Real-world evidence in medicine regulation

Real-world evidence (RWE) refers to clinical evidence regarding the use, benefits, or risks of a medicine derived from the analysis of real-world data (RWD). Traditionally, medicines are evaluated through randomised controlled trials (RCTs), which are highly controlled experiments conducted before a product reaches the market. While RCTs remain the gold standard for establishing whether a medicine works, they often do not perfectly reflect the reality of everyday medical practice. Regulatory authorities are increasingly looking to RWE to understand how a medicine performs once it is approved and prescribed to the general public. This shift recognises that controlled trials, while rigorous, have inherent limitations when it comes to understanding long-term safety and effectiveness.

Randomised trials versus real-world evidence

RCTs are designed to isolate the effect of a medicine by carefully selecting participants. They commonly exclude individuals with multiple health conditions, those taking other concurrent medications, and sometimes the elderly or children. This controlled environment is excellent for proving efficacy under ideal conditions, but it can create a gap between trial results and everyday clinical practice. Once a medicine reaches the market, it is prescribed to a much broader and more varied population.

Real-world evidence fills this gap by capturing outcomes in routine clinical practice. Rather than replacing RCTs, real-world evidence supplements them by providing a broader picture of a medicine’s safety and effectiveness across diverse, real-life populations. It helps answer questions about how a medicine performs when patients occasionally miss doses, take over-the-counter supplements alongside it, or have comorbidities that would have excluded them from the initial trials.

Sources of real-world data

To generate real-world evidence, researchers draw on real-world data from a variety of sources. These commonly include electronic health records, insurance and medical aid billing claims, pharmacy dispensing databases, and patient registries. A patient registry is an organised system that collects observational data about patients who share a specific condition or are taking a particular medicine over an extended period. In some cases, data from wearable devices and mobile health applications are also being explored as supplementary sources.

The key distinction is that this information is collected as part of routine healthcare delivery, rather than as part of a pre-planned, strictly controlled experimental study. The sheer volume of this data allows researchers and regulators to observe patterns that might take decades to appear in a traditional clinical trial setting.

How regulators use real-world evidence

Regulatory authorities like the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have established frameworks to incorporate real-world evidence into their decision-making processes. One of the most common uses is pharmacovigilance—the ongoing monitoring of the safety of medicines after they reach the market. If a rare side effect is suspected, regulators can query large health databases to see if the signal is genuine or a statistical anomaly.

RWE is also used to support label expansions, where a medicine already on the market is approved for a new use based on observational data rather than a new trial. Additionally, it is highly valuable for evaluating treatments for rare diseases, where recruiting enough patients for a traditional clinical trial is often not feasible. In South Africa, the South African Health Products Regulatory Authority (SAHPRA) similarly monitors post-market safety, and tools like the HealthSA search tool help users trace registered medicines that might be subject to such ongoing safety evaluations or labelling updates.

Limitations and challenges of real-world evidence

Despite its growing importance, real-world evidence has significant limitations. Because the data is collected during routine care, it is often messy, incomplete, or inconsistently recorded by different healthcare providers. Unlike in a clinical trial, there is no placebo control group, making it difficult to prove that a medicine directly caused a specific outcome rather than another external factor—a statistical problem known as confounding.

Patients who receive a new medicine might be systematically different from those who received an older treatment, complicating direct comparisons. Furthermore, relying on billing codes can sometimes result in inaccurate diagnoses being recorded. For these reasons, regulators generally require real-world evidence to be rigorously analysed and validated. They rarely use it as the sole basis for an initial marketing approval. Instead, it is viewed as a powerful complementary tool that enhances the understanding of a medicine after it has already proven its fundamental safety and efficacy in clinical trials.