The Right to a Trial?

July 6, 2007 7:48 AM

The fight over an experimental cancer therapy gets ugly. The FDA's decision to delay approval of Provenge, an experimental therapy for advanced prostate cancer, has incensed patients and advocacy groups, who have launched a sophisticated lobbying effort calling for the drug's approval and questioning the motives of critics. Of course, investors in Dendreon, the creators of Provenge, have a strong financial interest in seeing Provenge approved. The New Yorker covers the complicated issues surrounding patient access to experimental therapies in this story.
posted by myeviltwin (28 comments total)

Guaranteeing drug safety has been part of the agency’s mandate since 1938, when Congress passed the Federal Food, Drug, and Cosmetic Act after more than a hundred people died from taking a medicine for strep throat which contained diethylene glycol, an active ingredient in antifreeze.

Well that's a weird resonance with what's going on in China these days.
posted by delmoi at 8:17 AM on July 6, 2007

Advocacy groups who fight against scientists do nothing to help the world. There's outrage if something bad happens when the FDA approves drugs while the evidence is still under review, and there's outrage when the FDA waits until the evidence is in before approving drugs so something bad won't happen. You can't have it both ways, people.
posted by zennie at 8:38 AM on July 6, 2007

The notion of regulating the safety of food and drugs is noble, but the process in America is broken. At this point it is not about science, but about an intractable bureaucracy that is holding up potentially therapeutic cancer treatments that are less dangerous than chemo. The FDA is not run by scientists.
posted by chlorus at 8:48 AM on July 6, 2007

zennie: There are lots of "scientists" on both sides of this debate. From the article:

<sub>Tom (a pseudonym), a physician living near Boston, belonged to this group. He had developed a cytomegalovirus infection in his retina and was slowly going blind, but each time he visited the clinic he pressed me for information about saquinavir and asked me to tell him when the clinical trial would begin. His father begged me to persuade Hoffman-LaRoche to bend its rules and admit Tom. I said that I would try but had little hope of succeeding, explaining that the trial was designed to assess the drug’s safety, and if Tom’s vision got worse while he was taking the protease inhibitor we would have to report it to the drug company as an “adverse event.” Although we might suspect the infection of his retina to be the cause, Hoffman-LaRoche would have to list “declining vision”—and the F.D.A. would have to consider it—as a possible side effect of the drug.

Saquinavir proved to be strikingly effective against H.I.V. Within a few months, the immune systems of most patients who had taken the drug improved and the amount of H.I.V. in their bodies decreased. They gained weight, and had fewer infections. Tom, who had been denied admission to the trial, soon lost his sight and, not surprisingly, became clinically depressed. I assured him that I would make every effort to see that he did not suffer. He developed seizures, and a brain scan revealed a large mass with the characteristics of a lymphoma. He refused further treatment, was placed on a morphine drip at home, and died with his family at his bedside.

At the time, newspapers were filled with stories of AIDS patients whose lives had been saved by the protease inhibitors. It was later discovered that the drugs caused significant side effects in some patients, including an increased risk of diabetes and elevated cholesterol, but, when used with other anti-viral drugs, protease inhibitors helped reduce the death rate from AIDS in the United States by at least seventy per cent. It is possible that Tom would still be alive if he had been able to take saquinavir.</sub>

Framing this debate as "against scientists" is completely disingenuous.
posted by delmoi at 8:50 AM on July 6, 2007

As I understand it nobody's asking the FDA to give their approval to drugs that haven't been proved safe and effective. They're asking for access to experimental drugs that don't have the approval yet, and are being told "no you can't experiment on yourself even though you're basically a walking dead man." I don't understand what the downside is to permitting access, with appropriate disclaimers--i.e., big red sticker on the vial, THIS DRUG IS NOT FDA-APPROVED, USE AT YOUR OWN RISK; except perhaps the fact that allowing people to do anything at their own risk goes against the nanny-state spirit of the times.
posted by jfuller at 8:51 AM on July 6, 2007 [3 favorites]

The FDA is not run by scientists.

Well now that's not true either. The FDA is most certainly run by scientists. And a lot of these drugs have the potential to cause harm, even in terminal patients.
posted by delmoi at 8:53 AM on July 6, 2007

And a lot of these drugs have the potential to cause harm, even in terminal patients.

Er, maybe I should expand on that a little, since it doesn't make too much sense. For one thing, a drug could reduce the time a person spends alive (there's another anecdote in the article about an AIDS drug that ended up making people much worse off)

For another thing, if there are so many experimental drugs out there, how do you pick which one to take. If the "market" for experimental drugs is saturated, there could be 10 or 20 different drugs out there only one of which might work for you.
posted by delmoi at 8:56 AM on July 6, 2007

It seems that the FDA is holding up the examples of Avandia (for diabetes) and Vioxx (for pain/inflammation) and the post-marketing health concerns that emerged with those drugs as a reason to delay approval of this drug.

But there is a big difference between providing a last resort to terminally ill patients and providing life-long maintenance treatment for a chronic condition. The two scenarios are not equivalent and it seems specious to use the same criteria for both. A more appropriate standard in this case might be that used for the drugs to treat HIV/AIDS.

Of course, I also think that the "blistering critiques" of the "irate" investors should be ignored entirely.
posted by tentacle at 8:58 AM on July 6, 2007

delmoi,
But even so, couldn't something like what jfuller is getting at be done? Have a program where, if certified terminal by a physician, a patient can be allowed to take drugs that are still in the testing stage? The biggest issue seems to be liability, so I think they could create a document the patient must sign stating that they understand that this drug is not yet approved, that they accept the risks of any side effect or damage, that they won't sue the FDA or the manufacturer, etc. If a patient volunteers to take these experimental drugs knowing the risks, why not? Perhaps it could even help the FDA a little by providing a (albeit very imperfect) chance to field test a bit.
posted by Sangermaine at 9:20 AM on July 6, 2007

Of course, I also think that the "blistering critiques" of the "irate" investors should be ignored entirely.

Or you could listen to the critiques and evaluate their merits.
posted by Kwantsar at 9:23 AM on July 6, 2007 [1 favorite]

The FDA is not run by scientists.
posted by chlorus at 11:48 AM on July 6

No, it's run by lawyers who have to contend with random accusations of corruption ("How could the FDA have approved this?") every time someone is injured by a side effect of an FDA approved drug.

zennie said, "You can't have it both ways people." Sure they can. Healthy people criticize the corporate greed and excess profits of drug companies charging too much for new drugs, but when they get sick they criticize them for not spending enough on their particular illness.

In fact, everyone is having it one way: the way that suits their individual best interests at that particular point in time.

delmoi:There are lots of "scientists" on both sides of this debate.

I don't want to offend anyone, but doctors aren't scientists merely by virtue of being doctors. Engineers and mechanics aren't scientists either.
posted by Pastabagel at 9:51 AM on July 6, 2007 [2 favorites]

Ah, but Sangermaine, you run into the problem that delmoi's excerpt was getting at--once you give the drug to someone, and you have the ability to track how it affects them, what do you do with that knowledge? The larger problem than liability, I suspect, is not that the terminally ill person (or their family) would sue but rather, if in 10 years it comes out that this drug actually does cause blindness in 1 out of every 10,000 cases, the drug company (or FDA) could be held liable for being a position to know that and not do anything. It's kind of like Pandora's Box--once you have the knowledge or data, you can't very well un-know it.

Ironically, the people who would be most likely to agree to waive all rights to sue if something went catastrophically wrong (that is, those in the most advanced stage of the disease or those with the most comorbidities/complications from their illness) are the exact ones that perhaps should not be getting the drugs during the clinical trials. Which, short-term at least, seems like a horrible position, but upon inspection--I don't know. Not to be all "in every omelette a few eggs must be broken" about it, but the alternative is that lifesaving drugs might be held of the market for months longer than necessary, or even permanently, because of noise getting in the way of testing and making it seem like these drugs have more or worse side effects than they actually do. (I was shocked by the mention of the billion dollar drug that was dropped for having 82 people die during the clinical trial. 82 people, out of what presumably was thousands of people participating--how heartbreaking would it be to find out in 20 years that this was actually a good drug that got sidelined because a few too-sick people were entered into the drug trial by an overly-sympathetic doctor? When heart disease kills so many people every year?)
posted by iminurmefi at 10:00 AM on July 6, 2007

I'd make them sign just about every legal document under the sun, then make all of their relatives and any possible claimants sign away any right to a lawsuit they had. A third-party scientist could evaluate the research and the reactions thus far before any medication would be doled out. Then, anyone wanting the drug would have to enter the kind of fun, controlled-environment setups that the professional guinea pigs endure, where sleep, food, and dosage regimens are tightly controlled.

Here is my testing scenario:

LABCOAT: You know this hasn't been approved yet, right?
SICK GUY: I know, I know, just let me sign the paper!
LABCOAT: Nope, no FDA approval. Anything could happen.
SICK GUY: Look, pal, I don't know how word got around, but Geezer magazine just offered me the July center spread. "My God, we heard you've got a prostate the size of an orange!" I want the drugs.
LABCOAT: First, you have to watch the video. See what it did to our little primate friends.

LABCOAT clicks on the VHS, a few seconds of static, followed by some placid-looking baboons consuming what appear to be Pez the color of bananas. Half of the baboons do nothing. BABOON 3 turns bright blue, then dissolves into a puddle of slime. BABOON 10's hair falls out completely, then it rips out its tongue and writes HELTER SKELTER on the walls in blood. BABOON 5 sneezes twice prior to its head exploding, Cronenberg-style. Number 20 just ages rapidly and crumbles to dust.

SICK GUY: You slipped in some footage from The Hunger, didn't you, just to scare me off! No chance of me developing any fun X-Men type mutations, is there?
LABCOAT: [yelling] Who told you about test subject 17!?! Just kidding, no. Now, smile for the video camera. We want a shot of a nice healthy test subject for the stockholders meeting.
SICK GUY: But I haven't taken any yet!
LABCOAT: Exactly.
posted by adipocere at 10:28 AM on July 6, 2007 [2 favorites]

> a good drug that got sidelined because a few too-sick people were entered into the drug trial

I wasn't actually suggesting that entering terminal patients into a drug trial just to get the drug to them is a good idea, since it pretty clearly isn't--you don't want to bollix up the trial design, for one thing. I was wondering what the drawback would be of creating a mechanism through which terminal patients could just take the unproved drug--all by themselves, as a stand-alone instance from which no medical conclusions would be drawn except anecdotally, and in circumstances where they have pretty much nothing to lose. In a time when there's a pretty serious constituency for the "right to die", where's the problem with letting somebody take a flying leap for life if they want, even if the chance of success is vanishingly small? Who would be harmed by that, and how? (That's not a rhetorical question. Am I actually overlooking some harm this would do?)
posted by jfuller at 10:36 AM on July 6, 2007

(I was shocked by the mention of the billion dollar drug that was dropped for having 82 people die during the clinical trial. 82 people, out of what presumably was thousands of people participating

That's funny--I was shocked that a Phase III trial was allowed to rack up a body count of 82 people before it got shut down. I work for a cancer research nonprofit, and I'm seeing an awful lot of weird assumptions and wild assertions about how clinical trials are conducted.
posted by Skot at 10:51 AM on July 6, 2007

I wasn't clear above--I know you weren't referring to entering these people into clinical trials; I'm saying that merely giving them drugs through any sort of compassionate exception program would itself create data that you then have to figure out how to deal with, particularly if that data shows large adverse effects:

To be eligible for the program, drugs would have to be at the end of Phase II trials or partway through Phase III, depending on the kind of drug and cancer involved. The oncologists who administer the drugs would be required to report their patients’ progress and any side effects to the F.D.A. and to the pharmaceutical companies. The doctors would also have to answer simple questions about the drug—whether patients did better on a high dose twice a day or on a lower dose three times a day, say, or whether it helped patients with an advanced stage of cancer.

Yes, I suppose we could stipulate that the FDA wasn't to take any action with the information it collected. But I think it's pretty unrealistic to expect that the FDA wouldn't err on the side of caution in an instance where they saw a number of serious side effects or deaths in a compassionate exception program. So in effect, you'd unintentionally create another trial, except one in which sicker-than-normal people are taking the drug and dealing with all sorts of medical issues that may or may not have anything to do with the drug itself. Given that a drug company was willing to toss out a billion dollar drug in Stage III trials over 82 deaths, I think that's a road we should be very very cautious going down just to maybe save a handful of lives.
posted by iminurmefi at 10:51 AM on July 6, 2007

Skot, that's fair--I don't know how many people were in the treatment group, and whether that 82 is the total number of deaths in the treatment group or the number of additional deaths above what occurred the control group. In my mind, I was thinking of a treatment group on the order of thousands in order to have sufficient power, and among a population that might already have chronic heart failure or other conditions with a fairly high mortality rate. If the treatment group was 200 people, and no one died in the control group, obviously 82 is quite high.
posted by iminurmefi at 10:57 AM on July 6, 2007

So in effect, you'd unintentionally create another trial, except one in which sicker-than-normal people are taking the drug and dealing with all sorts of medical issues that may or may not have anything to do with the drug itself.

As well as taking the drugs in wildly uncontrolled conditions with lots and lots of physicians of varying capability and attentiveness doing the monitoring.

The arguments on both sides are pretty compelling, but this one that probably tips the scale for me:

Moreover, the F.D.A.’s initiatives could make it more difficult to recruit patients for clinical trials. [. . .] If patients can obtain experimental drugs from physicians in their communities, they would have little reason to leave home to participate in a trial. Enrollments are particularly likely to suffer in the case of trials comparing an experimental drug with a standard therapy: what patient would want to risk receiving the standard treatment in a trial when he could get the experimental drug directly from his doctor?

One fascinating sidelight (some hairsplitters might call it a derail) of this issue is how much our attitudes about terminal illness have changed in my lifetime. When I was a kid, "cancer" or "heart attack" pretty much equaled "death sentence" in the public mind, and so anyone surviving cancer seemed a miraculous thing to be hugely grateful for. But we've made so much progress in therapies for many cancers that now (and I'm not criticizing the sick people who think this), there's almost a sense of entitlement to a cure. I mean, the FDA, for all its sins, is not killing any dads; prostate cancer is killing them. It's as if we can't grasp the concept that in this brave new world, there are still plenty of maladies for which there are -- and never will be -- cures. Death, for instance.
posted by FelliniBlank at 11:13 AM on July 6, 2007 [1 favorite]

er, "are not -- and never will be -- cures." Jaysus.
posted by FelliniBlank at 11:15 AM on July 6, 2007

No, it's run by lawyers who have to contend with random accusations of corruption ("How could the FDA have approved this?") every time someone is injured by a side effect of an FDA approved drug. -- Pastabagel

Why would anyone put Lawyers in charge of the FDA? They're not liable in case something goes wrong, and for all the charges random people might make, they are not really that accountable to anyone but congress, as far as I know, and to some extent the president.

Here's the resume of the current head of the FDA (from wikipeda):

* bachelor of science from St. Joseph's University in 1963
* MD from Georgetown University School of Medicine in 1967
* Residence at Pennsylvania Hospital in general surgery and urology
* taught urology at the University of Pennsylvania School of Medicine.
* chair of the department of urology at The University of Texas M. D. Anderson Cancer Center
* founding director of the Prostate Cancer Research Program in 1996

Etc. I don't see a law degree anywhere. The previous director was a veterinarian (heh). Do you have any evidence that the FDA is run by "lawyers"


I don't want to offend anyone, but doctors aren't scientists merely by virtue of being doctors. Engineers and mechanics aren't scientists either. -- Pastabagel

Oh, then what makes someone a scientist then? If doing research at an academic institution then many doctors would qualify, since many hospitals are attached to universities. If it's something else, then what?

Ah, but Sangermaine, you run into the problem that delmoi's excerpt was getting at--once you give the drug to someone, and you have the ability to track how it affects them, what do you do with that knowledge? The larger problem than liability, I suspect, is not that the terminally ill person (or their family) would sue but rather, if in 10 years it comes out that this drug actually does cause blindness in 1 out of every 10,000 cases, the drug company (or FDA) could be held liable for being a position to know that and not do anything.

Well, congress could make information gained through that process inadmissible in court if they wanted too. This isn't a black white issue with one side in the right or one in the wrong, but rather a complex grey area. If you sacrifice statistical integrity, more people might die later on.
posted by delmoi at 11:19 AM on July 6, 2007

Zennie has it exactly right; the whole point that these drugs are experimental means they have a lot of promise and have made it through a number of hurdles, but they may not work, or they may work, but not as well as the current treatments, or they may work but have side effects that are intolerable, or they may work wonderfully. The point is, we don't know and diverting resources away from the well-conducted trials needed to determine effectivess of drug helps no one, and generating a lot of anecdotal accounts only clouds the issue. Pastabagle is right too that physician and scientist are not synonymous; I am a physician and making that distinction does not offend me in the least. Lastly, the FDA is an entire bureaucacy with scientists, lawyers, political hacks, and others thrown into the mix. Having to deal with lobbying by various self-interested groups will not help the FDA make decisions based on fact, which should be the main criterion. I know it is naive to think we are anywhere close to that sort of world, but right now we are in a situation where the group that gets the best PR gets the most support. Take the example of breast cancer, which gets about 3 times as much money from the NIH as lung cancer, even though lung cancer kills far more women than breast cancer and affects men and women roughly equally.
posted by TedW at 11:32 AM on July 6, 2007

Felliniblank makes a very relevant point. In the case of childhood cancer, overall 80% of children diagnosed with cancer will survive 5 years; those who are disease-free at that point are considered cured. It took a lot of rigorous clinical trials to make that progress, however. And there is still a lot of progress to be made, especially when it comes to mitigating the long-term effects of chemotherapy on children (many survivors are now developing other cancers in their teens and twenties as a result of their initial cancer treatment). I feel sympathy for those desperate patients who want easier access to experimental treatment, but for the good of many more patients yet to come I hope the FDA holds firm.

And if anyone wants to see the original sources for the numbers I have been citing, they are all from the National Cancer institute, which has a pretty good website.
posted by TedW at 11:51 AM on July 6, 2007

Back-door uncontrolled (in the scientific sense) use of experimental medications is a horrible idea that will hurt/kill many people.
posted by Mister_A at 12:48 PM on July 6, 2007

In the case of childhood cancer, overall 80% of children diagnosed with cancer will survive 5 years; those who are disease-free at that point are considered cured. [. . .] many survivors are now developing other cancers in their teens and twenties as a result of their initial cancer treatment).

I bet a fair chunk of that 80% survive long enough to reproduce, and I'm genuinely happy for them, but yikes, homo sapiens has to be racing toward extinction at this point.
posted by FelliniBlank at 1:02 PM on July 6, 2007

delmoi, "what is a scientist?" is a somewhat philosophical question. In the world of research, they are accepted to be anyone doing, leading, or evaluating academic research employing a mathematically verifiable, controlled method of inquiry. Having a PhD helps, but non-PhDs can be scientists as well.

The current head of the FDA, and the former one, and those doctors in the WaPo article would all qualify.
posted by zennie at 1:32 PM on July 6, 2007

I bet a fair chunk of that 80% survive long enough to reproduce...

A fair number of them will be rendered infertile from their treatment, though. Surprisingly enough there is not a huge increase in birth defects or cancer rates among the children of those treated for cancer.
posted by TedW at 1:48 PM on July 6, 2007

"Provenge" sounds like a pill for getting revenge on one's prostate.
posted by jtron at 2:31 PM on July 6, 2007

Of course it does, and that is certainly deliberate. Ridiculous, of course, but deliberate.
posted by stavrosthewonderchicken at 11:42 PM on July 6, 2007