The FDA Stifles the Advance of Modern Molecular Medicine (original) (raw)

The Cure in the Code: How 20th Century Law Is Undermining 21st Century Medicine, by Peter Huber, Basic Books, 277 pages, $28.99

We are at a turning point in medicine. Knowledge of the individual's genetic makeup will soon allow molecular medicine to reach deep inside each of us to cure most of the maladies that afflict us—and perhaps even slow the rate at which we age. First we will learn to understand each person's genome; then we will learn to craft treatments tailored to his or her genetic constitution.

But it may not be so easy—and not for purely scientific reasons. Consider 23andMe, a commercial enterprise launched in 2006 that was merely looking to inform Americans about their potential genetic vulnerability to certain diseases. Regulators from the Food and Drug Administration have dropped the hammer on the company, citing baseless fears that its customers will do something dangerously stupid in reaction to the information that the tests provide. The FDA's regulatory labyrinth is not only slow to digest the science behind the genetic testing involved in 23andMe. It also can't quite figure out what to do with the proliferation of molecular biomarkers that can predict treatment efficacy more quickly than the conventional clinical trials the agency relies upon.

All this is just the tip of the iceberg, Peter Huber argues in The Cure in the Code, his urgent, compelling account of how 21st-century medicine is being hampered by a regulatory regime built for the science of the 20th century.

Basic Books

Mr. Huber begins by taking us back to the rise of public health and modern medicine in the late 19th and early 20th centuries. The advances made in this era were enormous: Infectious diseases were tamed by the construction of sewers, the provision of chlorinated water, widespread vaccination and the birth of antibiotics. These magic-bullet successes enabled us to live longer than humans had hitherto—long enough, in fact, that we now suffer more from a qualitatively different set of illnesses, diseases that emerge from the biochemical combinations of our genes and our lifestyles. Today's prominent maladies—cancer, diabetes, heart disease and dementia—take decades to develop, and successful treatments must begin decades before patients become clinically ill.

Our conception of illness has thus been transformed. Sequencing entire human genomes has revealed the tremendous biochemical diversity of human beings. Our susceptibilities are particular to each one of us, and the time when blockbuster drugs, such as penicillin, could treat nearly every patient is over. The biochemical roots of heart disease in two patients sharing a hospital room are very different and won't respond to the same drugs in the same way.

"Health care once mainly depended on killing germs," writes Mr. Huber. "Now most drugs are used to tune people." Lipitor tunes our artery-clogging cholesterol; Plavix our blood-clotting platelets; Prozac our depressed dopamine receptors; Cardizem our irregular heartbeats; and Gleevec toggles down our leukemia. Tomorrow's regimens, as Mr. Huber shows, will be guided and adjusted using relevant biomarkers specific to individual patients.

One can get a glimpse of the future of radically individualized medicine by considering how each woman's breast cancer is now treated in light of her tumor's genetic susceptibility to estrogen, progesterone and the HER2 protein. Breast cancer isn't a single illness. Rather, each woman's cancer may be its own distinct case of malignant disease. Oncologists now input a breast-cancer patient's genetic data into diagnostic algorithms to devise drug regimens just for her. Such therapy is less miss and a lot more hit.

Yet the FDA still operates according to the requirements of the age of mass drugs. Founded in 1906, when quack remedies were common, the FDA has evolved into a bureaucracy more concerned with avoiding risk than speeding the benefits of innovation to patients. Drug approvals still depend on large-scale trials that focus on statistical correlations to determine clinical efficacy. Regulators demand ever larger trials as a way to avoid approving drugs that will turn out to have significant side effects in some patients.

This obsession with side effects is misplaced. Side effects should more often be regarded as information indicating that a treatment that might be effective for many patients doesn't work for some. Too often, the FDA refuses to approve a new drug because it doesn't work for everyone, when the goal should be to find those patients for whom it does work. "The broader lesson here," says Mr. Huber, "is that every new, precisely targeted drug serves, in part, as a diagnostic instrument for exposing and classifying the molecular structure of diseases and the bodies that host them. As the drugs are developed and prove their worth, they redefine the diseases."

So what would a 21st-century drug system look like? The author argues that the current clinical-trial model must be replaced by adaptive trials in which both patients and physicians would continually learn and modify treatments along the way. Information about the molecular processes being targeted and the outcomes of each patient's therapeutic regimen would be reported to a broadly accessible digital knowledge network, which other doctors and patients could query to guide their choice of therapies.

Mr. Huber outlines how to reform the FDA, intellectual-property rights and our tort system so as to unleash "market forces to develop reasonable schemes that integrate the development of drug science with the sale of drugs for treatment." Among other recommendations, he suggests that the FDA permit patients and physicians access to treatments formulated by adaptive trials, whose regimens are constantly fine-tuned in light of molecular findings. In addition, stronger intellectual-property rights should be granted to discoverers of biomarkers and aggregators of clinical databases and predictive-knowledge tools. Such incentives will "reward those who develop new information faster and come up with new ways to distribute it widely at economically efficient prices," writes Mr. Huber.

These reforms would also cut health-care costs. Drugs and diagnostics are in essence distilled information with high upfront costs, but as with information technologies, their costs fall rapidly. Ever cheaper advanced molecular medicine will displace the increasingly expensive and often ineffective hands-on care of doctors and hospitals for cancer and heart disease—just as antibiotics and vaccines supplanted costly iron lungs and tubercular sanatariums.

This review first appeared in the Wall Street Journal on December 3.

See also reasontv's excellent interview with Peter Huber about The Cure Is In The Code below: