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

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.

A Review of Clinical Trials With an Adaptive Design and Health Economic Analysis.

OBJECTIVE: An adaptive design uses data collected as a clinical trial progresses to inform modifications to the trial. Hence, adaptive designs and health economics aim to facilitate efficient and accurate decision making. Nevertheless, it is unclear whether the methods are considered together in the design, analysis, and reporting of trials. This review aims to establish how health economic outcomes are used in the design, analysis, and reporting of adaptive designs. METHODS: Registered and published trials up to August 2016 with an adaptive design and health economic analysis were identified. The use of health economics in the design, analysis, and reporting was assessed. Summary statistics are presented and recommendations formed based on the research team's experiences and a practical interpretation of the results. RESULTS: Thirty-seven trials with an adaptive design and health economic analysis were identified. It was not clear whether the health economic analysis accounted for the adaptive design in 17/37 trials where this was thought necessary, nor whether health economic outcomes were used at the interim analysis for 18/19 of trials with results. The reporting of health economic results was suboptimal for the (17/19) trials with published results. CONCLUSIONS: Appropriate consideration is rarely given to the health economic analysis of adaptive designs. Opportunities to use health economic outcomes in the design and analysis of adaptive trials are being missed. Further work is needed to establish whether adaptive designs and health economic analyses can be used together to increase the efficiency of health technology assessments without compromising accuracy.

Adaptive trials for tuberculosis: early reflections on theory and practice.

SETTING: Adaptive designs (ADs) have been proposed for anti-tuberculosis treatment trials. This call for innovation occurs against the backdrop of fundamental changes in the acceptable evidence base in anti-tuberculosis treatment. OBJECTIVE: To contextualise ADs for tuberculosis (TB) and explore early responses from those working in the field. DESIGN: In this qualitative study investigating processes of theoretical and practical change in randomised controlled trials, 24 interviews were conducted with professionals involved in AD trials, half of whom worked in the TB field. RESULTS: Clinical trialists working on AD trials in TB are positive about the efficiency these designs offer, but remain cautious about their suitability. In addition to technical concerns, informants discussed the challenges of implementing AD in developing countries, including limited regulatory capacity to evaluate proposals, investments needed in infrastructure and site capacity, and challenges regarding informed consent. Respondents identified funding, interdisciplinary communication and regulatory and policy responses as additional concerns potentially affecting the success of AD for TB. CONCLUSION: Empirical research is needed into patient experiences of AD, including informed consent. Further consideration of the contexts of innovation in trial design is needed. These are fundamental to the successful translation of theory into practice.