Randomized phase III trials are the gold standard of evidence-based drug development. They provide robust data on efficacy and safety and form the basis for regulatory decisions.
However, with market approval, a new phase of evidence generation begins: the real-world care setting. This raises a central question:
How do patients experience a therapy in everyday life—outside controlled study settings?
Differences often arise between clinical evidence and real-world practice, for example in adherence, treatment burden, or perceived benefit. These dimensions are increasingly discussed under the term patient perspective and are often captured through patient-reported outcomes (PROs).
At the same time, the systematic integration of this perspective is methodologically demanding—and requires a careful understanding of the limitations of different data sources.
Phase III trials and their limitations in real-world care
Randomized controlled trials maximize internal validity. Strict inclusion and exclusion criteria, standardized treatment pathways, and intensive monitoring allow causal effects to be demonstrated reliably.
However, these characteristics can at the same time limit the transferability to real-world care.
Typical differences between study settings and real-world care are:
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selected patient populations
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close monitoring
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high treatment adherence
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clearly defined treatment protocols
In real-world care, treatment situations are often more complex. Multimorbidity, polypharmacy, individual life circumstances, and different healthcare systems significantly influence treatment experiences.
The European Medicines Agency (EMA) emphasizes in its Regulatory Science Strategy to 2025 that real-world data (RWD) and real-world evidence (RWE) are becoming increasingly important in order to better understand medicinal products under actual conditions of care.
Why the patient perspective is gaining importance
In addition to traditional clinical endpoints, patient-relevant dimensions are increasingly coming into focus:
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Quality of life
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Symptom burden
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Functional limitations
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Treatment burden
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Perceived benefit
Many of these aspects can only be captured through direct feedback from those affected.
The U.S. Food and Drug Administration FDA, through its initiative Patient-Focused Drug Development (PFDD), aims to systematically incorporate patient experiences into development and evaluation processes. The corresponding guidelines describe how patient input and PRO data can be collected in a methodologically robust manner.
Health technology assessment institutions are also increasingly taking patient-centered endpoints into account—especially when it comes to quality of life or functional limitations. This development reflects a broader shift toward more patient-centered evidence approaches, which is explored in more detail in the article “Patient engagement in transition: How real-world data open new perspectives on treatment outcomes“.
Adherence as an example of the importance of the patient perspective
One area in which the patient perspective is particularly relevant is treatment adherence.
The World Health Organization estimates that in chronic diseases, about 50 percent of patients do not take their medications as prescribed (WHO, 2003). This can have significant effects on treatment outcomes and healthcare costs.
Real-world data can often indicate that a therapy has been discontinued or switched. However, they provide only limited information about the underlying causes.
Why was the therapy discontinued?
Possible reasons may include:
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Side effects
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Lack of perceived benefit
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Complex dosing regimens
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Difficulties integrating the therapy into daily life
Such factors only become visible when the patient perspective is systematically collected.
The methodological challenges of traditional patient surveys
The methodological challenges of traditional patient surveys.
Several challenges are known:
Recall bias
Many surveys are based on retrospective assessments. Memories of symptoms or side effects may therefore be biased.
Selection bias
Participants in voluntary surveys often differ from the overall population. Certain patient groups may therefore be over- or underrepresented.
Validity of the instruments
Regulatory guidelines emphasize that PRO instruments must measure clearly defined concepts and be psychometrically validated in order to provide reliable results.
Lack of therapy context
If surveys are conducted independently of actual medication intake, the context of the specific treatment situation is often missing.
However, this context can be crucial for correctly interpreting treatment experiences.
An underestimated opportunity: data along real medication routines
One way to address some of these limitations is to collect patient data in the direct context of therapy use.
Digital medication solutions that accompany patients in everyday life can provide an interesting infrastructure for this purpose. They enable the combination of different data perspectives—an approach that is also discussed in the context of digital therapy support as a source of robust patient insights is discussed.
Passive real-world data from therapy use
During the use of such applications, data on real therapy processes are generated, for example:
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Medication intake confirmations
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Medication schedules
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Use of reminder functions
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Interactions with the application
This information provides insights into adherence, persistence, and usage patterns.
Contextualized patient surveys
In addition, short, target group-specific surveys can be used to capture subjective experiences—for example:
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Side effects
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Treatment burden
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perceived benefit
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satisfaction with the treatment
The advantage is that such feedback can be collected in the context of real therapy routines and not independently of actual medication intake.
Exploratory real-world insights versus regulatory evidence
Despite these potentials, it is important to note: Not every form of patient-generated data automatically meets regulatory evidence requirements.
Exploratory real-world data can be particularly valuable for:
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Hypothesis generation
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Healthcare analyses
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Patient engagement strategies
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Lifecycle management
However, significantly stricter requirements apply for regulatory decisions regarding study design, instrument validation, and statistical robustness.
The challenge, therefore, is less about prioritizing a single data source and more about meaningfully combining different types of evidence.
Conclusion: A more comprehensive picture of care
Phase III studies remain the foundation of evidence-based drug development.
With the transition into routine care, an additional dimension of evidence emerges: the experience of therapy in everyday life.
Patient reports, usage data from digital medication solutions, and classical real-world analyses can together help to create a more differentiated picture of care.
Particularly valuable in this context is the combination of passive real-world data and contextualized patient feedback. It enables the linking of therapy processes and therapy experiences.
For pharmaceutical companies, this creates the opportunity not only to understand whether a therapy works, but also how it is experienced and used in everyday life—an important foundation for patient engagement strategies and real-world insights along the medication therapy pathway. You can read more in our article “Patient engagement in transition: How real-world data opens new perspectives on treatment outcomes.”
Especially in complex treatment situations, this perspective can help to better understand care and to further develop patient-centered treatment concepts in the long term.
Sources
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European Medicines Agency (EMA). Regulatory Science Strategy to 2025.
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U.S. Food and Drug Administration (FDA). Patient-Focused Drug Development Guidance Series. 2020–2023.
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World Health Organization (WHO). Adherence to Long-Term Therapies: Evidence for Action. 2003.
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Basch E et al. Overall survival results of a trial assessing patient-reported outcomes for symptom monitoring. JAMA. 2017.
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Cutler RL et al. Economic impact of medication non-adherence. BMJ Open. 2018.