Randomized controlled trials (RCTs) have long been considered the gold standard to estimate the effectiveness of a new intervention or treatment. Homogeneity of the patient population is often desired in these registrational trials to minimize variance introduced by patient and disease characteristics. Randomization, blinding, and homogeneity in the trial patient population reduces bias and provides a rigorous tool to examine cause-effect relationships between an intervention and health outcomes.
A common limitation of RCT data is that the results obtained in a well-controlled setting for a relatively homogeneous patient population may not be generalizable to the target patient population. It is here that real-world evidence (RWE) can provide further insights and knowledge, especially in the case of a novel medicine or new class of therapies.
RWE serves as the next step in the evidentiary continuum to complement RCT data, fully understand the patient journey, and evaluate drug effectiveness, safety, and value as part of routine clinical practice.
The FDA describes RWE as clinical evidence on the usage and potential benefits and risks of a drug derived from real-world data, the data related to patient health status, and the delivery of healthcare routinely collected outside the scope of randomized controlled trials, including electronic health records, claims, registries, and patient-generated data. Because these data are observational and often routinely collected as standard of care, their collection presents a lower burden on patients, caregivers, and healthcare providers — this is particularly relevant in the area of Alzheimer’s disease, where a key objective of care should be alleviating the day-to-day burden on patients and caregivers. Additionally, real-world studies include larger patient populations that are historically underrepresented in randomized controlled trials (e.g., patients who are ethnically/racially/geographically diverse, have comorbid conditions, are taking concomitant medications) and thus help mitigate any potential generalizability issues that impact RCTs.
RWE has been used to supplement Phase III registration trial data, understand the patient journey, and assess drug safety and effectiveness in the real-world in a variety of therapeutic areas. Perhaps the most publicly visible example of the added value of RWE can be found in the ongoing efficacy and safety evaluations of the Covid-19 vaccines. Within months of FDA approval, a CDC study using data from a network covering 500,000 health care professionals across 33 sites in 25 U.S. states documented with robust evidence that mRNA vaccines are safe and effective against symptomatic illness in real-world conditions — demonstrating their value in record time, accelerating adoption, and saving countless lives.
Another great example of leveraging real-world data to generate critical information is the Cystic Fibrosis (CF) Foundation Patient Registry. This registry collects information on the health status of people with cystic fibrosis who receive care in CF Foundation-accredited care centers and agree to participate in the Registry. The RWE generated is used to create CF care guidelines, assist care teams providing care to individuals with CF, and guide quality improvement initiatives at care centers. Researchers also use the Registry to study CF treatments and outcomes and to design future CF clinical trials.
In Alzheimer’s disease specifically, lack of representation in clinical trials has been a problem for the entire industry. Alzheimer’s disease RCTs, including Biogen’s, have historically struggled to enroll participants from the Black / African American community. We are aware that common barriers to participating in clinical trials include mistrust of the healthcare system, inadequate information about research and opportunities to participate, access to sites and specialists, and logistical concerns, as well as the industry practice of working with large, well-established, and well-trained clinical specialized centers. To strengthen our outreach to diverse communities, Biogen and the National Minority Quality Forum (NMQF) are collaborating to help increase diversity in clinical trials.
These challenges can be addressed, in part, by generating data in real-world settings. New wearable technologies, broader patient eligibility criteria, inclusion of community-based medical centers, wider geographic outreach, and less administrative burden will make it easier to enroll a community of patients fully representative of the American population. This is why Biogen, together with organizations like the NMQF, are committed to generate more evidence and knowledge in Alzheimer’s disease through a multipronged strategy, using randomized controlled trials and real-world evidence powered by registry and observational longitudinal studies.