Research Article| Volume 38, ISSUE 6, P1474-1484.e2, June 2016

Engaging Participants in Rare Disease Research: A Qualitative Study of Duchenne Muscular Dystrophy



      Clinical trials in Duchenne muscular dystrophy (DMD) are increasing due to technical advances in genetics, muscle biology and muscle imaging, and translational science. Yet the ability to achieve and measure progress in clinical trials in DMD is severely constrained by recruitment difficulties and low levels of patient and family participation. Clinical trials that do not have full inclusion of patients may affect how well new therapies perform in clinical practice.


      This study qualitatively investigated family-centered and clinician-based knowledge, attitudes, and perceptions of engagement in clinical research in DMD. Thirteen focus-group sessions (8 parent based and 5 clinician based) were held at 5 demographically and geographically diverse sites (Houston, Texas; Minneapolis, Minnesota; Pittsburgh, Pennsylvania; Sacramento, California; and Washington, DC). Thematic analysis was used for identifying patterns of meaning across the dataset.


      Totals of 28 parents and 33 clinicians participated in innovative and thoughtful discussions regarding clinical research in DMD and approaches to eliciting family engagement. Five overarching themes emerged from our qualitative data. The theme of Information discussed the lack of accessible and coherent information, as well as the overabundance of fragmented information. The theme of Conversation demonstrated the importance of having open and in-depth dialogue about research with families in eliciting trust and obligation toward the research process. The Barriers and Incentives themes presented the parents’ and clinicians’ views of the life-altering sacrifices that families make to participate in research and ways to reduce these burdens. Under the Solutions theme, parents and clinicians also suggested innovative ways to incentivize families and clinics and thoughtful solutions to increase family engagement in research.


      Effective recruitment for clinical studies in rare diseases requires a truly committed and engaged study team, as well as the necessary resources to overcome the multitude of barriers that families face. A clearly delineated recruitment plan, developed together with families, should be the standard operating procedure during clinical trial development. Protocols utilizing direct family-centered strategies for providing information and for recruiting research participants in studies in rare diseases are essential.

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        • Thorat C.
        • Xu K.
        • Freeman S.N.
        • et al.
        What the orphan drug act has done lately for children with rare diseases: a 10-year analysis.
        Pediatrics. 2012; 129: 516-521
      1. Vickers PJ. Challenges and opportunities in the treatment of rare diseases. Drug Discovery World, spring 2013. Retrieved from: Accessed on January 22, 2016.

        • Bladen C.L.
        • Rafferty K.
        • Straub V.
        • et al.
        The TREAT-NMD Duchenne muscular dystrophy registries: conceptions, design and utilization by industry and academia.
        Human Mut. 2013; 34: 1449-1457
        • Bushby K.
        • Lynn S.
        • Straub T.
        • Network T.-N.
        Collaborating to bring new therapies to the patient—the TREAT-NMD model.
        Acta Myologica. 2009; 28: 12-15
        • DeWard S.J.
        • Wilson A.
        • Bausell H.
        • et al.
        Practical aspects of recruitment and retention in clinical trials of rare genetic diseases: the phenylketonuria (PKU) experience.
        J Genet Counseling. 2014; 23: 20-28
        • Augustine E.F.
        • Adams H.R.
        • Mink J.W.
        Clinical trials in rare disease: challenges and opportunities.
        J Child Neurol. 2013; 28: 1142-1150
        • Emery A.E.
        Population frequencies of inherited neuromuscular diseases—a world survey.
        Neuromuscul Disord. 1990; 1: 19-29
      2. Centers for Disease Control and Prevention. Prevalence of Duchenne/Becker muscular dystrophy among males aged 5-24 years—four states, 2007.
        Morbidity and Mortality Weekly Report. 2009; 58: 1119-1122
        • Romitti P.A.
        • Zhu Y.
        • Puzhankara S.
        • et al.
        Prevalence of Duchenne and Becker muscular dystrophies in the United States.
        Pediatrics. 2015; 135: 513-521
        • Mendell J.R.
        • Schilling C.
        • Leslie N.
        • et al.
        Evidence-based path to newborn screening for Duchenne muscular dystrophy.
        Ann Neurol. 2012; 71: 304-313
        • Moat S.J.
        • Bradley D.M.
        • Salmon R.
        • et al.
        Newborn bloodspot screening for Duchenne muscular dystrophy: 21 years’ experience in Wales (UK).
        Eur J Hum Genet. 2013; 21: 1049-1053
      3. U.S. National Library of Medicine, Rockville, MD. Retrieved from Accessed September 14, 2015.

        • Griggs R.C.
        • Batshaw M.
        • Dunkle M.
        • et al.
        and Rare Diseases Clinical Research Network. Clinical research for rare disease: opportunities, challenges, and solutions.
        Mol Genet Metab. 2008; 96: 20-26
        • Peay H.L.
        • Tibben A.
        • Fisher T.
        • et al.
        Expectations and experiences of investigators and parents involved in a clinical trial for Duchenne/Becker muscular dystrophy.
        Clin Trials. 2014; 11: 77-85
        • Ford J.G.
        • Howerton M.W.
        • Lai G.Y.
        • et al.
        Barriers to recruiting underrepresented populations to cancer clinical trials: a systematic review.
        Cancer. 2008; 112: 228-242
        • Williams I.C.
        • Corbie-Smith G.
        Investigator beliefs and reported success in recruiting minority participants.
        Contemp Clin Trials. 2006; 27: 580-586
        • Yancey A.K.
        • Ortega A.N.
        • Kumanyika S.K.
        Effective recruitment and retention of minority research participants.
        Annu Rev Public Health. 2006; 27: 1-18
        • Schieppati A.
        • Henter J.-I.
        • Daina E.
        • Aperia A.
        Why rare diseases are an important medical and social issue.
        Lancet. 2008; 371: 2039-2041
      4. U.S. Department of Health and Human Services. U.S. Food and Drug Administration. Duchenne muscular dystrophy and related dystrophinopathies: developing drugs for treatment: Guidance for industry. Retrieved from Accessed August 14, 2015.

        • Rodino-Klapac L.R.
        • Mendell J.R.
        • Sahenk Z.
        Update on the treatment of Duchenne muscular dystrophy.
        Curr Neurol Neurosci Rep. 2013; 13: 332
        • Mendell J.R.
        • Rodino-Klapac L.R.
        • Sahenk Z.
        • et al.
        Eteplirsen for the treatment of Duchenne muscular dystrophy.
        Ann Neurol. 2003; 74: 637-647
        • Flanigan K.M.
        • Voit T.
        • Rosales X.Q.
        • et al.
        Pharmacokinetics and safety of single doses of drisapersen in non-ambulant subjects with Duchenne muscular dystrophy: results of a double blind randomized clinical trial.
        Neuromuscul Disord. 2013; 24: 16-24
        • Finkel R.S.
        • Flanigan K.M.
        • Wong B.
        • et al.
        Phase 2a study of Ataluren-mediated dystrophin production in patients with nonsense mutation Duchenne muscular dystrophy.
        PLoS One. 2013; 8: e81302
        • Ruegg U.T.
        Pharmacological prospects in the treatment of Duchenne muscular dystrophy.
        Curr Opin Neurol. 2013; 26: 577-584
        • Peay H.L.
        • Hollin I.
        • Fischer R.
        • Bridges J.F.
        A community-engaged approach to quantifying caregiver preferences for the benefits and risks of emerging therapies for Duchenne muscular dystrophy.
        Clin Ther. 2014; 36: 624-637
        • Guest G.
        • Bunce A.
        • Johnson L.
        How many interviews are enough? An experiment with data saturation and variability.
        Field Methods. 2006; 18: 59-82
        • Braun V.
        • Clarke V.
        Using thematic analysis in psychology.
        Qual Res Psychol. 2006; 3: 77-101
        • Shenton A.K.
        Strategies for ensuring trustworthiness in qualitative research projects.
        Educ Information. 2004; 22: 63-75
        • Boeije H.
        Analysis in Qualitative.
        Research. Sage, Thousand Oaks, CA2010
        • Lincoln Y.S.
        • Guba E.G.
        Inquiry. Sage, Beverly Hills, CA1985
        • Patton M.Q.
        Evaluation and Research Methods. 2nd ed. Sage, Newbury Park, CA1990
        • Richesson R.L.
        • Lee H.S.
        • Cuthbertson D.
        • et al.
        An automated communication system in a contact registry for persons with rare diseases: scalable tools for identifying and recruiting clinical research participants.
        Contemp Clin Trials. 2009; 30: 55-62
        • Cottler L.B.
        • McCloskey D.J.
        • Aguilar-Gaxiola S.
        • et al.
        Community needs, concerns, and perceptions about health research: findings from the clinical and translational science award sentinel network.
        Am J Public Health. 2013; 103: 1685-1692
        • Woolfall K.
        • Shilling V.
        • Hickey H.
        • et al.
        Parents’ agendas in paediatric clinical trial recruitment are different from researchers’ and often remain unvoiced: a qualitative study.
        PLoS One. 2013; 8: e67352
        • Jones L.
        • Wells K.
        Strategies for academic and clinician engagement in community-participatory partnered research.
        JAMA. 2007; 297: 407-410
        • Penckofer S.
        • Byrn M.
        • Mumby P.
        • Ferrans C.E.
        Improving subject recruitment, retention, and participation research through Peplau’s theory of interpersonal relations.
        Nurs Sci Q. 2011; 24: 146-151
        • Landfeldt E.
        • Lindgren P.
        • Bell C.F.
        • et al.
        The burden of Duchenne muscular dystrophy: an international, cross-sectional study.
        Neurology. 2014; 83: 529-536
        • Garralda M.E.
        • McConachie H.
        • Le Couteur A.
        • et al.
        Emotional impact of genetic trials in progressive paediatric disorders: a dose‐ranging exon‐skipping trial in Duchenne muscular dystrophy.
        Child Care Health Dev. 2013; 39: 449-455
        • Krueger R.A.
        Focus Groups: A Practical Guide for Applied Research. 3rd ed. Sage, Thousand Oaks, CA2000