The recent ISPOR Europe 2025 conference, held under the inspiring theme ‘Powering Value and Access Through Patient-Centered Collaboration,’ featured a dedicated track on patient-centered research that underscored ISPOR’s commitment to embedding patient voices at the core of Health Economics and Outcomes Research (HEOR) innovation.
One of the sessions, External Control Studies – What Does it Take to Get Real?, brought together various stakeholder groups to discuss the scientific, regulatory, and ethical considerations around using external control arms (ECAs). Conversations like these are energizing the field and paving the way for more patient-centered trial designs.
I’d like to continue the conversation by expanding on how ECAs can redefine patient-centered research, tying back to the themes from ISPOR, and exploring what’s now, what’s next, and what truly matters to patients.
Redefining Patient-Centered Research
“Patient-centered” has long been more of an aspiration than a practical reality in clinical research. Traditional trial structures often place patients into control groups that deny them access to innovative therapies and impose a heavy procedural burden. ECAs change that equation.
ECAs, powered by real-world data (RWD) from physician-supplied longitudinal records, mirror what patients experience in routine care. Instead of idealized trial visits, they reflect standard-of-care pathways as they unfold in real life. This makes comparisons more meaningful to regulators and payers while aligning trial evidence with what matters most to patients: outcomes tied to everyday care, quality of life, and actual effectiveness.
Importantly, ECAs reduce the number of participants randomized away from promising therapies. Fewer patients are placed on placebo or outdated standards of care and more can access the innovative treatments under study. At the same time, trial-driven burdens such as extra clinic visits, redundant assessments, or unnecessary procedures are minimized for patients whose data form part of the external cohort.
This shift reframes patient-centeredness not just as a value statement, but as an operational reality in trial design.
Where ECAs Are Already Making an Impact
Some therapeutic areas are especially suited for ECAs, and adoption is advancing rapidly in these fields. Oncology and hematology are clear examples. Both involve heterogeneous patient populations, rapidly evolving standards of care, and frequent ethical concerns around withholding treatment. Similarly, advanced modalities such as CAR-T and other cell therapies present unique challenges because eligible patients are few and disease courses move quickly.
ECAs also demonstrate strong potential in rare diseases. For many rare conditions, patient populations are simply too small or fragmented across geographies to support randomized controls. Constructing fit-for-purpose comparators from curated real-world records is often the only credible way forward.
What unites these settings is the need for credible, representative comparators that regulators will accept without delaying trials or excluding patients from innovative therapies. ECAs make this possible.
The Patient View: Fewer Barriers, Faster Access
Patients stand to benefit from ECAs in three particularly meaningful ways.
- Greater access to innovation. With fewer patients randomized to placebo or outdated comparators, more participants can receive the investigational therapy itself.
- Lower trial burden. Evidence for the control group comes from existing routine-care records rather than requiring trial-driven procedures. That means fewer additional hospital visits, fewer invasive procedures, and less disruption to daily life.
- Faster availability of results. Because curated records can be assembled and validated more quickly than running a full control arm, trials can move faster. Projects that might otherwise take years can often be delivered in less than a year. For patients awaiting new treatment options, every month matters.
Taken together, these benefits embody what patient-centered research should strive for: maximizing the chance of accessing new therapies, minimizing burdens, and accelerating timelines—all without compromising scientific rigor.
Addressing Misconceptions About ECAs
Despite growing momentum, misconceptions still linger about ECAs.
- Myth 1: ECAs are less rigorous. In fact, high-quality ECAs are built through careful curation, representative sampling, validation, and advanced statistical methods. Far from being “shortcut science,” they are constructed with the same methodological discipline as randomized arms, just grounded in real-world evidence (RWE).
- Myth 2: ECAs are not representative. Well-designed ECAs intentionally address representativeness through proportional sampling across different care structures and facility types. This avoids the pitfalls of convenience sampling and ensures that cohorts reflect real clinical practice across diverse settings.
- Myth 3: Regulators won’t accept them. Regulatory and health technology assessment (HTA) bodies are increasingly open to high-quality RWE. Joint clinical assessment (JCA) and European Medicines Agency (EMA) guidance reflect this openness, and ECAs have already supported successful submissions and HTA reviews in oncology and rare disease. The key is early engagement with regulators and transparent methodology.
By confronting these misconceptions directly, the field can move toward broader acceptance and integration of ECAs in drug development.
How Close Are We to Standard Practice?
The question is no longer whether ECAs will be used, but how broadly. In oncology and rare disease, ECAs are already moving from exceptional cases to expected practice. The main enabler is trustworthy, representative data that regulators can confidently rely on.
Broader standardization across all therapeutic areas will require continued methodological alignment and consistent regulatory comfort. Yet the trajectory is clear: in areas where patient needs are urgent, ECAs are already established as a credible complement to traditional trial arms.
What Truly Matters: Keeping Patients at the Center
At ISPOR, much was said about “patient-centered collaboration.” ECAs make that principle actionable by ensuring patients are not passive participants in lengthy, burdensome trials, but active beneficiaries of research progress.
Patient-centered research must be more than rhetoric. It means designing trials that reduce unnecessary burdens, expand access to innovative therapies, and produce evidence that truly reflects patient experiences in real-world care. ECAs offer a way to achieve this balance by being scientifically rigorous, regulatorily credible, and ethically aligned with patient priorities.
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About Markus Rückert, PhD
Markus is a seasoned biopharmaceutical expert specializing in oncology and rare diseases. Proficient in clinical development and Medical Affairs, as well as experimental and RWE generation, Markus has successfully navigated various stages of drug development, from discovery to market launch, with a keen focus on advancing oncological and rare disease therapies for tangible patient benefits. Having achieved significant milestones in oncology and rare disease therapeutics, Markus now channels his diverse expertise towards broader pursuits in epidemiology, health service research, and the real-world impact of oncological treatments.