Martin Strandberg-Larsen

Haemophilia B: impact on patients and economic burden of disease.

Worldwide, haemophilia is the most common hereditary bleeding disorder. The incidence of haemophilia B, however, is considerably less than haemophilia A and consequently appears to have received less attention in the research literature. This article aims to summarise the available evidence documenting the patient and economic burden associated with haemophilia B and current methods of disease management. Both the immediate and long-term clinical consequences of haemophilia B can have significant implications for patients in terms of functional limitations and diminished health-related quality of life (HRQOL). Evidence demonstrates that primary prophylaxis is the optimal strategy for replacing missing clotting factor IX (FIX) and managing haemophilia B. Use of recombinant FIX (rFIX) over plasma-derived FIX (pd-FIX) is also generally preferred for safety reasons. Prophylaxis using currently available rFIX products, however, requires a demanding regimen of intravenous infusions 2-3 times a week which may have significant implications for adherence and ultimately the long-term efficacy of such regimens. Only limited assessments of the cost-effectiveness of prophylactic versus on-demand FIX treatment regimens have been conducted to date. Prophylaxis, however, is generally more costly as greater quantities of FIX are consumed. Any reduction in FIX replacement dosing frequency is expected to improve patient adherence and contribute to improved clinical outcomes, further supporting the cost-effectiveness of such interventions. Although a rare disease, as economic constraints for healthcare increase, generating further information regarding the key clinical, patient and economic outcomes associated with haemophilia B will be essential for supporting improvements in care for people with haemophilia B.

Patient-reported outcome measures for systemic lupus erythematosus clinical trials: a review of content validity, face validity and psychometric performance

BackgroundDespite overall progress in treatment of autoimmune diseases, patients with systemic lupus erythematosus (SLE) experience many inflammatory symptoms representing an unmet medical need. This study aimed to create a conceptual model of the humanistic and economic burden of SLE, and review the patient-reported outcomes (PROs) used to measure such concepts in SLE clinical trials.MethodsA conceptual model for SLE was developed from structured review of published articles from 2007 to August 2013 identified from literature databases (MEDLINE, EMBASE, PsycINFO, EconLit) plus other sources (PROLabels, FDA/EMA websites, Clinicaltrials.gov). PROs targeting key symptoms/impacts were identified from the literature. They were reviewed in the context of available guidance and assessed for face and content validity and psychometric properties to determine appropriateness for use in SLE trials.ResultsThe conceptual model identified fatigue, pain, cognition, daily activities, emotional well-being, physical/social functioning and work productivity as key SLE concepts. Of the 68 articles reviewed, 38 reported PRO data. From these and the other sources, 15 PROs were selected for review, including SLE-specific health-related quality of life (HRQoL) measures (n = 5), work productivity (n = 1), and generic measures of fatigue (n = 3), pain (n = 2), depression (n = 2) and HRQoL (n = 2). The Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-Fatigue), Brief Pain Inventory (BPI-SF) and LupusQoL demonstrated the strongest face validity, conceptual coverage and psychometric properties measuring key concepts in the conceptual model. All PROs reviewed, except for three Lupus-specific measures, lacked qualitative SLE patient involvement during development. The Hospital Anxiety and Depression Scale (HADS), Short Form [36 item] Health Survey version 2 (SF-36v2), EuroQoL 5-dimensions (EQ-5D-3L and EQ-5D-5L) and Work Productivity and Activity Impairment Questionnaire: Lupus (WPAI:Lupus) showed suitability for SLE economic models.ConclusionsBased on the identification of key symptoms and impacts of SLE using a scientifically sound conceptual model, we conclude that SLE is a condition associated with high unmet need and considerable burden to patients. This review highlights the availability and need for disease-specific and generic patient-reported measures of relevant domains of disease signs and symptoms, HRQoL and work productivity, providing useful insight for SLE clinical trial design.

A retrospective analysis of health systems in Denmark and Kaiser Permanente

BackgroundTo inform Danish health care reform efforts, we compared health care system inputs and performance and assessed the usefulness of these comparisons for informing policy.MethodsRetrospective analysis of secondary data in the Danish Health Care System (DHS) with 5.3 million citizens and the Kaiser Permanente integrated delivery system (KP) with 6.1 million members in California. We used secondary data to compare population characteristics, professional staff, delivery structure, utilisation and quality measures, and direct costs. We adjusted the cost data to increase comparability.ResultsA higher percentage of KP patients had chronic conditions than did patients in the DHS: 6.3% vs. 2.8% (diabetes) and 19% vs. 8.5% (hypertension), respectively. KP had fewer total physicians and staff compared to DHS, with134 physicians/100,000 individuals versus 311 physicians/100,000 individuals. KP physicians are salaried employees; in contrast, DHS primary care physicians own and run their practices, remunerated by a mixture of capitation and fee-for-service payments, while most specialists are employed at largely public hospitals. Hospitalisation rates and lengths of stay (LOS) were lower in KP, with mean acute admission LOS of 3.9 days versus 6.0 days in the DHS, and, for stroke admissions, 4.2 days versus 23 days. Screening rates also differed: 93% of KP members with diabetes received retinal screening; only 46% of patients in the DHS with diabetes did. Per capita operating expenditures were PPP

Development of a conceptual model evaluating the humanistic and economic burden of Crohn’s disease: implications for patient-reported outcomes measurement and economic evaluation

1,951 (KP) and PPP

Key data elements for use in cost-utility modeling of biological treatments for rheumatoid arthritis

1,845 (DHS).ConclusionCompared to the DHS, KP had a population with more documented disease and higher operating costs, while employing fewer physicians and resources like hospital beds. Observed quality measures also appear higher in KP. However, simple comparisons between health care systems may have limited value without detailed information on mechanisms underlying differences or identifying translatable care improvement strategies. We suggest items for more in-depth analyses that could improve the interpretability of findings and help identify lessons that can be transferred.

SAT0112 Improvements in Patient-Reported Physical Function, Pain and Global Disease Activity in Patients with Rheumatoid Arthritis after Treatment with Nnc0109-0012 (Anti-IL-20 Mab) in a Phase 2A Trial

The primary objective of this review is to develop a conceptual model for Crohn’s disease (CD) outlining the disease burden for patients, healthcare systems and wider society, as reported in the scientific literature. A search was conducted using MEDLINE, PsycINFO, EconLit, Health Economic Evaluation Database and Centre for Reviews and Dissemination databases. Patient-reported outcome (PRO) measures widely used in CD were reviewed according to the US FDA PRO Guidance for Industry. The resulting conceptual model highlights the characterization of CD by gastrointestinal disturbances, extra-intestinal and systemic symptoms. These symptoms impact physical functioning, ability to complete daily activities, emotional wellbeing, social functioning, sexual functioning and ability to work. Gaps in conceptual coverage and evidence of reliability and validity for some PRO measures were noted. Review findings also highlight the substantial direct and indirect costs associated with CD. Evidence from the literature confirms the substantial burden of CD to patients and wider society; however, future research is still needed to further understand burden from the perspective of patients and to accurately understand the economic burden of disease. Challenges with existing PRO measures also suggest the need for future research to refine or develop new measures.

Exploring the Humanistic and Economic Burden of Crohnʼs Disease: Considerations for Novel Compounds: P-68

Abstract Objectives: Economic evaluation is becoming more common and important as new biologic therapies for rheumatoid arthritis (RA) are developed. While much has been published about how to design cost-utility models for RA to conduct these evaluations, less has been written about the sources of data populating those models. The goal is to review the literature and to provide recommendations for future data collection efforts. Methods: This study reviewed RA cost-utility models published between January 2006 and February 2014 focusing on five key sources of data (health-related quality-of-life and utility, clinical outcomes, disease progression, course of treatment, and healthcare resource use and costs). It provided recommendations for collecting the appropriate data during clinical and other studies to support modeling of biologic treatments for RA. Results: Twenty-four publications met the selection criteria. Almost all used two steps to convert clinical outcomes data to utilities rather than more direct methods; most did not use clinical outcomes measures that captured absolute levels of disease activity and physical functioning; one-third of them, in contrast with clinical reality, assumed zero disease progression for biologic-treated patients; little more than half evaluated courses of treatment reflecting guideline-based or actual clinical care; and healthcare resource use and cost data were often incomplete. Conclusions: Based on these findings, it is recommended that future studies collect clinical outcomes and health-related quality-of-life data using appropriate instruments that can convert directly to utilities; collect data on actual disease progression; be designed to capture real-world courses of treatment; and collect detailed data on a wide range of healthcare resources and costs.

Measurement of integrated healthcare delivery: a systematic review of methods and future research directions

Background NNC0109-0012 (anti-IL-20 mAb) is a novel human monoclonal IgG4 antibody which binds to IL-20 and neutralises its activity. The primary endpoint in this multicentre, randomised, double-blind, placebo-controlled, parallel group trial (DAS28 response at Week 12) was achieved, as reported elsewhere. Objectives To assess the effect of NNC0109-0012 on patient-reported outcomes, a secondary endpoint in this phase 2a proof-of-principle trial. Methods 67 patients with active RA and inadequate responses to MTX were randomised to 12 once-weekly doses of 3mg/kg NNC0109-0012 (n=45) or placebo (n=22) and stable background MTX, and then followed for an additional 13 weeks. Of the 67 randomised patients 43 were Rheumatoid Factor [RF]- and anti-citrullinated peptide antibody [ACPA]-positive. Physical function was assessed by the Health Assessment Questionnaire – Disability Index (HAQ-DI). The level of pain and global disease activity were recorded by the patients on a 10 cm Visual Analogue Scale (VAS). All patient-reported outcomes were assessed weekly from baseline to week 12, and an additional 3 times in the 13 week follow-up period. A mixed-effects model repeated measures was fitted to the change from baseline for each of the patient-reported outcomes including treatment; time and interaction between treatment and time as fixed factors; baseline score and interaction between time and baseline score as continuous covariates and subject as random effect. Results In RF- and ACPA-positive patients all patient-reported outcomes were significantly improved. Physical function was significantly improved after 12 and 25 weeks (-0.45, p=0.047; -0.47, p=0.022, respectively). After 12 and 25 weeks, NNC0109-0012 versus placebo significantly reduced pain (-3.0 cm, p<0.001; -2.9 cm, p<0.001, respectively) and global disease activity (-2.8 cm, p=0.002; -2.8 cm, p<0.001, respectively). For both pain and global disease activity the effects in the RF- and ACPA-positive patients were up to 2 fold larger versus placebo than was observed for the Full Analysis Set. For the Full Analysis Set, physical function was not significantly improved for NNC0109-0012 versus placebo after end of treatment at 12 weeks (-0.26, p=0.130). Pain was significantly reduced for NNC0109-0012 versus placebo with a mean difference of -1.5 cm (p=0.034) after 12 weeks and -1.3 cm (p=0.046) at week 25. Global disease activity was significantly lower for patients treated with NNC0109-0012 versus placebo with a mean difference of -1.7 cm (p=0.018) after 12 weeks, and was maintained through the follow-up period with a mean difference of -1.4 cm (p=0.031) at week 25. Conclusions 12-weeks treatment with 3 mg/kg NNC0109-0012 effectively improved physical function, pain and global disease activity in RF- and ACPA-positive patients with RA on stable MTX. These improvements were clinically relevant and sustained when measured at the end of the 13 weeks follow-up. Disclosure of Interest L. Senolt: None Declared, B. Hansen Employee of: Novo Nordisk, M. Strandberg-Larsen Employee of: Novo Nordisk, E. Dokoupilova: None Declared

Coordination between primary and secondary healthcare in Denmark and Sweden

data regarding the prevalence of CDI in newly diagnosed IBD, and its effect on disease course. As a basis for future studies to determine the impact of CDI on the course of IBD, we sought to determine rate of CDI and CDI testing at diagnosis of IBD. METHODS: Rhode Island patients diagnosed with IBD after January 2008 and within one year of diagnosis were eligible to enroll in the Ocean State Crohn’s and Colitis Area Registry (OSCCAR), a prospective cohort started January 2008. Medically trained personnel confirmed diagnosis of IBD by chart review using standard criteria. All patients completed a questionnaire regarding symptoms at diagnosis. This included self-report of diarrhea (loose or watery bowel movements and/or increased frequency of stool) within 4 weeks before diagnosis of IBD. Trained data abstractors recorded occurrence of CDI toxin or PCR assay testing and results from medical records of the gastroenterologist and/or surgeon who reported a new diagnosis, or inpatient records if diagnosed during hospitalization. RESULTS: Among 338 patients enrolled from January 2008 to June 2011, 260 (76.9%) reported diarrhea. Of the 260 patients, results of CDI testing were recorded in diagnosing physicians’ records for 120 patients (46.2%). CDI testing was not recorded or possibly not performed for the remaining 140 patients who presented with diarrhea. An additional 21 patients were tested for CDI but did not report having diarrhea or did not have a symptom inventory on record. Of the 141 patients tested for CDI, 74 were female; 65 were diagnosed with ulcerative colitis, 65 with Crohn’s disease, and 11 patients had IBD undetermined. Seven (4.9%) of the 141 patients tested were positive for CDI (2.1% of all patients). CONCLUSION(S): Testing for CDI is lower than expected at diagnosis of IBD especially among patients who presented with diarrhea. Although the prevalence of CDI among tested patients is only 5%, low rate of testing and possible delayed diagnosis of CDI in newly diagnosed IBD may be a significant quality issue. A limitation of the study is that we are unable to determine whether CDI testing was done prior to specialty referral and thus we may underestimate the rate of CDI testing.