Since the discovery of the gene responsible for cystic fibrosis (CF) in 1989, hopes have been pinned on a future with novel therapies tackling the basis of the disease rather than its symptoms. These have become a reality over the last decade with the development through to the clinic of CF transmembrane conductance regulator (CFTR) modulators. These are oral drugs which improve CFTR protein function through either increasing the time the channel pore is open (potentiators) or facilitating its trafficking through the cell to its location on the cell membrane (correctors). The first potentiator, ivacaftor, is now licensed and available clinically in many parts of the world. It is highly effective with impressive clinical impact in the lungs and gastrointestinal tract; longer‐term data from patient registries show fewer exacerbations, a slower rate of lung function loss and reduced need for transplantation in patients receiving ivacaftor. However, as a single drug, it is suitable for only a small minority of patients. The commonest CFTR mutation, F508del, requires both correction and potentiation for clinical efficacy. Two dual‐agent drugs (lumacaftor/ivacaftor and tezacaftor/ivacaftor) have progressed through to licensing, although their short term impact is more modest than that of ivacaftor; this is likely due to only partial correction of protein misfolding and trafficking. Most recently, triple compounds have been developed: two different corrector molecules (elexacaftor and tezacaftor) which, by addressing different regions in the misfolded F508del protein, more effectively improve trafficking. In addition to large improvements in clinical outcomes in people with two copies of F508del, the combination is sufficiently effective that it works in patients with only one copy of F508del and a second, nonmodulator responsive mutation. For the first time, we thus have a drug suitable for around 85% of people with CF. Even more gains are likely to be possible when these drugs can be used in younger children, although more sensitive outcome measures are needed for this age group. Special consideration is needed for people with very rare mutations; those with nonmodulatable mutation combinations will likely require gene or messenger RNA‐based therapeutic approaches, many of which are being explored. Although this progress is hugely to be celebrated, we still have more work to do. The international collaboration between trials networks, pharma, patient organizations, registries, and people with CF is something we are all rightly proud of, but innovative trial design and implementation will be needed if we are to continue to build on this progress and further develop drugs for people with CF.

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BackgroundIt is increasingly recognised that incorporating patients’ views in trial development improves feasibility, satisfaction and efficiency in health research. To date, there is little research on the impact of institutional organisational factors on patients‘ research experiences.AimsTo examine how organisational factors in our respiratory CRF impact on the research experience for patients, and to understand the factors influencing recruitment, retention and satisfaction. Through understanding these, we hope to incorporate patients’ views into trial implementation at our site, and suggest elements that may be transferable to other centres.MethodsA researcher independent from the CRF conducted semi-structured interviews. Patients were invited to participate on completion of one of three projects, selected to encompass different trial designs and include features previously proposed as controversial or challenging aspects of participation. A purposive, non-stratified cohort was used. Interviews were recorded, transcribed and analysed by constant comparative approach.Results25 subjects were interviewed; 17 with COPD, 4 OSA and 4 healthy volunteers. 16% had received their diagnosis within a week of parent-trial enrolment. 20% work fulltime. Patient satisfaction was high, although those newly diagnosed at parent-trial enrolment tended towards lower satisfaction and perceived their role differently. Factors motivating recruitment and retention were numerous and interlocked. Only four patients participated expecting direct health benefits. Communication, appointment flexibility and respect for time outweighed the effects of pain, fatigue and anxiety in patient retention. Social benefits of participation and feeling like a team player were important. The dedicated research facility made patients feel safer and the project was valued. Payment for participation was controversial. Reimbursement of expenses was necessary for our predominantly retired population. Transport provision was vital to breathless patients. Participation negatively impacted health perception for some.ConclusionsAn appreciation of how participants perceive their role may aid targeting recruitment strategies. Staff must recognise that valuing patients’ time and making them feel like an integral team-player improves satisfaction and retention. Researchers should consider transport provision, appointment flexibility, physical environment and reimbursing expenses when resourcing trials. Healthcare professionals should be sensitive to the impact of trial participation on health-perception, particularly for those with progressive disease.

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The rapidly changing cystic fibrosis (CF) trial landscape brings exciting opportunities and new challenges. Securing screening slots into recent late phase trials of CFTR modulators

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IntroductionEngaging people with cystic fibrosis (CF) in clinical trials is critical to improving outcomes for this fatal disease. Following extensive exploration of engagement in CF trials we believe six key concepts require a quantitative understanding of their influence in the current CF trials landscape including how controversial issues like placebos, washouts, stipend provision and location of trial visits are viewed by the CF community and how these might be modified depending on the type of medicine being investigated and the mechanism of access to the drug on trial completion.Methods and analysisWe have designed and will administer an online discrete choice experiment to elicit and quantify preferences of people with CF for these trials’ attributes and estimate the relative importance of an attribute when choosing to participate in a trial. The cross-sectional data generated will be explored using conditional multinomial logit model. Mixed logit models such as the random-parameters logit and a latent class models will be used to explore preference heterogeneity. To determine the relative importance of an attribute, the difference between the attribute level with the highest preference weight and the level with the lowest preference weight will be calculated.Ethics and disseminationImperial College London Joint Research Compliance Office has granted ethical approval for this study. Patient consent will be sought following full explanation. No identifying information will be collected. Dissemination will be via international conferences, peer-review publication and patient accessible forums. Major CF trials networks have agreed to incorporate our findings into their review process, meaning our results can realistically influence and optimise CF trial delivery.PROSPERO registration numberCRD42020184886.