Abigail Alliance

Glenn Cohen (guest-blogging at Prawfsblawg) has an excellent post on the significance of the upcoming en banc rehearing of the Abigail Alliance decision.  The case is extremely important for a variety of reasons, and Cohen brings considerable insight and perspective on the case (while working at DOJ, he helped draft the government's petition for rehearing).

Here is the issue: whether

the due process clause of the federal constitution provides a fundamental right that prevents the Food and Drug Administration (FDA) from blocking competent, terminally ill patients from having access to potentially lifesaving drugs that have cleared Phase 1 clinical testing but have gone no further in the drug approval process, when usage is based on the advice of doctors.

The panel opinion, authored by J. Rogers and joined by C.J. Ginsburg, concluded that such a right does exist:

The D.C. Circuit panel majority held that the due process clause creates a fundamental “right of a mentally competent, terminally ill adult patient to access potentially life-saving post–PhaseI investigational new drugs, upon a doctor’s advice, even where that medication carries risks for the patient.” The majority found this right to be “deeply rooted in this Nation’s history and tradition," as reflected in various common law doctrines (the defense of necessity, the freedom from battery, the tort of intentional interference with a rescue).

Judge Griffith dissented, arguing that he could find no compelling reason for removing the power to balance the risks and benefits of pharmaceuticals from the democratic branches of government.

Cohen suggests that the first question is "does the Constitution compel Congress and FDA to adopt a certain policy as to the regulation and approval of drugs as applied to terminally ill patients?" He argues that it does not, contra to the majority's assessment, and I happen to agree with him on this point.  This is a technical question of constitutional law, and is not equivalent to the arguably more difficult policy question: "Even if we assume Congress and FDA have the power to regulate drugs for the terminally ill in the way they are already doing, should they switch to a system with increased access?"

The entire post is eminently worth reading.  I am hesitant to stand athwart a potential door to lifesaving treatment for desperately ill patients, and yet, commentators (notably, Cassell) have explained the extreme fear and vulnerability of such patients makes it all the more important to (paternalistically, perhaps) attempt to shield them from an arguably unethical exposure to risks of pain and suffering for little benefits.  This contention, of course, is contestable for a variety of reasons, but I agree with Cohen that it is at the heart of some of the difficult policy issues presented by this case.

The sad saga of the litigation over the use of high dose chemotherapy with autologous bone marrow transplants for patients with advanced breast cancer seems quite analogous here.  These patients sued insurers and HMOs for denying coverage for the procedure; the latter argued that it was experimental.  Several of these suits were successful, but a worldwide study eventually proved -- after a significant case of research fraud in South Africa that falsified findings of efficacy -- that the study was of no benefit.  It is possible that some women suffered and even died more hastily because of the intervention (note: I intentionally did not term it "therapy" in this instance).

On the one hand, it would seem difficult to tell these desperate, suffering patients that what they perceive as their last hope ought not be made available to them, and on the other hand, to paraphrase from Wittgenstein, one must be careful of attempting to open doors that are painted on to walls, especially when doing so may carry significant risk.  These are truly difficult issues of research ethics.

Comments

[Kelly Hills]

I think, however, we often project that fear and vulnerability onto the terminally ill. While there are undoubtedly those grasping at any and all straws without thought, there are equally many terminally ill folk who have grace in the face of their illness - but still want to try. They want to live, they want to advance knowledge, they want to do something rather than just passively die.

And I'm not sure any of us have the right to tell someone no, to that. That sorry, we know better.

While some therapies do eventually end up having little to no empirical, medical benefit, I think it's much harder to quantify the placebo effect that the experimental medication might have - both in the traditional sense of placebo effect, but also because, for many people, it is the effort, the 'fight', that matters. And if they're doing something, they're fighting - tying to the earlier post on war metaphor in disease.

If ethicists can come in and judge a person competent for other medical procedures, I don't see why they can't also certify someone as competent to make the decision to undergo radical, experimental treatment, when other options have been exhausted.

For some people, passive resignation is going to generate a worse QoL than any of the pain and suffering attached to experimental treatments.

[Dan]

Provenge, Accessability, and Denial For Prostate Cancer Terminally Ill Patients

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 a 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. So, the FDA may not be an ideal judge regarding such issues as treatment options for very sick patients.

Prostate cancer is rather frequent, 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, the more difficult it is to treat such patients.

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 requires the removal of white blood cells of the diseased patient and, after altered, are re-injected into this patient now designed to attack within the diseased body what is called PAP, which is on prostate cancer cells only. This treatment requires only three such injections in a period of six weeks. This results 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. This was expected by many, as Provenge was given Fast Track status by the FDA because of the potential of this therapy for terminal patients.

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! Many found this ruling completely unbelievable.

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 to provide support for this similar prostate cancer drug treatment 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 were fabricated in these letters, it is believed. 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. Because most are willing to assume any risks of unapproved, yet potentially beneficial treatments such as Provenge. Because they have a terminal illness, possible benefits clearly take priority over safety issues of unapproved treatments for them. The controversy could be concluded by a terminal patient signing a waiver of some sort, perhaps, stating that they are responsible for the consequences of an unapproved treatment regimen such as Provenge. Yet the FDA, with reckless disregard and overt harshness, denied what likely was a great treatment method for these very ill patients, so the FDA ultimately harmed others more by not approving Provenge, or offering any exceptions with such cases, which in this situation seems most rational, considering the available data with Provenge.

The FDA does in fact presently have the ability to grant what is called conditional approval for such treatment methods as Provenge at this time, 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, regardless of thier present health state today. Because of the FDA's flaws in the past regarding drugs taken off the market along with increasing black box warnings of other drugs, which happens often with both, the individual should be the deciding factor in such matters of deciding thier treatment course along with thier health care provider, and not an unreliable Administration.

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

Dan Abshear
authors note: what has been annotated has been based upon information and belief