Dying for Lifesaving Drugs

Will desperate patients destroy the pharmaceutical system that produces tomorrow's treatments?

Kerry Howley from the August/September 2007 issue

(Page 2 of 5)

The group's complaint was dismissed, but last year a three-judge panel of the U.S. Court of Appeals for the D.C. Circuit overturned that decision. "A right of control over one's body has deep roots in the common law," Judge Judith Rogers concluded in the majority opinion. "The prerogative asserted by the FDA...impinges upon an individual liberty deeply rooted in our Nation's history and tradition of self-preservation."

The appeals court decision drew little attention, but the media coverage it did attract was almost uniformly negative. "A court makes up a right," snarked the Washington Post editorial page. A June 2006 article in The New Republic said the court's logic would put us "back in the snake-oil days," and The Journal of the American Medical Association lamented "a new era of unapproved drugs."

The FDA sought a rehearing by the D.C. Circuit, and a 10-judge panel heard the arguments of both sides in March. No matter how the court rules, the Abigail Alliance expects its legal battle to end in the Supreme Court.

After Burroughs, the man who spends the most time promoting the Abigail Alliance's cause is a geologist named Steve Walker. In December 2000, Walker and his wife of 20 years--Jennifer McNeillie, also a geologist--were in the process of adopting a child abroad. The two had paid an agency, were looking at pictures, and were preparing to go to Russia to make their final arrangements. Before they got there, Jennifer was diagnosed with Stage 4 colon cancer. At 45, she was told she had a slim chance of making it to 50.

McNeillie's bleak prognosis coincided with a flurry of promising research in colon cancer treatment. Three new drugs, Erbitux, Eloxatin, and Avastin, were in development, and McNeillie decided that the risks of being a test subject were worth taking. She would wait years, her cancer progressing, for the chance to try one. There were no Eloxatin trials in progress at the time, and Erbitux and Avastin trials were both closed to new enrollment. "The drugs were simply unavailable," says Walker. "We couldn't get into the trials."

In September 2002, a bedridden McNeillie was finally admitted into a small Erbitux trial. "The drug resurrected her," says Walker. "We went skiing in Colorado. We went hiking." Without the drug, cancer cells that lined McNeillie's stomach would appear, expand, leak fluid. McNeillie would blow up like a balloon every four days and have to go to the hospital, looking six months pregnant, to be drained through a catheter. On Erbitux, her worst side effect was a rash. She went back to work.

Six months after she started taking the drug, doctors spotted a new tumor on her colon. By the rules of the trial--rules set to ensure the FDA would accept the results--McNeillie could no longer participate. No trial meant no drug. When Walker pleaded with McNeillie's physician to keep dispensing the drug, the doctor pleaded back: Giving out more Erbitux could mean giving up his license to practice medicine.

Determined to dig up more Erbitux, Walker spent six weeks shuttling between the drug's manufacturer, ImClone, and the FDA. ImClone responded quickly, offering to set up an entirely new trial just for McNeillie so her treatment would conform to protocol. It took ImClone 10 days to set up the trial. The FDA then delayed for two and a half weeks, mulling approval. "This is to give the same drug the same way by the same doctor," says Walker. "During this time my wife is dying. She is tremendously suffering." At the same time, Walker was trying to get his wife into an Avastin trial. She didn't qualify.

Six weeks after she'd been kicked out of the trial, McNeillie was given a dose of Erbitux. She passed away after six months on the drug, in June 2003. Eight months later, the FDA deemed Erbitux and Avastin safe and effective treatments for colon cancer.

The Abigail Alliance has collected many such stories. There is David Baxter, a high school student suffering from colorectal cancer, denied admission to trials for a promising drug because he was too young to qualify. He died at 17 in 2001. Alita Randazzo, also suffering from colorectal cancer, spent years flying to France to get Eloxatin, which had been approved there but not yet in the U.S. When Eloxatin stopped working, she was told by her doctors that her last hope was Erbitux. Trials for Erbitux had closed. She died in 2002, still fighting for access.

A Hard ACT UP to Follow
Enraged patients have jolted the FDA into action before. In New York in 1987, protestors from the AIDS Coalition to Unleash Power (ACT UP) hanged an effigy of FDA chief Frank Young on Wall Street. Activists complained that AIDS drugs were too slow in being approved and too expensive when they went to market. A year later ACT UP brought 1,000 protesters to the FDA's headquarters, vowing to shut the agency down. The FDA stayed open, and 180 protesters were arrested.

Graced with voluminous media coverage, AIDS activists found their confrontational tactics rewarded. AZT had been rushed through the process before the activists showed up at the FDA's doors, the protease inhibitor Saquinavir was approved three months after it was submitted for approval, and a similar drug, ritonavir, was approved 24 hours after an FDA panel recommended that it be allowed on the market. It was as if they'd slipped the FDA a massive dose of Adderall.

In the early 1990s, under congressional pressure to reform, the FDA introduced "fast track" regulations to speed review of certain drugs and complex "expanded access programs" through which terminally ill patients could potentially receive medication. In 1997 then-President Clinton signed the Food and Drug Modernization Act, part of which allowed individual patients to request access to developmental drugs.

But many of the gains applied exclusively to AIDS patients, and from where Burroughs is standing, even the systematic reforms appear inadequate. Setting up an expanded access program, he argues, is such a bureaucratic nightmare that the program is "essentially inoperative." The process involves a significant amount of paperwork for the patient's doctor, who may not be aware of drugs in development; the pharmaceutical company, which has no real incentive to participate; and the FDA, which is not known for its alacrity in tackling administrative tasks. Drugs aren't eligible for such programs until late in the clinical trial process. Still, such programs do exist and they are occasionally utilized. Two patients have won the right to try TransMID through such a program.

As the heyday of activism passed and the AIDS movement matured, pressure for radical change began to wane. The Abigail Alliance is no ACT UP, and Walker and Burroughs look with envy upon the group's ability to jam drugs through the FDA bureaucracy. "Originally, we tried to get support from the AIDS community," Burroughs recalls.

"But we didn't. They had won their victory." The 1980s marked the first time dying patients had risen against the FDA, and no movement of similar strength has emerged since.

Comments

|7.25.07 @ 12:04PM|#

Read this in the print version. It was a thoughtful piece that didn't gloss over the complexities of the situation. Very nice.

thoreau|7.25.07 @ 12:09PM|#

I agree. That was excellent science reporting.

|7.25.07 @ 12:37PM|#

Another feather in Kerry's headdress.

|7.25.07 @ 12:38PM|#

I read the print version over the weekend. The reporting is solid and Howley's observations are thought-provoking.

|7.25.07 @ 12:50PM|#

As someone who works in the biotech industry (but thankfully, no longer works with life-saving drugs; it's very depressing), I'd like to highlight a point that was mentioned in the article, but perhaps not as strongly as many others. The double-blind clinical test methodology is in place because for non-life-threatening situations (the vast majority of clinical trials,) it is simply the best. It provides the most, highest quality data in the shortest period of time with far fewer ethical complications than those situations where people's lives are on the line. So that explains WHY that system is in place. Now as to why that model is then draped over a situation as different as life-threatening diseases, there comes a legitimate argument over what is or is not life-threatening. There is no magical line in the sand that can be drawn that will satisfy all (or most) people as "now it's okay, now it isn't." And I think we can all agree that a case-by-case basis is ripe for abuse.

And as an aside, I would like to mention that in clinical volumes (especially in phase 2), drug manufacturing costs are often very high. So even if drug companies were allowed to make their drugs available to patients that were not part of their trials, small companies (or low-profit divisions at large companies) would still have little financial incentive to do so.

An excellent article, Ms. Howley, including a realistic discussion of many of the tradeoffs in what is an emotionally trying field. Very well done.

thoreau|7.25.07 @ 1:42PM|#

I don't think that a freer market for medicine would necessarily mean the end of controlled studies for medicines. It might mean the end of placebo-controlled studies for life-threatening illnesses, but studies controlled with a previously tested drug could still go on. And people could be persuaded to participate if the treatment (new or old) was offered free.

As to why anybody would take a chance of going for the old treatment, there's only an incentive to spurn the old treatment if you actually know that the new one is better. If you're not yet sure about that, then taking the old one that's known to work in some fraction of cases is no worse of a gamble than taking the new one that might be better or might be worse.

Not everybody would go for that bet, but I suspect a lot of people would. Especially if both treatments were free. So controlled studies (with willing volunteers, private funds, yadda yadda) could continue while other people opt to pay for experimental treatments outside a controlled study.

|7.25.07 @ 2:09PM|#

It seems to me that an unspoken component in this whole issue is power. Who has power and who gets to yield that power. Doctors, the FDA, and the Pharmas have power while patients are merely the inputs to maintaining that power (yes a bit extreme and cynical, but like I said this is a component of this debate that is rarely discussed.)

Regards,
TDL

|7.25.07 @ 2:26PM|#

see: thalidomide babies

|7.25.07 @ 2:53PM|#

Good story, enjoyed it quite a bit.

Also, I have a friend who just saw SICKO a few days ago, and he won't shut up about how "eye opening" it was.

I showed him my new issue of Reason, specifically the aforementioned article, and he hasn't said a word about SICKO since.

Russ 2000|7.25.07 @ 3:44PM|#

And people could be persuaded to participate if the treatment (new or old) was offered free.

Free isn't enough. Some trials require relocation and giving up one's occupation. Even if the medical care is free and living expenses are covered, the price is still high. My late brother-in-law had to make the decision - relocate for a period of time and give up his income for the unknown odds of tacking on a few more years to his life OR work as hard as he could in the time he had remaining so that his kids would have their college tuition covered.

LarryA|7.25.07 @ 7:31PM|#

What we need is "No Patient Left Behind."

Robert|7.25.07 @ 8:40PM|#

It was pointed out to me years ago what eventually strikes anyone in this field: that there is no ethical way to test treatments on humans in almost any circumstances. If you have enough reason to be testing A vs. B, it's because you suspect one is better than the other, in which case your judgement should be to use the one you think is better, no matter how uncertain you are, rather than to test them.

|7.25.07 @ 10:17PM|#

Add me to the list-- "Well done!"

Almost tempts me to pay for this rag... :o)

David Bevan|7.26.07 @ 6:08AM|#

No Robert, that won't do...ethics must have a comparative dimension, because ethics consists of choices between different acts. Given that treatment of disease with effective drugs is ethical, testing them properly on humans to see if they are effective is more ethical than not testing them.

As for 'suspecting' one drug to be better than another (or placebo) and therefore sidestepping the whole clinical trial project, that raises the spectre of ten thousand doctors all giving different treatments according to their own subjective, ignorant, unreliable or predjudiced thinking, or medical dogma - in other words, the way it was pre 1900 when most medicine was utterly ineffective.

New drug X may be better and safer than old drug Y, but may also be dangerous and worse. Try thinking of randomised studies as tests of whether new drugs are worse...

|7.26.07 @ 6:56AM|#

I used to believe that double blind controlled trials were the end all, final word in good science. Doulbe blind trials are very useful, but as examples from Vioxx to Avandia demonstrate, burrowing down into data gives one inescapable conclusion: we are unique - - each drug is a lifesaver and each drug is a killer - it doesn't do you (an individual) much good to know what the "average" response is.

|7.26.07 @ 7:55AM|#

Again, rather than debating the ultimate regulatory or scientific testing framework, I believe the thrust of the article was that individuals have the right to do with their lives what they choose. In the sense that patients have a "right to the drugs," I disagree. I would agree that they have a right to risk their lives to see if a drug will work for them, and the drug producer has the right to decide whether or not to include them. As usual, the 9000 pound Government gorilla does not need to be in the room.

Our medical establishment, like our government, assumes that because they are smart, we all must be dumb and incapable of even understanding what is going on, and certainly not allowed to make any decisions for ourselves. This arrogance and elitism pervades both fields, and like most situations, only free exchange of ideas, goods, and money will solve the problem.

Robert|7.26.07 @ 10:39AM|#

"Given that treatment of disease with effective drugs is ethical, testing them properly on humans to see if they are effective is more ethical than not testing them."

Not on the individual test subject, at least not with normal doctor-patient ethics.

"As for 'suspecting' one drug to be better than another (or placebo) and therefore sidestepping the whole clinical trial project, that raises the spectre of ten thousand doctors all giving different treatments according to their own subjective, ignorant, unreliable or predjudiced thinking, or medical dogma - in other words, the way it was pre 1900 when most medicine was utterly ineffective."

Of course. But it still couldn't, and can't, be done ethically. (And don't exaggerate -- medicine wasn't utterly ineffective in 1900.)

This is not my invention. All medical ethicists can explain it. Normal medical ethics has to be suspended during testing.

There's no way around this by pretending that below a certain level of certainty, there is only ignorance regarding A vs. B. They won't even let you test on humans unless you give them good reason to believe a particular one of those (the new one) is better than the other. (The other may be doing nothing, or may be an existing rx.)

|7.26.07 @ 10:56AM|#

@Legate Damar

I'd like to highlight a point that was mentioned in the article, but perhaps not as strongly as many others. The double-blind clinical test methodology is in place because for non-life-threatening situations (the vast majority of clinical trials,) it is simply the best. It provides the most, highest quality data in the shortest period of time with far fewer ethical complications than those situations where people's lives are on the line.

I agree. It's easy enough to paint a sympathetic portrait of an Abigail Burroughs, who dies from being denied what could possibly be a life-saving drug. What you don't see is what I believe economists call an "opportunity cost" - the people who would die due to insufficient data because the trials didn't occur.

I understand the libertarian dilemma - the government is essentially deciding who will live and who will die "for the greater good". Nobody likes the idea of the government arbitrarily gambling with people's lives.

The problem is, in this case it's actually placing some pretty good bets with a high return. Occasional Thalidomide disasters notwithstanding, on balance the smart money says the data collected by the trials has saved more lives than if the trials hadn't occurred.

|7.26.07 @ 12:05PM|#

When the femist revolution was at its height, its proponents kept saying things like "Our bodies -- ourselves." A woman's right to an aborton was advanced in terms of bodily autonomy. Eloquent arguments were advanced in support of the notion that one had an absolute right to do whatever one wished with one's body, so long as it did not directly harm others.

Where are those exponents when right-to-treatment issues arise? If one has a right to remove an unwanted growth from one's womb, surely one has a right to remove an unwanted growth from one's brain by whatever means necessary.

My guess is that many, if not most, of the proponents of "Our-bodies, ourselves" ideology were, or have become "nanny-staters," and would, if anything, support the FDA's right to control access to life-saving drugs in the name of the greater pulic good. But it is difficult for me to draw a distinction between a government whose laws prevent one from exercising control over one's reproductive organs and laws which prevent one from exercising control over one's tumors.

|7.26.07 @ 12:53PM|#

I'd like to highlight a point that was mentioned in the article, but perhaps not as strongly as many others. The double-blind clinical test methodology is in place because for NON-life-threatening situations (the vast majority of clinical trials,) it is simply the best. It provides the most, highest quality data in the shortest period of time with far fewer ethical complications than those situations WHERE PEOPLE'S LIVES are on the line.
I also thought the L Damar comments were good, but what I took from them is that the rationale for clinical trials when your dealing with terminal illness is not so overwhelming. The fact remains that medical progress only happens with experimentation. Anything that hinders increasing the number of patients treated diminishes the amount of data generated to evaluate the drug.
However, the more substantial reason of non-availability of these drugs is cost. But if the firm's investors believe that the drug works, and makes it avaliable so patients can afford it, and a patient with no alternative is willing to take the risk, it would benefit society to increase treatments with these new therapies.

Ben|7.30.07 @ 8:03AM|#

We should be able to give up our right to sue in any limited or unlimited context we choose. Period. Or any other right. Formally. In light of our being found competent, perhaps, but no more than that.

When the feds tell us we can't do something, it had better be in a sentence that says "to this other entity over here" or else it is pure and utter coercion.

The government often makes the case that it is protecting us from ourselves. I do not solicit such protection and if I only could, I would opt out. This is because I am quite certain that I any threat I would pose to myself will be balanced by potential benefits I am looking for, and that any risk I face I can evaluate with a clear mind.

Having said that, I am forced to observe that no one seems to be able to protect me from the government; furthermore, no one even seems to be interested. In today's society, the maxim seems to be that "the quest to deliver good to the many justifies utterly destroying the liberties of the individual, and if convenient, the individual as well."

In its terminator-like campaign to give everyone what is "good for them", the government has destroyed a thing I once held very dear: hope.

Bob Armstrong|7.30.07 @ 10:18PM|#

The idea that the FDA has any life or death power over individual choices is offensive .

The arguments for government restricted testing versus open market based evaluation are bogus . Just as with Amazon or YouTube consumer ratings and commentary , both effective and dangerous products would be perhaps more quickly recognized and as data accumulates it can be mined for the statistics of efficacy , etc . It didn't take double blind studies to determine the dangers of smoking . Nor would it for any proposed nostrum , no coercion necessary .

As my old professor Donald T Campbell used to stress , life is unavoidably experimental .

Restricting freedom just slows it down .