M 15: Identifying Symptoms and Functional Impact Reported by Persons with Multiple Sclerosis: A Qualitative Literature Review
U.S. Food and Drug Administration United States
A systematic literature review was conducted to identify patient-reported symptoms and functional impact of multiple sclerosis (MS) to inform selection of content/concepts that should be included in patient-reported outcome (PRO) measures used to support efficacy endpoints in MS treatment trials.
Searches were conducted in MEDLINE and PsycINFO using a pre-determined search strategy. Abstracts were included for full-text review if they met the following criteria: (1) referenced the use of qualitative methods, and (2) identified MS symptoms and functional impact from a patient’s perspective.
Sixteen articles identified key symptoms and/or functional impact relating to the patients’ experience with MS. Standard qualitative methods of face-to-face/telephone interviews (n=10), focus groups (n=5), and written, open-ended questions (n=1) were used to obtain data in the reviewed studies. Six studies indicated the MS subtype(s) of the study population: relapsing-remitting MS (n=6); primary-progressive MS (n=3); secondary-progressive MS (n=4). Twelve major symptoms (as acknowledged by the National MS Society as “more common” symptoms) were identified within the studies: depression (n=7); pain (n=9); numbness/tingling (n=9); sexual dysfunction (n=5); fatigue (n=14); spasticity (n=4); lower extremity impairment/walking impairment (n=13); upper extremity impairment (n=5); bowel/bladder problems (n=6); vision problems (n=7); dizziness/vertigo (n=2); cognitive impairments (n=7). Other less frequently observed symptoms such as sleeping problems, headaches, speech problems, heat intolerance, and emotional problems were indicated. Four main domains in relation to functional impact due to MS were reported: social life (n=9); work life (n=6); relationships and family (n=12); independence (n=6).
The key symptoms reported by patients in the published studies were concordant with those identified by the National MS Society. Many of the symptoms identified were reported as co-occurring (e.g., spasticity and pain) causing further distress according to patients. In addition, these symptoms impacted patients in their daily lives which resulted in their inability to participate in social and work activities, live independently, and optimally maintain relationships. These findings provide a framework to assist in the development or selection of PRO instruments used for assessing symptoms and functional impact as part of an efficacy endpoint strategy for clinical trials in MS patients. Additional qualitative research will be needed to determine whether the symptoms and functional impacts differ based on patients’ specific MS subtype. This review was conducted for and supported by the Patient-Reported Outcome Consortium’s Multiple Sclerosis Working Group at the Critical Path Institute.