> ## Content Index
> Fetch the complete content index at: https://www.fdaweb.com/llms.txt
> Use this file to discover other available public pages before exploring further.

# Is FDA Relying More on ‘Confirmatory Evidence’?
- URL: https://www.fdaweb.com/is-fda-relying-more-on-confirmatory-evidence/
- Published: 2022-10-12T12:00:00.000Z
- Updated: 2026-09-14T18:02:48.000Z
- Author: David McFarland
- Tags: Drugs, #legacy-id-D5152955

Three Hyman, Phelps & McNamara attorneys say that despite the lack of a draft guidance on confirmatory evidence, FDA’s use of a confirmatory evidence standard in several drug approvals indicates the agency’s emerging, explicit interest in this portion of the Federal Food, Drug, and Cosmetic Act. “Even in the absence of a standalone guidance,” the three [write](https://www.thefdalawblog.com/2022/10/is-confirmatory-evidence-having-a-moment/?ref=fdaweb.com) in their firm’s *FDA Law Blog*, we sense that confirmatory evidence may be having a moment all its own.”

The attorneys note that a confirmatory evidence guidance has been on CDER’s guidance agenda for the past two years. “To be fair,” they write, “the annual guidance agenda consistently presents a lengthy and somewhat aspirational to-do list, and it is not surprising when one slips through the cracks. However, we wonder whether recent and ongoing approval decisions are shaping FDA’s thinking, possibly pushing back the issuance of a draft.”

The post says that some drug approvals over the past few years have given considerable insight into FDA’s current thinking and how it is applying the standard. The latest, they say, was the 9/20 approval of Amylyx Pharmaceutical’s Relyvrio to treat amyotrophic lateral sclerosis.

In a 12/2019 draft guidance, the attorneys say, the agency listed four examples of what could constitute confirmatory evidence to be used with a single clinical trial. The examples were:

- supportive evidence from existing adequate and well-controlled clinical investigations in a closely related approved indication;
- evidence from data that provide strong mechanistic support;
- compelling results from the single adequate and well-controlled clinical evidence supported by additional data from the natural history of the disease; and
- support from scientific knowledge about the effectiveness of other drugs in the same pharmacological class.

“While the guidance clearly describes these as just four illustrations of confirmatory evidence,” the attorneys write, “it has been our experience that individual review divisions within FDA have not always shared this view. We have at times encountered not only a reluctance to apply the ‘confirmatory evidence’ standard but even experienced refusal to recognize other sources of evidence not explicitly mentioned in the guidance (but equally capable of substantiating a single pivotal trial’s results). Despite these experiences, we have been involved with several ‘confirmatory evidence’ approvals, especially for rare serious conditions, in the past few years that suggest that FDA may be taking confirmatory evidence more seriously.”

The authors conclude that the Relyvrio approval may be the latest and perhaps most high-profile confirmatory evidence approval precedent to date, but it reinforces the interpretation that FDA’s discussion of confirmatory evidence in the 12/2019 draft guidance was meant to illustrate what is possible and was not intended to set rigid bounds or limitations on the nature or scope of types of confirmatory evidence.