Development of a Clinical Global Impression of Change (CGI-C) and a Caregiver Global Impression of Change (CaGI-C) measure for ambulant individuals with Duchenne muscular dystrophy

Abstract

Background In clinical trials for rare diseases, such as Duchenne muscular dystrophy, clinical outcome assessments (COA) used to assess treatment benefit are often generic and may not be sensitive enough to detect change in specific patient populations. Thus, there is a need for disease specific COAs that track meaningful change among individuals. When developing such measures, input from clinicians, caregivers and patients is critical for assessing clinically relevant concepts and ensuring validity of the measure. Method The aim of this study was to develop two Duchenne-specific global impression items for use in clinical trials. The development of the Duchenne Clinical Global Impression of Change (CGI-C) and Caregiver Global Impression of Change (CaGI-C) was informed by findings from concept elicitation (CE) interviews with clinicians, caregivers and individuals with Duchenne. Through cognitive debriefing (CD) interviews, clinicians and caregivers evaluated draft CGI-C and CaGI-C items to ensure relevance and understanding of the items and instructions. Suggestions made during the CD interviews were incorporated into the finalized CGI-C and CaGI-C measures. Results The symptoms most frequently reported by clinicians, caregivers and individuals with Duchenne were muscle weakness, fatigue, cardiac difficulties and pain. Regarding physical functioning, all three populations noted that small changes in functional ability were meaningful, particularly when independence was impacted. Caregivers and clinicians reported that changes in speed, endurance and quality of movement were important, as was improvement in the ability of individuals to keep up with their peers. A change in the ability to complete everyday activities was also significant to families. These results were used to create two global impression of change items and instruction documents for use by clinicians (CGI-C) and caregivers (CaGI-C). Overall, both items were well understood by participants. The descriptions and examples developed from the CE interviews were reported to be relevant and appropriate for illustrating different levels of meaningful change in patients with Duchenne. Modifications were made based on caregiver and clinician CD feedback . Conclusions As part of a holistic measurement strategy, such COA can be incorporated into the clinical trial setting to assess global changes in relevant symptoms and functional impacts associated with Duchenne.

Safety, Tolerability, and Immunogenicity of the ACI-24 Vaccine in Adults With Down Syndrome

“…Assessment of adverse events (AEs), causality and cognitive and behavioral test results were subjective evaluations of study participants and were therefore not permitted to be conducted by the unblinded dispenser or administrator. Cognitive and behavioral tests included the Cambridge Neuropsychological Test Automated Battery (which measures brain function across 3 cognitive domains: visual memory, attention, and functional components of executive function), 25 the Brief Praxis Test (which screens for early features of dementia in adults with intellectual disability), 26 the Vineland II Adaptive Behavior Scales (which measure adaptive behaviors, including ability to cope with environmental changes, learn new skills, and dem-onstrate independence), 27 the Neuropsychiatric Inventory (which measures neuropsychiatric symptoms), 28 the Clinician Global Impression of Change (which measures symptom severity, treatment response, and treatment efficacy), 29 a global assessment of tolerability (performed by W.C.M., B.G.S., and A.D.B. ), and the Columbia-Suicide Severity Rating Scale (which measures suicidal ideation and behavior).…”

Therapeutic opportunities and clinical outcome measures in Duchenne muscular dystrophy

“…A subsequent study of Lilien et al [ 54 ] explored the digital biomarker in home-based monitoring using a wearable magneto-inertial sensor (VMIS) for 23 ambulant DMD patients. The study demonstrated that the device’s variables were correlated with the clinical validated scores and are sensitive to change in the DMD patients over 6 months, thus providing objective and reliable data.…”

A qualitative study to understand the Duchenne muscular dystrophy experience from the parent/patient perspective

“…Corticosteroids are the most common supportive treatment for DMD and are able to delay the loss of ambulation and may reduce the likelihood of needing spinal surgery to treat scoliosis [ 5 , 14 , 15 ]. More recently, exon-skipping treatments for patients with specific genotypes have been shown to attenuate pulmonary and ambulatory decline compared with mutation-matched natural history controls; however, only a small portion of the overall patient population (approximately 30%) can benefit from these advancements [ 16 – 22 ]. Emerging molecular and gene therapies designed to treat underlying disease process across the spectrum of possible genotypes in DMD are expected to change future DMD management [ 3 ].…”

“…To date, only a handful of qualitative studies have described the symptoms and impacts of DMD on patients [ 22 , 24 – 26 ]. These studies were limited to ambulatory boys and included relatively small sample sizes (< 10 patients and/or caregivers).…”