To characterize Health-Related Quality of Life (HRQoL) in ambulant individuals with RYR1-RM and to determine if a qualitative PRO tool (subjective self-assessment) complements PROMIS and Neuro-QoL scales to detect changes in HRQoL in ambulant individuals with RYR1-RM post N-acetylcysteine (NAC) treatment.
The study used a mixed methods research (MMR) design applying methodological triangulation. Qualitative data were collected via semi-structured interviews using open-ended questions. Quantitative data were gathered through PROMIS and Neuro-QoL instruments. Additionally, qualitative data were transformed into quantitative data for subjective self-assessment and frequency analyses.
Qualitative results identified five domains and 33 subdomains as areas of interest. The most valuable were the importance of social impacts, the development of several coping strategies, both physical and psychological, and the identification of fatigue and weakness as key symptoms. Data transformation then categorized more than 3100 citations on frequency analyses, globally and by domain, visit, and participant. Regarding quantitative results, there was no clear evidence that any of the three PRO tools captured positive changes as a result of NAC treatment.
Qualitative results showed a comprehensive characterization of HRQoL in this population based on a symptom/patient-centered approach. These findings will inform future studies. Furthermore, given the similar findings across our multiple methods and endpoints, the introduction of MMR may be a valuable, complementary approach to clinical trials. MMR may be especially useful to incorporate in order to address and follow the FDA’s guidance and prioritization on the inclusion of affected individuals’ perspectives in clinical trials.
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The authors would like to thank all study participants for their sacrifice and commitment to be in this study. We also appreciate the support provided during the study by Ms. Karez Hawkins, Ms. Monique O. Shelton, and Dr. Joshua J. Todd (Neuromuscular Symptoms Unit, National Institute of Nursing Research, National Institutes of Health). We would like to thank Dr. Paule V. Joseph (Sensory Science and Metabolism Unit, National Institute of Nursing Research, National Institutes of Health) and Dr. Joan K. Austin (Department of Environments for Health, School of Nursing, Indiana University-Purdue University Indianapolis) for reviewing the manuscript. Also, we acknowledge the RYR1 Foundation for assistance with recruitment for this study.
This study was funded by the Intramural Programs of the National Institute of Nursing Research, National Institute of Neurological Disorders and Stroke, the National Institutes of Health Clinical Center, and Bench to Bedside Award (10-2013/Office of Rare Disease/NINR).
Conflict of interest
Dr. Carlos Capella-Peris, Ms. Mary M. Cosgrove, Ms. Irene C. Chrismer, Dr. Magalie Emile-Backer, Ms. M. Sonia Razaqyar, Mr. Jeffrey S. Elliott, Ms. Anna Kuo, and Dr. Paul G. Wakim have no conflicts of interest. Dr. Katherine G. Meilleur has received support from the RYR-1 Foundation, and an NIH Clinical Center Bench to Bedside Award (10-2013/Office of Rare Disease/NINR).
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Capella-Peris, C., Cosgrove, M.M., Chrismer, I.C. et al. Mixed methods analysis of Health-Related Quality of Life in ambulant individuals affected with RYR1-related myopathies pre-post-N-acetylcysteine therapy. Qual Life Res 29, 1641–1653 (2020). https://doi.org/10.1007/s11136-020-02428-2
- Neuromuscular disorders
- Natural history study
- Clinical trial
- Health-Related Quality of Life
- Mixed methods