How Does the FDA Use Real-World Evidence to Approve Medications?

Before medications are FDA-approved, they typically go through randomized controlled trials (RCTs). RCTs study a medication in a controlled environment under ideal conditions. But this can be a long and expensive process. And it can be difficult to recruit enough people for certain studies, too.

In December 2016, Congress passed the 21st Century Cures Act. The law intended to help bring new and innovative medical products to market faster. This includes approving new uses for FDA-approved medications more efficiently. But regulation was still needed. So the FDA created a program that uses real-world evidence to help make these decisions.

Real-world evidence isn’t necessarily a substitute for RCTs. But in some cases, it can be used in combination or as a potentially faster alternative. But what exactly is real-world evidence? We'll explain what it is and how it's used by the FDA in making regulatory decisions.

What is real-world evidence?

Real-world evidence is evidence about a medical product from sources outside of RCTs. This can involve a variety of study types. For example, observational studies collect data on people in their normal environment.

This type of evidence can provide insight into the product’s use and potential benefits and risks. It can be used to watch for safety concerns after a product is on the market. And it can be used to support new uses for the product, too.

Real-world evidence comes from reviewing real-world data. Real-world data is health information collected from a variety of sources. This could include sources like patient registries and electronic health records. And with the rise of digital health products (e.g., smart devices), there are more opportunities for real-world data collection.

But how do researchers create real-world evidence from this data? 

How is real-world evidence created?

Let’s use the example of patient registries. These provide information about people with certain medical conditions. They can contain useful information about risk factors, treatments, and outcomes.

Healthcare providers sometimes prescribe a medication in a way that’s not FDA-approved. This information may be found in the patient registry. Researchers could use this data to conduct an observational study. This could create real-world evidence that shows the medication works for this unapproved use.

In this case, the real-world evidence could be used to support the FDA-approval of this use. More on how this works next.

How is it used for FDA approvals?

The FDA sometimes uses real-world evidence as the primary evidence for approval. But more often than not, it’s used as supportive evidence. That means it helps influence the FDA’s decision — but isn’t the only factor.

When using real-world evidence to request approval, the medication still needs to meet the FDA’s regulatory standards. But this doesn’t always happen. That’s because real-world evidence isn’t perfect.

For example, the underlying real-world data might have quality issues. And higher-quality databases with better data aren’t always available to researchers. Plus, the FDA also needs to be able to verify the data itself. Selecting a good study design is also important.

The FDA will determine if the real-world evidence is enough to sway its decision. It usually comes down to study design and how the data was collected and reviewed. But early communication with the FDA can help flag and address potential issues.

Recently, the FDA published several draft guidance documents about real-world evidence and data. These documents give recommendations on data sources, data standards, and regulatory considerations. This can help pharmaceutical companies understand how the FDA uses this information to make decisions.

What are some examples of medications approved using real-world evidence?

Over the years, the FDA started using real-world evidence to approve new uses of medications more often. Below are three notable approvals from the last few years using real-world evidence.

Ibrance (palbociclib)

In April 2019, the FDA expanded the approval of Ibrance (palbociclib) to treat certain types of breast cancer in men. Before the approval, Ibrance was only approved for use in women. In this case, the manufacturer used real-world data from three databases to provide evidence for approval.

Real-world evidence was useful in this instance since breast cancer isn’t as common in men. So, recruiting enough participants for RCTs would be difficult. Now, men with certain types of breast cancer have an approved treatment option.

Prograf (tacrolimus)

In July 2021, the FDA approved Prograf (tacrolimus) to prevent lung transplant rejection in adults and children. Before this, Prograf was FDA-approved to prevent liver, kidney, and heart transplant rejection.

Healthcare providers, though, had been using Prograf for lung transplant rejection before this approval. Because of this, there was real-world data available.

Researchers compared data from the transplant recipient registry and death records. They looked to see if Prograf made a difference. This was an observational study because it collected data on people in their normal environment.

Study findings showed good outcomes in the lung transplant recipients who took Prograf. Plus, Prograf had gone through clinical trials showing it works for other types of transplant rejection. This combined information led to its latest approval.

Orencia (abatacept)

In December 2021, the FDA approved Orencia (abatacept) to prevent graft versus host disease (GVHD). GVHD occurs when a stem cell or bone marrow donor’s immune cells attack the recipient’s body. Orencia became the first FDA-approved medication to prevent GVHD.

Researchers reviewed real-world data from a registry. They looked at outcomes of stem cell transplant recipients. People who received Orencia with standard treatment had a better survival rate 6 months after transplant than those who didn’t receive Orencia.

These findings, along with positive phase 2 trial evidence, led to Orencia’s approval for GVHD.

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Written by:

Alyssa Billingsley, PharmD

Alyssa Billingsley, PharmD, is the director of pharmacy content for GoodRx. She has over a decade of experience as a pharmacist and has worked in clinical, academic, and administrative roles.

Reviewed by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

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