Earlier today the Food and Drug Administration’s (FDA) Oncologic Drugs Advisory Committee voted to withdraw the accelerated approval that the FDA had granted the drug Avastin for use in treating breast cancer. This process was started last December, and will reach some kind of resolution by the end of next month. Today’s meeting was a first-of-its-kind review requested by the drug manufacturer, Genentech.
The rationale behind the withdrawal, per the FDA announcement last December (boldface mine):
“The agency is making this recommendation after reviewing the results of four clinical studies of Avastin in women with breast cancer and determining that the data indicate that the drug does not prolong overall survival in breast cancer patients or provide a sufficient benefit in slowing disease progression to outweigh the significant risk to patients. These risks include severe high blood pressure; bleeding and hemorrhage; the development of perforations (or “holes”) in the body, including in the nose, stomach, and intestines; and heart attack or heart failure.”
This kind of argument should be familiar to those who have followed debates over changes to screening procedures that were an attempt to respond to the significant side effects of those screenings, or the questionable effectiveness of the screenings. The regulators are trying to balance the risks of the disease (which affects a small segment of the population), against the consequences of the treatment or screening (which may affect a larger percentage of the population, or have a larger overall negative impact). That kind of risk calculation doesn’t happen for those who have the disease or a family history of the disease.
As you might expect, patient advocates are not keen on the FDA decision, and several protested the hearing. Some see the setback as an example of a regulatory agency walking back the accelerated approval process in favor of more government control. But the language used in one part of this Wall Street Journal editorial suggests how this isn’t really about the science, because that’s what they talk about. Dr. Pazdur heads the FDA office responsible for cancer drugs (boldface mine):
“Dr. Pazdur’s defenders claim all this is guided by “the science,” as if that was some immutable thing and not a dynamic process of cumulative learning and clinical practice. The future of cancer treatment is therapies targeted to subpopulations identified by individual molecular biomarkers.”
The first sentence is interesting, because to my mind, the same argument could be applied to justify the actions of the FDA in rescinding its approval of Avastin for breast cancer. Initial research and review suggested yes, subsequent studies suggested that the side effects were too severe to justify continuing the broad approval of the drug. Again from the December announcement:
“Subsequent studies failed to confirm the benefit observed in the original trial. None of the studies demonstrated that patients receiving Avastin lived longer and patients receiving Avastin experienced a significant increase in serious side effects. The limited effects of Avastin combined with the significant risks led us to this difficult decision. The results of these studies are disappointing. We encourage the company to conduct additional research to identify if there may be select groups of patients who might benefit from this drug.”
But really, this debate is about risk. Those affected by the disease have different conceptions of risks and benefit than those who are responsible for the health and safety of a larger population.
The quote from the Wall Street Journal editorial also highlights an emerging problem for medicine and medicine-related policy going forward. How can treatments that are effective for only certain parts of the population be effectively tested, regulated and distributed? Will current tests be sufficient to the task? Epidemiologists have been challenged by small populations when they track diseases and/or exposures to harmful chemicals. The ways to control for this that I’m familiar with are more resource intensive, and I wouldn’t be surprised if that proved to be true for treatments for subpopulations.
But getting back to the drug at hand. This debate is indeed over risk. That it likely won’t be discussed in those terms will do science policy no favors.