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The Digital Future of Molecular Medicine: Rethinking FDA Regulation

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The Digital Future of Molecular Medicine: Rethinking FDA Regulation

May 15, 2013
Health PolicyOtherFDA Reform

Executive Summary

Pharmacology is fast becoming an information industry. Biochemists can read every letter of life's core genetic code and determine the composition and structure of all its molecular progeny—the downstream proteins and other biochemicals that shape our health, for better or worse. They have the tools to design a drug that can control almost any molecular target. The power in nature's code and our mirror-image drugs resides in minuscule packets of material that technologies now in hand can read, copy, and manipulate. And these technologies are getting cheaper and improving even faster than their digital siblings.

But biochemists have arrived on the scene billions of years behind nature, which neglected to provide manuals that explain how all the molecular slivers of code that it has created fit together and interact. The search for a new drug is increasingly a search for information about how a molecule of our design will interact with different arrays of molecules that it will encounter in future patients and how those interactions will affect a patient's health. That search accounts for a rapidly rising fraction of the front-end cost and medical value of most drugs. Repeated again and again, with one drug after the next, the information acquired will end up in massive and very valuable databases. The analysis of the data using extremely powerful computers will expose the architectures and dynamics of countless molecular networks that make human bodies function well or badly and that the right drugs can control.

The private sector is already actively engaged in collecting and analyzing the data. Led by a rapidly growing group of companies as diverse as IBM, Myriad Genetics, and 23andMe, the digital community has grasped—far ahead of the FDA and much of the medical community—how fast molecular medicine can now advance by taking full advantage of the recent convergence of astonishingly powerful biochemical and digital technologies. Never before have two such powerful technological revolutions converged to advance a single objective of such universal importance. But unleashing the enormous power and economies of innovation on this last frontier of the information revolution will require fundamental changes in public policy.

The FDA has spent the last 30 years pondering how, if at all, molecular science might be shoehorned into the clinical trial protocols that Washington first used over 70 years ago and formalized in licensing rules developed in the 1960s. The regulatory system is now frozen in the headlights. Its drug-testing protocols cannot handle the torrents of complex data that propel the advance of modern molecular medicine. For all practical purposes, those protocols make it impossible to license most of the drugs and complex treatment regimens that are needed to control the biochemically complex disorders that these data torrents reveal.

Developed at a time when nobody could see or track the molecules that matter, the FDA's current testing protocols rely entirely on empirical studies and statistical correlations. They aim to guard, above all, against just one kind of error in the licensing process: selection bias. But modern pharmacology hinges on the scientific selection of the right drug-patient molecular combinations. The only practical way to work out most of the drug-patient science is to study how the drug actually performs in patients. And the first opportunity to do that systematically is during the drug-licensing trials.

As recommended in a recent report issued by President Obama's Council of Advisors on Science and Technology, the FDA should use its existing accelerated approval rule as a starting point for developing adaptive trial protocols to be used "for all drugs meeting—an unmet medical need for a serious or life threatening illness." These protocols should promote the meticulous, data-intensive study of the drug's molecular performance during clinical trials. And they should use modern statistical designs to choreograph the adaptive trials needed to ascertain when a drug that provides only some degree of clinical benefit to some subsets of patients can become a useful component of complex molecular medicine.

Part 1 of this paper discusses the rapidly widening chasm that now separates modern pharmacology and the practice of molecular medicine from the drug-patient science developed and certified the Washington way. The chasm reflects obsolete policies and rules put into place to regulate ignorance, not knowledge; it reflects the dearth of molecular medical science, not the science itself or its efficient, orderly development. Part 2 discusses what it will take to unleash the full power of the precision molecular medicine that biochemical science, powered by digital technology, can now deliver.