Business Ethos Blog

Drug Denial

By Dr. David Mielke, Dean of the College of Business,
Eastern Michigan University

The story of Avastin has become a random trial pitting the FDA’s power against potentially life-saving drugs for terminally ill patients.  Two weeks ago FDA Commissioner Margaret Hamburg decided to withdraw this biologic medicine as a treatment for metastatic breast cancer.  In her decision, Dr. Hamburg denied Genentech’s last appeal, claiming that FDA approval requires “credible, objective evidence”.  However, there is no FDA definition or guidance as to what “credible, objective evidence” means.  Some state that this is merely another way of imposing a government abstraction over the individual choices of a patient and her doctor.


Here is some background information.  In 2008, Avastin was initially cleared for breast cancer in combination with chemotherapy under an “accelerated approval” process.  This process was created in response to the AIDS crisis to speed drugs for incurable diseases and other medical needs to the market.  Avastin was first approved on the basis of progression-free survival, the time women live without the disease spreading or worsening.  In 2009, Genentech applied to convert to full approval, with new studies that showed improvements, even if less statistically robust than the initial trials.  The FDA moved to delay review citing safety risks.


The safety risks are well understood and manageable especially in end stage oncology where there are no good options.  Last year the FDA withdrew Avastin’s breast cancer approval—leading to Genentech’s appeal and a two day trial.  Dr. Hamburg denied the appeal.  Was this the “Right Thing to do?”  Was the decision based on sound policy and science or were there other possible motives?  The Cancer Network, a highly respected consortium of US oncology programs has four times reaffirmed its recommendation that Avastin is an appropriate therapeutic option.


1.  Was the decision based on sound policies?  In her decision, Dr. Hamburg concedes that there are groups of “super responders” who experience dramatic improvements.  However, she says they don’t count because it is impossible to determine if there is some subset of patients within the population as a whole that may have had a meaningful benefit.  She also concedes that the drug may produce better results when used with chemotherapies, but those prospects haven’t been sufficiently tested.  Isn’t it then logical that if there is a certain segment that gets dramatic improvement that the drug should be available?


2. She also writes that the threshold at which a trial would pass from failure to success has been difficult to draw ahead of time with great precision and it would be inappropriate to announce a bright line cutoff of median improvement that would be necessary to establish safety and effectiveness.  Is this sound policy—there is no benchmark or threshold that she can state that moves a drug from disapproval to approval?  There are no cut offs that can determine if a drug is safe and effective?  Is it by divine intervention that she will know it when she sees it?


3. Perhaps the most stunning passage in her report is when she rejects the Cancer Network’s endorsement because the FDA’s judgment is superior because its experts have extensive qualifications in clinical trial and design.  Are they oncologists?


It appears that Dr. Hamburg has not done the Right Thing.  Is this another move against big pharma?  Is it politically motivated because she doesn’t like the quick approval process initially used to get accelerated approval?  What is for sure, Dr. Hamburg’s decision is an awful turn for anticancer progress and innovation, and especially for women who may lose a treatment option in the time they have left to live.