FDA and the Future of Healthcare Innovation
A recent report written by the outgoing House Energy & Commerce (E&C) Committee majority staff argues that the FDA “ignored the science “when it approved Aduhelm (a treatment to slow the progression of Alzheimer's Disease). The Democrats claim the developer of the medicine, Biogen, inappropriately conspired with the FDA to cut corners resulting in an approval without clear evidence of effectiveness.
The truth of the matter is that the FDA approval was the result of re-analyzing the clinical trial data using artificial intelligence-driven simulations of the clinical risks and benefits of Alzheimer's patients with various degrees of severity. Such computational models can predict outcomes as reliably as traditional clinical trials in a fraction of the time and cost. Importantly, Biogen will continue to evaluate the clinical risks and benefits of Aduhelm in a real-world clinical environment.
The decision by senior FDA executives to re-examine the data by machine-learning driven simulations was "atypical." But such methods have been used before, particularly in rare cancer drug reviews. Even though some divisional reviewers have refused to use them, the 21st Century Cures Act requires the FDA to use advanced computational methods throughout product evaluation and the agency has issued several guidances to support such approaches. The E&C staff report alleges these methods glossed over Aduhelm's poor performance. On the contrary, regulatory science applied by senior leaders over the objections of staff identified both rationale and reasons for approval.
The staff report criticizes the use of surrogate endpoints – markers of the predicted treatment response – instead of measuring the response itself. However, as FDA’s Principal Deputy Commissioner, Dr. Janet Woodcock noted:
"Surrogate endpoints serve as stand-ins for clinical endpoints that measure the real benefits of drugs: whether a patient feels better or can function better, or lives longer. Surrogate endpoints generally allow clinical studies to be conducted in smaller populations of individuals over shorter periods, reducing both the time and cost of drug development."
Advanced computational methods, including causal inference and Bayesian network analysis, have allowed the testing of the same medicine for different groups. In combination with the analysis of surrogate endpoints, it is now possible to continually modify the participants and objectives of studies to focus on those patients that would benefit most.
That progress has been built upon the experience of the FDA and the industries it regulates. The results facilitate innovation resulting in new and critical medical technologies like Aduhelm and other medicines currently in the pipeline for Alzheimer's Disease and other severe and life-threatening conditions.
Welcome to science!
Critics of the FDA decision are correct to point out that uncertainties remain. Yet, those critics want to abandon the tools that help to identify incremental innovations. These advances improve quality of life or slow progression until the next generation of products comes along to enhance well-being and extend life.
The same approaches – applied to identify incremental but significant clinical advances – have been used to approve HIV drugs and treatments for rare blood disorders and cancers that disproportionately affect people of color. If the E&C report authors and their allies oversaw the FDA, would medicines for Alzheimer's, COVID-19, HIV, and cancer be available?
We must embrace innovation while monitoring products in the real world to ensure they maintain a solid benefit/risk profile. Kudos to the FDA for choosing the course of action with the most potential upside for Alzheimer's patients, their families, and our health system. Going backward to an outdated standard isn't an option.
Peter J. Pitts, a former FDA Associate Commissioner, is President of the Center for Medicine in the Public Interest and a Visiting Professor at the University of Paris School of Medicine. Dr. Robert Goldberg is Vice President of Research Programs at the Center for Medicine in the Public Interest.
