February 26, 2008
On Avastin: A Reply
Dr. Paul Bellman, in a response today on this website, seconded my proposal that the government require practicing physicians to register patient outcomes when they use marginally effective drugs like Avastin. I thought the issues he raised were important enough to merit top billing on this site. Also, if you visit the comments to the original article, you'll find out from Art Levin of the Center for Medical Consumers that pediatric cancer physicians through their network have been doing this for years, and have made remarkable progress in fighting many forms of childhood cancer as a result. Thanks, Paul and Art, for writing:
Use the real clinical experience of real doctors taking care of real patients using a new drug like Avastin to learn how to better treat patients for a difficult to treat disease like metastatic breast cancer? The idea seems quaint and well intentioned but unscientific these days.
The notion that "observational data is not the same as data from a well controlled clinical trial" has been effectively used by drug companies like Genentech and regulatory agencies like the FDA to remove the clinical experience and potential expertise of practicing doctors from the equation of both drug approval and standards of care.
I would argue that the the data from well controlled clinical trials reflects the intent of the trial design and yields results that reflect that intent. Well controlled clinical trials do not intrinsically advance knowledge such as how to best treat difficult to treat patients where many potential factors can impact on clinical outcomes.
The idea that randomized clinical trials are intrinsically better than an observational data base as a way of advancing clinical knowledge needs to be critically examined. What is needed is a strategic approach in which clinical experience and well designed clinical trials feed each other.
I totally agree with the idea to create a treatment registry to track clinical outcomes for patients with difficult to treat diseases. This would bring the doctor and patient back into the knowledge acquisition process ... something very threatening to the narrow interests of drug companies like Genentech and their sponsored physician experts/Key Opinion Leaders who shape clinical practice and clinical research.
Its ironic that the best support for approving Avastin rests on the hope that some doctors will figure out a way to use it in clinical practice that gives better results than the randomized clinical trial.
Something is very "rotten in the state of Denmark" when billions of dollars can be extracted from our beleagured health care system now that the FDA has approved Avastin on ther basis of the results of the randomized clinical trial that showed it delayed progression of breast cancer but didn't extend life.
There needs to be a mechanism requiring drug companies to support and pay for the kind pof treatment registries that would help doctors learn how to best use their drugs to treat their patients. The often Pharma-supported patient centered consumer groups need to start to demand this.
Posted by gooznews at February 26, 2008 02:16 PMA clinical trial is not the real world. Just because a drug leads to a statistically significant improvement by shrinking a tumor, doesn't guarantee that the desired effect - an increase in overall survival - will follow. Often your doctor is left to make a decision based his/her clinical experience and expertise.
Evidence Based Medicine is based on a number of false assumptions. One is the 'ecological fallacy' that the individuals in a group study reflect the averages of the groups. A second is that randomized trials provide evidence that is applicable to individual subjects.
In regards to choosing a cancer therapy among many, with the absence of effective laboratory tests to guide physicians, many patients do not even get a second chance at treatment when their disease progresses. Spending six to eight weeks to diagnose treatment failure often consumes a substantial portion of a patient's remaining survival, not to mention toxicities and mutagenic effects.
There are molecular and cellular tests available to weed out those cancer patients that chemotherapy wouldn't have any benefit, what chemotherapy works the best for those that chemotherapy would benefit, and further monitor treatment success or disease progression.
No matter how reliable a drug appears to be, there's simply little hard evidence it would make a long-term difference in a person's prolonged survival. Drugs are tested to show they are safe and effective before being approved by the FDA. But a clinical study is not the real world, and just because a drug leads to a statistically significant improvement doesn't guarantee that the desired effect will follow. The physician is still left to make a decision based at least in part on faith, bias or educated guess.
There is no proof beyond reasonable doubt for any approach to treating advanced cancer today. In life or death situations, one must make judgements based upon preponderance of available evidence as opposed to proof beyond reasonable doubt.
Posted by: Gregory D. Pawelski at February 26, 2008 05:05 PM"The often Pharma-supported patient centered consumer groups need to start to demand this."
And isn't it interesting that the group that led the fight against approval of Avastin for advanced BC -- Breast Cancer Action -- explicitly refuses to accept funding from the pharmaceutical industry?
'Anecdotal evidence' Dirty words to REAL doctors. Only drug company evidence is valid. Trials that only last weeks or months and don't include failures. Doctors who prescribe medications for longterm use who HAVE NO IDEA WHAT THE CONSEQUENCES ARE. GRRRRR.
What a great idea...share knowledge of the real world.