ESTRO 2025 - Abstract Book

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Invited Speaker

ESTRO 2025

• Improved recruitment – patients are already part of an observational cohort • More representative results – real-world clinical care is mirrored in trial design • Minimised contamination – control patients are unaware of their non-selection • Efficient infrastructure – multiple trials can be conducted within the same cohort

These strengths are particularly relevant in oncology, where recruitment can be challenging. For example, the Dutch UMBRELLA cohort in breast cancer (Netherlands) has successfully recruited 1,308 participants, with 87% consenting to future randomisation. Similarly, the Graham Roberts Study in bladder cancer (UK) is leveraging TwiCs to build an efficient trial platform linked to a Cancer Biobank.

Challenges: What Still Needs Work? Despite its promise, TwiCs face several methodological and ethical challenges:

• Selection bias & generalisability – cohort-based recruitment may exclude certain patient subgroups, and random selection from eligible patients can introduce bias • Intervention uptake & adherence – not all patients offered an intervention agree to participate, leading to lower-than-expected acceptance rates • Statistical complexity – comparing intervention vs. usual care requires advanced modelling to account for potential biases • Ethical concerns – staged informed consent raises questions about transparency and fairness. To address these challenges, pilot studies are essential for estimating acceptance rates and refining recruitment strategies, while methodological innovations in statistical modelling and consent processes can further strengthen TwiCs applications. Looking Ahead: The Future of TwiCs TwiCs offer a pragmatic, patient-centred alternative to traditional RCTs, particularly in oncology research. While their ability to streamline trials and enhance real-world relevance is clear, further work is needed to optimise intervention uptake, and standardise methodologies. By continuously refining its approach, TwiCs has the potential to transform clinical research, making trials more accessible, efficient, and impactful.

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Speaker Abstracts Are pragmatic trials the solution? Felix Oppong Statistics, European Organisation for. Research and Treatment of Cancer, Brussels, Belgium

Abstract: The landscape of clinical trials has evolved significantly, with industry funding playing a dominant role in shaping trial design and endpoint selection. While industry-sponsored trials drive innovation, their commercial motives often prioritize regulatory approval over patient-centred outcomes. This has led to a limited focus on non-profitable treatment strategies. As a result, surrogate endpoints are frequently used, though their ability to reflect meaningful clinical benefits remains uncertain. In radiation oncology, where treatment goals extend beyond survival, endpoints such as symptom relief, toxicity, and functional outcomes are essential. However, many trials do not incorporate these measures, raising concerns about the applicability of their findings to real-world patients. Pragmatic trials offer a potential solution by assessing treatments in routine clinical practice and focusing on outcomes that matter to patients. Pragmatic trials differ from explanatory trials by evaluating effectiveness under real-world conditions. Explanatory trials aim to determine efficacy in ideal settings, often using strict eligibility criteria and standardized interventions.