A mixed methods study in cystic fibrosis following the widespread availability of elexacaftor/tezacaftor/ivacaftor. Understanding the impact of context change in long-term condition care

This study explored how the introduction of elexacaftor/tezacaftor/ivacaftor (ETI) has
shaped cystic fibrosis (CF) care. This pragmatic, mixed-methods Realist Evaluation
examined how clinicians and people with CF (pwCF) made sense of and responded to
this contextual change, focussing on adherence to inhaled medicines and the evolving
configuration of specialist CF services.

Initial Programme Theory was developed through interviews with CF clinicians across the
UK. It was refined through a national survey and realist focus groups with pwCF. Feasible
elements of Programme Theory were tested in a multivariable regression analysis.
The refined Programme Theory identified key mechanisms shaping post-ETI care.
Restored wellness has led pwCF and clinicians to re-evaluate the role of burdensome
inhaled medicines and models of care. Many pwCF feel empowered to autonomously
reduce inhaled medicines, giving primacy to subjective health indicators, such as
symptom burden. In the absence of published evidence, many clinicians are hesitant to
support these approaches. Clinicians often prioritise objective health indicators, such
as lung function, over subjective measures. The resulting epistemological dissonance
between pwCF and clinicians leads to concealment of actual behaviour, uncertainty,
and variation, leaving some clinicians feeling professionally disempowered. While some
pwCF find adoption of virtual appointments liberating in the context of improved health,
others experience abrupt transitions as abandonment, highlighting the enduring
importance of relational continuity.

These findings reinforce the need for shared decision-making and personalised care in
the post-ETI era. Ten recommendations aim to guide service design, including an
acknowledgement of emotional and relational needs, adoption of shared decision-
making, and a more holistic model of care. As the first Realist Evaluation in CF, this thesis
provides novel insights into the generative mechanisms underpinning behaviours. It
introduced the PLUTO framework to support shared decision-making and emphasised
habit as key mediator of adherence behaviours, which can generalise to other long-term
conditions.