should adolescents control their own research participation decisions? There has been no prior systematic investigation of the views of DMD adolescents and their parents about gene transfer and ethical issues of research participation. The primary goal of this study was to elicit the perspectives of the DMD community on the risks and benefits of prospective approaches to gene therapy so that their views can inform the ethical design and conduct of genetic research and other trials.

Method: This qualitative, exploratory study used semi-structured interviews to generate in-depth responses from participants about their perceptions of ethical issues and decision making about gene transfer research. Participants were recruited at the 2009 conference of the Parent Project Muscular Dystrophy (PPMD), by invitation posted on the PPMD Community and DuchenneConnect websites, and from the neuromuscular clinic at a northeastern pediatric hospital. Twenty-two parents (17 mothers, 5 fathers) and 10 adolescents participated. Interviews were conducted in person (N=11) and by telephone (N=21), digitally recorded, and transcribed verbatim. Following a grounded theory approach, after eight transcripts underwent a process of open coding by two coders, broad categories were identified to capture important themes from participant responses. Using Nvivo, ongoing analysis, with resolution of coding discrepancies by consensus, produced a comprehensive coding scheme in which major categories were divided into specific sub-groupings and analyzed in relation to one another.

Results: Decision making for research participation is influenced by many factors, some of which raise challenging ethical issues for researchers. For many parents, clinical trials represent hope, even among parents who recognize participation will not provide therapeutic benefit. In addition, a boy's level of impairment appears to play a significant role for many parents in their perception of acceptable risk and uncertainty. Parents of less-impaired children tend to believe they will accept greater risks of participation later when there is “nothing left to lose.” However, parents of more impaired boys and the boys themselves tend to focus on immediate quality of life and don't want participation to jeopardize it. Finally, parents with little research experience tend to under-appreciate the burdens of participation that those with experience recount.

Conclusions and Implications: This study provides new understandings for social work researchers and practitioners, working in gene transfer settings, about complex ethical decisions for parents and adolescents with fatal diseases, who contemplate participation in gene therapy research in DSM and other areas. Factors influencing research participation decisions for these parents/adolescents include more than a rational process of weighing risks against benefits, but rather consideration of hopes, expectations, and perceptions of quality of life.