The Problem with the FDA Drug Approval Process

Published June 1, 2007

Excerpted from More Choices, Better Health: Free to Choose Experimental Drugs, by Bartley J. Madden–the first in a several-part series. The complete booklet is available for sale in the online store at

Forever etched in golf fans’ memories is not the remarkable 65 shot by Tom Watson in the first round of the 2003 U.S. Open, but the courage of his caddy, Bruce Edwards.

Edwards, who had been Watson’s caddie for 30 years, had Lou Gehrig’s disease, which is always terminal. The outpouring of fans’ affection throughout the tournament was deeply touching. Edwards died the following year.

Even today, there is no Food and Drug Administration (FDA)-approved drug that gives people suffering with amyotrophic lateral sclerosis (ALS, commonly referred to as Lou Gehrig’s disease) a reason to be hopeful. But what if there were an experimental ALS drug in the early stages of FDA clinical trials showing breakthrough potential? Should Edwards have been free to purchase it if all available risk-reward information were known to him and his doctors?

Screening Drugs

We have grown accustomed to the FDA’s monopoly on market access to drugs. But prior to 1962, new drugs had to pass only safety trials to be legally marketed. Effectiveness was left to consumers and doctors to evaluate.

Today, for drugs to be marketed as FDA-approved, they must pass a Phase I safety trial, followed by Phase II safety as well as effectiveness testing in a small sample of patients, followed by a Phase III clinical trial with a much larger number of patients.

On average, the three clinical trials take seven years. Next comes a new drug application (NDA) containing relevant data to be examined by the FDA. On average, that review process takes an additional 18 months. Thus, those who might benefit from a promising new drug cannot get it for, on average, eight-and-a-half years after it enters FDA clinical testing.

Not only do the clinical trials and NDA submission take time, they also take money. Drug developers experience a substantial outflow of hard cash, a long delay in possible revenues, … and no guarantees the drug will be approved at all. That combination boosts drug prices for consumers.

Making Tradeoffs

With its current clinical trial procedures, FDA must deal with a difficult tradeoff situation. Since no drug is completely safe, FDA can mistakenly approve a drug that subsequently produces harmful side effects that greatly outweigh therapeutic benefits. Alternatively, FDA can delay or deny approval for a drug that subsequently shows clear effectiveness and possibly lifesaving ability.

When FDA errs on the side of excessive caution, thousands of patients may die who could have been saved. But those deaths are rarely documented and never make the nightly news. Thus, it should not be surprising that in practice FDA is much more concerned with avoiding highly visible errors and clearly identified victims than with the hidden, rarely identified victims of denied access to drugs in the FDA approval pipeline.

For FDA officials, approving an unsafe drug brings public humiliation from the media, affected patients, and politicians. That far outweighs any benefit they might receive for more quickly approving an effective new drug.

What has been the overall effect of FDA’s extreme focus on minimizing bad publicity? Daniel Klein and Alexander Tabarrok have assembled a large body of research on FDA. In their essay “Is the FDA Safe and Effective?” they conclude:

“We argue that FDA control over drugs and devices has large and often overlooked costs that almost certainly exceed the benefits. We believe that FDA regulation of the medical industry has suppressed and delayed new drugs and devices, and has increased costs, with a net result of more morbidity and mortality. A large body of academic research has investigated the FDA and with unusual consensus has reached the same conclusion.”

Focusing the Debate

A serious debate about FDA’s regulatory role should begin with a focus on the common-sense principle that the power to make medical decisions rightly belongs first and foremost to patients and their doctors. Last year, the U.S. Court of Appeals of the D.C. Circuit gave support to this principle by affirming the right of dying patients to access not-yet-FDA-approved drugs, in Abigail Alliance for Better Access to Developmental Drugs v. von Eschenbach.

Because of FDA’s lengthy drug-approval process, a second focus should be on the harm done by the long delays before drug innovations reach the public. FDA’s one-size-fits-all approval procedure is simply not attuned to the fast pace of twenty-first medical innovations.

A third focus should be on solving an emerging dilemma facing pharmaceutical companies that are gaining insights into how diseases (often rare diseases) relate to patients’ genetic profiles. The dilemma is that the greater the gain in personalizing medicine, the smaller the target population for such drugs, the smaller the prospective revenues, and the less likely there will be a worthwhile return on investment.

This is due, for the most part, to the high cost of having to conduct the full set of FDA clinical trials.

Given these top priorities, what could be the structure and optimum level of FDA regulatory power? Neither Congress nor FDA knows, because the optimum level depends on the tradeoff decisions (risk versus benefits) that only individuals and their doctors should make. The current FDA regulatory approach ignores or suppresses these decisions.

Bartley J. Madden ([email protected]) is an independent researcher in Naperville, Illinois.

For more information …

“Is the FDA Safe and Effective?” by Daniel Klein and Alexander Tabarrok, The Independent Institute,