An Early Health Economic Analysis of the Potential Cost Effectiveness of an Adherence Intervention to Improve Outcomes for Patients with Cystic Fibrosis

Background Cystic fibrosis (CF) negatively impacts upon health-related quality of life and survival. Adherence to nebulised treatments is low; improving adherence is hypothesised to reduce rates of exacerbation requiring intravenous antibiotics and lung function decline. Objective A state transition model was developed to assess the cost effectiveness of an intervention aimed at increasing patient adherence to nebulised and inhaled antibiotics compared with current CF care, in advance of the forthcoming CFHealthHub randomised controlled trial (RCT). Methods The model estimated the costs and health outcomes for each option from the perspective of the UK National Health Service and Personal Social Services over a lifetime horizon. Health gains were valued in terms of quality-adjusted life-years (QALYs) gained. Forced expiratory volume in 1 second (FEV1) trajectories were predicted over three lung function strata: (1) FEV1 ≥70%, (2) FEV1 40–69% and (3) FEV1 <40%. Additional states were included to represent ‘post-lung transplantation’ and ‘dead’. The model was populated using CF Registry data, literature and expert opinion. Costs were presented at 2016 values. Uncertainty was assessed using deterministic and probabilistic sensitivity analyses. Results If effective, the adherence intervention is expected to produce an additional 0.19 QALYs and cost savings of £64,078 per patient. Across all analyses, the intervention dominated current care. Over a 5-year period, the intervention is expected to generate cost savings of £49.5 million for the estimated 2979 patients with CF with Pseudomonas aeruginosa currently aged ≥16 years in the UK. If applied to a broader population of adult patients with CF receiving any nebulised therapy, the expected savings could be considerably greater. Conclusions If effective, the adherence intervention is expected to produce additional health gains at a lower cost than current CF care. However, the economic analysis should be revisited upon completion of the full RCT. More generally, the analysis suggests that considerable gains could be accrued through the implementation of adherence interventions that shift care from expensive hospital-based rescue to community-based prevention

A pragmatic behavior-based habit index for adherence to nebulized treatments among adults with cystic fibrosis

Zhe Hui Hoo,1,2 Martin J Wildman,1,2 Michael J Campbell,1 Stephen J Walters,1 Benjamin Gardner3 1School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK; 2Sheffield Adult Cystic Fibrosis Centre, Northern General Hospital, Sheffield, UK; 3Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience (IoPPN) King&rsquo;s College London, London, UK Background: Habit, a psychological process that automatically generates urges to perform a behavior in associated settings, is potentially an important determinant of medication adherence. Habit is challenging to measure because, as a psychological construct, it cannot be directly observed. We describe a method of using routinely available objective adherence data from electronic data capture (EDC) to generate a behavior-based index of adherence habit and demonstrate how this index can be applied.Methods to generate the habit index: Our proposed habit index is a &ldquo;frequency in context&rdquo; measure. It estimates habit as a multiplicative product of behavior frequency (generated from weekly percentage adherence) and context stability (inferred from time of nebulizer use). Although different timescales can be used, we chose to generate weekly habit scores since we believe that this is the most granular level at which context stability can be reasonably calculated.An application of the habit index: A hallmark of habit is to predict future behavior, hence we used time series method to cross-correlate the habit index with nebulizer adherence in the subsequent week among 123 adults with cystic fibrosis (52, 42.3% female; median age 25 years) over a median duration of 153 weeks (IQR 74&ndash;198 weeks). The mean cross-correlation coefficient (R) between the habit index and subsequent adherence was 0.40 (95% CI 0.36&ndash;0.44). Adjusting for current adherence, the unstandardized regression coefficient (B) for the habit index was 0.30 (95% CI -1.04 to 1.65).Conclusion: We have described a pragmatic method to infer &ldquo;habit&rdquo; from adherence data routinely captured with EDC and provided proof-of-principle evidence regarding the feasibility of this concept. The continuous stream of data from EDC allows the habit index to unobtrusively assess &ldquo;habit&rdquo; at various time points over prolonged periods, and hence the habit index may be applicable in habit formation studies. Keywords: cystic fibrosis, medication adherence, nebulizers and vaporizers, habits &nbsp

Accurate reporting of adherence to inhaled therapies in adults with cystic fibrosis: methods to calculate normative adherence

Zhe Hui Hoo,1,2 Rachael Curley,1,2 Michael J Campbell,1 Stephen J Walters,1 Daniel Hind,3 Martin J Wildman1,2 1School of Health and Related Research (ScHARR), University of&nbsp;Sheffield, 2Sheffield Adult Cystic Fibrosis Centre, Northern General Hospital, 3Sheffield Clinical Trials Research Unit, University of Sheffield, Sheffield, UK Background: Preventative inhaled treatments in cystic fibrosis will only be effective in maintaining lung health if used appropriately. An accurate adherence index should therefore reflect treatment effectiveness, but the standard method of reporting adherence, that is, as a percentage of the agreed regimen between clinicians and people with cystic fibrosis, does not account for the appropriateness of the treatment regimen. We describe two different indices of inhaled therapy adherence for adults with cystic fibrosis which take into account effectiveness, that is, &ldquo;simple&rdquo; and &ldquo;sophisticated&rdquo; normative adherence. Methods to calculate normative adherence: Denominator adjustment involves fixing a minimum appropriate value based on the recommended therapy given a person&rsquo;s characteristics. For simple normative adherence, the denominator is determined by the person&rsquo;s Pseudomonas status. For sophisticated normative adherence, the denominator is determined by the person&rsquo;s Pseudomonas status and history of pulmonary exacerbations over the previous year. Numerator adjustment involves capping the daily maximum inhaled therapy use at 100% so that medication overuse does not artificially inflate the adherence level. Three illustrative cases: Case A is an example of inhaled therapy under prescription based on Pseudomonas status resulting in lower simple normative adherence compared to unadjusted adherence. Case B is an example of inhaled therapy under-prescription based on previous exacerbation history resulting in lower sophisticated normative adherence compared to unadjusted adherence and simple normative adherence. Case C is an example of nebulizer overuse exaggerating the magnitude of unadjusted adherence. Conclusion: Different methods of reporting adherence can result in different magnitudes of adherence. We have proposed two methods of standardizing the calculation of adherence which should better reflect treatment effectiveness. The value of these indices can be tested empirically in clinical trials in which there is careful definition of treatment regimens related to key patient characteristics, alongside accurate measurement of health outcomes. Keywords: cystic fibrosis, medication adherence, nebulizers and vaporizers, epidemiologic method

Promoting adherence to nebulized therapy in cystic fibrosis: poster development and&nbsp;a&nbsp;qualitative exploration of adherence

Stephen Jones,1 Nathan Babiker,2 Emma Gardner,2,3 Jane Royle,2 Rachael Curley,3,4 Zhe Hui Hoo,3,4 Martin J Wildman3,4 1Psychology Department, University of Sheffield, 2Psychological Services, Sheffield Teaching Hospitals NHS Foundation Trust, 3Adult Cystic Fibrosis Unit, Northern General Hospital, 4School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK Background: Cystic fibrosis (CF) health care professionals recognize the need to motivate people with CF to adhere to nebulizer treatments, yet little is known about how best to achieve this. We aimed to produce motivational posters to support nebulizer adherence by using social marketing involving people with CF in the development of those posters. Methods: The Sheffield CF multidisciplinary team produced preliminary ideas that were elaborated upon with semi-structured interviews among people with CF to explore barriers and facilitators to the use of nebulized therapy. Initial themes and poster designs were refined using an online focus group to finalize the poster designs. Results: People with CF preferred aspirational posters describing what could be achieved through adherence in contrast to posters that highlighted the adverse consequences of nonadherence. A total of 14 posters were produced through this process. Conclusion: People with CF can be engaged to develop promotional material to support adherence, providing a unique perspective differing from that of the CF multidisciplinary team. Further research is needed to evaluate the effectiveness of these posters to support nebulizer adherence. Keywords: behavior change, social marketing, patient participation, nebulizers, medication adherenc