The FDA's Cancer Chief Speaks Out

In a discussion with BusinessWeek, Dr. Richard Pazdur talks about clinical trials, small biotechs, and anxious patients

Dr. Richard Pazdur, 55, is one of the most powerful men in medicine. An oncologist by training, he has overseen the U.S. Food & Drug Administration's cancer drug division since 1999, and in 2005 was named director of the FDA's newly created Office of Oncologic Drugs, giving him authority over the largest area of drug development. Consequently, Pazdur is a lightning rod for both criticism and praise in the cancer community every time a drug is approved or turned down. He recently met with BusinessWeek Senior Writer Catherine Arnst at FDA headquarters in Silver Spring, Md., to discuss why so many cancer drugs fail in clinical trials, and what can be done. Below are edited excerpts:

What should the pharmaceutical industry do to improve its track record of getting drugs through the clinical trial process?

The real progress in cancer will be a better understanding of the molecular basis of the disease. Drug companies are very good at developing drugs. We're asking them to do something different here, which is to develop a better understanding of the disease. Traditionally that has not been their major goal. But what we're looking at is a shift in the paradigm, an understanding of the disease process and how the drug works in relationship to that progress.

The FDA is often criticized for being too conservative when it comes to cancer drug reviews, particularly by biotech companies. But these companies also lack regulatory experience. How would you apportion the blame, if any?

One of the things we have seen is a reluctance, sometimes, of smaller companies to make really critical decisions regarding their drugs, whether to curtail the development of a drug. Large companies, because they have a portfolio of drugs, generally if a drug fails to meet specified goals they'll look to abandon that drug—i.e., cut their losses. Whereas as a smaller company, if you only have one drug, then sometimes that is not an option.

The big pharmaceutical companies don't want to waste their time with the FDA. They want to have a long-term relationship with the FDA. They certainly don't want to have to plea to the FDA that the drug should be used and marketed, even though it doesn't work, on an emotional basis.

There is considerable discussion in the drug industry about looking at how a drug performs in subgroups of trial participants, even if it has failed to meet its goal in the larger trial. What is your view of this approach?

One of the problems we've had is people coming to us after a drug fails because they've invested millions and millions of dollars into a drug; and then it's, "How can we salvage this?" In other words, failing your primary endpoint and then trying to salvage a trial by looking at subgroups of patients. That's akin to shooting an arrow and having it land on a wall and then drawing a target around it. It's an attempt to resurrect a trial that has failed.

We have to have proof that a drug works. Its not: "Let's have a debate about whether the drug works." It's not: "Might the drug work?" The onus is on the sponsor to demonstrate that the drug works. We have numerous examples where people have come and argued with us that a subset shows efficacy, and subsequent trials were done and the subsequent trials failed to demonstrate efficacy.

The FDA regularly uses panels of outside experts to advise it on cancer drugs, but sometimes seems to ignore the advisory panel's guidance. How do you explain that contradiction?

The advisory committee is advisory. Period. It is not a judge and jury. It is not the O.J. trial. It is not: "If the glove fits, you must acquit." It is the advice we are looking at, not the vote. We are more interested in the reasons why people are voting.

We cannot approve drugs on the basis of emotion. It should be on the safety and efficacy being demonstrated. We are not moved by comments by committee members who say they want this drug approved because they say the approval will foster the development of a particular field.

You treated cancer patients for decades. How do you respond to the emotional pleas from patients that drugs should be approved even if the evidence is shaky?

I grew up on the south side of Chicago. I'd hate to have some steel mill worker, from my father's generation, say "I spent all my life working in a steel mill, and I paid all my taxes for all of these years. I'm now dying from cancer and now my government is preventing me from getting the drug." It's heartbreaking to hear that, because it is a misrepresentation of the actual story. We can't make drugs available at the expense of lowering standards of approval. I don't think anyone wants to see drugs out there that don't work. I'd have a problem with that.

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