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Friday, April 07, 2006

The FDA, the Tysabri conundrum, and our cultural incapacity for single payor healthcare 

One of the biggest problems with our system for regulating pharmaceuticals is that we carefully measure all the harm a drug may have done, but do not weigh against it all the good it certainly can do. This asymmetry between sins of commission, which both the FDA and the tort system consider grave, and sins of omission, which neither take into account in any systematic way, means that it is very difficult to gain the approval of drugs that may do tremendous good for virtually all patients, but grievous harm to a tiny percentage of the people who take them. The risk to the tiny percentage overwhelms the benefits to the millions in the minds of risk averse bureaucrats, and the FDA prevents or delays the approval of the drug.

An example of this is the FDA's hanky-twisting over the multiple sclerosis drug Tysabri, which is orders of magnitude more effective against that nerve-killing disease than existing therapies. Unfortunately, Tysabri has been "linked" -- tenuously, at best -- with a rare brain infection in fewer than five patients out of the many thousands who have taken it. The FDA pressured Biogen and Elan to pull the drug last year, and it has not cleared the drug for relaunch notwithstanding the unanimous recommendation of a non-binding expert advisory panel. Why? Because it fears the quick death of one or two people more than it values the lifespans of hundreds of thousands of people.

The Wall Street Journal has an editorial on this very subject this morning. It is behind the subscriber wall, but MS is a subject that is close to me so I am going to go out on a limb and reproduce the entire editorial at the bottom of this post. (Here's to hoping that those tough Dow Jones lawyers cut me some slack.)

The politics of the FDA and the tort system are tricky, and wrapped up in the popular fear and loathing of the pharmaceutical industry. Progressives have a particularly interesting political and philosophical conflict to resolve. Politically, the tort system is almost as serious a barrier as FDA to the introduction of high benefit/potentially lethal drugs such as Tysabri, yet people with degenerative diseases are -- or at least should be -- high on the list of people that progressives would be inclined to be sympathetic to. The Democrats almost always resolve this tension by siding with the trial lawyers, for obvious reasons, usually by clinging to an absurd law and economics rationale. Drug companies just need to price drugs like Tysabri to take into account future compensation for the few people who will be harmed by the drug. Of course, progressives will next argue that we need to control the prices of breakthrough drugs because they are the fountainhead of obscene profits...

The more interesting conflict, though, is for progressives who want to go to a single payor "public health" model for medical care in this country. The emphasis of the FDA and the tort system on sins of commission, rather than sins of omission, is directly in conflict with the rules of decision that govern single payor systems. Single payor healthcare systems routinely make judgments about the costs and benefits of healthcare interventions across populations. For example - and this is but one of thousands -- the Dutch have decided (correctly, in my judgment) that giving women Pap smears more often than every five years is a waste of money that could be spent on other interventions elsewhere in the system. Why? Because cervical cancer is slow to develop, and the returns to the costs of screening diminish very quickly if you do it more frequently than twice a decade.

Of course, a decision like this generates an average result. There are individual women who pay the price of this Dutch policy with their lives. They will develop one of the rare fast spreading cervical adenocarcinomas, or perhaps their semi-decennial smear will be a false negative and they will go ten years without an effective test. Either way, their lives (or at least their uteri) will have been sacrificed for the benefit of somebody else in the system whose life is lengthened or improved with the money saved from "too-frequent" Pap smear screening.

This is, of course, precisely the sort of judgment that the FDA needs to make with drugs that are effective for most users, and dangerous for a few. It needs to decide that the lives of the few are a sufficiently small price to pay to confer great benefit to the many. Unfortunately, it doesn't do this well. It defers the decision as long as possible while the nerves of tens of thousands of people die, never to return. If the FDA is bad at this, what makes us think we Americans will have the political and moral stones necessary to make these sorts of decisions throughout the health care system? Until somebody persuades me that we can and we will weigh the costs of failure to act as gravely as we weigh the costs of taking action, I am deeply skeptical that the American legal and political culture can sustain a single payor healthcare system.
_______________________________________________________
The FDA and MS
April 7, 2006; Page A12

"Every day I'm a little bit worse," Audrey Greenfield tells us. The former New York law partner used to travel the country representing real estate developers. But the multiple sclerosis that she first noticed 15 years ago when she lost coordination in her right foot has now progressed to the point she needs a wheelchair. And she isn't comforted by the fact that she's being denied an effective treatment by the Food and Drug Administration, which is once again harming patients with overcaution.

The therapy in question is Tysabri, and for many MS patients it appears to halt progression of the degenerative neurological disorder. But a year ago -- just months after it was approved -- corporate partners Biogen and Elan "voluntarily" withdrew their drug because of FDA pressure and litigation fear after two patients developed a rare brain infection. That infection might have been linked to Tysabri, since the drug works by suppressing parts of the immune system. But these patients also had other immuno-suppressive therapies, and in any case the MS patients were almost all willing to run the risk.

Just a few weeks ago prospects were looking better for Ms. Greenfield. She and scores of other MS patients had made their voices heard at an FDA advisory panel, which voted unanimously to return Tysabri to the market. The agency was due to rule on the issue by late last month.

But shortly before the deadline, the FDA announced it would take a 90-day extension until the end of June because of concerns over Tysabri's "risk management" plan -- a preposterous excuse given that Tysabri is delivered by injection and only under the supervision of doctors. With its delay, the FDA is denying very-well-informed doctors and patients the freedom to "manage" the risks of untreated MS. "I haven't had any treatment in over a year," says Ms. Greenfield, who got one injection of Tysabri before it was withdrawn.

Bartira Tibertius of Chicago faces the same predicament. She received Tysabri for a full 28 months as part of a clinical trial. "I was doing great. I even forgot that I was sick," Ms. Tibertius, a language teacher and translator, tells us. "But now I'm getting very, very scared. It's deteriorating and I know that," describing numbness and tingling in her hands, arms, feet and face. As for any possible risks from the drug, she says, "I'm more scared of not having Tysabri than having Tysabri. If you told me the Tysabri would shorten 10 years of my life I would do it. I want quality of life, not quantity."

Her risk-benefit analysis is backed by the latest scientific evidence. Several recent studies reported in the New England Journal of Medicine conclude that, among other benefits, Tysabri appears to cut the number of new or expanding brain lesions in MS patients by 83%, and for many induces near-complete remission. Yet the FDA was unable to get its act together and meet its March deadline. It's still likely that Tysabri will return to the market, but the agency's apparent nonchalance in the face of progressive neurological damage is a sad spectacle.

One lesson is that Tysabri should never have been withdrawn in the first place, when a "Dear Doctor" warning letter would have sufficed. But the possible side effects came to light at the height of the Vioxx panic (another relatively small risk, by the way), and then-acting FDA chief Lester Crawford wasn't going to take any difficult stands while he was awaiting confirmation. We hope Andrew von Eschenbach, the latest nominee to head the FDA, won't follow Mr. Crawford's lead. The FDA badly needs public leadership to explain that almost all live-saving and life-improving drugs do have some risks.

The Tysabri story is also further evidence of the need for Congress to pass "Kianna's Law" -- legislation introduced by Senator Sam Brownback (R., Kan.) that would require the FDA to move faster on drugs for terminal and degenerative disease. The tendency of FDA bureaucrats is always to delay decisions on drugs that might turn out to have some nasty side effects. But as Audrey Greenfield, Bartira Tibertius and thousands of other MS patients have had to learn over the past year, too much caution can have nasty side effects too.

7 Comments:

By Blogger Cardinalpark, at Fri Apr 07, 10:12:00 AM:

This really is analagous to the notion of informed consent to surgery. Bad things happen in a small percentage of operations, but people give informed consent to the procedure having been informed of the risks.

Why not have Tysabri users sign a similar form, and waive certain tort rights they might otherwise have pursued?  

By Blogger Cassandra, at Fri Apr 07, 10:20:00 AM:

I can tell you why: because some clever attorney will allege their "consent" was not really informed or was made under duress or strain of illness.

This is what aggravates me so about the legal profession: we have made it so easy to sue that the ease of litigation is now backfiring on plaintiffs.

It is madness. Adults should be presumed to be capable and informed unless there is some pretty damned strong evidence otherwise: the BOP should be on the plaintiff in this case to prove why their "consent" was not informed or voluntary or why they were incompetent, and that ought to be a very, very steep evidentiary mountain to climb.

Otherwise, medical decisions are taken out of the hands of patients and their families and placed in the hands of government. Do we really want that? I know I don't.  

By Blogger sirius_sir, at Fri Apr 07, 12:38:00 PM:

...almost all life-saving and life-improving drugs do have some risks.

Exactly. I doubt there is a drug that is absolutely safe in all instances. Aspirin would be considered a wonder drug if introduced today, and yet one wonders what the FDA would make of its link to Reye syndrome or its tendency to promote bleeding.

Using a drug provides benefit in the face of some risk. We accept the risk for the benefit. The choice of treatment should be left to doctors and patients, not to the vagaries of bureacratic meddling.  

By Blogger Lanky_Bastard, at Sat Apr 08, 05:55:00 PM:

Wow, I agree with the post and all the comments. I think the FDA is still gunshy from Vioxx and that diet pill.

In the FDA's defense, they do allow more severe side-effects for the treatment of more dangeous conditions. (for example: the side-effects of chemotherapy drugs)

Still it's way up there on my list of federal agencies that needs to focus more on helping people and less on covering their ass.  

By Blogger Fred, at Tue Apr 18, 02:44:00 PM:

one clarification, MS is not a fatal disease, so there aren't thousands of people dying from MS because of a FDA delay in approving Tysabri.  

By Anonymous Anonymous, at Thu May 04, 02:00:00 AM:

True, MS is not usually fatal. It just makes you wish you were dead, but it isn't kind enough to kill you...
(Wife has it...)  

By Anonymous Danny Haszard, at Fri Jun 02, 04:40:00 PM:

Well said,i applaud your blog,mental health consumers are the least capable of self advocacy,my doctors made me take zyprexa for 4 years which was ineffective for my symptoms.I now have a victims support page against Eli Lilly for it's Zyprexa product causing my diabetes.--Daniel Haszard www.zyprexa-victims.com  

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