FDA Draft Guidance on Demonstrating Substantial Evidence of Effectiveness for Drugs and Biologics

The US Food and Drug Administration (FDA) issued draft guidance on demonstrating “substantial evidence” of effectiveness for drugs and biologics, expanding on decades old guidance issued to address statutory changes brought on by the Food and Drug Administration Modernization Act of 1997. Specifically, the 18-page draft guidance builds on FDA’s 1998 guidance, Providing Clinical Evidence of Effectiveness for Human Drug and Biological Products, which detailed FDA’s expectations for evidence to support the approval of new drugs and biologics or applications for supplemental indications in light of FDAMA’s clarification that a single adequate and well-controlled clinical trial and confirmatory evidence can be used to support approval.

Draft Guidance

FDA notes that although FDA’s evidentiary standard for effectiveness has not changed since 1998, the evolution of drug development and science has led to changes in the types of drug development programs submitted to the FDA. Specifically, there are more programs studying serious diseases lacking effective treatment, more programs in rare diseases, and more programs for therapies targeted at disease subsets. There is a need for more FDA guidance on the flexibility in the amount and type of evidence needed to meet the substantial evidence standard in these circumstances. The approaches discussed in this guidance can yield evidence that meets the statutory standard for substantial evidence and reflect the evolving landscape of drug development.

“As our scientific knowledge advances, and drugs and biologics with novel mechanisms are being developed to treat conditions that were previously without treatments, there is a need for additional guidance on the flexibility in the amount and type of evidence needed to establish their effectiveness,” said FDA Principal Deputy Commissioner Amy Abernethy.

Within the guidance, FDA discusses the level of quality and the quantity of clinical evidence needed to demonstrate effectiveness and provides examples of “circumstances where additional flexibility may be warranted,” such as for treatments for rare diseases or life-threatening or severely debilitating conditions where there is an unmet medical need.

“There are circumstances where evidence generated using a variety of clinical trial designs, endpoints and statistical methodology can support effectiveness, such as in certain drug development programs for rare diseases,” Abernethy said.