Cancer May 21, 2008, 7:59PM EST text size: TT
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.
======================
All Reader Comments
Wendell Wood May 23, 2008 3:59 PM GMT So if a drug came along that cured cancer, but no one could explain it.... then according to Dr. Pazdur, who wants "a better understanding of the molecular basis of the disease"..... and considers the FDA's Advisory Committee, which might recommend it unanimously.... then Dr. Pazdur & the FDA..... ....would look to see if the drug MET it's clinical endpoints of reducing some weird number or idea floating in Pazdur's brain.... ...and REJECT THE DRUG REGARDLESS OF HOW MANY PEOPLE DIE JUST BECAUSE HIS FDA DOESN'T UNDERSTAND HOW THE DRUG WORKS? Sounds like Dr. Pazdur has replaced the Hippocratic Oath's... "never do deliberate harm to anyone" to a Hypocritical Oath of... "do deliberate harm".... ...just to keep existing cancer therapies and hospitals full! It's a good thing Dr. Pazdur didn't have to APPROVE Dr. Louis Pasteur's vaccine for rabies! Even Dr. Pasteur didn't know for sure how or why it worked "at the molecular level" back then. He just knew that many people LIVED with his vaccinations!
Link to this comment
Jim May 23, 2008 1:29 PM GMT Why is Dr. Padzur so worried about the Congressional Investigation of the FDA's decision on Provenge, as requested by Congressman Michaud and others? To use Dr. Padzur's own words, Congress "wants to know why the FDA Advisors voted the way they did". In particular Congress wants to know why Dr. Howard Scher voted/lobbied against Provenge when he had financial and professional interests in a directly competing drug/company called Asentar/Novacea and board membership/onwership in the investment bank PROQUEST, which largely owned Novacea. Congress wants to know how much money Dr. Scher made in the 2 weeks following the FDA Provenge decision when Novacea then signed a license agreement with Schering Plough for $440 million. Congress wants to know what role Dr. Padzur played in abetting Dr. Scher in his extra-FDA Advisory Committee lobbying & leaking of private/confidential letters to the public media. Why is Dr. Padzur so afraid of having Congressional oversight of his role as the most powerful person in oncology in the US? Should this power simply operate unchecked?
Link to this comment
Steve Walker May 23, 2008 12:27 PM GMT The FDA's access programs, which it refuses to change, are almost entirely inoperative. Mike makes a good point, but unfortunately the approval process mandated by FDA cannot be completely divorced from the issue of access. FDA's refusal to change its ineffective access policies is based on its insistance that tens of thousands of dying Americans must be kept in a desperate, untreated condition so a very few of them can be forced into often unnecessary, increasingly unethical, randomized, double-blind, placebo-only controlled, no cross over (to the active therapy) clinical trials demanded by agency physician-statisticians. Both the FDA and the American Society of Clinical Oncology (ASCO), with whom FDA is far too close, expressly took this position in our lawsuit. Sadly, nearly all of the tens of thousands of patients left untreated are abandoned by the system to die, unable to qualify for any clinical trial. Refusing them treatment is cruelly pointless, but belief in the current system at FDA (and ASCO) is not rational. Real change comes to FDA only when it is imposed from the outside. Patients now have a voice in the Access Act. Support it! Steve Walker, Abigail Alliance.
Link to this comment
Mike May 22, 2008 6:05 PM GMT It would help everyone if people distingushed between the idea of access to unapproved agents (for those who have run out of other options) and approval of new cancer drugs because they met the pre-agreed criteria for approval. Unfortunately these two very different goals are all too often mixed together as if in a regulatory soup. We need better and broader methods of access to unapproved drugs for those who have run out of other options. We do NOT need approval of drugs (even for treatment of cancer) that have an unacceptable risk/benefit profile, particularly when the benefit is not demonstrated by the pivotal clinical trials.
Link to this comment
Sean May 22, 2008 4:00 PM GMT Cancer is a profitable business. It also keeps the public in line. Life can no longer be lived without pleading to institutions for assistance for which, you must pay and beg and plead. The media trumpets the recent *slight* decline in cancer deaths. They do not note the catastrophic increase in cancer rates and cancer deaths since the early 20th century. Prevailing US law allows any chemical to be introduced into the public domain unless someone proves it isn't safe. The default rule should require proof of safety before it is introduced. The US and multinational chemical companies fought Europe on its REACH accord because it would cost an estimated $5 billion to test *every single chemical used in the public domain* for carcinogenicity and safety. Let's gift hundreds of billions to big pharma and biotech via universities to seek expensive treatments (preferably lifetime as those are the most profitable), but let's not spend 1/1,000,000th as much identifying a cause. Scientists project within 20 years 1 in 2 men will suffer from cancer in their lifetimes. Subjecting one's self to the machine for painful treatment while living in fear of death - that's the noble goal.
Link to this comment
Scott Riccio May 22, 2008 3:36 PM GMT Here???s an example of a recent new therapy for men dying of prostate cancer that the FDA delayed. The primary trial enrolled 127 patients. The doctors will tell you that this therapy had tremendous benefit on their patients. Do we need a statistical analysis to overrule the clear patient benefits seen by seasoned experts? Further, when a survival analysis was done, the clear survival benefit the treating doctors had seen was confirmed as being only 1% likely due to chance and 99% likely due to drug, but the doctors already knew that of course, as did the patients getting active therapy, 33% of whom were still alive three years after starting therapy, compared to about 11% getting placebo. Sadly, this is but one example of more than dozens that cost us the lives of tens and even hundreds of thousands of our loved ones every year. Patients and their doctors are already lining up in support of the new ACCESS Act because they don???t need the statistics to tell them what happens in the status quo where they can???t get access to new treatment options. Patients die, far too quickly, with far too much certainty. It need not be that way. Scott Riccio, A Right To Live
Link to this comment
Scott Riccio May 22, 2008 3:33 PM GMT Dr. Pazdur???s words about the role of the advisory committees is interesting, given the FDA???s own Science Board self-evaluation report which stated quite clearly that FDA reviewers do not understand many of the new scientific approaches they are evaluating in their life and death decision-making process. Of course, the world-reknowned experts often called to give advice to FDA through these Advisory Committees understand the science of the new therapy better than anyone, but they aren???t slaves to the statistical fanatacism that seems to permeate FDA, so of course their opinions are often ignored. The respected experts on the FDA's Science Board actually recommend more reliance on advisory committees that could take advantage of the knowledge about treating terminal diseases and using groundbreaking new therapies that so many outside FDA have to offer. It's a sad reality that FDA leadership, including Dr. Pazdur, would rather belittle advisory committee members and their decisions than learn from their expertise in saving lives. Scott Riccio, A Right To Live
Link to this comment
Ron Trowbridge May 22, 2008 2:56 PM GMT Ms. Arnst: John Stuart Mill observed that "He who knows only his own side of the case knows little of that." He encouraged debate because it takes us closer to truth. Dr. Pazdur has given one side of the argument. For the other side, read the ACCESS Act introduced on Capitol Hill May 21, with bipartisan support in both the House and Senate. It's only fair that you include the other side in your coverage. The Act is written in oncological jargon, so interview Steve Walker (his e-mail is above)who knows literally more than anyone in the country about this matter of the FDA and investigational drugs. My wife got an investigational drug that the FDA soon after took off the market. It worked miracles for her, totally eliminating her morphine-treated, torturous pain. Abigail Alliance wants countless thousands of cancer victims to get the same merciful treatment my wife did. Who knows, Ted Kennedy might get precisely such an investigational drug outside a clinical trial. If he has a glioblastoma, doctors will likely give him any drug that improves the quality of his remaining life. Ron Trowbridge, Ph. D Abigail Alliance volunteer
Link to this comment
B May 22, 2008 2:20 PM GMT True, most cancer drugs developed do not work, but defining a set of unbendable rules does not constitute leadership. The FDA needs to be more than a bureaucracy driven by a few quotable maxims.
Link to this comment
Steven Walker May 22, 2008 2:01 PM GMT What is missing from this interview is a discussion of Dr. Pazdur's "Decelerated Approval Initiative." In 2003 Dr. Pazdur publicly announced his plan to substantially increase clinical trial requirements for approval of the most promising new cancer drugs, delaying them for years. He also imposed a rigid requirement of ???statistical perfection??? for all drugs submitted to his office for approval, no matter how compelling the overall evidence is that they work. The result is an Office of Oncology Drug Products functioning as a heavy-handed barrier to progress against cancer. The cost in human life has been immense, exceeding a million lives ended prematurely over the last several years. The questions now being debated by many, including former Commissioner's of the FDA, are (1) why did FDA leadership allow this to happen, and (2) what is FDA leadership doing to fix it. We have asked these questions repeatedly at the highest levels of the agency. We have yet to receive an answer. Steven Walker Abigail Alliance
Merrill Goozner May 22, 2008 1:38 PM GMT Dr. Pazdur is a courageous public servant, and should be congratulated for standing up for scientific principle at the FDA while under pressure from extremist elements of the U.S. press. And the Wall Street Journal editorial page knows who I am talking about. |
