FDA Touts Use of Real-World Evidence in Prograf Approval
Three FDA officials say the recent approval of Astellas’ Prograf (tacrolimus) in combination with other immunosuppressants for the new indication of preventing organ rejection in adult and pediatric patients receiving lung transplantation reflects how a well-designed, non-interventional study relying on fit-for-purpose real-world data (RWD), when compared to a suitable control, can be considered adequate and well-controlled under agency regulations. Writing in an online post, the three say real-world evidence (RWE) “can play a significant role in regulatory decision-making when appropriate.”
The post says that fit-for-purpose RWD may be used to generate RWE that FDA can consider when making regulatory decisions about medical product safety and effectiveness, such as identifying new safety issues with a drug after it is approved or helping to determine the effectiveness of a drug for a new indication or patient population.
The authors say the agency determined that the non-interventional study supporting Prograf approval for the lung transplant indication, when compared with historical controls, met FDA’s evidentiary standards for an adequate and well-controlled study. The study used RWD from the U.S. Scientific Registry of Transplant Recipients that is supported by HHS. “A dramatic improvement in outcomes was observed among lung transplant patients receiving Prograf as part of their immunosuppression regimen compared to the well-documented natural history of patients receiving a transplanted lung with no or minimal immunosuppressive therapy,” the article says. “The clinical benefit seen with the tacrolimus-containing immunosuppressive regimen was so large compared to these controls that bias was highly unlikely to explain the outcome differences.”
“This approval may prompt stakeholders to consider the role that RWD can play in various study designs,” the article concludes. “Given that treatment assignment in a non-interventional study is based on clinical judgment rather than a protocol-based assignment, confounding and other sources of bias can create challenges in determining whether the drug led to the observed outcome or if other factors that led a practitioner to select a particular drug for a patient influenced the outcome. Although these concerns were addressed in the Prograf study, randomized and other types of clinical trials are still generally the most reliable way to assess the potential effectiveness of a drug and these trials will remain a critical part of the drug development process. Accordingly, FDA will continue to individually review each drug development program and marketing application that includes RWE based on legal and scientific standards.”