CFHealthHub: Intervention to support adherence to treatment in adults with Cystic Fibrosis

The Clinical Trials Research Unit and ScHARR have been awarded a prestigious five-year programme grant by the National Institute for Health Research Programme Grants for Applied Research. ‘Develop and evaluate an intervention to support Adherence to treatment in adults with Cystic Fibrosis’.

On
CFHealthHub logo

CFHealthHub: Intervention to support adherence to treatment in adults with Cystic Fibrosis

The Challenges

The aim of the programme was to develop and evaluate a complex behaviour change intervention (BCI) to support medication adherence for adults with Cystic Fibrosis (CF). The BCI included the development of a web portal, CFHealthHub, to capture adherence data from patients’ nebulisers and display this to clinicians and patients with CF (PWCF). CFHealthHub also facilitated a range of evidence-based interventions including problem solving and setting implementation plans to increase treatment adherence.

The Research

Developing the intervention (month 1-14), conducting the Feasibility study (month 15-19), and the RCT

A number of distinct work packages, outlined below, aimed to develop, iterate and test the BCI. The table below outlines the progress made with each of the work packages to date.

Work package 1 - Developing the CFHH platform via programming to produce a functional website and mobile application, March 2015 - April 2016

Work package Expected outcomes Planned start and end date Outcomes achieved
1.1 Adherence data capture programming to allow data capture from eFlow/iNeb and dry powders. March 2015 - July 2017
Initial developments of system complete prior to start of feasibility study. Ongoing iterations to continue through to July 17 before RCT starts.
  • eTrack programming complete to allow use of eTracks in Pilot study
  • iNeb programming and testing started Sept16
  • dry powder device negotiations ongoing
1.2 Develop CFHH web interface and website with all components (1.2a) incorporating the iterative work conducted within WP 2.2B (1.2b) March 2015 – Jan 2016 CFHH programming for the full website including a “pretty” front end user interface developed and completed over 14 months. Work completed by 30 April 2016 ready for start of the Pilot study.
The work integrated feedback from participants recruited to WP2.2b(1) and 2.2b (see below).

Work package 2 - Developing the behaviour change intervention: CFHH manual and training, March 2015 - April 2016

Work package Expected outcomes Planned start and end date Outcomes achieved
2.1a Qualitative interviews to elicit treatment views and beliefs in patients with CF (PWCF) to feed into the development of CFHH. March 2015 – August 2015
First participant recruited: 22/03/2015
Start: 01/03/2015 End: 31/08/2015
(n=18)		 COMPLETE
A qualitative interview study to understand factors influencing adherence to nebuliser medication in adults with Cystic Fibrosis. Semi structured interviews conducted with 18 PWCF. Feedback incorporated into development of the intervention and website.
2.2b(1) and 2.2b Early look at adherence data within CFHH and development (2.2b1) and subsequent iterative work with PWCF to refine the intervention (2.2b) ready for the Feasibility study. 2.2B(1) REC application
First participant recruited: 04/08/2015
Start: 04/05/2015
End: 31/01/2016 (n=5)
2.2B REC application
First participant recruited: 29/09/2015
Start: 01/09/2015
End: 01/04/2016 (n=22)		 COMPLETE
A study to understand how to use the eTrack nebuliser and Qulacomm Hub to support people with CF (PWCF) to adhere to their nebuliser treatment and to develop and refine the behaviour change intervention (including CFHealthHub). All work was completed as scheduled prior to the start of the Feasibility study.
Completion of the development of the behaviour change intervention to support medication adherence with 27 participants (2.2b1 n=5, 2.2b n=22). The intervention includes data displays and a website, coproduced with patients. These components of the complex intervention are useable by, as well as acceptable and appropriate to PWCF.
2.1C To produce and develop talking heads videos for CFHealthhub. The videos will tell patient stories in relation to PWCF managing medication adherence and strategies they employ to help with this. REC application
First participant recruited: 18/11/2015
Start: 25/05/2015
End: 31/08/2017
(n=14)		 COMPLETE
Development and evaluation of an intervention to support adherence to treatment in adults with Cystic Fibrosis: A sub study to record patient story videos for the behaviour change intervention. Participants described their personal experiences of using nebulisers for CF, what had motivated them to want to improve their adherence, and strategies that worked for them.
2.3/2.1b Development of the intervention manual, training programme, and assessment of fidelity for use in a pilot trial n/a COMPLETE
We have developed an intervention manual which provides instructions on how to use CFHH and the tools contained within in it. It also provides a structured intervention delivery procedure, and a reporting system that forms part of the assessment of the fidelity of intervention delivery. Alongside this manual we have developed a training programme consisting of face-to-face delivery, online learning, structured tutorial support and feedback.

Work package 3 - Feasibility study with embedded pilot trial, May 2016-April 2017

Work package Expected outcomes Planned start and end date Outcomes achieved
3.1 Feasibility study with embedded pilot trial starting May 2016.
  • an ‘external pilot RCT’ to establish the feasibility of recruitment to a larger, definitive study; and,
  • a ‘process evaluation’ which will help us understand the strengths and weaknesses of both the intervention and research protocols, and ways of addressing any weaknesses
 May 2016 – April 2017

COMPLETE
Feasibility outcomes achieved

  • n=64 participants randomised to date within the 16 week period therefore achieving the recruitment feasibility target


Process evaluation outcome

  • n=14 interviews with intervention participants
  • n=5 interviews with control participants
  • n=3 interviews with interventionists
  • n=5 interviews with CF team members

Work package 3.1

Following the development of the BCI, the programme moved to test the feasibility of conducting a larger scale trial. Recruitment to the pilot trial occurred in two CF units, across three NHS organisations. Participants were randomised to receive either: (1) CFHealthHub (CFHH) – a complex intervention based on Social Cognitive Theory and Control Theory. CFHH links collection and systematic feedback of adherence data via a chipped nebuliser (eTrack) and software platform, with strategies to empower self-management delivered online and in six face-to-face meetings over 5m with trained interventionists (n=32); (2) usual care, typically face-to-face meetings every 3m with CF team (n=32). The objectives of the pilot trial were to determine whether a full scale trial was feasible in terms of recruitment and retention; test the acceptability of CFHH; and, test the procedures for a full-scale trial. The pilot trial also involved qualitative data collection from the initial intervention sessions, control arm consultations and semi structured interviews with participants in the intervention arm, control arm and interventionists. The stop-go criterion was met with 64 participants being recruited in the allocated recruitment window. The interventionists conducted intervention sessions during the follow up period and completed the research follow up visits 5 months after entry into the study. The main trial is feasible based on recruitment to the pilot trial between May and September 2016, and participant retention and study procedures were satisfactory. 

Work package 3.2

Following the successful pilot trial, a large scale RCT is currently being conducted. The aim of this 19 centre RCT is to determine whether the complex intervention is more effective than standard care in improving outcomes for PWCF and to determine the best way to deliver the intervention. As with the pilot trial, participants were randomised to receive either: (1) CFHealthHub (CFHH) – a complex intervention (n=308); (2) usual care, typically face-to-face meetings every 3m with CF team (n=300). The objectives of the RCT are to determine the effect of the intervention on both clinical and participant related outcomes. In addition a process evaluation is underway which will facilitate interpretation of the RCT results and offer insights about how best to deliver the intervention in the real world. The RCT involves semi-structured interviews with participants in the intervention arm, interventionists and the PI. The RCT closed to recruitment on 31st May 2018, having successfully passed the original recruitment target of 556 participants, recruiting 608 participants in total. The trial is currently in follow up. Following the final 12-month research visit, some additional data collection will continue, with participant’s permission until, 30th June 2019. At this point, the study closes and the involvement of all participants ceases. After the trial ends (30/06/19), participants will have the option to enter into further CFHealthHub research should they wish.

This project is funded by the NIHR's Programme Grants for Applied Research.

The Results

Randomised controlled trial – 608 participants were randomised to the intervention (n = 305) or usual care (n = 303). To our knowledge, this was the largest randomised controlled trial in cystic fibrosis undertaken in the UK. The adjusted rate of exacerbations per year (primary outcome) was 1.63 in the intervention and 1.77 in the usual-care arm (incidence rate ratio 0.96, 95% confidence interval 0.83 to 1.12; p = 0.638) after adjustment for covariates. The adjusted difference in mean weekly normative adherence was 9.5% (95% confidence interval 8.6% to 10.4%) across 1 year, favouring the intervention. Adjusted mean difference in forced expiratory volume in 1 second (per cent) predicted at 12 months was 1.4% (95% confidence interval –0.2% to 3.0%). No adverse events were related to the intervention. Process evaluation – fidelity of intervention delivery was high, the intervention was acceptable to people with cystic fibrosis, participants engaged with the intervention [287/305 (94%) attended the first intervention visit], expected mechanisms of action were identified and contextual factors varied between randomised controlled trial sites. Qualitative interviews with 22 people with cystic fibrosis and 26 interventionists identified that people with cystic fibrosis welcomed the objective adherence data as proof of actions to self and others, and valued the relationship that they built with the interventionists. Economic modelling – the within-trial analysis suggests that the intervention generated 0.01 additional quality-adjusted life-years at an additional cost of £865.91 per patient, leading to an incremental cost-effectiveness ratio of £71,136 per quality-adjusted life-year gained. This should be interpreted with caution owing to the short time horizon. The health economic model suggests that the intervention is expected to generate 0.17 additional quality-adjusted life-years and cost savings of £1790 over a lifetime (70-year) horizon; hence, the intervention is expected to dominate usual care. Assuming a willingness-to-pay threshold of £20,000 per quality-adjusted life-year gained, the probability that the intervention generates more net benefit than usual care is 0.89. The model results are dependent on assumptions regarding the duration over which costs and effects of the intervention apply, the impact of the intervention on forced expiratory volume in 1 second (per cent) predicted and the relationship between increased adherence and drug-prescribing levels.

The Impact

Several wide-reaching impacts have been made from the CFHealthHub programmes of research (including the Learning health System/Data Observatory). 

  • NICE guidelines updated to include adherence as a key performance indicator for CF care
  • NICE recommendations on the use of CFHealthHub in CF care published
  • CFHealthHub received continued funding by NHS England as part of Commissioning for Quality and Innovation, allowing 1000+ patients and their care teams to continue to access objective adherence data. Ongoing analysis of the health benefits of this can be found on the CFHealthHub website
  • Use of CFHealthHub during the pandemic for remote monitoring of CF patients health

Publications

Wildman, M.J., O’Cathain, A., Hind, D., Maguire, C., Arden, M.A., Hutchings, M., Bradley, J., Walters, S.J., Whelan, P., Ainsworth, J. and Tappenden, P., 2021. An intervention to support adherence to inhaled medication in adults with cystic fibrosis: the ACtiF research programme including RCT.

https://www.ncbi.nlm.nih.gov/books/NBK574648/ 

Wildman, M.J., O’Cathain, A., Maguire, C., Arden, M.A., Hutchings, M., Bradley, J., Walters, S.J., Whelan, P., Ainsworth, J., Buchan, I. and Mandefield, L., 2021. Self-management intervention to reduce pulmonary exacerbations by supporting treatment adherence in adults with cystic fibrosis: a randomised controlled trial. Thorax.

https://thorax.bmj.com/content/early/2021/09/23/thoraxjnl-2021-217594.abstract 

Arden, M.A., Hutchings, M., Whelan, P., Drabble, S.J., Beever, D., Bradley, J.M., Hind, D., Ainsworth, J., Maguire, C., Cantrill, H. and O’Cathain, A., 2021. Development of an intervention to increase adherence to nebuliser treatment in adults with cystic fibrosis: CFHealthHub. Pilot and feasibility studies, 7(1), pp.1-18.
https://pilotfeasibilitystudies.biomedcentral.com/articles/10.1186/s40814-020-00739-2 

Drabble, S.J., O'Cathain, A., Scott, A.J., Arden, M.A., Keating, S., Hutchings, M., Maguire, C. and Wildman, M., 2020. Mechanisms of action of a web-based intervention with health professional support to increase adherence to nebulizer treatments in adults with cystic fibrosis: qualitative interview study. Journal of Medical Internet Research, 22(10), p.e16782.

https://www.jmir.org/2020/10/e16782/

Hind, D., Drabble, S.J., Arden, M.A., Mandefield, L., Waterhouse, S., Maguire, C., Cantrill, H., Robinson, L., Beever, D., Scott, A. and Keating, S., 2020. Feasibility study for supporting medication adherence for adults with cystic fibrosis: mixed-methods process evaluation. BMJ open, 10(10), p.e039089.

https://bmjopen.bmj.com/content/10/10/e039089.abstract

Arden, M.A., Drabble, S., O'Cathain, A., Hutchings, M. and Wildman, M., 2019. Adherence to medication in adults with cystic fibrosis: an investigation using objective adherence data and the theoretical domains framework. British journal of health psychology, 24(2), pp.357-380.

https://bpspsychub.onlinelibrary.wiley.com/doi/full/10.1111/bjhp.12357

Gao, J., Arden, M., Hoo, Z.H. and Wildman, M., 2019. Understanding patient activation and adherence to nebuliser treatment in adults with cystic fibrosis: responses to the UK version of PAM-13 and a think aloud study. BMC health services research, 19(1), pp.1-12.

https://link.springer.com/article/10.1186/s12913-019-4260-5

Drabble, S.J., O’Cathain, A., Arden, M.A., Hutchings, M., Beever, D. and Wildman, M., 2019. When is forgetting not forgetting? A discursive analysis of differences in forgetting talk between adults with cystic fibrosis with different levels of adherence to nebulizer treatments. Qualitative health research, 29(14), pp.2119-2131.

https://journals.sagepub.com/doi/full/10.1177/1049732319856580

Hind, D., Drabble, S.J., Arden, M.A., Mandefield, L., Waterhouse, S., Maguire, C., Cantrill, H., Robinson, L., Beever, D., Scott, A.J. and Keating, S., 2019. Supporting medication adherence for adults with cystic fibrosis: a randomised feasibility study. BMC pulmonary medicine, 19(1), pp.1-13.  

https://bmcpulmmed.biomedcentral.com/articles/10.1186/s12890-019-0834-6

Tappenden, P., Sadler, S. and Wildman, M., 2017. An early health economic analysis of the potential cost effectiveness of an adherence intervention to improve outcomes for patients with cystic fibrosis. Pharmacoeconomics, 35(6), pp.647-659.

https://link.springer.com/article/10.1007/s40273-017-0500-x

Sadler, S., Wildman, M. and Tappenden, P., 2016. 267 cost-effectiveness of a complex adherence intervention to improve prevention in cystic fibrosis by empowering effective self-management: an exploratory health economic evaluation using UK registry data. Journal of Cystic Fibrosis, 1(15), pp.S119-S120.

https://www.infona.pl/resource/bwmeta1.element.elsevier-5ce208dc-2252-3fae-85e8-c678c58426a5

Project team

Name Role Organisation Contact
Dr Martin Wildman Chief Investigator Sheffield Teaching Hospitals NHS Foundation Trust martin.wildman@sth.nhs.uk
Professor Alicia O'Cathain Chief Investigator University of Sheffield a.ocathain@sheffield.ac.uk
Marlene Hutchings Research Physiotherapist Sheffield Teaching Hospitals NHS Foundation Trust marlene.hutchings@sth.nhs.uk
Professor Maddy Arden Behaviour Change Intervention Lead Sheffield Hallam University m.arden@shu.ac.uk
Chin Maguire Project Manager University of Sheffield c.maguire@sheffield.ac.uk
Louisa Robinson Research Assistant University of Sheffield louisa.robinson@sheffield.ac.uk
Dr Anne Scott Research Assistant University of Sheffield anne.scott@sheffield.ac.uk
Louise Turner Trials Support Officer University of Sheffield louise.turner@sheffield.ac.uk
Dr Daniel Hind CTRU oversight University of Sheffield d.hind@sheffield.ac.uk
Dan Beever Person with CF, PPI Lead University of Sheffield d.a.beever@sheffield.ac.uk
Dr Sarah Drabble Qualitative Lead University of Sheffield S.J.Drabble@sheffield.ac.uk
Professor Judy Bradley Professor of Physiotherapy and Health Services Research University of Ulster judy.bradley@qub.ac.uk
Dr Pauline Whelan Lead Software Developer/mHealth Applications Manager University of Manchester pauline.whelan@manchester.ac.uk
Ricardo Ortega Website Designer Keep It Usable ricardo@keepitusable.com
Susan Kirkpatrick Senior Qualitative Researcher University of Oxford susan.kirkpatrick@phc.ox.ac.uk

Co-applicants

Name Position Institution
Dr John Ainsworth Senior Research Fellow The Farr Institute of Health Informatics Research, University of Manchester
Professor Iain Buchan Clinical Professor in Public Health Informatics The Farr Institute of Health Informatics Research, University of Manchester
Professor Stuart Elborn Consultant Physician, Respiratory Medicine Belfast Health and Social Care Trust
Professor Rachel Elliott Lord Trent Professor of Medicines and Health The University of Nottingham
Marie McKenniff Operations Director, Sheffield Teaching Hospitals Sheffield Teaching Hospitals NHS Foundation Trust
Professor Susan Michie Professor of Health Psychology University College London
Professor Mohammed A Mohammed Professor of Quality and Effectiveness University of Bradford
Professor Jon Nicholl Dean of School (ScHARR) ScHARR, The University of Sheffield
Dr Paul Tappenden Reader in Health Economic Modelling ScHARR, The University of Sheffield
Professor Stephen Walters Professor of Medical Statistics and Clinical Trials ScHARR, The University of Sheffield

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