The End of Old Regulatory Rituals

Reforming the FDA for a new millennium


The U.S. Food and Drug Administration is soooo 20th Century! The dawning era of medicines developed especially for you means that the model the FDA has used for more than 50 years needs to change.

Today, the FDA requires that drugs go through a three-phase approval process before patients are allowed to have them. In Phase I clinical trials, researchers test a new drug or treatment in a small group of people (20–80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects. In Phase II clinical trials, the study drug or treatment is given to a larger group of people (100–300) to see if it is effective and to further evaluate its safety. In Phase III studies, the new drug or treatment is given to still larger groups of people (1,000–3,000) to confirm its effectiveness, monitor side effects, compare it to alternative treatments, and collect information that will allow the drug or treatment to be used safely. Total cost: $800 million per new drug approved. Time elapsed: 10 to 15 years.

With such high development costs and such long lead times, pharmaceutical companies aim for blockbuster drugs for common conditions and that are basically good for everybody. A prime example is Pfizer's cholesterol lowering drug, Lipitor, the world's best selling drug at $12 billion per year. There will still be blockbusters in the future, but researchers realize that more and more drugs will be tailor-made for smaller groups of patients and, in some cases, even for individual patients.

The advent of individualized medicine can be discerned now. Consider BiDil, the new combination drug that is effective for treating heart failure in black patients. Last year, Roche Diagnostics introduced its AmpliChip test that screens for variants of the Cytochrome P450 gene. Variants of that gene determine whether a patient's liver metabolizes anti-depressants, beta-blockers, and some chemotherapy drugs too fast, too slowly or not at all. The AmpliChip test helps doctors personalize dosages for each patient.

One big roadblock to getting drugs to patients is the FDA requirement for Phase III clinical trials. What to do? First, the FDA needs to remove the requirement that a drug be shown to be effective before allowing physicians and patients to access it. Drug companies would still have to go through Phases I and II to test for safety and dosage, but Phase III would become a post-approval process. Modern communication and information technologies make Phase III clinical trials redundant. In the future, patients and their physicians could be required to register in a post-approval process in which they would report both therapeutic results and any adverse effects. Patients taking new drugs could be given a hotline that they could call to report any side effects of their treatments.

In fact, this kind of monitored follow up procedure would serve as a more effective early warning system of problems than does the current system. Today, new drugs are tested on thousands of people. But even such expensive tests sometimes fail to uncover subtle or rare side effects that become apparent when the drug is prescribed to hundreds of thousands or millions of patients. Today, once a drug has received FDA approval there is no comprehensive system for patient follow up. That will change in the 21st century.

The drug approval system is already evolving. Take the case of Lotronex, a medicine used to treat irritable bowel syndrome (IBS). The FDA approved it in 2000, and hundreds of thousands of prescriptions were written for it. However, a few patients taking the drug died when the blood supply to their intestines was cut off. Ten months after it had been approved, the drug was voluntarily removed from the market by its manufacturer, GlaxoSmithKline. IBS patients rose up in protest and the FDA agreed to reapprove Lotronex with additional precautions in 2002.

Earlier this year, the biotech companies Biogen and Elan voluntarily withdrew their new multiple sclerosis drug Tysabri because two MS patients taking it died of a rare fatal disease. But some MS patients who were benefiting from Tysabri are now saying that they are willing to accept the risks that may be involved with the drug.

In the new era, patients who want to take advantage of the latest treatments will also have to agree to take more responsibility for the risks that come with using them. This century's biomedical revolution will sweep away the FDA's outmoded regulatory rituals; it's just a question of whether it will be sooner rather than later.

Ronald Bailey is Reason's science correspondent. His book Liberation Biology: The Scientific and Moral Case for the Biotech Revolution is now available from Prometheus Books.