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 5 of 5)

In January of this year, Rossi was busy scouring the globe in search of eligible tumors. The planned Phase III trial would require 363 patients, of which Rossi had found only half. But in February TransMID met with yet another obstacle. Celtic Pharma decided to terminate Phase III testing "on commercial grounds," citing the unlikelihood that the drug would meet efficacy requirements in the late-stage patients it was testing on. TransMID's future is once again unclear; Celtic may undertake new trials in patients with early-stage tumors, sell TransMID to yet another sponsor, or terminate the drug's development altogether. The 143 patients already enrolled in Phase III testing will have to petition the company if they want more of the drug.

As drug approval progresses in fits and starts, patients are liable to fall into the gaps. When Gotschall's tumor returned in 2002, Phase II of the clinical trials had concluded, and production of TransMID had been halted during a merger. There was simply no new drug to give him.

Rossi petitioned the FDA for permission to dispense some TransMID left over from Phase II, but the FDA would not grant permission to use the remaining drug without potency and stability analyses. TransMID's backers ordered the relevant tests. When those results were in, Rossi reapplied for permission. The process took over 3 months. "By the time we got approval to use the Phase II material," recalls Rossi, "they gave John only days to live." Gotschall finally got the treatment, his tumor rapidly growing. He died six months later.

In the nexus between men like Gotschall, who surrendered himself to the whims of researchers, and Abigail Burroughs, who never got the chance, lie uncomfortable truths about drug experimentation and patients. At the very least, men like Frank Burroughs and Steve Walker force us to acknowledge what we give up by insisting on the cold order of randomized trials; they cast the trade-off in the starkest of terms, because the lives of people they loved were part of what was traded. Whereas patients once had the right to treat their bodies as laboratories, their selves as subjects, the right to experiment on individuals is no longer the province of the individuals themselves. Patients fight for the right to be test subjects for others, and consider themselves lucky to be chosen.

At the end of our last long interview, after Walker delivered his usual hyperarticulate assessment of the cruelty of the clinical trial system, capped off with another description of his wife's final days, his voice grew suddenly weary. "God, I hate talking about this," he said quietly. Patients of the present and future should hope he keeps talking. Perfect information comes at a cost. And as Walker keeps reminding researchers who don't want to listen, that cost does not fall on everyone equally.

Kerry Howley is a senior editor of Reason.

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 .