Tuesday, January 15, 2008

Access to Experimental Drugs - the Supreme Court Gets it Right

Today’s Los Angeles Times reports that the Supreme Court has turned down an appeal that claimed a right for dying patients to have access to experimental drugs not yet approved by the FDA. The appeal was brought by the Abigail Alliance, founded in memory of Abigail Burroughs, a beautiful young woman whose picture is on the website. Abigail got a rare head and neck cancer in 1999. Her Johns Hopkins physician wanted to give her an experimental medication, but was not able to. Abigail died in 2001. The drug subsequently received FDA approval. A short, powerful statement of the Abigail Alliance’s argument is in the January 11 Wall Street Journal.

The constitutional right the appeal argued for is based on the fifth amendment guarantee that no person shall “be deprived of life, liberty, or property, without due process of law.” Patients in “last chance” situations, when standard treatment offers no hope – are facing death. The Abagail Alliance argues that by not facilitating access to drugs that have passed through Phase 1 trial, the FDA is depriving them of the right to opt for to a potentially life-saving intervention.

As heartbreaking as it is to contemplate the death of 21 year old Abigail Burroughs and others like her, I think the Supreme Court got it right, for four main reasons. The court recognized the first two:

* The appeal argued for a terminally ill patient’s right to weigh the benefits and risks of taking the experimental medication and to pay for it with their own means. But Phase 1 testing does not provide the kind of information required for truly informed physician recommendation or patient consent, especially in desperate circumstances. The public, through the FDA, has a legitimate interest in the public safety implications of the FDA restrictions.

* Substantially unfettered access to experimental medications would severely undermine the ability to conduct rigorous controlled trials. Patients would be much less willing to enter a double blinded study if they could get access to the experimental agent by another route. Here too, the public has a legitimate interest in fostering rigorous testing of proposed new treatments.

* Although the appeal was limited to drugs in last chance situations and required self payment for access, there is every reason to expect that public and private insurance programs would soon be asked to cover the cost, and that patients with serious but not terminal conditions would press for the same kind of access. The cost of health care is already causing serious harms through uninsurance and job loss from diminished economic competitiveness. The public has a legitimate interest in mitigating the harms caused by runaway cost increases.

* Finally, the appellant’s argument would add to public confusion about the difference between evidence-based treatment and wishful thinking about experimental agents. Our health system is already permeated by magical thinking and denial of death. As well-intentioned as the appeal is, it would add to this unfortunate aspect of U.S. culture.

(For those with time and inclination to read a 22 page document, the decision of the District of Columbia Circuit Court, which the Supreme Court upheld by declining to hear an appeal, makes fascinating reading.)


SN said...

The first principle of individual rights is that each person has the right to his/her life.

When a government goes beyond ensuring informed consent, and -- instead -- bans a person from getting a drug they want, the government violates individual rights.

The FDA’s procedures are unconscionable. I think the law should roll back the restrictions dramatically. Instead of restricting the new drug completely, there should be some procedures ensuring a level of informed consent. That’s all. After that, each individual should be free to make an evaluation and make any gamble.

I say, "Legalize drugs (medical drugs) now!"

Jim Sabin said...

Hi "softwarenerd" -

Thanks for your comment. You see the situation much as the Abagail Alliance does, and I would guess that a national poll would show that you are in the majority. I agree with you about the importance of informed consent, even when life and death are not at stake. And I agree that for drugs that have been approved, it is up to the individual to make any gamble they want, not for others to tell them that the risk outweights the benefit. But I don't think the individual has a right to say, at the same time, that others have to pay for their choice.



SN said...

So the argument is that if one person pays for something, another will want their insurance to pay for it; and, therefore the first person should be forced to do without it.

Clearly the SCOTUS does not hold individual rights to be of primary constitutional importance. The payer is not his brother's keeper -- not according to the constitution.

Jim Sabin said...

Hello again softwarenerd:

I apologize for the long delay in responding to your thoughtful comment. Thanks for your further thoughts!

You are arguing in a very consistent manner, giving the value of individual choice top priority, perhaps with the ability to trump all other values. I give more weight than you do to the core mission of the FDA (quoted from the FDA website):

"The FDA is responsible for protecting the public health by assuring the safety, efficacy, and security of human and veterinary drugs, biological products, medical devices, our nation’s food supply, cosmetics, and products that emit radiation. The FDA is also responsible for advancing the public health by helping to speed innovations that make medicines and foods more effective, safer, and more affordable; and helping the public get the accurate, science-based information they need to use medicines and foods to improve their health."

Some patient advocates concentrate on improving the FDA's Compassionate Use program for access to unapproved agents. These proposals address the interests of desperately sick individuals that you emphasize so well, but also address the orderly development of scientific knowledge. That's the route I am drawn to.



SN said...

Fair enough, Jim, I suppose we'll just agree to disagree on the underlying principle. Meanwhile, I think any attempt to get drugs to folks who want them -- while working more "within the system" are laudable.

The idea of the FDA "allowing" me to use something sounds a bit like monarchical dispensation. That right is not theirs to give.

Yes, I understand that their mission might give them such an express power, and I understand that it might be impractical to expect them to change their mission, in an environment where public opinion does -- in fact -- want the government to retain such monarchical privileges.

So, my objection is not about the immediate pracitcal next-step, but more about the underlying long-term principles involved.

Jim Sabin said...

Hi softwareNerd -

I really appreciate your continuing the discussion. I do think we have clarified our different perspectives substantially.

This is a bit of a fine point, but I don't think we "disagree on the underlying principle." Rather, I think we give different weights to underlying principles. In my clinical practice I have been very un-monarchial. I believe VERY strongly, as you do, in self-determination. But two things lead me to support the FDA mission here. First, I think there is tremendous risk of misbehavior with regard to unproven treatments driven by (a) greed for the money to be made by selling to desperate people and (b) medical narcissism, that can lead to feeling we know the truth. That leads me to see the FDA role (in principle) as sound collective self-care through governmental process, not as "monarchial" or "Nanny state." But I do think there is a real argument here, and you make it well. Second, I know from following our health system that there are and will continue to be tremendous pressures to pay for these unproven treatments, which drives up health care costs and ultimately leads to loss of individual opportunity for choice through decreased availability of insurance.

Again, thank you for your perseverance in probing these issues. I hope you'll continue to keep me honest in the future!



Anonymous said...

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, 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 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

Unknown said...

I find it interesting that you think the Supreme Court got it right by deciding not to hear a case. Are you saying that this issue isn't worth being heard in the highest court in the land, or that it shouldn't even have the opportunity to get a favorable ruling? Let justice be done though the heavens fall. Shouldn't justice be realized regardless of the consequence?

My experience with the FDA has not been nearly as positive as yours appearently has been. It is, in my opinion, attempting to over step its authority and decide how doctors practice medicine. Case in point, the agency recently decided to 'allow' extremely limited access of an approved drug called iplex to patients with lou gehrig's disease. Doctors currently cannot prescribe this drug off label to people with lou gehrig's disease, when 20 percent of the drugs prescribed in this country are for off label uses.

This country needs to error more on the side of freedom doc...

Jim Sabin said...

Hello Blackjames1 -

Thank you for raising these important issues.

By not hearing the case the Supreme Court, in effect, endorsed the decision of the lower court. That's why I take its action as upholding a point of view, not as an evasion.

Your position - that we should err on the side of freedom with regard to medicine - is certainly a widely held view, perhaps the majority. That position gives maximum weight to the value of potentially helping an individual in need. I give more weight to the impact that position has on the population as a whole via its contribution to runaway costs. I'm not informed about Iplex for ALS, but if there is a case for trying it I would favor doing so as part of an organized study that would yield real knowledge rather than in the haphazard way that off label uses are currently applied in the U.S.

Again, thanks for the thoughtful comment!