Critical inhaler errors in asthma and COPD: a systematic review of impact on health outcomes.

BACKGROUND: Inhaled drug delivery is the cornerstone treatment for asthma and chronic obstructive pulmonary disease (COPD). However, use of inhaler devices can be challenging, potentially leading to critical errors in handling that can significantly reduce drug delivery to the lungs and effectiveness of treatment. METHODS: A systematic review was conducted to define 'critical' errors and their impact on health outcomes and resource use between 2004 and 2016, using key search terms for inhaler errors in asthma and COPD (Search-1) and associated health-economic and patient burden (Search-2). RESULTS: Search-1 identified 62 manuscripts, 47 abstracts, and 5 conference proceedings (n = 114 total). Search-2 identified 9 studies. We observed 299 descriptions of critical error. Age, education status, previous inhaler instruction, comorbidities and socioeconomic status were associated with worse handling error frequency. A significant association was found between inhaler errors and poor disease outcomes (exacerbations), and greater health-economic burden. CONCLUSIONS: We have shown wide variations in how critical errors are defined, and the evidence shows an important association between inhaler errors and worsened health outcomes. Given the negative impact diminished disease outcomes impose on resource use, our findings highlight the importance of achieving optimal inhaler technique, and a need for a consensus on defining critical and non-critical errors.

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

BACKGROUND: Despite 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. METHODS: A 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. RESULTS: The 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. CONCLUSIONS: Based 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.

Assessment of the comprehensiveness of paediatric national immunisation programmes in Europe: expert validation and future perspectives.

BACKGROUND: The breadth of protection of National Immunisation Programmes (NIPs) across Europe varies, however, this has not been assessed within published literature. Therefore, a framework was developed to assess the comprehensiveness of pediatric NIPs in Europe. This study aimed to validate and further develop criteria used to cluster countries into three tiers. RESEARCH DESIGN AND METHODS: Independent Europe-based experts (n = 23) in the field of pediatric vaccination were invited to participate in a double-blinded modified Delphi panel, with two online survey rounds and a virtual consensus meeting. Consensus was defined as ≥ 80% of experts rating their agreement/disagreement on a 9-point Likert scale. RESULTS: The number of preventable diseases covered by an NIP, simplification of the vaccination calendar, strengthened protection by increasing serotype, degree of funding and epidemiological factors were considered key concepts for consideration of the comprehensiveness of pediatric NIPs in Europe. Experts highlighted that the framework should be extended to include adolescent vaccines and populations up to 18 years of age. Consensus regarding further amendments to the framework was also reached. CONCLUSIONS: This Delphi panel validated a framework to assess the comprehensiveness of European NIPs. The framework can be used to facilitate discussions to help countries improve and expand the breadth of protection provided by their NIP.

Definition and measurement of post-COVID-19 conditions in real-world practice: a global systematic literature review.

Post-COVID-19 conditions (PCC) is an umbrella term that encompasses a range of signs, symptoms and conditions present weeks after the acute phase of a SARS-CoV-2 infection. This systematic literature review summarises the heterogeneous methodology used to measure PCC across real-world studies and highlights trends by region, age group, PCC follow-up period and data source. METHODS: Medline, EMBASE and the Cochrane Library were searched and supplemented with conference and grey literature searches. Eligible studies included individuals with (1) PCC or (2) a positive SARS-CoV-2 test or COVID-19 diagnosis who were followed over time. Included studies were published in English between 1 January 2020 and 14 November 2022. FINDINGS: Of 291 publications included, 175 (60%) followed individuals with confirmed COVID-19 over time for PCC and 116 (40%) used a prespecified PCC definition. There was substantial heterogeneity in study design, geography, age group, PCC conditions/symptoms assessed and their classification and duration of follow-up. Among studies using a prespecified PCC definition, author-defined criteria (51%) were more common than criteria recommended by major public health organisations (19%). Measurement periods for PCC outcomes from date of acute COVID-19 test were primarily 3 to <6 months (39.2%), followed by 6 to <12 months (27.5%) and <3 months (22.9%). When classified by organ/system, constitutional-related PCC were the most frequently assessed in adult (86%) and paediatric (87%) populations. Within constitutional symptoms, fatigue was most frequently assessed in adult (91.6%) and paediatric (95.0%) populations, followed by fever/chills (37.9% and 55%, respectively). CONCLUSIONS: PCC definitions are heterogenous across real-world studies, which limits reliable comparisons between studies. However, some similarities were observed in terms of the most frequently measured PCC-associated symptoms/conditions, which may aid clinical management of patients with PCC.CRD42022376111.

Living with the burden of relapse in multiple myeloma from the patient and physician perspective.

Multiple myeloma (MM) is a progressive plasma cell malignancy, with a range of clinical features including bone lesions, renal insufficiency, anaemia, and hypercalcaemia. Novel agents have significantly improved patient survival, however most patients will suffer multiple relapses. Although clinical challenges and economic costs of relapse are recognised, the psychological impact of relapse is not fully appreciated. Additionally, there is little information on how physicians perceive the impact of relapse on their patients' emotional state and how this might affect patient management. Through face-to-face interviews with 50 relapsed and/or refractory MM patients and 30 haematologists across ten countries, we have used real-world evidence to explore and characterise the burden of living with MM, particularly the impact of relapsed disease. This exploratory study illustrates the impact of the disease on friends and family, and the physical and emotional burden experienced by the patient resulting from both MM and its treatment. Haematologists feel poorly equipped to deal with the emotional aspects of patient relapse, lacking the time and resources to adequately deal with these issues. Focused educational and support tools/resources targeted at both physicians and patients are required to facilitate physician-patient communication to help reduce the emotional burden of living with MM.

FP/FORM Versus FP/SAL Within Clinical Practice: An Updated Budget Impact Analysis in Asthma.

INTRODUCTION: Pressurized metered-dose inhalers (pMDI) such as fluticasone propionate and salmeterol (FP/SAL) are commonly used for the treatment of asthma in the UK. Previously, a budget impact analysis demonstrated that use of FP and formoterol fumarate (FP/FORM) pMDI as an alternative to FP/SAL pMDI, would be a cost-saving option for the UK National Health Service (NHS). This budget impact analysis aimed to update the existing analysis with prescription volume data and real-world evidence since the introduction of FP/FORM to the UK market. METHODS: Patient Data (IMS Information Solutions UK Ltd) moving annual total (MAT) August 2015 were used to ascertain the number of units of pMDI prescribed. Annual costs to the NHS in terms of drug, administration, monitoring and adverse event costs, were used to estimate the potential budget impact for FP/FORM and FP/SAL. Costs were calculated for current prescription volumes (12% FP/FORM, 88% FP/SAL), and for different prescription volume scenarios (FP/FORM at 0%, 25%, 50% and 100%). Real-world evidence and budget impact at a clinical commissioning group (CCG) level were also considered. RESULTS: Total annual costs per person year were less with FP/FORM (£625) than with FP/SAL (£734). Annual costs to the NHS based on the current prescription volumes and clinical trial data were estimated at £210.0M, however, based on real-world evidence, costs were estimated at £179.8M. For all scenarios with increased FP/FORM prescription volumes, the annual total costs to the NHS decreased. This was reflected at a CCG level. CONCLUSION: The use of FP/FORM as an alternative to FP/SAL can result in cost savings for the NHS when assessing drug, administration, monitoring and adverse events costs. The inclusion of data released since the launch of FP/FORM within the budget impact analysis demonstrates that the potential cost savings to the NHS that were previously published are being translated to clinical practice. FUNDING: Mundipharma, UK.

Treatment patterns of advanced malignant melanoma (stage III-IV) - A review of current standards in Europe.

AIMS AND BACKGROUND: With the recent emergence of immunotherapies and novel targeted treatments for advanced and metastatic melanoma such as selective B-Raf inhibitors and checkpoint inhibitors, the treatment landscape in Europe has changed considerably. The aim of this review was to provide an overview of current treatment pathways in Europe for the treatment of advanced melanoma, unresectable stage III-IV. METHODS: A literature search of four databases was conducted to identify publications reporting on the treatment patterns of advanced and metastatic melanoma (stage III-IV) in European populations. RESULTS: Seven full-text publications and two conference abstracts reported on observational studies of melanoma treatment practices in France, Italy and the United Kingdom. Treatment patterns were identified for two time periods: 2005-2009 and 2011-2012. Common treatments reported for both periods included chemotherapy with dacarbazine, fotemustine or temozolomide. The main differences between the two periods were the introduction and prescription of immunotherapy ipilimumab and targeted therapy vemurafenib between 2011 and 2012. Across the three countries studied, the types of treatments prescribed between 2005 and 2009 were relatively similar, however, with noticeable differences in the frequency and priority of administration. CONCLUSION: Treatment practices for advanced melanoma vary markedly across different European countries and continue to evolve with the introduction of new therapies. The results of this review highlight a considerable evidence gap with regards to recent treatment patterns for advanced melanoma in Europe, especially post-2011 after the introduction of novel therapeutic agents, and more recently with the introduction of programmed cell death 1 inhibitors.

BEACON: A Summary Framework to Overcome Potential Reimbursement Hurdles.

OBJECTIVE: To provide a framework for addressing payers' criteria during the development of pharmaceuticals. METHODS: A conceptual framework was presented to an international health economic expert panel for discussion. A structured literature search (from 2010 to May 2015), using the following databases in Ovid: Medline(®) and Medline(®) In-Process (PubMed), Embase (Ovid), EconLit (EBSCOhost) and the National Health Service Economic Evaluation Database (NHS EED), and a 'grey literature' search, were conducted to identify existing criteria from the payer perspective. The criteria assessed by existing frameworks and guidelines were collated; the most commonly reported criteria were considered for inclusion in the framework. A mnemonic was conceived as a memory aide to summarise these criteria. RESULTS: Overall, 41 publications were identified as potentially relevant to the objective. Following further screening, 26 were excluded upon full-text review on the basis of no framework presented (n = 13), redundancy (n = 11) or abstract only (n = 2). Frameworks that captured criteria developed for or utilised by the pharmaceutical industry (n = 5) and reimbursement guidance (n = 10) were reviewed. The most commonly identified criteria-unmet need/patient burden, safety, efficacy, quality-of-life outcomes, environment, evidence quality, budget impact and comparator-were incorporated into the summary framework. For ease of communication, the following mnemonic was developed: BEACON (Burden/target population, Environment, Affordability/value, Comparator, Outcomes, Number of studies/quality of evidence). CONCLUSIONS: The BEACON framework aims to capture the 'essence' of payer requirements by addressing the most commonly described criteria requested by payers regarding the introduction of a new pharmaceutical.

Patient reported burden of asthma on resource use and productivity across 11 countries in Europe.

INTRODUCTION: Asthma affects 30 million people in Western Europe, leading to substantial burden on healthcare systems and economies. REcognise Asthma and LInk to Symptoms and Experience (REALISE™) was a large European survey across 11 countries assessing patient attitudes and behaviors towards their asthma. The present study utilizes REALISE™ data to understand resource use and absenteeism in asthma. METHODS: Data were collected on absenteeism and healthcare resource use from 8000 asthma patients (aged 18-50 years) across the 11 countries. All data were patient reported. Odds ratios (ORs) were calculated against the country with the lowest proportion of respondents for hospitalization (as a proxy for lowest resource use). RESULTS: Patient characteristics were broadly similar across countries. However, self-reported asthma control status varied. More than 50% of respondents in most countries considered primary healthcare professionals (HCPs), i.e., general practitioners and nurses, the main HCP they see about their asthma. However, in some countries, specialists or nurses were considered the main HCP. Hospitalization was lowest amongst patients in the Netherlands. Resource use and productivity loss varied widely across the countries; ORs for hospitalization ranged from 1 in Sweden to 4 in Norway and for productivity loss from 0.6 in Sweden to 2.6 in Italy, compared with the Netherlands. CONCLUSION: This study quantified utilization of healthcare resources in asthma (number of visits of HCPs, hospitalization, and accident and emergency visits) as well as absenteeism and showed that differences exist across countries. The differences in primary care and specialist use suggest a possible difference in healthcare delivery across countries. FUNDING: Mundipharma International Limited, Cambridge, UK.

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

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.

Budget impact analysis of a fixed-dose combination of fluticasone propionate and formoterol fumarate (FP/FORM) in a pressurized metered-dose inhaler (pMDI) for asthma.

INTRODUCTION: The economic burden of asthma on the UK National Health Service (NHS) is the largest among allergic diseases. Current asthma guidelines recommend adding a long acting ß2-agonist (LABA) to a low-dose inhaled corticosteroid (ICS) in patients who are on ICS monotherapy and have uncontrolled asthma. The fixed-dose combination of fluticasone propionate and salmeterol xinafoate (FP/SAL), available in a pressurized metered-dose inhaler (pMDI) device, is the most commonly prescribed ICS/LABA combination. An additional fixed-dose combination of fluticasone propionate and formoterol fumarate (FP/FORM) in pMDI is now available. In a 12-week non-inferiority study, FP/FORM demonstrated comparable efficacy to FP/SAL. The present analysis estimates the annual budget impact for the UK NHS using FP/FORM as an alternative to FP/SAL. METHODS: Current pMDI prescribing data were from a real-world UK patient database (Cegedim Strategic Data). Annual costs to the NHS for drug acquisition, administration, and monitoring were estimated for FP/FORM and FP/SAL and used to assess the potential budget impact for the NHS for the use of FP/FORM instead of FP/SAL. Varying rates of uptake, adherence, adverse event-related costs, and resource use associated with switching treatment were assessed in scenario analyses. RESULTS: Assuming similar levels of ICS use with both regimens, annual drug acquisition costs per person were lower with FP/FORM (£412) than with FP/SAL (£509). The difference in acquisition costs and otherwise comparable input costs between the treatments, results in potential annual savings of £15,110,279 to the NHS, assuming uptake of FP/FORM over FP/SAL in 50% of existing patients. The introduction of FP/FORM results in cost savings for the NHS in all of the assessed scenario analyses. CONCLUSIONS: The comparable efficacy and lower acquisition costs of FP/FORM compared with FP/SAL make it a cost-saving option for the UK NHS for the treatment of asthma patients requiring combination maintenance therapy using a pMDI.

Cost-effectiveness of modified-release prednisone in the treatment of moderate to severe rheumatoid arthritis with morning stiffness based on directly elicited public preference values.

BACKGROUND: Assessing the cost-effectiveness of treatments in rheumatoid arthritis (RA) is of growing importance due to the chronic nature of the disease, rising treatment costs, and budget-constrained health care systems. This analysis assesses the cost-effectiveness of modified-release (MR) prednisone compared with immediate-release (IR) prednisone for the treatment of morning stiffness due to RA. METHODS: A health state transition model was used to categorize RA patients into four health states, defined by duration of morning stiffness. The model applied a 1-year time horizon and adopted a UK National Health Service (NHS) perspective. Health benefits were measured in quality-adjusted life years (QALYs) and the final output was the incremental cost-effectiveness ratio (ICER). Efficacy data were derived from the CAPRA-1 (Circadian Administration of Prednisone in Rheumatoid Arthritis) study, drug costs from the British National Formulary (BNF), and utility data from a direct elicitation time-trade-off (TTO) study in the general population. Sensitivity analyses were conducted. RESULTS: Mean treatment costs per patient were higher for MR-prednisone (£649.70) than for IR-prednisone (£46.54) for the duration of the model. However, the model generated an incremental QALY of 0.044 in favor of MR-prednisone which resulted in an ICER of £13,577. Deterministic sensitivity analyses did not lead to significant changes in the ICER. Probabilistic sensitivity analysis reported that MR-prednisone had an 84% probability of being cost-effective at a willingness-to-pay threshold of £30,000 per QALY. The model only considers drug costs and there was a lack of comparative long-term data for IR-prednisone. Furthermore, utility benefits were not captured in the clinical setting. CONCLUSION: This analysis demonstrates that, based on the CAPRA-1 trial and directly elicited public preference values, MR-prednisone is a cost-effective treatment option when compared with IR-prednisone for RA patients with morning stiffness over one year, according to commonly applied UK thresholds (£20,000-£30,000 per QALY). Further research into the costs of morning stiffness in RA is required.

Cognitive impairment associated with schizophrenia: a review of the humanistic burden.

INTRODUCTION: Nearly every individual with schizophrenia is affected by cognitive decline. The aim of this literature review was to: (a) describe the humanistic burden of cognitive impairment associated with schizophrenia (CIAS); (b) develop a conceptual model that depicts the signs and symptoms of CIAS along with key concepts important to patients; and (c) consider the adequacy of potential patient-reported outcome (PRO) instruments for assessing future treatments. METHODS: The following electronic databases were searched for articles published between January 1999 and November 2009 related to CIAS and PROs, or cost of illness: Medline; Embase; PsycINFO; the Health Economic Evaluation Database; and the National Health Service Economic Evaluation Database and Health Technology Assessment databases at the Centre for Reviews and Dissemination, University of York. RESULTS: The literature search revealed 3950 abstracts, of which 101 articles were reviewed in detail. Cognitive functions affected include memory, attention/concentration, problem solving, learning, executive function, processing speed, and social cognition. Cognitive impairment impacts the ability of individuals to carry out activities of daily living, work productively, function socially, and adhere to treatment. These effects have economic ramifications through increased direct and indirect costs associated with the treatment of schizophrenia. The literature revealed 39 PRO instruments that have been used to assess functioning. However, no single instrument captures all key concepts of importance to patients with schizophrenia. CONCLUSION: The significant burden from CIAS for patients and society has implications for designing future treatments and health strategies to improve functional outcomes.

Adherence to oral tyrosine kinase inhibitor therapies in chronic myeloid leukemia.

Ensuring adherence to therapy is a challenge in chronic diseases, particularly in cancers such as chronic myeloid leukemia (CML), where there has been increased availability and use of oral formulations. A conceptual model of adherence was developed based on findings from a comprehensive literature review, to inform strategies for improving adherence to oral CML therapies. A complex interplay of factors (including clinical, psychological and behavioural) influence adherence to such therapies. Healthcare professionals have a key role in promoting and facilitating adherence and future strategies should place greater emphasis on understanding patient-level experiences in order to create personalized solutions.