SURF: A Screening Tool (for Sponsors) to Evaluate Whether Using Real-World Data to Support an Effectiveness Claim in an FDA Application Has Regulatory Feasibility.

Based on recent guidance and publicly available approvals, the US Food and Drug Administration (FDA) has demonstrated its openness to considering evidence of effectiveness from real-world data (RWD) and nonrandomized studies (or "real-world evidence (RWE)") in its decision making. Through analysis of the FDA approvals, several authors have identified methodologic issues commonly discussed by FDA reviewers. However, in our analysis of FDA guidance and use cases, acceptability of RWE also critically depends on whether the characteristics of the clinical development program align with circumstances in which the FDA may have flexibility in considering evidence from real-world study designs relative to more robust designs.

The Role of Real-World Evidence in FDA-Approved New Drug and Biologics License Applications.

The US Food and Drug Administration (FDA) is open to accepting real-world evidence (RWE) to support its assessment of medical products. However, RWE stakeholders lack a shared understanding of FDA's evidentiary expectations for the use of RWE in applications for new drugs and biologics. We conducted a systematic review of publicly available FDA approval documents from January 2019 to June 2021.

Addressing Pharmaceutical Injuries: The US Landscape.

The legal landscape for addressing an injury related to the use of a pharmaceutical product varies from country to country. Approximately 10 countries have adopted some form of no-fault compensation, in which an individual must establish that they sustained an injury caused by the medicine, but need not demonstrate that the manufacturer acted negligently in order to recover. This commentary compares and contrasts the approach taken in Japan with that in the United States.

Activation of mutant enzyme function in vivo by proteasome inhibitors and treatments that induce Hsp70.

Missense mutant proteins, such as those produced in individuals with genetic diseases, are often misfolded and subject to processing by intracellular quality control systems. Previously, we have shown using a yeast system that enzymatic function could be restored to I278T cystathionine beta-synthase (CBS), a cause of homocystinuria, by treatments that affect the intracellular chaperone environment. Here, we extend these studies and show that it is possible to restore significant levels of enzyme activity to 17 of 18 (94%) disease causing missense mutations in human cystathionine beta-synthase (CBS) expressed in Saccharomyces cerevisiae by exposure to ethanol, proteasome inhibitors, or deletion of the Hsp26 small heat shock protein.