Innovative approaches like synthetic control arms based on real-world data may help overcome the unique challenges faced in clinical trials for rare diseases.
At a recent meeting, Channa Debruyne, global clinical development lead, late-stage and LCM oncology, at Servier, explained how real-world data from similar patient populations to those in a study cohort can be utilised as a comparator. The data should preferably be at the patient level and populations should be matched in terms of key demographics and prognostic baseline variables, she said, while speaking at the Clinical Trials in Rare Diseases Europe 2025 conference, which took place 26–27 November in Munich, Germany.
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In some cases, limited patient populations mean that randomised placebo-controlled trials are not feasible or may not be ethical to conduct. In recent times, several drugs have been approved based on single-arm trials that used real-world data as an external comparator, but Debruyne said this is “just the beginning”.
The US Food and Drug Administration (FDA) has indicated some acceptance of synthetic control arm data for rare diseases. For example, Bavencio (avelumab), co-developed by Merck KGaA and Pfizer, was approved for treating metastatic Merkel cell carcinoma.
Debruyne also highlighted the importance of the quality of the data feeding into the synthetic control arms. Standardised and robust data collection and storage, as well as careful management of potential biases is essential, she said.
Furthermore, data from multiple registries with different parameters needs to be harmonised, which will require close collaboration among stakeholders, and this is currently one of the biggest challenges in this space, according to Debruyne.
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By GlobalDataIn the future, Debruyne says high-quality patient registries need to be expanded, and partnerships and interactions between the clinicians, researchers, non-profit organisations, regulatory bodies, patient associations, and industry, need to be strengthened.
Speaking at a different panel later in the conference, Clara Cali Mella, data strategy lead at Bayer said “the data is there” but explained that the main roadblock is access and regulations. She said the challenges lie in navigating complex data protection regulation laws but spurring a willingness to share anonymised data among owners could be a huge opportunity.
She mentioned Finland as an example of a region openly sharing its anonymised patient data, and called on more countries to follow suit, saying this could be a game changer for rare diseases.
Synthetic control arms in the age of AI
In another talk, Eslam Katab, global clinical development manager at Sandoz, shared how artificial intelligence (AI) can transform the use of real-world data in synthetic control arms.
He said AI could be used to enhance the process of leveraging historical real-world data into synthetic control arms so that these are matched on key prognostic factors and propensity weighting can be applied appropriately.
This could not only accelerate enrolment timelines and mean that more patients receive the active treatment rather than placebo, but it could also reduce trial costs, said Katab.
Presenters spoke based on personal opinion, not on behalf of their company.
