Researchers have developed a new approach to help determine the optimal dose of cancer drugs, aiming to make early-stage clinical trials more transparent and better aligned with patient needs.
Led by The Institute of Cancer Research, London, the study introduces a statistical method called WIN-DOSE, which is designed to support clearer and more structured decision-making when selecting optimal doses to take forward in drug development. WIN-DOSE could help clinicians balance multiple factors when identifying the most appropriate dose – including safety, effectiveness and patient experience.
The work was funded by The Institute of Cancer Research (ICR) – which is both a research institute and a charity – and Cancer Research UK. The findings have been published in the journal Clinical Cancer Research.
A common challenge in early trials
Early-stage clinical trials play a crucial role in cancer drug development, especially when determining suitable doses of new treatments to ensure that they are both safe and beneficial.
However, making these decisions can be complex. Clinical trial teams need to consider several forms of gathered evidence at once, including side effects, early signs of effectiveness and how well patients tolerate the treatment. While these factors are all important, the way they are weighed against each other is not always clearly defined. This makes it difficult for research teams to explain why one dose has been chosen over another, which can lead to dose decision-making inconsistencies across different trials.
To address this, the research team developed WIN-DOSE – a simple dose-optimisation design for clinical trials that facilitates the comparison of different doses using a pre-agreed set of priorities. This design sets out a hierarchy of pre-specified outcomes – or endpoints – before a trial begins. For example, a study might prioritise safety first, followed by signs of effectiveness and patient tolerability. Other endpoints, such as how the drug affects the body (pharmacodynamics) or how the body affects the drug (pharmacokinetics), might also be included.
The patient voice
A key feature of this new approach is the ability to incorporate patient-reported outcomes (PROs) – where patients provide their subjective experience of treatment, including the impact of side effects and disease symptoms. These PROs can capture aspects of tolerability that may not be fully reflected in clinical measurements alone, such as fatigue. Including this information ensures that the patient experience is considered from the earliest stages of drug development.
By integrating multiple types of evidence – such as PROs and safety, early effectiveness and biological data – WIN-DOSE provides a more holistic view on how different doses perform.
Future implications
The team believes WIN-DOSE could make dose optimisation more consistent and easier to implement across a wide range of clinical trials.
First author Emily Alger, a PhD student in the Early Phase and Adaptive Trials Group in the Clinical Trials and Statistics Unit at the ICR (ICR-CTSU), said:
“As this framework does not rely on complex statistical modelling, it may be particularly useful for clinical trial teams working in resource-constrained settings, where simpler and more practical approaches are needed.
"In the longer term, our method could help make dosing choices more apparent and consistent by allowing stakeholders to set out in advance how different types of evidence, including PROs, are prioritised. For patients, this could support the selection of doses that better balance potential benefit with tolerability.”
The same general approach could also be applied beyond oncology to any dose-optimisation trials where multiple endpoints are used to justify why one dose is preferred over another.
What comes next?
An important next step before WIN-DOSE can be adopted into clinical practice is to engage with patients, clinicians and trial teams to decide how different outcomes should be prioritised when determining optimal doses within different clinical settings. This includes developing best practice guidance to translate preferences into a clear and pre-specified hierarchy so that dose-optimisation decisions are transparent, reproducible and reflective of real-world decision-making.
Senior author Professor Christina Yap, Professor of Clinical Trials Biostatistics and Group Leader of the ICR-CTSU Early Phase and Adaptive Trials Group, said:
“WIN-DOSE represents an important step towards more patient-centred and evidence-based clinical trials. While it is too early to estimate how many patients could benefit, our approach has broad potential and is relevant across a wide range of oncology programmes in the UK and internationally.
"As dose optimisation underpins the development of many new treatments, improving how these decisions are made could have far-reaching implications across cancer research and beyond.”
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