Evaluating medical treatments and interventions involves different approaches to understand their effects. Clinical trials and real-world evidence are two primary methods for gathering this understanding. Both offer distinct perspectives on how treatments perform, providing a comprehensive picture of their utility.
Clinical Trials
Clinical trials are structured studies evaluating the safety and efficacy of new medical interventions, such as drugs, devices, or therapies, in human volunteers. These trials follow rigorous protocols and ethical and regulatory guidelines to ensure reliable results. They are conducted in a controlled environment where variables are managed to isolate the intervention’s effects.
Clinical trials proceed through several phases. Phase I trials involve a small group of people to assess the treatment’s safety, determine a safe dosage, and identify side effects. If a treatment demonstrates acceptable safety, it moves to Phase II, involving a larger group of 25 to 100 patients with the specific condition to evaluate its effectiveness and monitor safety.
Phase III trials compare the new treatment with existing standard treatments in large groups of patients. These trials aim to confirm effectiveness, monitor side effects, and gather information for its safe use. Successful trials can lead to regulatory approval. After approval, Phase IV trials involve ongoing surveillance in the general population to monitor long-term safety, effectiveness, and optimal use.
Randomization is a defining characteristic of many clinical trials, especially Phase III, where participants are assigned to treatment or control groups by chance. This minimizes bias, ensuring groups are comparable at the study’s start. Blinding is another feature, where participants, and sometimes researchers, are unaware of which treatment is received. This prevents personal preferences or subjective assessments from influencing outcomes.
Real-World Evidence
Real-world evidence (RWE) is information about the use, safety, and effectiveness of medical products derived from data in routine healthcare settings. This contrasts with the controlled conditions of clinical trials. RWE provides insights into how treatments perform in diverse patient populations, reflecting actual clinical practice.
Real-world data (RWD), the basis for RWE, comes from various sources. These include electronic health records (EHRs), which include diagnoses, treatments, and lab results. Patient registries, which collect data on specific diseases or treatments, also contribute information.
Additional sources of RWD include insurance claims and billing data, providing insights into healthcare utilization and costs. Patient-generated data, such as wearable devices, mobile health apps, and patient diaries, captures patient experiences and outcomes outside of clinical visits. Surveys of patients and healthcare professionals also supplement these data sources, offering perspectives not captured elsewhere.
Analyzing this diverse RWD generates RWE, which offers a broader understanding of disease mechanisms and treatment effects. This evidence can reveal unexpected benefits or less common side effects in patient subgroups not studied in initial clinical trials. It helps researchers understand what happens to a patient over their entire life, not just during a trial, providing a more comprehensive view of treatment effectiveness.
How They Differ and Complement Each Other
Clinical trials and real-world evidence have distinct methodologies, yet they complement each other in advancing medical knowledge. Clinical trials are meticulously designed experiments under controlled conditions, often with strict participant criteria. This controlled environment allows researchers to establish an intervention’s efficacy and safety under ideal circumstances, minimizing confounding factors and biases through randomization and blinding.
In contrast, RWE is derived from real-world data collected during routine clinical practice, reflecting a broader, more diverse patient population with varying characteristics and comorbidities. While clinical trials measure prespecified outcomes over limited timeframes, RWD captures a wider range of outcomes, such as patient-reported outcomes, quality of life, hospitalizations, and costs, over longer periods. This difference means RWE can reflect variability in real-world treatment patterns and patient adherence, which are not controlled in trials.
Despite their differences, clinical trials and RWE are complementary. Clinical trials provide the foundational evidence for new medical products, demonstrating initial safety and efficacy. RWE then complements this by offering insights into how treatments perform in the broader population and over extended periods. RWE can also generate hypotheses for further exploration in new clinical trials, creating a continuous cycle of evidence generation.
The insights from RWE broaden the understanding gained from trials by assessing the generalizability of results to diverse healthcare settings and patient groups. For instance, a drug initially approved based on clinical trials might later have its indication expanded based on real-world effectiveness and safety data from EHRs and insurance claims. This synergy provides a more complete picture of a treatment’s effects.
When Each Approach Is Most Valuable
Clinical trials are valuable for establishing the initial efficacy and safety of new drugs or devices for regulatory approval. Their controlled nature, including randomization and blinding, allows clear demonstration of whether a treatment works and is safe under specific, well-defined conditions. This structured approach isolates the direct effect of an intervention and minimizes bias in determining causality.
Real-world evidence offers value in scenarios where clinical trials have limitations or where broader, more practical insights are needed. RWE is useful for understanding long-term safety and effectiveness in diverse patient populations, including those with comorbidities or varying adherence patterns often excluded from trials. It helps identify rare side effects that emerge when a treatment is used by a larger group over time.
RWE also provides information for health economics, assessing the cost-effectiveness and value of new therapies in routine clinical practice. For rare diseases, where recruiting large cohorts for trials is challenging, RWE can provide data by casting a broader, more inclusive net. This approach helps fill research gaps and contributes to a personalized understanding of treatment outcomes.