Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Trials
Published in: Trials 1/2020

Open Access 01-12-2020 | Research

How can health economics be used in the design and analysis of adaptive clinical trials? A qualitative analysis

Authors: Laura Flight, Steven Julious, Alan Brennan, Susan Todd, Daniel Hind

Published in: Trials | Issue 1/2020

Login to get access

Abstract

Introduction

Adaptive designs offer a flexible approach, allowing changes to a trial based on examinations of the data as it progresses. Adaptive clinical trials are becoming a popular choice, as the prudent use of finite research budgets and accurate decision-making are priorities for healthcare providers around the world. The methods of health economics, which aim to maximise the health gained for money spent, could be incorporated into the design and analysis of adaptive clinical trials to make them more efficient. We aimed to understand the perspectives of stakeholders in health technology assessments to inform recommendations for the use of health economics in adaptive clinical trials.

Methods

A qualitative study explored the attitudes of key stakeholders—including researchers, decision-makers and members of the public—towards the use of health economics in the design and analysis of adaptive clinical trials. Data were collected using interviews and focus groups (29 participants). A framework analysis was used to identify themes in the transcripts.

Results

It was considered that answering the clinical research question should be the priority in a clinical trial, notwithstanding the importance of cost-effectiveness for decision-making. Concerns raised by participants included handling the volatile nature of cost data at interim analyses; implementing this approach in global trials; resourcing adaptive trials which are designed and adapted based on health economic outcomes; and training stakeholders in these methods so that they can be implemented and appropriately interpreted.

Conclusion

The use of health economics in the design and analysis of adaptive clinical trials has the potential to increase the efficiency of health technology assessments worldwide. Recommendations are made concerning the development of methods allowing the use of health economics in adaptive clinical trials, and suggestions are given to facilitate their implementation in practice.
Appendix
Available only for authorised users
Literature
1.
2.
3.
Australian Government: Department of Health and Ageing. Guidelines for preparing submissions to the Pharmaceutical Benefits Advisory Committee (Version 4.3). Technical report. 2008. https://​pbac.​pbs.​gov.​au/​.
4.
Drummond MF, Sculpher MJ, Claxton K, Stoddart GL, Torrance GW. Methods for the economic evaluation of health care programmes. Oxford: Oxford University Press; 2015.
5.
6.
Strong M, Oakley JE, Brennan A, Breeze P. Estimating the expected value of sample information using the probabilistic sensitivity analysis sample: a fast, nonparametric regression-based method. Med Dec Making. 2015; 35(5):570–83.CrossRef
7.
Bauer P, Brannath W. The advantages and disadvantages of adaptive designs for clinical trials. Drug Discov Today. 2004; 9(8):351–7.PubMedCrossRef
8.
9.
Jennison C, Turnbull BW. Group sequential methods with applications to clinical trials. Boca Raton: Chapman and Hall/CRC; 2000.
10.
11.
Flight L, Arshad F, Barnsley R, Patel K, Julious S, Brennan A, Todd S. A review of clinical trials with an adaptive design and health economic analysis. Value Health. 2019; 22(4):391–8.PubMedCrossRef
12.
Creswell JW. Research design: qualitative, quantitative, and mixed methods approaches. Thousand Oaks: SAGE Publications; 2013.
13.
14.
15.
16.
Clarke V, Braun V. Successful qualitative research: a practical guide for beginners. London: SAGE Publications Inc.; 2013.
17.
Guest G, Bunce A, Johnson L. How many interviews are enough? An experiment with data saturation and variability. Fam Health Int. 2006; 18(1):59–82.
18.
Pope C, Mays N. Qualitative research in health care, 2nd ed. Oxford: BMJ Publishing; 2000.
19.
Creswell JW, Hanson WE, Clark Plano VL, Morales A. Qualitative research designs: selection and implementation. Couns Psychol. 2007; 35(2):236–64.CrossRef
20.
21.
Francis JJ, Johnston M, Robertson C, Glidewell L, Entwistle V, Eccles MP, Grimshaw JM. What is an adequate sample size? Operationalising data saturation for theory-based interview studies. Psychol Health. 2010; 25(10):1229–45.PubMedCrossRef
22.
Ritchie J, Spencer L. Qualitative data analysis for applied policy research. Analysing Qual Data. 1993:;173–94.
23.
Gale NK, Heath G, Cameron E, Rashid S, Redwood S. Using the framework method for the analysis of qualitative data in multi-disciplinary health research,. BMC Med Res Methodol. 2013; 13(1):117.PubMedPubMedCentralCrossRef
24.
Tong A, Sainsbury P, Craig J. Consolidated criteria for reporting qualitative research (COREQ): a 32-item checklist for interviews and focus groups. Int J Qual Health Care. 2007; 19(6):349–57.PubMedCrossRef
25.
Beauchamp TL, Childress JF, et al.Principles of biomedical ethics. Oxford: Oxford University Press; 2001.
26.
Rawls J. A theory of justice. Cambridge: Belknap; 1971.
27.
28.
29.
30.
Chow S-C, Corey R, Lin M. On the independence of data monitoring committee in adaptive design clinical trials,. J Biopharm Stat. 2012; 22(4):853–67.PubMedCrossRef
31.
Whitehead J. The design and analysis of sequential clinical trials. Chichester: Wiley; 1997.CrossRef
32.
Pallmann P, Bedding AW, Choodari-Oskooei B, Dimairo M, Flight L, Hampson LV, Holmes J, Mander AP, Sydes MR, Villar SS, et al.Adaptive designs in clinical trials: why use them, and how to run and report them. BMC Med. 2018; 16(1):29.PubMedPubMedCentralCrossRef
33.
Bothwell LE, Avorn J, Khan NF, Kesselheim AS. Adaptive design clinical trials: a review of the literature and ClinicalTrials. gov. BMJ Open. 2018; 8(2):018320.CrossRef
34.
Mohiuddin S, Fenwick E, Payne K. Use of value of information in UK health technology assessments. Int J Technol Assess Health Care. 2014; 30(6):553–70.PubMedCrossRef
35.
Dimairo M, Coates E, Pallmann P, Todd S, Julious SA, Jaki T, Wason J, Mander AP, Weir CJ, Koenig F, et al.Development process of a consensus-driven CONSORT extension for randomised trials using an adaptive design. BMC Med. 2018; 16(1):210.PubMedPubMedCentralCrossRef
36.
37.
Heath A, Kunst NR, Jackson C, Strong M, Alarid-Escudero F, Goldhaber-Fiebert JD, Baio G, Menzies NA, Jalal H. Calculating the expected value of sample information in practice: considerations from three case studies. arXiv preprint arXiv:1905.12013. 2019.
38.
Kunst NR, Wilson E, Alarid-Escudero F, Baio G, Brennan A, Fairley M, Glynn D, Goldhaber-Fiebert JD, Jackson C, Jalal H, et al.Computing the expected value of sample information efficiently: expertise and skills required for four model-based methods. arXiv preprint arXiv:1910.03368. 2019.
39.
DAMOCLES Study Group. A proposed charter for clinical trial data monitoring committees: helping them to do their job well. Lancet. 2005; 365(9460):711–22.CrossRef
40.
41.
42.
Thorn J, Ridyard C, Hughes D, Wordsworth S, Mihaylova B, Noble SM, Hollingworth W. Health economics analysis plans: the current state of play. Trials. 2017; 18(Suppl 1):P144.
43.
Forster M, Brealey S, Chick S, Keding A, Corbacho B, Alban A, Rangan A, et al.Cost-effective clinical trial design: application of a Bayesian sequential stopping rule to the ProFHER pragmatic trial. Technical report. 2019.
44.
Husbands SK. PhD Thesis, Model-building process. University of Birmingham. 2016; (February).
45.
Koerkamp B, Nikken J, Oei E, Stijnen T. Value of information analysis used to determine the necessity of additional research: MR imaging in acute knee trauma as an example. Radiology. 2008; 246(2):420–5.CrossRef
46.
Legocki LJ, Meurer WJ, Frederiksen S, Lewis RJ, Durkalski VL, Berry DA, Barsan WG, Fetters MD. Clinical trialist perspectives on the ethics of adaptive clinical trials: a mixed-methods analysis. BMC Med Ethics. 2015; 16(1):27.PubMedPubMedCentralCrossRef
47.
Meurer WJ, Legocki L, Mawocha S, Frederiksen SM, Guetterman TC, Barsan W, et al.Attitudes and opinions regarding confirmatory adaptive clinical trials: a mixed methods analysis from the Adaptive Designs Accelerating Promising Trials into Treatments (ADAPT-IT) project. Trials. 2016; 17(1):373.PubMedPubMedCentralCrossRef
48.
49.
Cook J, Drummond M, Heyse J. Multiple primary endpoints in clinical trials. Stat Methods Med Res. 2004; 13:157–76.PubMedCrossRef
50.
Koerkamp BG, Spronk S, Stijnen T, Hunink MGM. Value of information analyses of economic randomized controlled trials: the treatment of intermittent claudication. Value Health. 2010; 13(2):242–50.CrossRef
51.
Tuffaha HW, Reynolds H, Gordon LG, Rickard CM, Scuffham P. Value of information analysis optimizing future trial design from a pilot study on catheter securement devices. Clin Trials (London, England). 2014; 11(6):648–56.CrossRef
52.
Trotta F, Apolone G, Garattini S, Tafuri G. Stopping a trial early in oncology: for patients or for industry?Ann Oncol. 2008; 19(7):1347–53.PubMedCrossRef
53.
Ashby D, Tanb S-B. Where’s the utility of clinical trials? Bayesian data-monitoring. Clin Trials. 2005; 2:197–208.PubMedCrossRef
54.
Hollingworth W, McKell-Redwood D, Hampson L, Metcalfe C. Cost–utility analysis conducted alongside randomized controlled trials: are economic end points considered in sample size calculations and does it matter?Clin Trials. 2013; 10(1):43–53.PubMedCrossRef
55.
Briggs AH, Gray AM. Power and sample size calculations for stochastic cost-effectiveness analysis. Med Decis Making Int J Soc Med Decis Making. 1998; 18(2):81–92.CrossRef
56.
O’Brien BJ, Drummond MF, Labelle RJ, Willan A. In search of power and significance: issues in the design and analysis of stochastic cost-effectiveness studies in health care. Medical Care. 1994; 32(2):150–63.PubMedCrossRef
57.
58.
Metadata
Title
How can health economics be used in the design and analysis of adaptive clinical trials? A qualitative analysis
Authors
Laura Flight
Steven Julious
Alan Brennan
Susan Todd
Daniel Hind
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Trials / Issue 1/2020
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-020-4137-2

Other articles of this Issue 1/2020

Trials 1/2020 Go to the issue

Study protocol

Effects of Transcranial Direct Current Stimulation (tDCS) and Approach Bias Modification (ABM) training on food cravings in people taking antipsychotic medication

Study protocol

Esophagectomy versus definitive chemoradiotherapy for patients with clinical stage N0 and pathological stage T1b esophageal squamous cell carcinoma after endoscopic submucosal dissection: study protocol for a multicenter randomized controlled trial (Ad-ESD Trial)

Research

Bronchiectasis Information and Education: a randomised, controlled feasibility trial

Study protocol

Radiation therapy alone versus radiation therapy plus radiofrequency ablation/vertebral augmentation for spine metastasis: study protocol for a randomized controlled trial

Study protocol

Brief motivational therapy versus enhanced usual care for alcohol use disorders in primary care in Chile: study protocol for an exploratory randomized trial

Letter

Safety and Efficacy of Ixekizumab and Antiviral Treatment for Patients with COVID-19: A structured summary of a study protocol for a Pilot Randomized Controlled Trial