On False Hope

I recently learned of the publication of a book entitled False Hope: Bone Marrow Transplantation for Breast Cancer.  Oxford Press published it in 2007, and it is authored by Richard A. Rettig, Peter D. Jacobson, Cynthia M. Farquar, and Wade M. Aubry.  Here is the blurb:

In the late 1980s, a promising new treatment for breast cancer emerged: high-dose chemotherapy with autologous bone marrow transplantation or HDC/ABMT. By the 1990s, it had burst upon the oncology scene and disseminated rapidly before having been carefully evaluated. By the time published studies showed that the procedure was ineffective, more than 30,000 women had received the treatment, shortening their lives and adding to their suffering. This book tells of the rise and demise of HDC/ABMT for metastatic and early stage breast cancer, and fully explores the story's implications, which go well beyond the immediate procedure, and beyond breast cancer, to how we in the United States evaluate other medical procedures, especially life-saving ones. It details how the factors that drove clinical use--patient demand, physician enthusiasm, media reporting, litigation, economic exploitation, and legislative and administrative mandates--converged to propel the procedure forward despite a lack of proven clinical effectiveness. It also analyzes the limited effect of the technology assessments and randomized clinical trials that evaluated the procedure and the ramifications of this flawed system on healthcare today. Sections of the book consider the initial conditions surrounding the emergence of the new breast cancer treatment, the drivers of clinical use, and the struggle for evidence-based medicine. A concluding section considers the significance of the story for our healthcare system.

I have both mentioned this narrative on MH Blog as well as written on it, and this book, which I have just ordered, promises to be an important contribution.  Particularly important, this narrative invalidates the oft-heard contention that terminally ill patients should be given unfettered access to such experimental protocols because they have nothing to lose.  This is a technically invalid argument.  There are legitimate arguments in favor of granting such patients access to experimental protocols -- the heart of the Abigail Alliance case -- but the notion that the patients "have nothing to lose" is not one of them.  Such patients have a very great deal to lose.  Their lives could be shortened, which would seem a particularly cruel result for a terminally ill patient who presumably values greatly the time left to them.  In addition, such patients could suffer terribly, as many who underwent HDT/ABMT did (it is a ghastly procedure with significant mortality risks).

The point is that in the discourse over whether terminally ill patients should be granted access to experimental protocols -- and who should pay for them -- attention should be given to the history of HDT/ABMT for illness sufferers with advanced breast cancer, to demonstrate the fallacy of maintaining that the illness sufferers have nothing to lose.  Whatever the arguments in favor of such access -- and there are formidable arguments among them -- this is not one of them.  Finally, the story also demonstrates the power and scope of the therapeutic misconception, which is also at the heart of the Abigail Alliance litigation.

Comments

[Steven Walker]

With all due respect, you have entirely misconstrued our claim and our arguments. In fact, the arguments you make, that our case is about patients having nothing to lose, or that we are pursuing unfettered access, are the claims being made by our opponents. They have never been made by us.

Of course patients have something to lose, which is why we absolutely did not and are not pursuing unfettered access. Have you read our Citizen's Petition or the Access Act and taken the time to understand them? In order to understand those documents you also have to understand how they fit into the existing framework of FDA regulations and the FD&C Act. It takes time, and it is hard work. We did that hard work in crafting our proposals for change and our lawsuit.

You are informing yourself about high-dose chemotherapy and stem cell rescue by reading a book. That will get you part of the way there, but are you aware that you are talking about an off-label use of approved drugs that has virtually nothing at all to do with the regulatory situation we are addressing?

If you look at our proposals for regulatory and legislative reform, and take the time to understand them, you will learn that we have built in strong safeguards against the use of earlier access as a mechanism to run down blind alleys, and if we win the suit, those same safeguards would get built into the resulting changes to make our drug development and approval system more humane and responsive to patients.

I encourage you to call us so you can inform yourself about what we are actually saying, and why. We are on the web. Call Founder Frank Burroughs and ask him for my contact information. I would be more than happy to explain to you what we are really saying, and what our lawsuit, our Citizen's Petition and pending legislation in Congress are really about. After that, if you still feel you want to make the statements you are making in your blog, we have no aversion to debate, but your readers should know that the claims you make about our proposals and lawsuit are quite simply, wrong.

There is a lot of misinformation and poorly-informed opinion flying around regarding our issue. So to anyone who wants to really understand it, as part of your research you are going to have to come to us. You may still disagree, but at least you will be working with facts.

Respectfully,
Steve Walker
Co-Founder, Abigail Alliance

[Daniel Goldberg]

Steven,

you have entirely misconstrued our claim and our arguments. In fact, the arguments you make, that our case is about patients having nothing to lose, or that we are pursuing unfettered access, are the claims being made by our opponents. They have never been made by us.

Nothing in my post attributes such a claim to the Abigail Alliancve itself. The Alliance may well disavow any such claim, which is fortunate given the fallacy of the proposition. However, I disagree that only the opponents of the Alliance are making such a claim, as I have heard this argument made time and again, within and without the media, by those who favor granting such access.

Of course patients have something to lose, which is why we absolutely did not and are not pursuing unfettered access.

Outstanding. Would that all stakeholders would understand the issues as clearly as the Alliance.

Have you read our Citizen's Petition or the Access Act and taken the time to understand them?

Yes.

In order to understand those documents you also have to understand how they fit into the existing framework of FDA regulations and the FD&C Act.

I can assure you I am intimately familiar and comfortable with the applicable regs and statutes.

You are informing yourself about high-dose chemotherapy and stem cell rescue by reading a book.

Really? Where do you derive this claim? If you read my post, you'll notice I quite plainly state I have not read this book. Rather, I have written and thought about this issue for years, and have taken the time to inform myself on the issue by engaging a wide variety of resources and stakeholders. Your assumption to the contrary does not do your argument credit.

but are you aware that you are talking about an off-label use of approved drugs that has virtually nothing at all to do with the regulatory situation we are addressing?

I agree with the first part of your claim, but not the second. It has a very great deal to do with some of the underlying ethical and conceptual issues, though, again, I was careful not to assert that the Alliance itself was advancing such claims.

I encourage you to call us so you can inform yourself about what we are actually saying, and why.

I would certainly like to engage you and the Alliance in further detail on these issues.

After that, if you still feel you want to make the statements you are making in your blog, we have no aversion to debate, but your readers should know that the claims you make about our proposals and lawsuit are quite simply, wrong.

Thus far, you have not identified any erroneous claims I have made. I welcome discourse and debate, particularly with the Alliance. I have not in this post, nor have I ever taken a position on the merits of the Alliance's claims. In fact, I was careful to note that there exist formidable arguments in favor of the Alliance's position. My point was simply to note that the notion that there is "nothing to lose" is not among the formidable set of arguments, so it would be well if some of those who support expanded access would perceive that as clearly as the Alliance does. More so, the notion that there is a very great deal to lose is absolutely relevant to the discourse over how we as a society ought to structure the regulatory system by which biologics are approved to enter the stream of commerce.

Did you notice the advisory report released by the FDA Science Board on Friday? The one that indicated that the FDA is incapable of properly protecting public health in a variety of arenas and contexts? This, of course, is simply the latest report to find as such.

Of course, such reports do not demonstrate that the Alliance's claims lack merit, but I absolutely maintain that they do illustrate the ongoing relevance of the notion that there remains much at stake for experimental protocols for terminally ill patients.

Thanks for commenting.

[Dan]

Provenge and Our F.D.A.’s Overt Absent of Loyalty

Terminal patients are those who are not expected to live due to usually illness such as advanced cancer. If the patient has 6 months or less to live, those patients are considered terminally ill. Regardless, if a patient is terminal, they are without a cure or tolerable treatment for their illness. Since such patients will likely die in a short period of time, treatment options, even if unproven, are often desired by such patients. This is understandable, because at such a severe stage of illness, such as prostate cancer, possible extension of their lives with comfort is worth it to them, regardless of lack of evidence of proof of whatever treatment that may be advantageous to them regarding these issues. The FDA, however, claims authority on the treatment options of such patients, although that administration has proven itself over the years to be rather inadequate with its frequent drug recalls and black box warnings, and they do these things only under pressure from the public, usually.

Prostate cancer is a rather frequent occurrence- with between 10 to 20 percent of men predicted to acquire the disease during their lifespan, resulting in about 30,000 deaths a year from this disease. Furthermore, there are different stages of prostate cancer, and the more severe the prostate cancer cases are which is determined by such methods as bone scans and Gleason’s scores, which is a score that assesses prostate tissue after it is biopsied and if it is determined that the stage of cancer is severe by this,, the more difficult it is to treat such patients. Typically, the initial suspicion of prostate cancer is determined by the results of what is called a PSA blood test, as PSA is a protein produced by prostate cancer cells. If the PSA blood test is above normal limits, a prostate biopsy is performed to determine and confirm not only the diagnosis, but also the severity of the disease on such a patient.

Yet innovation still exists in medicine. A few years ago, a small Biotechnology company called Dendreon was working on a conceptually new treatment for the worst prostate cancer patients, and this treatment therapy created by Dendreon was named Provenge. Provenge is the first immunotherapy biologic treatment for the progressed prostate cancer patients. Usually, these patients are unresponsive to usual treatment methods for prostate cancer, and are left with chemotherapy as their only treatment option at such a traumatic stage of prostate cancer.

Understandably, most patients at this stage refuse treatment entirely, largely due to the brutal side effects of such chemotherapy treatments as taxodere. The immunotherapy method developed by Dendreon required the removal of white blood cells of the diseased patient and, after altered, are re-injected into this patient now designed to attack what is called PAP, which is on prostate cancer cells only. This treatment required only three such injections in a period of six weeks. This resulted in life extension twice that of chemotherapy treated prostate cancer patients of this severity, and without the concerning side effects of chemotherapy. The medical community and survivors of prostate cancer were elated and waited with great anticipation for access to this treatment method.

Fortunately, as the years passed, Provenge, by 2007, had convinced others of its safety and efficacy in its benefit for severe prostate cancer patients. This caused great joy to such patients and their families. Perhaps greater elation was experienced by the caregivers and specialists of such a disease, such as Urologists and Oncologists who treat such patients. While Provenge was on fast track status at this time at the FDA, the FDA panel recommended with clarity the approval of Provenge based on its proven and substancial efficacy and safety demonstrated in its trials, as they announced in March of 2007.

Now for the bad news:

With great shock and surprise, the FDA agency rejected the approval of this great treatment for very sick patients due to, they said, ‘lack of data’ in May of 2007. This contradicts their favorable opinion of Provenge weeks before delivering this terrible news. Especially when one considers the FDA Commissioner is a prostate cancer survival himself!
Soon after this judgment was passed by the FDA, conflicts of interest were discovered by others. For example, a member of the FDA agency who was evaluating Provenge, Dr. Scher, was found to have a financial commitment to a future competitor of Provenge that was being produced by a company called Novacea, and this company had signed a co-promotion agreement with Schering with this similar prostate cancer drug being developed by this company. Dr. Scher never disclosed this conflict during the approval process of Provenge. As it turns out, this anticipated prostate cancer drug made by Novacea was discovered to have serious flaws, and Schering pulled out of the agreement with Novacea. In addition to this incident and before May of 2007, baseless letters were anonymously delivered to the FDA stating negative qualities about Provenge that were without Merit and speculative claims about the treatment. Yet overall, the disapproval by the FDA of Provenge angered many, and a newly formed advocacy group called Care to Live filed a lawsuit against the FDA for their clear lack of protocol or knowledge about such complex treatment agents as Provenge at the end of last year.

Terminal patients, I surmise, desire comfort during their progressive disease that has placed them in the last chapter of their lives, and certainly should have a right to choose any treatment that possibly could benefit them. At this stage of such a patient, one could argue, safety of any treatment option is not of concern to these patients, because they are going to die anyway. Yet the FDA, with reckless disregard and overt harshness for these very ill patients, ultimately harmed others more by not approving Provenge.

The FDA does in fact presently have the ability to grant what is called conditional approval for such treatment methods as Provenge, and why they have not remains completely unknown. What is known is that they are harming those they pledged to protect so long ago. So now the FDA appears to be a bought, corrupt, and incompetent administration without loyalty and dedication to the public and its health. This needs to be corrected in any way possible for the lives of others.

“Facts do not cease to exist because they are ignored.” --- Aldous Huxley

Dan Abshear