Chirag Dave

The effect of domiciliary noninvasive ventilation on clinical outcomes in stable and recently hospitalized patients with COPD: a systematic review and meta-analysis

Introduction Noninvasive ventilation (NIV) improves survival among patients with hypercapnic respiratory failure in hospital, but evidence for its use in domiciliary settings is limited. A patient’s underlying risk of having an exacerbation may affect any potential benefit that can be gained from domiciliary NIV. This is the first comprehensive systematic review to stratify patients based on a proxy for exacerbation risk: patients in a stable state and those immediately post-exacerbation hospitalization. Methods A systematic review of nonrandomized and randomized controlled trials (RCTs) was undertaken in order to compare the relative effectiveness of different types of domiciliary NIV and usual care on hospital admissions, mortality, and health-related quality of life. Standard systematic review methods were used for identifying studies (until September 2014), quality appraisal, and synthesis. Data were presented in forest plots and pooled where appropriate using random-effects meta-analysis. Results Thirty-one studies were included. For stable patients, there was no evidence of a survival benefit from NIV (relative risk [RR] 0.88 [0.55, 1.43], I2=60.4%, n=7 RCTs), but there was a possible trend toward fewer hospitalizations (weighted mean difference −0.46 [−1.02, 0.09], I2=59.2%, n=5 RCTs) and improved health-related quality of life. For posthospital patients, survival benefit could not be demonstrated within the three RCTs (RR 0.89 [0.53, 1.49], I2=25.1%), although there was evidence of benefit from four non-RCTs (RR 0.45 [0.32, 0.65], I2=0%). Effects on hospitalizations were inconsistent. Post hoc analyses suggested that NIV-related improvements in hypercapnia were associated with reduced hospital admissions across both populations. Little data were available comparing different types of NIV. Conclusion The effectiveness of domiciliary NIV remains uncertain; however, some patients may benefit. Further research is required to identify these patients and to explore the relevance of improvements in hypercapnia in influencing clinical outcomes. Optimum time points for commencing domiciliary NIV and equipment settings need to be established.

Utility of respiratory ward-based NIV in acidotic hypercapnic respiratory failure

We sought to elicit predictors of in‐hospital mortality for first and subsequent admissions with acidotic hypercapnic respiratory failure (AHRF) in a cohort of chronic obstructive pulmonary disease patients who have undergone ward‐based non‐invasive ventilation (NIV), and identify features associated with long‐term survival.

Protocol for a systematic review and economic evaluation of the clinical and cost-effectiveness of non-hospital-based non-invasive ventilation (NIV) in patients with stable end-stage COPD with hypercapnic respiratory failure

BackgroundChronic obstructive pulmonary disease (COPD) remains a significant public health burden. Non-invasive ventilation (NIV) is a method of supported breathing used as standard care for acutely unwell patients in hospital with COPD, but there is uncertainty around the potential benefits of using NIV in the treatment of stable patients in a non-hospital setting. This is a protocol for systematic reviews of the clinical and cost-effectiveness of NIV in this context, being undertaken in support of a model based economic evaluation.Methods/DesignStandard systematic review methods aimed at minimising bias will be employed for study identification, selection and data extraction for both the clinical and economic systematic reviews. Bibliographic databases (for example MEDLINE, EMBASE) and ongoing trials registers will be searched from 1980 onwards. The search strategy will combine terms for the population with those for the intervention. Studies will be selected for review if the population includes adult patients with COPD and hypercapnic respiratory failure, however defined. Systematic reviews, randomised controlled trials and observational studies (with n >1) will be included, and quality assessment will be tailored to the different study designs. The primary outcome measures of interest are survival, quality of life, and healthcare utilisations (hospitalisation and Accident and Emergency attendances). Meta-analyses will be undertaken where clinical and methodological homogeneity exists, supported by predefined subgroup analyses where appropriate. A systematic review of the evidence on the cost-effectiveness of non-hospital NIV will be completed, and a model-based cost-utility analysis undertaken to determine the cost-effectiveness of non-hospital-based NIV compared with standard care.DiscussionThese reviews will attempt to clarify the clinical effectiveness of non-hospital NIV in COPD patients as well as the cost-effectiveness. The findings may indicate whether NIV in a non-hospital setting should be considered more routinely in this patient group, and what the likely cost implications will be.PROSPERO registration2012:CRD42012003286.

Adapting to domiciliary non-invasive ventilation in chronic obstructive pulmonary disease: A qualitative interview study

Background: Domiciliary non-invasive ventilation may be used in palliative care of patients with chronic obstructive pulmonary disease, although there is uncertainty regarding effect on quality of life. Aim: Explore experiences of domiciliary non-invasive ventilation in chronic obstructive pulmonary disease, to understand decision-making processes and improve future palliative care. Design: Qualitative interview study, based on constructivist grounded theory, and using the framework method for data management and analysis. Participants: 20 chronic obstructive pulmonary disease patients, 4 carers and 15 healthcare professionals. Results: Most patients had very severe chronic obstructive pulmonary disease. Data were categorised into four domains – clinical, technical, socio-economic and experiential. Healthcare professionals felt uncertain regarding clinical evidence, emphasising social support and tolerance as deciding factors in non-invasive ventilation use. Conversely, patients reported symptomatic benefit, which generally outweighed negative experiences and led to continued use. Healthcare professionals felt that patients chose to be on non-invasive ventilation; however, most patients felt that they had no choice as healthcare professionals recommended non-invasive ventilation or their poor health mandated it. Conclusions: Our study identifies ‘adapting to non-invasive ventilation’ as the central process enabling long-term use in palliative care, although the way in which this is approached by healthcare professionals and patients does not always converge. We present ideas emerging from the data on potential interventions to improve patient experience and adaptation.

The cost-effectiveness of domiciliary non-invasive ventilation in patients with end-stage chronic obstructive pulmonary disease: a systematic review and economic evaluation

BACKGROUND Chronic obstructive pulmonary disease (COPD) is a chronic progressive lung disease characterised by non-reversible airflow obstruction. Exacerbations are a key cause of morbidity and mortality and place a considerable burden on health-care systems. While there is evidence that patients benefit from non-invasive ventilation (NIV) in hospital during an acute exacerbation, evidence supporting home use for more stable COPD patients is limited. In the U.K., domiciliary NIV is considered on health economic grounds in patients after three hospital admissions for acute hypercapnic respiratory failure. OBJECTIVE To assess the clinical effectiveness and cost-effectiveness of domiciliary NIV by systematic review and economic evaluation. DATA SOURCES Bibliographic databases, conference proceedings and ongoing trial registries up to September 2014. METHODS Standard systematic review methods were used for identifying relevant clinical effectiveness and cost-effectiveness studies assessing NIV compared with usual care or comparing different types of NIV. Risk of bias was assessed using Cochrane guidelines and relevant economic checklists. Results for primary effectiveness outcomes (mortality, hospitalisations, exacerbations and quality of life) were presented, where possible, in forest plots. A speculative Markov decision model was developed to compare the cost-effectiveness of domiciliary NIV with usual care from a UK perspective for post-hospital and more stable populations separately. RESULTS Thirty-one controlled effectiveness studies were identified, which report a variety of outcomes. For stable patients, a modest volume of evidence found no benefit from domiciliary NIV for survival and some non-significant beneficial trends for hospitalisations and quality of life. For post-hospital patients, no benefit from NIV could be shown in terms of survival (from randomised controlled trials) and findings for hospital admissions were inconsistent and based on limited evidence. No conclusions could be drawn regarding potential benefit from different types of NIV. No cost-effectiveness studies of domiciliary NIV were identified. Economic modelling suggested that NIV may be cost-effective in a stable population at a threshold of £30,000 per quality-adjusted life-year (QALY) gained (incremental cost-effectiveness ratio £28,162), but this is associated with uncertainty. In the case of the post-hospital population, results for three separate base cases ranged from usual care dominating to NIV being cost-effective, with an incremental cost-effectiveness ratio of less than £10,000 per QALY gained. All estimates were sensitive to effectiveness estimates, length of benefit from NIV (currently unknown) and some costs. Modelling suggested that reductions in the rate of hospital admissions per patient per year of 24% and 15% in the stable and post-hospital populations, respectively, are required for NIV to be cost-effective. LIMITATIONS Evidence on key clinical outcomes remains limited, particularly quality-of-life and long-term (> 2 years) effects. Economic modelling should be viewed as speculative because of uncertainty around effect estimates, baseline risks, length of benefit of NIV and limited quality-of-life/utility data. CONCLUSIONS The cost-effectiveness of domiciliary NIV remains uncertain and the findings in this report are sensitive to emergent data. Further evidence is required to identify patients most likely to benefit from domiciliary NIV and to establish optimum time points for starting NIV and equipment settings. FUTURE WORK RECOMMENDATIONS The results from this report will need to be re-examined in the light of any new trial results, particularly in terms of reducing the uncertainty in the economic model. Any new randomised controlled trials should consider including a sham non-invasive ventilation arm and/or a higher- and lower-pressure arm. Individual participant data analyses may help to determine whether or not there are any patient characteristics or equipment settings that are predictive of a benefit of NIV and to establish optimum time points for starting (and potentially discounting) NIV. STUDY REGISTRATION This study is registered as PROSPERO CRD42012003286. FUNDING The National Institute for Health Research Health Technology Assessment programme.

S83 An Economic Evaluation Of Domiciliary Non-invasive Ventilation (niv) In Patients With End-stage Copd In The Uk

This abstract summarises independent research funded by the National Institute for Health Research (NIHR) under its HTA Programme (Ref 11/27/01). The views expressed are those of the author (s) and not necessarily those of the NHS, the NIHR or the Department of Health. Background NIV is an established treatment for the management of acute exacerbation of COPD but less is known about the effectiveness of NIV in the home setting. Many clinicians consider domiciliary NIV to be cost-effective in patients that have experienced three or more exacerbations however no economic evaluations, using decision modelling have been conducted. Methods The findings of a systematic clinical review of the clinical effectiveness of domiciliary NIV in COPD were applied in a Markov model, to estimate cost-effectiveness, from a UK perspective, when compared to usual care. Outcomes were measured in Quality Adjust Life Years (QALYs). Two end-stage COPD populations were considered; patients that were stable for at least twelve weeks (stable population) and those recently discharged for exacerbation (post-admission population). Given the uncertainty around the effect of domiciliary NIV on admissions and mortality in both populations, extensive sensitivity analysis was conducted to quantify and likelihood of NIV being cost-effective at a thresholds of £30,000 per QALY and the model’s sensitivity to key parameters. Results This model indicated that domiciliary NIV is unlikely to be cost-effective in stable populations but is more likely to be cost-effective post-admission. However, there was considerable uncertainty around the results for both populations. The model was most sensitive to changes in the risk ratio for admission and the duration of the effect but was also sensitive to changes in baseline risk of admissions. Conclusion This model indicates that domiciliary NIV is unlikely to be cost-effective in stable patients but maybe cost-effective in patients with a history of admissions. This speculative economic model describes the uncertainty around these conclusions.

P149 Characteristic And Prognosis Of Patients With Copd And Type 2 Respiratory Failure

Introduction Factors associated with type 2 respiratory failure (T2RF) in COPD have been poorly described. Co-existent obstructive sleep apnoea is thought to play a part,1 and episodes of worsening hypercapnia, associated with acidosis (AHRF), at the time of exacerbations is a well recognised feature.2 We hypothesised that the development of hypercapnia or type 2 respiratory failure would associate with a higher risk of subsequent AHRF and higher mortality. Methods 292 patients who had been prescribed oxygen for their COPD during 2006–2010 were studied. Medical records were reviewed for lung function, blood gases in the stable state, episodes of AHRF and mortality up to the end of March 2014. Cross-sectional analyses seeking associations of hypercapnia and T2RF were carried out, together with comparisons of FEV1 decline, AHRF and mortality between those with and without T2RF. Results Mean follow up duration was 6.7 years. 164 patients died and 90 had one or more episodes of AHRF; AHRF was more common in T2RF (p = 0.046). Cox regression analysis, adjusting for age, demonstrated that death was more likely in those with T2RF compared to T1RF (Figure 1; p = 0.018). A rise in CO2 after administration of oxygen during the test of LTOT eligibility showed a similar association, but it was less strong (p = 0.041). Lung function was strongly associated with T2RF and subsequent use of NIV for AHRF; 53% of those with FEV1 <30% predicted eventually required it. This increased to 81% if FEV1 was less than 20% predicted. After adjusting for baseline FEV1 in the regression model, FEV1 decline did not differ between T2RF and T1RF. Conclusions LTOT patients with T2RF are at higher risk of AHRF and death, thus should be followed up more closely and more effort made to record advance wishes regarding NIV, if appropriate. References Obesity and respiratory diseases. Murugan AT, Sharma G. Chron Respir Dis. 2008; 5(4):233–42 Acidosis, non-invasive ventilation and mortality in hospitalised COPD exacerbation. Roberts CM, Stone RA, Buckingham RJ, Pursey NA, Lowe D. Thorax (2011) 66(1): 43–8 Abstract P149 Figure 1