Outcomes and endpoints reported in studies of pulmonary exacerbations in people with cystic fibrosis: A systematic review

McLeod, Charlie; Wood, Jamie; Schultz, André; Norman, Richard; Smith, Sherie; Blyth, Christopher C; Webb, Steve; Smyth, Alan; Snelling, Tom

doi:10.1016/j.jcf.2020.08.015

Cited by 16 publications

(17 citation statements)

References 122 publications

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“…Similarly to this review, a recent systematic review investigating outcomes and endpoints used in CF pulmonary exacerbation studies also reported a wide range of outcomes used [37], with FEV 1 being the most common. The authors suggested the choice of outcomes may have historically been in uenced by cost, available expertise and equipment [37]. This may also be the case for previous ACT trials, with spirometry and sputum weight being cheap and relatively easy [3].…”

Section: Discussionmentioning

confidence: 92%

“…This may also be the case for previous ACT trials, with spirometry and sputum weight being cheap and relatively easy [3]. The authors highlighted a need for a core outcome set for use in research into pulmonary exacerbations as described by the Core Outcome Measures in Effectiveness Trials (COMET) initiative [38] and emphasised that these endpoints should ful l the desired characteristics of being both clinimetrically validated and clinically meaningful to people with CF [37], something which ACT research also requires.…”

Section: Discussionmentioning

confidence: 99%

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Clinimetric Analysis of Outcome Measures for Airway Clearance in Adults with Cystic Fibrosis: A Systematic Review

Stanford

Jones

Charman

et al. 2021

Preprint

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Background Airway clearance techniques (ACTs) are integral to cystic fibrosis (CF) management. However, there is no consensus as to which outcome measures (OMs) are best for assessing ACT efficacy. Objectives: To summarise OMs that have been assessed for their clinimetric properties (including validity, feasibility, reliability & reproducibility) within the context of ACT research. MethodsEligibility Criteria - Any parallel or cross-over randomised controlled trial (RCT) investigating outcome measures for ACT in the CF population. Information sources: Five medical databases; clinicaltrials.gov; abstracts from international CF conferences. Risk of Bias - The authors planned to independently assess study quality and risk of bias using the COSMIN risk of bias checklist with external validity assessment based upon study details (participants and study intervention).Synthesis of Results – Two review authors (GS and MJ) independently screened search results against inclusion criteria, further data extraction was planned but not required.ResultsIncluded studies - No completed RCTs from the 187 studies identified met inclusion criteria for the primary or post-hoc secondary objective. Two ongoing trials were identified.DiscussionLimitations of evidence: The search strategy may have missed some lesser-known terms for ACT or manuscripts reporting clinimetric properties solely within text. Studies validating outcome measures for use in other aspects of CF, which may be relevant to ACT, are not included.Interpretation - High-quality RCTs are urgently needed to investigate & validate the clinimetric properties of OMs used to assess ACT efficacy. With the changing demographics of CF combined with the introduction of CFTR modulator therapies, an accurate assessment of the current benefit of ACT or the effect of ACT withdrawal is a high priority for clinical practice and future research and OMs which have been validated for this purpose are essential.OtherFunding: NIHR/HEE Clinical Doctoral Fellowship grant for GS (reference CDRF-2014-05-055).Systematic review registration number - PROSPERO no.CRD42020206033

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Clinimetric Analysis of Outcome Measures for Airway Clearance in Adults with Cystic Fibrosis: A Systematic Review

Stanford

Jones

Charman

et al. 2021

Preprint

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“…Outcome domains (such as lung function) will be defined as an aspect of health that is likely to be impacted by a healthcare intervention. Outcomes (such as forced expiratory volume in 1 s) identified from the systematic review 13 and preliminary workshops 21 will be mapped to domains by members of the steering committee in order to structure a list for evaluation in the eDelphi survey. An international two-round eDelphi will be conducted to generate consensus about outcome domains of importance to key stakeholders (figure 1).…”

Section: Methods and Analysismentioning

confidence: 99%

“…Open access facilitate collaboration, avoid duplication and to improve the value of the research that is conducted. 12 We have reviewed the range of outcomes previously reported in studies of pulmonary exacerbations in people with CF 13 and the methods used for measuring these outcomes. 14 We have engaged Australian stakeholders including clinicians, people 13 years and above with CF and carers of children less than 18 years of age with CF to identify outcomes of importance to them.…”

Section: Strengths and Limitations Of This Studymentioning

confidence: 99%

Protocol for establishing a core outcome set for evaluation in studies of pulmonary exacerbations in people with cystic fibrosis

et al. 2022

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IntroductionPulmonary exacerbations are associated with increased morbidity and mortality in people with cystic fibrosis (CF). There is no consensus about which outcomes should be evaluated in studies of pulmonary exacerbations or how these outcomes should be measured. Outcomes of importance to people with lived experience of the disease are frequently omitted or inconsistently reported in studies, which limits the value of such studies for informing practice and policy. To better standardise outcome reporting and measurement, we aim to develop a core outcome set for studies of pulmonary exacerbations in people with CF (COS-PEX) and consensus recommendations for measurement of core outcomes.Methods and analysisPreliminary work for development of COS-PEX has been reported, including (1) systematic reviews of outcomes and methods for measurement reported in existing studies of pulmonary exacerbations; (2) workshops with people affected by CF within Australia; and (3) a Bayesian knowledge expert elicitation workshop with health professionals to ascertain outcomes of importance. Here we describe a protocol for the additional stages required for COS-PEX development and consensus methods for measurement of core outcomes. These include (1) an international two-round online Delphi survey and (2) consensus workshops to review and endorse the proposed COS-PEX and to agree with methods for measurement.Ethics and disseminationNational mutual ethics scheme approval has been provided by the Child and Adolescent Health Service Human Research Ethics Committee (RGS 4926). Results will be disseminated via consumer and research networks and peer-reviewed publications. This study is registered with the Core Outcome Measures in Effectiveness Trials database.

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“…To inform reimbursement decisions of new medicines, many European jurisdictions perform health technology assessment (HTA) ( Morel et al, 2013 ). For rare disease therapies such as these CFTR modulators, however, high uncertainty on medicine performance exists due to the limited and genetically heterogeneous population as well as adoption of surrogate endpoints in clinical settings ( Kent et al, 2014 ; McLeod et al, 2020 ). To allow market access of Vertex’ products while accounting for clinical uncertainties and high costs, some healthcare authorities closed mutual agreements with the manufacturer ( Morel et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

A Comparative Analysis of Pricing and Reimbursement of Cystic Fibrosis Transmembrane Conductance Regulator Modulators in Europe

et al. 2021

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Objectives: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators, Kalydeco® (ivacaftor), Orkambi® (lumacaftor/ivacaftor) and Symkevi® (tezacaftor/ivacaftor), have substantially improved patients’ lives yet significantly burden healthcare budgets. This analysis aims to compare pricing and reimbursement of aforementioned cystic fibrosis medicines, across European countries.Methods: Clinical trial registries, national databases, health technology assessment reports and grey literature of Austria, Belgium, Denmark, France, Germany, Ireland, Poland, Spain, Sweden, Switzerland, Netherlands, the United Kingdom were consulted. Publicly available prices, reimbursement statuses, economic evaluations, budget impact analyses and managed entry agreements of CFTR modulators were examined. Results: In Belgium, lowest list prices were observed for Kalydeco® (ivacaftor) and Symkevi® (tezacaftor/ivacaftor) at €417 per defined daily dose (DDD) and €372 per average daily dose (ADD), respectively. Whereas, Switzerland had the lowest price for Orkambi® (lumacaftor/ivacaftor) listed at €309 per DDD. Spain had the highest prices for Kalydeco® (ivacaftor) and Symkevi® (tezacaftor/ivacaftor) at €850 per DDD and €761 per ADD, whereas Orkambi® (lumacaftor/ivacaftor) was most expensive in Poland at €983 per DDD. However, list prices were subject to confidential discounts and likely varied from actual costs. In all countries, these treatments were deemed not to be cost-effective. The annual budget impact of the CFTR modulators varied between countries and depended on factors such as local product prices, size of target population, scope of costs and discounting. However, all modulators were fully reimbursed in ten of the evaluated countries except for Sweden and Poland that, respectively, granted reimbursement to one and none of the therapies. Managed entry agreements were confidential but commonly adopted to address financial uncertainties.Conclusion: Discrepancies concerning prices, reimbursement and access were detected for Kalydeco® (ivacaftor), Orkambi® (lumacaftor/ivacaftor) and Symkevi® (tezacaftor/ivacaftor) across European countries.

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Outcomes and endpoints reported in studies of pulmonary exacerbations in people with cystic fibrosis: A systematic review

Cited by 16 publications

References 122 publications

Clinimetric Analysis of Outcome Measures for Airway Clearance in Adults with Cystic Fibrosis: A Systematic Review

Clinimetric Analysis of Outcome Measures for Airway Clearance in Adults with Cystic Fibrosis: A Systematic Review

Protocol for establishing a core outcome set for evaluation in studies of pulmonary exacerbations in people with cystic fibrosis

A Comparative Analysis of Pricing and Reimbursement of Cystic Fibrosis Transmembrane Conductance Regulator Modulators in Europe

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