The House is set for a Wednesday vote on the 21st Century Cures Act, the product of nearly three years of intense bipartisan collaboration, consultation with experts and patient groups, and dialogue with medical regulators on the future of biomedical innovation in the U.S.
The FDA’s traditional approval paradigm for medicines... is simply too expensive and time consuming to be used to answer every important question that faces regulators, developers, patients, and physicians.
If passed, the legislation could help companies, researchers, and regulators develop improved paradigms for evaluating medicines developed based on cutting edge science, allowing for safer and more effective medicines to reach patients faster.
The FDA’s traditional approval paradigm for medicines—which typically requires three stages designed to collect preliminary evidence on safety and efficacy, and culminates in two large, randomized controlled trials before approval—is simply too expensive and time consuming to be used to answer every important question that faces regulators, developers, patients, and physicians.
Researchers at Tufts University estimate that, on average, it takes about a decade and costs $2.6 billion to bring a single new medicine to patients. In fact, only about 11-12 percent of all medicines tested in humans ever reach FDA approval. For some diseases, like Alzheimer’s, the failure rate is over 99 percent.
As FDA Commissioner Dr. Robert Califf noted at a recent FasterCures conference, “Medical product development is a lot like soccer. You take a lot of shots on goal, and every once in a while one goes in the goal.” The biggest deterrent to getting more, and better, medicines to patients, Dr. Califf said, is the high cost of “clinical trials the way they are done now.”
A modern FDA need not abandon classical trial designs—far from it—but it should supplement them with new approaches that can answer the same questions faster, at less cost—not only in terms of dollars spent, but lives lost testing ineffective or dangerous treatments.
Without such a supplement, randomized controlled trials—the FDA’s current “gold standard”—have important limitations.
For instance, it may be impossible to run traditional trials large enough to demonstrate statistically significant effects in patients with extremely rare diseases. Or symptom-based clinical trials—like memory loss in Alzheimer’s—may turn out to be the result of breakdowns in different molecular pathways. Drugs that might be effective in certain molecular sub-types can thus look ineffective when they’re tested in trials defined by clinical symptoms. Other important questions about safety or efficacy—like large, head-to-head clinical trials of different treatment strategies—might be better answered by pooling large patient registries that track health outcomes over time, after medicines are approved. (Here, randomization can be employed at the point of care, when doctors really don’t know which treatment is best.)
The Cures Act tackles these challenges head on. It requires the FDA set clearer standards for using novel clinical trial designs that can be run with fewer patients, but still generate robust data. It sets up a framework for public-private consortiums that can help the FDA develop a scientific framework for validating molecular or imaging biomarkers that can be used to customize medicines for sub-groups of patients. It also allows the FDA to make regulatory decisions based on “real world” evidence that might better reflect how patients are really feeling and functioning.
Critically, for patients with rare diseases, it also allows the FDA to approve medicines based on genetic data submitted with previously approved medicines when there is good reason to believe that the same mechanism is implicated in a rare disease.
This list just scratches the surface. The bill also funds President Obama’s Precision Medicine Initiative (to study the effects of genetic differences on health outcomes), the Cancer Moonshot (to improve how cancer medicines are tested and developed), and makes new investments in neuroscience research than can unlock the underlying causes of devastating brain disorders.
Critics of the bill seek to paint it as a weakening of the FDA standards or a giveaway to industry. This is a mistake. The Cures Act recognizes that modern medical science must become more collaborative and networked. The Cures Act breaks down antiquated barriers between clinical practice and blue-sky research—and between regulators, patients, and innovators.
It will help us ask better questions and answer them with the right data.
Perhaps most importantly, the Cures Act is a refreshing reminder that policymakers can rise beyond partisan disagreements and recognize the common ties that bind us. The best parallel to the Cures Act is to the nation's fight against HIV/AIDS in the 1990s. Congress responded then by modernizing the FDA, giving it new tools and authorities - today, thanks to those reforms, we've transformed an HIV infection from a death sentence into a manageable chronic disease.
Today, the health challenges facing the nation and patients-cancer, Alzheimer's, Parkinson's, Duchenne's-are no less deadly than HIV, and perhaps more complex. But we can rise to the occassion. Hopefully, the House and Seante will do just that, and send the Cures Act to the President Obama's desk, capping a deeply partisan election with a truly bipartisan achievement.
This piece originally appeared at The Hill