Glenn Phillips

Background: Chronic autoimmune diseases such as Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), Multifocal Motor Neuropathy (MMN), and Thyroid Eye Disease (TED) impose a considerable burden on affected individuals. Patient-reported outcome measures (PROMs)—both disease-specific and generic—are widely used to assess functioning, quality of life, and treatment effects in these populations. However, most PROMs currently lack reference values derived from the general population, limiting the interpretability of patient scores. Objective: The GENESIS (GENEral population normS—An International Survey) study aims to establish general population norms for a range of PROMs used in CIDP, MMN, and TED across six countries: Germany, Italy, Japan, Spain, the United Kingdom, and the United States. These norms will improve patient score interpretation and help quantify unmet needs in patients with these rare autoimmune diseases. Methods: GENESIS is an observational, cross-sectional, online survey of the adult general population (N=21,000). Participants will be recruited to be representative by age, gender, region, and education. The survey includes validated instruments such as the EQ-5D-5L, I-RODS, MMN-RODS, CAP-PRI, GO-QoL, BPI-SF, RT-FSS, FACIT-Fatigue, HADS, and WPAI, along with items on demographics, caregiver need, and healthcare utilization. To reduce respondent burden, participants will be randomized into two groups, each completing a subset of the full questionnaire. A subset of respondents (n=2,333) will be re-surveyed after two months to support psychometric validation. Data will be analyzed descriptively to generate normative values for each PROM by country and in aggregate. Results and Dissemination: Data collection is scheduled to begin in August 2025, with results expected by Q4 2025. Findings will be disseminated via peer-reviewed publications and conference presentations. Conclusion: GENESIS will provide foundational normative data across six countries for PROMs commonly used in rare autoimmune diseases. These data will support more meaningful interpretation of PROM scores in both clinical practice and research settings.

Introduction: Prescription drug list prices, often cited in policy discussions, do not account for rebates negotiated between manufacturers and payers. Methods: This study examines factors influencing rebates in the US, focusing on specialty drugs – i.e., high priced therapies (often biologics) for which payers issue specific coverage policies. Rebate data came from SSR Health and drug attributes from the Tufts Medical Center Specialty Drug Evidence and Coverage Database. We stratified rebate data by drug type and characteristics. Results: We identified 161 drugs found in SSR Health and SPEC as of December 2023. We found that rebates vary substantially across drugs (median of 27%, IQR 16-53%). Biosimilar and originator drugs have the highest, most variable rebates (median of 71%, IQR 53-79%), while rebates for cancer treatments and orphan drugs are lower (medians of 19% and 23%, respectively) and vary less (IQR of 12-28% and 14-29%, respectively). Drugs that face more competition from alternative options within the same therapeutic class, are self- administered, or received Food and Drug Administration (FDA) approval further in the past have higher rebates. Conclusion: Our findings indicate that rebates are sizeable and vary along several dimensions, many relating to market competition, complicating policy discussions around drug pricing.

Background: This study aimed to estimate population norms in the US, Canada, UK, Italy, Spain, Germany, The Netherlands, and Belgium for the EQ-5D-5-L with six bolt-on dimensions (vision, breathing, tiredness, sleep, social relationships, self-confidence), and for the Health Utilities Index-Mark 3 (HUI-3). Methods: A digital study was conducted among 9,000 general population participants, representative of age, sex, education, and region within each country. Data collection included demographics, health conditions, EQ-5D-5-L and bolt-ons, and the HUI-3. National population norms were calculated for each dimension and for utility values. Testing for differences between subgroups was performed with a Generalized Linear Model. Results: The proportion of respondents reporting severe-to-extreme problems at dimension level was highest on the EQ-5D-5-L dimensions pain/discomfort (5.5%) and anxiety/depression (5.6%), and on the HUI-3 dimensions pain (5.7%), emotion (5.4%), and cognition (4.1%). Severe-to-extreme problems on the EQ-5D-5-L bolt-on dimensions were social relationships (8.0%), sleep (7.6%), tiredness (7.4%), self-confidence (5.1%), vision (3.7%), and breathing (2.0%). Mean EQ-5D-5-L utility values for all countries combined displayed a U-shape by age and ranged between 0.819 and 0.871, whereas HUI-3 utility values ranged between 0.717 and 0.768 without a clear pattern. The impact of age by sex on EQ-5D-5-L utility values was country-specific. HUI-3 utilities did not show a linear trend by age, and no difference was found by sex. Italy had the highest mean EQ-5D-5-L utility values, while the Netherlands and Spain had the highest values according to the HUI-3. The lowest utility values were observed in the UK, for both instruments. Utility values differed significantly by education, employment, place of residence, needing a caregiver, being on sick leave and having health conditions such as dementia, MS, depression, rheumatoid arthritis, systemic lupus erythematosus and heart failure. Conclusions: Important differences in reporting problems and in utility values were found between countries and subgroups, highlighting the need for country-specific population norms.

Introduction/aims: Informal caregivers play an important role in the lives of people with Myasthenia gravis (MG). This study aims to assess the caregiver burden (CB) experienced by caregivers of MG patients. Methods: A cross-sectional study design collected patient and caregiver data in Germany, Italy, Spain, the UK, and France. The Zarit Burden Interview (ZBI-22), EQ-5D-5L and bolt-on questions, and PROMIS Global Health-10 were used to measure CB and overall health-related quality of life (HRQoL). Results: Caregivers (N = 69) reported a mean ZBI-22 score of 24.3, with 40.6% reporting no burden, 47.8% mild-to-moderate burden, 8.7% moderate-to-severe burden, and 2.9% severe burden. The most impacted ZBI-22 dimensions were “losing control over one’s life”, “financial burden” and “relationships with relatives”. Based on a generic health-related quality of life scale (EQ-5D-5L plus bolt-on questions), the dimensions that were more frequently reported among MG caregivers to cause moderate-to-extreme problems were: tiredness (43%), self-confidence (32%), and anxiety/depression (28%). EQ-5D-5L utilities (values from -1 to 1, reflecting overall HRQoL) were negatively associated with higher ZBI-22 scores (little or no burden: 0.942, mild-to-moderate burden: 0.864, moderate-to-severe burden: 0.783, severe burden: 0.570). Regarding PROMIS-10 items, 48% of caregivers reported often/always being bothered by anxiety, depression, or irritation; 47% reported being not at all or little able to carry out daily activities; and 37% reported having (very) severe fatigue. Conclusion: Informal caregivers of MG patients experience a substantial burden, impacting their physical, emotional, and financial well-being. Findings highlight the need for tailored interventions to alleviate CB and enhance the caregivers’ overall HRQoL.

This study protocol outlines the Population Norms Study (POPUP), a multinational digital survey aimed at establishing general population norms for medical resource use, comorbidities, sick leave, caregiver support, quality of life, and functioning across eight countries: United States (US), Canada, United Kingdom (UK), the Netherlands, Belgium, Spain, Italy, and Germany. Data will be collected through an online self-administered survey in two waves: the first in Q1 2021 and the second in Q1 2023, when first-wave responders will be recontacted. A total of 15,500 responses will be gathered across both waves: 9,000 in the first wave and 4,500 re-contacts in the second, with an additional 2,000 new contacts if needed. Representative panels will be recruited by a research company from each country based on age, gender, education, and region. Participants will complete the survey after providing informed consent. No personal identifiers will be recorded. The observational study involves no medical interventions, drugs, or devices, and will be submitted for Ethical Committee approval in each country. Descriptive statistics will be used for data analysis. The results are expected to provide a baseline for comparing health outcomes in specific patient populations and quantifying disease burden.

Introduction Myasthenia gravis (MG) is a rare neuromuscular disorder marked by a variable combination of weakness of eye, bulbar, respiratory, axial, and limb muscles. This study compared the experience of people with MG regarding breathing, fatigue, sleep, pain/discomfort, mental health, and usual activities with the general population. Methods The MyRealWorld-MG digital, multinational study enrolled patients with MG and collected demographics, PROMIS-Dyspnea, PROMIS-Sleep Disturbance, FACIT-Fatigue, EQ-5D-5L, Health Utilities Index (HUI-3), Hospital Anxiety and Depression Scale (HADS), MG-Activities of Daily Living (MG-ADL), and MG-Quality-of-Life (MG-QoL-15r). Comparisons with the general population were based on PROMIS population norms, published literature, or on data from a digital, multinational, observational study which enrolled a representative sample of the general population (POPUP). Results In MyRealWorld-MG (N = 2074), patients experienced higher intensity, frequency, and duration of PROMIS shortness of breath than a US population (p < 0.0001). Patients with MG had higher PROMIS-Sleep Disturbance scores than POPUP (53.7 vs 50.0, p < 0.0001), and 54.9% of patients had clinically severe FACIT-Fatigue scores vs 6.8% in POPUP (p < 0.0001). Among patients with MG, 69.6% and 18.5% had moderate-to-severe HADS-Anxiety and HADS-Depression compared to 20.3% and 6.9% in POPUP (p < 0.001). Statistically significant and strong associations were found between fatigue, sleep, dyspnea, usual activities, and emotions. All outcomes worsened with more severe disease. Conclusion A considerable burden was observed in this comparison of breathing, sleep, fatigue, mental health, and usual activities between patients with MG and the general population, using data from two international studies and published population norms. Even mildly affected patients had significantly worse outcomes than the general population.

Introduction Myasthenia gravis (MG) is a neuromuscular disease causing extreme muscular fatigue, triggering problems with vision, swallowing, speech, mobility, dexterity, and breathing. This analysis intended to estimate the health-related quality-of-life impact, the medical burden, and the need for caregiver help of people diagnosed with MG. Methods MyRealWorld-MG (MRW) is an observational study among adults diagnosed with MG in 9 countries. The General Population Norms (POPUP) observational study enrolled representative members of the general population in 8 countries. In both digital studies, respondents entered personal characteristics and provided data on medical conditions, EQ-5D-5L, HUI3, MG-Activities of Daily Living (MG-ADL), sick leave, caregiver help, and medical care utilization. Results In MRW (n = 1859), 58.4% of respondents had moderate-to-severe MG. Average utility values were lower in MRW versus POPUP (0.739 vs. 0.843 for EQ-5D-5L; 0.493 vs. 0.746 for HUI3), and declined with more severe disease (0.872, 0.707, 0.511 EQ-5D-5L utilities and 0.695, 0.443, 0.168 HUI3 utilities for mild, moderate, and severe MG, respectively). Taking sick leave in the past month was 2.6 times more frequent among people diagnosed with MG compared to the general population (34.4% vs. 13.2%) and four times more people diagnosed with MG reported needing help from a caregiver (34.8% vs. 8.3%). Use of medical care was twice as likely in MRW in comparison with POPUP (51.9% vs. 24.6%). Conclusion This direct comparison of people diagnosed with MG and the general population using two large international studies revealed significant negative impact of MG. Results were consistent across all outcomes, in all countries.