Adaptive design clinical trials and their impact on the health economic analysis of healthcare technologies

An in-depth look at the research project by Laura Flight, National Institute for Health Research Doctoral Research Fellow (NIHR DRF).


Plain English summary 

In the United Kingdom (UK) the National Institute for Health Research (NIHR) make decisions about which research should be given money. All types of research compete for this limited funding and so the NIHR need to weigh up what the new research will tell them and how much it will cost. 

The National Institute for Health and Care Excellence (NICE) in the UK, decide which treatments are given to patients on the National Health Service (NHS). NICE often rely on information from clinical trials. In a clinical trial, treatments are compared in groups of people who are likely to receive the treatment if it is to be provided by the NHS. This information helps NICE decide whether a treatment improves health, is clinically effective and whether it is going to be value for money, is cost-effective. 

In my research, I am interested in clinical trials that use an adaptive design. An adaptive design allows researchers to look at the information collected during a trial, rather than waiting until the trial has ended. This early information is used to make changes to the trial, such as stopping early or adding new treatments to be compared. This can save time and money as well as get the best treatments to patients as soon as possible. 

My research aimed to understand how value for money could be used with adaptive designs to make better use of the limited money available for conducting research and funding treatments on the NHS. I wanted to show how this could work in practice to make sure this approach gives NICE accurate information to decide which treatments should be made available and that the public, researchers and decision makers were happy with the new approach. 

I looked at how researchers currently assess whether a treatment and research is value for money before and during adaptive designs. Despite researchers having looked at how these methods might work in theory, I found very few trials were using these methods in practice. 

To understand why this was the case, I asked researchers, decision-makers and the public what they thought about potentially using value for money in clinical trials with an adaptive design. I found that, to those who took part, it was important that the aim of a clinical trial should be to show that a treatment works (is clinically effective) and that value for money considerations, while important, should not be the focus. Researchers and decision makers felt that they needed more training to use this approach in their trials. They also thought there would need to be changes to how research is funded to allow more time and money to incorporate value for money when designing and running adaptive trials.

Previous research has shown that adaptive designs can cause estimates of how well the treatment works to be over exaggerated or under exaggerated if the right methods are not used. I was concerned that this could also affect how we show value for money. Using the wrong methods could mean the wrong decisions are made about which treatments are made available to patients on the NHS.  To understand this, I imagined running a clinical trial with an adaptive design and calculated whether the treatment was cost-effective using methods that account for the adaptive design and methods that do not. I showed that in some situations using methods that did not allow for the adaptive design could make a treatment seem cost-effective when really it is not. Therefore, I recommend researchers present results that use these adjustment methods in all adaptive trials.

I also wanted to think about how we could use value for money to help choose the best design for adaptive clinical trials. I took existing methods known as value of information analysis that help us to choose a cost-effective design for a clinical trial and thought about how they could work for adaptive designs. To reflect the importance of showing a treatment works to the public, researchers and decision makers I made sure the focus of the trial was to show clinical effectiveness and that value for money was only thought about before the trial began. I have made recommendations to help researchers apply this approach accurately in the design of their own trials, advising them on how to adjust the methods to allow for the adaptive nature of the trial and to calculate the costs of running the trial.

Overall, my research shows that the public, researchers and decision makers are willing to think about value for money in clinical trials with an adaptive design, but this is not carried out at the moment. I have shown that, by applying existing methods in a new way and thinking carefully about how an adaptive design might affect value for money calculations, the public and the NHS can continue to benefit from using adaptive designs and potentially maximise limited budgets so that more research can be conducted. 

Funding Statement

Laura Flight was funded by a National Institute for Health Research (NIHR) Doctoral Research Fellowship for this project. This article presents independent research funded by the NIHR. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health and Social Care or the University of Sheffield.

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Funding acknowledgement

This is independent research arising from a Doctoral Research Fellowship (DRF-2015-08-013) supported by the National Institute for Health Research. The views expressed are those of the author and not necessarily those of the NHS, the National Institute for Health Research, the Department of Health or the University of Sheffield.

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