FDA Officials Defend Agency's Flexibility Under Current Regulatory Framework

Posted 24 February 2017 By Michael Mezher

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Top officials at the US Food and Drug Administration (FDA) are defending the agency's flexibility to accelerate the availability of products by considering diverse data sources in product submissions.

In an article in Nature Reviews Drug Discovery on Friday, Rachel Sherman, deputy commissioner for medical products and tobacco in the Office of the Commissioner at FDA, writing alongside former FDA Commissioner Robert Califf and other high-ranking agency officials, argue that misconceptions about the agency's ability to assess data from diverse sources, including real-world data, contributes to the so-called "evidence gap" between the data used to support regulatory approval and the data needed to inform clinical decision-making.

According to the authors, "widely held views that current regulatory structures cannot accommodate a modern, robust and diverse evidence base, and that these regulatory structures are predicated on narrowly targeted premarket evaluations of medical products," hinder progress toward generating data that could more accurately reflect a product's real-world use.

The issue, the authors say, is that clinical trials to support product approval tend to focus on answering narrowly defined questions that do not always reflect the total patient population for a disease or how a product will be used by doctors, which leads to uncertainty about a treatment in clinical practice.

However, the authors say that this rigid interpretation of approval requirements doesn't match up with FDA's approach to weighing the "totality of evidence," which could include the agency's understanding of the therapy, disease, alternative treatments and patient preferences, all of which can evolve over time.

To counter this view, the authors point to FDA's accelerated approval of Johnson & Johnson's Darzalex (daratumumab) for multiple myeloma in November 2015. Darzalex was granted accelerated approved based on data from two open label studies: a single-arm, Phase II trial of 106 patients measuring a surrogate endpoint (overall response rate) and a Phase I/II dose-ranging and safety study. A year later, in November 2016, FDA approved Darzalex in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone based on the results of two randomized open-label studies.

By taking this flexible approach, the authors say FDA was able to quickly address an unmet need before additional data on combinations and optimal dosing became available.

As such, the authors encourage drugmakers and device manufacturers to think about how they can generate broader evidence for their products in a manner that "more closely resemble[s] clinical practice."

"We believe that recognition that the evidence needed to support regulatory approval or clearance and the evidence needed to inform treatment decisions are both part of a single continuum creates a powerful direct incentive for manufacturers and/or study sponsors to appropriately evaluate the benefits and risks of a product in real-world conditions and among the groups of patients likely to be treated once the product is marketed," the authors write.

Accelerating development of scientific evidence for medical products within the existing US regulatory framework

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Categories: Biologics and biotechnology, Drugs, Medical Devices, Clinical, Submission and registration, News

Tags: Real-world data, Accelerated approval

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