RWE 101 – Protocol Considerations

Real-world evidence (RWE) study protocols and clinical trial protocols both outline the design and conduct of a study. However, they are distinctly different in several ways given the differences in objectives, methodologies, settings, and populations involved in clinical trials versus RWE studies.
[1] Objectives: The main objective of a clinical trial is to evaluate the efficacy and safety of a medical intervention in a controlled environment, usually by comparing it to a placebo or standard treatment. On the other hand, RWE studies typically aim to understand how an intervention works in routine clinical practice, often focusing on outcomes such as long-term effectiveness, side-effects, quality of life, and cost-effectiveness.
[2] Study Design and Methodology: Clinical trials, especially phase III, are predominantly randomized controlled trials (RCTs) where subjects are randomly assigned to the intervention or control group to minimize bias. They follow a pre-specified protocol and are conducted under tightly controlled conditions. RWE studies, on the other hand, are typically observational in nature and analyze data from sources like electronic health records (EHRs), claims databases, or patient registries.
[3] Setting: Clinical trials are conducted in specific, controlled environments and follow a strict protocol. RWE studies are conducted in routine clinical practice settings, making them more representative of ‘real-world’ conditions.
[4] Population: Clinical trials often have strict inclusion and exclusion criteria, resulting in a relatively homogeneous group of participants. This can limit the generalizability of the results. RWE studies, in contrast, involve broader, more diverse populations (including those often excluded from trials like the elderly, people with multiple co-morbidities, etc.), making the findings more generalizable to everyday practice.
[5] Data Collection: In clinical trials, data collection is rigorous, detailed, and specific to the trial endpoints. Adverse events are actively sought and documented. RWE studies primarily rely on existing data sources such as EHRs, patient registries, or insurance claims data. This can potentially lead to incomplete or inaccurate data.
[6] Intervention: In clinical trials, the intervention (dosage, frequency, duration, etc.) is pre-specified and strictly monitored. In RWE studies, interventions reflect routine clinical practice and may vary widely.
[7] Follow-up: Clinical trials have a defined follow-up period while RWE studies can often provide information on long-term outcomes, given they use data from routine clinical practice over longer periods.
While clinical trials provide the highest level of evidence for determining a treatment’s efficacy, RWE studies complement this by providing evidence on real-world effectiveness and long-term safety.

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