Internal Psychometric Validation of an International Burden of Illness Survey for Idiopathic Multicentric Castleman Disease.

INTRODUCTION: Idiopathic multicentric Castleman disease (iMCD) is a rare, chronic, debilitating lymphoproliferative disorder where the mainstay of treatment is symptom management. Our recent international patient survey showed that patients with iMCD have a high symptom burden that has a significant negative patient-reported impact on several aspects of daily life. As part of our ongoing work towards the development of an iMCD symptom burden scale, assessing the survey's psychometric properties is a critical step in understanding its adequacy, relevance, and usefulness. As iMCD is a rare disease, there are challenges to conducting such psychometric analyses which we describe. METHODS: As part of the exploratory psychometric analysis, three a priori hypothesis sets (HS) were generated by interviewing an iMCD-experienced clinician, a patient, and a caregiver to explore the iMCD patient survey's internal construct validity, given no gold standard iMCD measure exists for external construct validation. HS-1 hypothesized that a convergent or discriminant relationship exists with the patients' self-assessment of symptom effect on daily life between two potentially related or unrelated symptoms, respectively. HS-2 hypothesized that having a greater number of symptoms has a positive convergent relationship with the patients' assessment of symptoms' effect on daily life. Finally, HS-3 hypothesized that patients receiving treatment versus no treatment was associated with patients reporting less effect of symptom burden on their daily life. Spearman's rank absolute correlation strength (ACS) was used for HS-1 and HS-2 (convergent relationship, ACS ≥ 0.3 and p value < 0.05; divergent relationship, ACS < 0.3), and Cohen's d to quantify standardized absolute effect sizes (AES) for HS-3 (AES ≥ 0.5 and p value < 0.05). RESULTS: Our analyses partially supported HS-1. None of the three positive convergent relationships were supported. Of the six discriminant relationships, only dizziness with impaired cognitive function and tiredness with dizziness were supported. HS-2 analyses showed there was convergent validity between the number of symptoms and their effect on aspects of daily life. HS-3 analyses did not provide evidence to support the hypothesis. CONCLUSION: These internal psychometric construct analyses provide initial support for the bespoke iMCD patient survey and will guide additional work towards the development of the first iMCD-specific symptom burden scale.

Symptom burden in patients with idiopathic multicentric Castleman disease and its impact on daily life: an international patient and caregiver survey.

Background: Idiopathic Multicentric Castleman Disease (iMCD) is a rare inflammatory lymphoproliferative disorder with heterogenous clinical presentations. The symptomatology in iMCD patients remains poorly understood. The aim of this study was to identify the type, frequency and severity of iMCD-related symptoms and the impact of these on the daily lives of iMCD patients and informal-caregivers. Methods: We conducted two bespoke 45-question online surveys for iMCD patients and informal-caregivers of patients recruited from the US, UK, Australia and Canada between April 14 and November 8, 2021. Descriptive data was collected, and a Likert scale was used to quantify the impact of symptoms on various aspects of daily life. Ordinal logistic regression analysis was used to determine associations between age, gender, employment status and symptom burden with aspects of daily life. Findings: Eligible respondents included 51 iMCD patients and 11 informal-caregivers. Patients reported up to 27 unique symptoms, the mean number of symptoms experienced by a patient was 6.7 (range 0-22 symptoms). Most symptoms had a moderate to severe impact on patients' daily lives, with 'pain/discomfort', 'ability to travel', and 'sexual functioning' being the most impacted. iMCD patient characteristics such as being 40 years or older, female, and either disabled or unemployed was significantly associated with adverse impact on several aspects of daily life. Among caregivers, the aspects of daily life that were disproportionately affected was their own social life and freedom, emotional wellbeing, travel/relocation, and work. Interpretation: iMCD patients have widely varied and unappreciated symptomatology. High symptom burden adversely impacts several aspects of patient daily lives as well as their caregivers. Funding: Funding was provided by EUSA Pharma.

Cost-Effectiveness Analysis of Siltuximab for Australian Public Investment in the Rare Condition Idiopathic Multicentric Castleman Disease.

OBJECTIVES: This paper presents an Australian model that formed part of the health technology assessment for public investment in siltuximab for the rare condition of idiopathic Multicentric Castleman Disease (iMCD) in Australia. METHODS: Two literature reviews were conducted to identify the appropriate comparator and model structure. Survival gain based on available clinical trial data were modelled using an Excel-based model semi-Markov model including time-varying transition probabilities, an adjustment for trial crossover and long-term data. A 20-year horizon was taken, and an Australian healthcare system perspective was adopted, with both benefits and costs discounted at 5%. The model was informed with an inclusive stakeholder approach that included a review of the model by an independent economist, Australian clinical expert opinion and feedback from the Pharmaceutical Benefits Advisory Committee (PBAC). The price used in the economic evaluation reflects a confidential discounted price, which was agreed to with the PBAC. RESULTS: An incremental cost-effectiveness ratio of A$84,935 per quality-adjusted life-year (QALY) gained was estimated. At a willingness-to-pay threshold of A$100,000 per QALY, siltuximab has a 72.1% probability of being cost-effective compared with placebo and best supportive care. Sensitivity analyses results were most sensitive to the length of interval between administrations (from 3- to 6-weekly) and crossover adjustments. CONCLUSION: Within a collaborative and inclusive stakeholder framework, the model submitted to the Australian PBAC found siltuximab to be cost-effective for the treatment of iMCD.

Patient survey to identify reasons for non-adherence and elicitation of quality of life concepts associated with immunosuppressant therapy in kidney transplant recipients.

BACKGROUND: Renal transplantation (RT) is considered the treatment of choice for end-stage renal disease compared to dialysis, offering better health-related quality of life (HRQoL) and higher survival rates. However, immunosuppressants are essential for the long-term survival of kidney grafts and patients' non-adherence to their medication leads to poor outcomes. Immunosuppressants can also significantly alter patients' HRQoL because of their side effects and the complex chronic medication regimen they represent. PURPOSE: To elicit key concepts related to adherence to immunosuppressant therapy (IT) and reasons for non-adherence in terms of patient reported outcomes, side effects, and the impact of the medication on HRQoL in RT population, including patient preference of once daily over twice-daily immunosuppressive regimen. Results were used to develop an IT-specific conceptual framework and provide suggestions for improving patients' adherence to IT. MATERIALS AND METHODS: Interviews were conducted with three clinical experts to determine key concepts related to RT and immunosuppressants. Thirty-seven participants in four focus groups were asked to cite important concepts related to adherence and impact of IT on HRQoL and to rate them. Qualitative analysis was conducted to code participants' responses. RESULTS: Non-adherence among participants where admitted was unintentional. The reason for this included forgetfulness, interference with lifestyle, being asleep at the time the medication should be taken, change in routine, and impact of side effects. Overall, participants reported that the evening dose was more problematic to remember and that the exclusion of this dose could make them more adherent. Participants also reported that IT impacted on their HRQoL in a number of ways including: placing restrictions on their lifestyle, causing anxiety, or impairing their ability to work. CONCLUSION: This study provides qualitative evidence about the barriers to IT adherence and the components of HRQoL that are important from the perspective of RT patients. The developed conceptual framework of IT-HRQoL in RT transplants, including social, psychological, and work life domains, can be used to inform the development of a new IT-specific measure of HRQoL in RT patients for use in head-to-head clinical trials or observational studies. Despite limitations associated with the number and the age range of patients recruited, this study suggests that a change in the regimen from twice-daily to once daily among other measures could improve their adherence to IT and their HRQoL by placing less restrictions on their lifestyles.

Annual public health and economic benefits of seasonal influenza vaccination: a European estimate.

BACKGROUND: Vaccination is currently the most effective means of preventing influenza infection. Yet evidence of vaccine performance, and the impact and value of seasonal influenza vaccination across risk groups and between seasons, continue to generate much discussion. Moreover, vaccination coverage is below recommended levels. METHODS: A model was generated to assess the annual public health benefits and economic importance of influenza vaccination in 5 WHO recommended vaccination target groups (children 6 - 23 months of age; persons with underlying chronic health conditions; pregnant women; health care workers; and, the elderly, 65 years of age) in 27 countries of the European Union. Model estimations were based on standard calculation methods, conservative assumptions, age-based and country-specific data. RESULTS: Out of approximately 180 million Europeans for whom influenza vaccination is recommended, only about 80 million persons are vaccinated. Seasonal influenza vaccination currently prevents an annual average of between 1.6 million and 2.1 million cases of influenza, 45,300 to 65,600 hospitalizations, and 25,200 to 37,200 deaths. To reach the 75% vaccination coverage target set by the EU Council Recommendation in 2009, an additional 57.4 million person would need to be vaccinated in the elderly and other risk groups. By achieving the 75% target rate set in EU-27 countries, average annual influenza- related events averted would increase from current levels to an additional +1.6 to +1.7 million cases, +23,800 to +31,400 hospitalization, +9,800 to +14,300 deaths, +678,500 to +767,800 physician visits, and +883,800 to +1,015,100 lost days of work yearly. Influenza-related costs averted because of vaccination would increase by an additional + €190 to + €226 million yearly, in vaccination target groups. CONCLUSIONS: Full implementation of current influenza vaccination recommendations of 75% vaccination coverage rate (VCR) in Europe by the 2014-2015 influenza season could immediately reduce an important public health and economic burden.