Evaluating a novel model of hepatitis B care, Hep B PAST, in the Northern Territory of Australia: results from a prospective, population-based study.

Background: The Northern Territory (NT) has the highest prevalence of chronic hepatitis B (CHB) in Australia. The Hep B PAST program aims to improve health outcomes for people living with CHB. Methods: This mixed methods study involves First Nations peoples living in the NT. We used participatory action research principles across three steps: 1. Foundation step: establishing hepatitis B virus (HBV) status and linkage to care; 2. Capacity building: training the health workforce; 3. Supported transition to primary healthcare: implementation of the "Hub and Spoke" model and in-language resources. Analysis occurred at three time points: 1. Pre-Hep B PAST (2018); 2. Foundation step (2020); and 3. Completion of Hep B PAST (2023). Evaluation focuses on four key indicators, the number of people: 1) with documented HBV status; 2) diagnosed with CHB; 3) receiving care; and 4) receiving treatment. Findings: Hep B PAST (2018-23) reached 40,555 people. HBV status was documented in 11% (1192/10,853), 79.2% (26,075/32,915) and 90.8% (28,675/31,588) of people at pre-Hep B PAST, foundation step, and completion respectively. An estimated 99.9% (821/822) of people were diagnosed, 86.3% (709/822) engaged in care, and 24.1% (198/822) on antiviral treatment at completion. CHB prevalence in the study population is 2.6%, decreasing from 6.1% to 0.4% in the pre- and post-vaccination cohorts. Interpretation: Hep B PAST is an effective model of care. Partner health services are exceeding elimination targets. This model could enable other countries to enhance the cascade of care and work towards eliminating HBV. Funding: National Health and Medical Research Council.

Financial incentives to motivate treatment for hepatitis C with direct acting antivirals among Australian adults (The Methodical evaluation and Optimisation of Targeted IncentiVes for Accessing Treatment of Early-stage hepatitis C: MOTIVATE-C): protocol for a dose-response randomised controlled study.

BACKGROUND: Untreated hepatitis C virus (HCV) infection can result in cirrhosis and hepatocellular cancer. Direct-acting antiviral (DAA) therapies are highly effective and have few side effects compared to older interferon-based therapy. Despite the Australian government providing subsidised and unrestricted access to DAA therapy for chronic HCV infection, uptake has not been sufficient to meet the global target of eliminating HCV as a public health threat by 2030. This study will offer people with HCV financial incentives of varying values in order to evaluate its effect on initiation of DAA therapy in primary care. METHODS: Australian adults (18 years or older) who self-report as having current untreated HCV infection can register to participate via an automated SMS-based system. Following self-screening for eligibility, registrants are offered a financial incentive of randomised value (AUD 0 to 1000) to initiate DAA therapy. Study treatment navigators contact registrants who have consented to be contacted, to complete eligibility assessment, outline the study procedures (including the requirement for participants to consult a primary care provider), obtain consent, and finalise enrolment. Enrolled participants receive their offered incentive on provision of evidence of DAA therapy initiation within 12 weeks of registration (primary endpoint). Balanced randomisation is used across the incentive range until the first analysis, after which response-adaptive randomisation will be used to update the assignment probabilities. For the primary analysis, a Bayesian 4-parameter EMAX model will be used to estimate the dose-response curve and contrast treatment initiation at each incentive value against the control arm (AUD 0). Specified secondary statistical and economic analyses will evaluate the effect of incentives on adherence to DAA therapy, virological response, and cost-effectiveness. DISCUSSION: This project seeks to gain an understanding of the dose-response relationship between incentive value and DAA treatment initiation, while maximising the number of people treated for HCV within fixed budget and time constraints. In doing so, we hope to offer policy-relevant recommendation(s) for the use of financial incentives as a pragmatic, efficient, and cost-effective approach to achieving elimination of HCV from Australia. TRIAL REGISTRATION: ANZCTR (anzctr.org.au), Identifier ACTRN12623000024640, Registered 11 January 2023 ( https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=384923&isReview=true ).

An evaluation and refinement of the "Hep B Story" app, tailored to meet the community's cultural needs.

BACKGROUND: Hepatitis B is endemic amongst the Australian Aboriginal population in the Northern Territory. A participatory action research project identified the lack of culturally appropriate education tools and led to the development of the "Hep B Story" app in the Aboriginal language Yolŋu Matha. This paper describes a formal evaluation of the app's first version, which informed improvements and translation into a further ten Aboriginal languages. METHODS: The evaluation employed Participatory Action Research (PAR) principles to work within Indigenous research methodologies and prioritise Indigenous knowledge to improve the app iteratively. Semi-structured interviews and focus groups were conducted across the Northern Territory with 11 different language groups. Local Community Based Researchers and Aboriginal Research team members coordinated sessions. The recorded, translated conversations were transcribed verbatim and thematically analysed using an inductive and deductive approach. RESULTS: Between November 2018 and September 2020, 94 individuals from 11 language groups participated in 25 semi-structured interviews and 10 focus groups. All participants identified as Aboriginal. Most participants felt the app would be culturally appropriate for Aboriginal communities in the Northern Territory and improve knowledge surrounding hepatitis B. The information gathered from these interviews allowed for identifying five main themes: support for app, relationships, concept versus language, shame, and perceptions of images, along with errors that required modification. CONCLUSIONS: A "real-life" evaluation of the app was comprehensively completed using a PAR approach blended with Indigenous research methods. This evaluation allowed us to develop an updated and enhanced version of the app before creating the additional ten language versions. An iterative approach alongside strong community engagement was pivotal in ensuring the app's cultural safety and appropriateness. We recommend avoiding the use of knowledge-based evaluations in an Aboriginal setting to ensure relevant and culturally appropriate feedback is obtained.

Neutrophil-to-lymphocyte ratio as a biomarker of acute pulmonary exacerbations in children with cystic fibrosis: a retrospective cohort study.

BACKGROUND: Neutrophils are key contributors to chronic airway inflammation in cystic fibrosis (CF) lung disease, although airway and blood-based neutrophil markers are seldom used. The neutrophil-to-lymphocyte ratio (NLR) is an accessible biomarker, the clinical utility of which has not been adequately studied. OBJECTIVE: This study aimed to investigate the characteristics of the NLR in children with CF and its correlations with acute pulmonary exacerbations and spirometry. DESIGN: A previous study had collected clinical data from children with CF for a 3-year period between 2016 and 2021. Retrospectively, NLR values were categorised according to patients' clinical status during blood sample collection as 'stable', 'acute pulmonary exacerbation' or 'elective admission for chronic clinical concern'. MAIN OUTCOME MEASURES: Demographic characteristics associated with the NLR; changes in NLR values in relation to clinical status; relationship between NLR and lung function. RESULTS: 141 children with CF were included. NLR values during clinical stability were higher in females and increased with age. For children admitted for intravenous antibiotics, NLR values significantly increased from clinical stability (median (IQR)=1.13 (0.75-1.51)) to acute pulmonary exacerbations (median (IQR)=1.50 (0.96-2.65), p=0.001), but similar changes were not observed in elective admissions. The NLR was not associated with lung function. CONCLUSIONS: The NLR demonstrated associations with clinical status in children with CF with significant elevations during acute pulmonary exacerbations. While its utility as a single-marker measure is limited, monitoring the NLR over time may help identify periods of increased inflammation.

Levelling the playing field through the London Network of the UK clinical trials accelerator platform.

Cystic fibrosis (CF) is a multisystem, genetic disease with a significantly reduced life expectancy. Despite substantial progress in therapies in the last 10-15 years, there is still no cure. There are dozens of drugs in the development pipeline and multiple clinical trials are being conducted across the globe. The UK Cystic Fibrosis Trust's (CFT) Clinical Trials Accelerator Platform (CTAP) is a national initiative bringing together 25 UK based CF centres to support the CF community in accessing and participating in CF clinical trials. CTAP enables more CF centres to run a broader portfolio of trials and increases the range of CF studies available for UK patients. There are four large specialist CF centres based in London, all within a small geographical region as well as two smaller centres which deliver CF care. At the launch of CTAP, these centres formed a sub-network in a consortium-style collaboration. The purpose of the network was to ensure equity of access to trials for patients across the UK's capital, and to share experience and knowledge. Four years into the programme we have reviewed our practices through working group meetings and an online survey. We sought to identify strengths and areas for improvement. We share our findings here, as we believe they are relevant to others delivering research in regions outside of London and in other chronic diseases.

Standards for the care of people with cystic fibrosis (CF); Planning for a longer life.

This is the final of four papers updating standards for the care of people with CF. That this paper "Planning a longer life" was considered necessary, highlights how much CF care has progressed over the past decade. Several factors underpin this progress, notably increased numbers of people with CF with access to CFTR modulator therapy. As the landscape for CF changes, so do the hopes and aspirations of people with CF and their families. This paper reflects the need to consider people with CF not as a "problem" to be solved, but as a success, a potential and a voice to be heard. People with CF and the wider CF community have driven this approach, reflecting many of the topics in this paper. This exercise involved wide stakeholder engagement. People with CF are keen to contribute to research priorities and be involved in all stages of research. People with CF want healthcare professionals to respect them as individuals and consider the impact of our actions on the world around us. Navigating life presents challenges to all, but for people with CF these challenges are heightened and complex. In this paper we highlight the concerns and life moments that impact people with CF, and events that the CF team should aim to support, including the challenges around having a family. People with CF and their care teams must embrace the updated standards outlined in these four papers to enjoy the full potential for a healthier life.

The feasibility of introducing a whole blood component for traumatic haemorrhage in the UK.

BACKGROUND: The interest in re-introducing whole blood (WB) transfusion for the management of traumatic major haemorrhage is increasing. However, due to the current leucodepletion filters used in the UK a WB component was not readily available. Instead, an alternative but similar component, leucocyte depleted red cell and plasma (LD-RCP), which provided a unique experience in assessing the feasibility of a WB component was used whilst a WB component was being manufactured. STUDY DESIGN AND METHODS: Between November 2018 and October 2020, LD-RCP replaced RBC as standard of care for all trauma patients with major haemorrhage in London. The aims of the study were to assess (a) deliverability, (b) component wastage and (c) safety. RESULTS: Over the study period a total of 1208 LD-RCP units were delivered, of which 96.5% were delivered 'On Time In Full' (OTIF). Of the 1208 units, 733 (60.68%) were transfused and 475 (39.3%) units were wasted. Component wastage reduced significantly throughout the study (p = 0.001). A total of 177 patients had a blood group recorded, 86 were group O and 91 were non-group O. There was no statistically significantly difference between haemoglobin (p = 0.422), or bilirubin levels (p = 0.084) between group O and non-group O patients. DISCUSSION: It was feasible for NHS Blood and Transplant to deliver LD-RCP on time in full, however component wastage was high due to short shelf life and limited use of the component. Low titre group O LD-RCP units were not associated with clinical evidence of haemolysis.

Adapting and translating the 'Hep B Story' App the right way: A transferable toolkit to develop health resources with, and for, Aboriginal people.

ISSUE ADDRESSED: In 2014 the 'Hep B Story App', the first hepatitis B educational app in an Aboriginal language was released. Subsequently, in 2018, it was assessed and adapted before translation into an additional 10 Aboriginal languages. The translation process developed iteratively into a model that may be applied when creating any health resource in Aboriginal languages. METHODS: The adaptation and translation of the 'Hep B Story' followed a tailored participatory action research (PAR) process involving crucial steps such as extensive community consultation, adaptation of the original material, forward and back translation of the script, content accuracy verification, voiceover recording, and thorough review before the publication of the new version. RESULTS: Iterative PAR cycles shaped the translation process, leading to a refined model applicable to creating health resources in any Aboriginal language. The community-wide consultation yielded widespread chronic hepatitis B education, prompting participants to share the story within their families, advocating for hepatitis B check-ups. The project offered numerous insights and lessons, such as the significance of allocating sufficient time and resources to undertake the process. Additionally, it highlighted the importance of implementing flexible work arrangements and eliminating barriers to work for the translators. CONCLUSIONS: Through our extensive work across the Northern Territory, we produced an educational tool for Aboriginal people in their preferred languages and developed a translation model to create resources for different cultural and linguistic groups. SO WHAT?: This translation model provides a rigorous, transferable method for creating accurate health resources for culturally and linguistically diverse populations.

An exploration of managing emotional labour and maintaining professional integrity in children's hospice nursing.

BACKGROUND: Research exploring nurse-parent relationships in children's hospices is rare. AIM: To investigate how children's hospice nurses manage emotional labour and professional integrity in their long-term relationships with parents. METHODS: A purposive sample of six children's nurses, from hospices across England, recorded audio diaries and participated in telephone interviews. Narratives were thematically analysed. FINDINGS: Three overarching, cross-cutting themes were identified-purposeful positioning; balancing personability and professionalism; coping with and counterbalancing emotional labour. All themes were indicative of and/or built upon emotional intelligence constructs, such as self-awareness, self-regulation, appropriate (managed) empathy, social skills and intrinsic motivation. Innate features of children's hospice work were important for perpetuating intrinsic motivation and satisfaction. CONCLUSION: This study provided an insight into the management of emotional labour and professional integrity by experienced children's hospice nurses. The identification of emotional intelligence skills merits further exploration in this environment, as well as other children's palliative care settings.

Safety and efficacy of ivacaftor in infants aged 1 to less than 4 months with cystic fibrosis.

BACKGROUND: Ivacaftor (IVA) has been shown to be safe and efficacious in children aged ≥4 months with cystic fibrosis (CF) and CFTR gating variants. We evaluated safety, pharmacokinetics (PK), and efficacy of IVA in a small cohort of infants aged 1 to <4 months with CF. METHODS: In this phase 3, open-label study, infants 1 to <4 months with CF and an IVA-responsive CFTR variant received an initial low dose of IVA based on age and weight. Because IVA is a sensitive CYP3A substrate and CYP3A maturation is uncertain in infants, doses were adjusted at day 15 to better match median adult exposures based on individual PK measurements taken on day 4. Primary endpoints were safety and PK measurements. RESULTS: Seven infants (residual function CFTR variants [n=5]; minimal function CFTR variants [n=2]) received ≥1 dose of IVA. Six infants had doses adjusted at day 15 and one infant did not require dose adjustment; subsequent PK analyses showed mean trough concentrations for IVA and metabolites were within range of prior clinical experience. Four infants (57.1%) had adverse events (AEs); no serious AEs were noted. One infant discontinued study drug due to a non-serious AE of elevated alanine aminotransferase >8x the upper limit of normal. Mean sweat chloride concentration decreased (-40.3 mmol/L [SD: 29.2]) through week 24. Improvements in biomarkers of pancreatic function and intestinal inflammation, as well as growth parameters, were observed. CONCLUSIONS: In this small, open-label study, IVA dosing in infants achieved exposures previously shown to be safe and efficacious. Because PK was predictable, a dosing regimen based on age and weight is proposed. IVA was generally safe and well tolerated, and led to improvements in CFTR function, markers of pancreatic function and intestinal inflammation, and growth parameters, supporting use in infants as young as 1 month of age.

Hepatitis C Virus Antiviral Drug Resistance and Salvage Therapy Outcomes Across Australia.

Background: Hepatitis C virus (HCV) infection can now be cured with well-tolerated direct-acting antiviral (DAA) therapy. However, a potential barrier to HCV elimination is the emergence of resistance-associated substitutions (RASs) that reduce the efficacy of antiviral drugs, but real-world studies assessing the clinical impact of RASs are limited. Here, an analysis of the impact of RASs on retreatment outcomes for different salvage regimens in patients nationally who failed first-line DAA therapy is reported. Methods: We collected data from 363 Australian patients who failed first-line DAA therapy, including: age, sex, fibrosis stage, HCV genotype, NS3/NS5A/NS5B RASs, details of failed first-line regimen, subsequent salvage regimens, and treatment outcome. Results: Of 240 patients who were initially retreated as per protocol, 210 (87.5%) achieved sustained virologic response (SVR) and 30 (12.5%) relapsed or did not respond. The SVR rate for salvage regimens that included sofosbuvir/velpatasvir/voxilaprevir was 94.3% (n = 140), sofosbuvir/velpatasvir 75.0% (n = 52), elbasvir/grazoprevir 81.6% (n = 38), and glecaprevir/pibrentasvir 84.6% (n = 13). NS5A RASs were present in 71.0% (n = 210) of patients who achieved SVR and in 66.7% (n = 30) of patients who subsequently relapsed. NS3 RASs were detected in 20 patients (20%) in the SVR group and 1 patient in the relapse group. NS5B RASs were observed in only 3 patients. Cirrhosis was a predictor of relapse after retreatment, as was previous treatment with sofosbuvir/velpatasvir. Conclusions: In our cohort, the SVR rate for sofosbuvir/velpatasvir/voxilaprevir was higher than with other salvage regimens. The presence of NS5A, NS5B, or NS3 RASs did not appear to negatively influence retreatment outcomes.

What is cystic fibrosis screen positive inconclusive diagnosis? And what is it not?

Since screening for cystic fibrosis (CF) was incorporated into the newborn screening program, the number of recognised variants in the CF transmembrane conductance regulator (CFTR) gene has significantly increased. This has led to the discovery of combinations of gene variants with an uncertain prognosis. One outcome is the designation of 'cystic fibrosis screen positive inconclusive diagnosis' (CFSPID). While the majority of these children are expected to be unaffected by their CFTR variants, a small proportion have been seen to develop symptoms or increasing sweat chloride levels over time, which may reflect dysfunction of the CFTR protein.As the number of children with CFSPID increases, paediatricians and those working in primary care are more likely to encounter them in their practice. It is important that professionals have an understanding of CFSPID: what it is and, importantly, what it is not (ie, they do not have CF). In this article, we hope to explore this using some example cases, illustrating the ways in which these children may present symptomatically and how to manage them.

"Putting the power back into community": A mixed methods evaluation of a chronic hepatitis B training course for the Aboriginal health workforce of Australia's Northern Territory.

BACKGROUND: Chronic hepatitis B (CHB) is endemic in the Aboriginal and Torres Strait Islander population of Australia's Northern Territory. Progression to liver disease can be prevented if holistic care is provided. Low health literacy amongst health professionals is a known barrier to caring for people living with CHB. We co-designed and delivered a culturally safe "Managing hepatitis B" training course for the Aboriginal health workforce. Here, we present an evaluation of the course. OBJECTIVES: 1. To improve course participants CHB-related knowledge, attitudes, and clinical practice. 2. To evaluate the "Managing hepatitis B" training course. 3. To enable participants to have the skills and confidence to be part of the care team. METHODS: We used participatory action research and culturally safe principles. We used purpose-built quantitative and qualitative evaluation tools to evaluate our "Managing hepatitis B" training course. We integrated the two forms of data, deductively analysing codes, grouped into categories, and assessed pedagogical outcomes against Kirkpatrick's training evaluation framework. RESULTS: Eight courses were delivered between 2019 and 2023, with 130 participants from 32 communities. Pre- and post-course questionnaires demonstrated statistically significant improvements in all domains, p<0.001 on 93 matched pairs. Thematic network analysis demonstrated high levels of course acceptability and significant knowledge acquisition. Other themes identified include cultural safety, shame, previous misinformation, and misconceptions about transmission. Observations demonstrate improvements in post-course engagement, a deep understanding of CHB as well as increased participation in clinical care teams. CONCLUSIONS: The "Managing hepatitis B" training course led to a sustained improvement in the knowledge and attitudes of the Aboriginal health workforce, resulting in improved care and treatment uptake for people living with CHB. Important non-clinical outcomes included strengthening teaching and leadership skills, and empowerment.

Hepatitis B genotypes in Aboriginal and Torres Strait Islander Australians: correlation with clinical course and implications for management.

BACKGROUND: The prevalence of chronic hepatitis B (CHB) in Aboriginal and Torres Strait Islander Australians in Far North Queensland (FNQ) is greater than twice that of the general Australian population. CHB is common in Torres Strait Islanders diagnosed with hepatocellular carcinoma (HCC) - and in Aboriginals with HCC living in the Northern Territory - however, Aboriginals diagnosed with HCC in FNQ very rarely have CHB. The explanation for this apparent disparity is uncertain. AIMS: To determine the HBV genotypes in the FNQ Aboriginal and Torres Strait Islander population and their correlation with clinical phenotype. METHODS: We determined the HBV genotype of Aboriginal and Torres Strait Islander Australians living with CHB in FNQ and correlated this with demographic and clinical findings. RESULTS: 134/197 (68%) enrolled individuals had a sufficient viral load for genotyping. All 40 people with HBV/D genotype had Aboriginal heritage, whereas 85/93 (91%) with HBV/C had Torres Strait Islander heritage (P < 0.0001). Individuals with HBV/D were younger than those with HBV/C (median (interquartile range) age: 43 (39-48) vs 53 (42-66) years, P = 0.0002). However, they were less likely to be HBeAg positive (1/40 (3%) vs 23/93 (25%), P = 0.001). All three HCCs developed in Torres Strait Islanders; two-thirds were infected with HBV/C14; genotyping was not possible in the other individual. All 10 diagnoses of cirrhosis occurred in Torres Strait Islanders, 6/10 were infected with HBV/C14, genotyping was not possible in the other four individuals. CONCLUSIONS: HBV genotypes in Aboriginal and Torres Strait Islander Australians in FNQ differ markedly, which could explain the significant differences in the clinical phenotype in the two populations and might be used to inform cost-effective CHB care in the region.

A discrete choice experiment to quantify the influence of trial features on the decision to participate in cystic fibrosis trials.

BACKGROUND: Patient-centred trial design optimises recruitment and retention, reduces trial failure rates and increases the diversity of trial cohorts. This allows safe and effective treatments to reach clinic more quickly. To achieve this, patients' views must be incorporated into trial design. METHODS: A discrete choice experiment was used to quantify preferences of pwCF for trials features; medicine type, trial location, stipend, washout, drug access on trial completion and trial design. Respondents were presented pairs of hypothetical trial scenarios with different level combinations assigned through experimental design. Respondents were asked to pick their preferred option or decline both. The cross-sectional data were explored using a Random Parameters Logit model. RESULTS: We received 207 eligible responses between Oct2020-Jan2021. The strongest influence on the decision to participate was trial location; pwCF favour participation at their usual clinical centre. Greater travel distances made respondents less willing to participate. Post-trial drug access ranked second. pwCF would rather participate in modulator trials than trials of other drugs. In general, pwCF did not favour a washout period, but were more prepared to washout non-modulators than modulators. Stipend provision was not ranked highly, but higher stipends increased intention to participate. Trial design (placebo vs open-label) had minimal influence on the decision to participate. There are complex interactions between placebos and washouts. CONCLUSIONS: We used quantitative methods to systematically elicit preferences of pwCF for clinical trials' features. We explore the relevance of our findings to trial design and delivery in the current CF trials landscape.

Avoiding misclassification of acute kidney injury: Timing is everything.

Accurate detection of acute kidney injury (AKI) in clinical trials is important. Using a 'baseline' creatinine from trial enrolment may not be ideal for understanding a participant's true baseline kidney function. We aimed to determine if a 'pre-trial baseline creatinine' resulted in comparable creatinine concentrations to a 'trial baseline creatinine', and how the timing of baseline creatinine affected the incidence of AKI in the Combination Antibiotic therapy for MEthicillin Resistant Staphylococcus aureus (CAMERA2) randomised trial. Study sites retrospectively collected a pre-trial baseline creatinine from up to 1 year before CAMERA2 trial enrolment ideally when the patient was medically stable. Baseline creatinine from CAMERA2 (the 'trial baseline creatinine'), was the highest creatinine measurement in the 24 h preceding trial randomisation. We used Wilcoxon sign rank test to compare pre-trial and trial baseline creatinine concentrations. We included 217 patients. The median pre-trial baseline creatinine was significantly lower than the median trial baseline creatinine (82 µmol/L [IQR 65-104 µmol/L] versus 86 µmol/L [IQR 66-152 µmol/L] p = <0.001). Using pre-trial baseline creatinine, 48 of 217 patients (22%) met criteria for an AKI at CAMERA2 enrolment and only 5 of these patients met criteria for an AKI using the CAMERA2 study protocol (using baseline creatinine from trial entry). Using a baseline creatinine from the time of trial enrolment failed to detect many patients with AKI. Trial protocols should consider the optimal timing of baseline creatinine and the limitations of using a baseline creatinine during an acute illness.

How representative are clinical trial cohorts of the general CF population? Implications for trial planning.

Understanding the number of patients eligible to participate in research is important to design protocols and define research priorities. We reviewed the records of all patients with CF, age 12+, who receive care at our centre. We assessed their eligibility for trial participation based on common trial inclusion/exclusion criteria. 643 patients were included in the analysis, 31 were modulator ineligible(MI). Only 198(31 %) of the total cohort and 7(23 %) of the MI cohort were eligible for participation based on the hypothetical criteria. The most common reason for ineligibility was ppFEV1 ≥90 % followed by clinical instability, complex comorbidity and anticipated inability to adhere to the protocol. We suggest this would be a useful exercise for centres planning to either participate in, or refer subjects into, upcoming trials to undertake for their own cohort. We also make suggestions for protocol designs that optimise the number of patients who are eligible to participate.