Compassionate Use, Clinical Trials, and Social Media

July 15, 2015 2:14 PM

Sick kids, desperate parents, and the battle for experimental drugs There’s growing unrest with the realization that when a company denies a request, patient voices are getting louder. The power of the Internet and especially social media has allowed patients and their families to take their plea to the masses and, in some cases, see their story go viral.
posted by Michele in California (14 comments total)

“Patients have demanded and have taken a place at the table,” says Richard Moscicki, deputy center director for science operations at FDA’s Center for Drug Evaluation and Research. “So we recognize that, and we are committed to trying to figure out how to incorporate that into our own internal thinking.”

Though not yet an issue for compassionate use, it is important to be cautious about patients or families of patients becoming proxies for drug companies that want to sell expensive medicines.
posted by a lungful of dragon at 2:25 PM on July 15, 2015 [3 favorites]

Thanks for posting this. I was impressed that they included the pharma's perspective, and the reasons why a company might refuse to either create a compassionate use program, or offer a drug to someone who might need it. It's easy to demonize pharmaceutical companies, especially when lives are on the line. Harder to consider deeper issues, tho. The patients have nothing to lose, and everything to gain. Compassion and empathy and morality all say, give them the drugs and hope for the best. But still, it's not that easy. There are other ramifications.

There are reasons companies are reluctant to adopt compassionate use programs. They can cost millions to establish. While the programs’ intentions are noble, a dollar spent underwriting the compassionate use of a drug is a dollar diverted from developing the drug for future patients — a choice favoring one individual over others.

Companies also assume significant risks, many of which the public is unaware of, with expanded access programs. The FDA wants to be informed of all serious side effects thought to be linked to a drug provided via compassionate use. On the other hand, any hints that the drug works are not taken into account during review.

This makes sense, since efficacy needs to be measured carefully in clinical trials. Still, it’s hard to imagine any other industry where a manufacturer is willing (or pressured) to release a prototype in an uncontrolled setting, knowing that its regulators are closely watching for instances where that product causes harm.

If major side effects surface via compassionate use, it’s much harder to understand why the side effects occurred, since these patients tend to be much sicker. And this can mean trouble with the FDA.

That’s what happened last year to Los Angeles-based oncology drug company CytRx Corp. after the death of a patient who had obtained the company’s cancer drug via compassionate use. The FDA ordered all of the company’s clinical trials of the drug to be stopped. The hold, which only meant new patients could not be enrolled, lasted two months.

And that's a really important point. For the sake of one life, how many others will lose out because an untested drug is being judged by the FDA as if it had been used in controlled study settings, with a carefully screened patient who is not at death's door? Can't blame the FDA for being supremely careful, either. They have a protective responsibility to fulfill.

And yet when someone's life literally may depend on being able to obtain experimental medicine, don't we have a moral obligation to let them at least have that chance?

Lots to consider here.
posted by zarq at 2:27 PM on July 15, 2015 [8 favorites]

And yet when someone's life literally may depend on being able to obtain experimental medicine, don't we have a moral obligation to let them at least have that chance?

As an addendum to this question: paid for by whom? Insurance sure won't cover it. And as much as every single one of us loves to hate on Big Pharma, there are experimental drugs coming from Mid Pharma and even Tiny Pharma.
posted by DarlingBri at 3:00 PM on July 15, 2015 [2 favorites]

And yet when someone's life literally may depend on being able to obtain experimental medicine, don't we have a moral obligation to let them at least have that chance?

Also, what if an experimental drug shortens a person's life rather than lengthening it? What if the patient lives longer, but is in such extreme pain that they take their own life? What if the drug causes the patient to lose their mind to the point where they go to the mall and start shooting people. Are the patients (and their families) willing to sign a ironclad release of indemnity? Can they even legally do so?

Seems to me the drug companies would need a 100% guarantee against any sort of litigation before getting on board with this.
posted by sideshow at 3:27 PM on July 15, 2015 [2 favorites]

Idemnity is a standard part of signing up for experimental drugs and trails, yes, sideshow.
posted by DarlingBri at 3:57 PM on July 15, 2015

Can't blame the FDA for being supremely careful, either. They have a protective responsibility to fulfill.

Yes, I can too.

The incentive structure for the FDA is all out of balance. If a drug is rejected which could save a lot of lives, and thus those people all die, the FDA doesn't get blamed. But if a drug gets approved and a handful of people get sick from it and/or die, the FDA gets roasted. So the incentive for the FDA is to keep saying "no" until they have absolutely no excuse for not saying "yes".

From the FDA's point of view, better that 1000 people die untreated than that 1 person die from taking the drug. They don't get blamed for those 1000 people, but they would be blamed for the 1.

I personally have suffered because of that. I have a pretty serious genetic disease and none of the standard treatments help me. 10 years ago I got into a clinical test of a new drug, and it was a miracle. I felt better than I had in years.

Then the test ended, and I couldn't get any more of it. Meanwhile, the FDA rejected the drug because it caused some relatively minor side effects in a toxicology test involving beagles.

My disease has largely destroyed my life by this point. If I could have gotten that drug for regular use, I'd be able to hold down a job, make friends with people, and live something like a normal life. But I can't, and I don't do any of those things.

What I'd like is for Congress to reject "First, do no harm" in favor of "If the overall result of approving the drug is better than rejecting it, then approve" standard for the FDA. I vote in favor of the 1000 over the 1.
posted by Chocolate Pickle at 4:29 PM on July 15, 2015 [8 favorites]

Like Chocolate Pickle, I have a debilitating, incurable genetic condition. I have gone to real extremes to get off all medication and use diet and home remedies to manage. At one point, what was basically a non drug treatment got denied because some people got lung bleeds from it in the trial. This treatment was similar to one of the home remedies I used for a time. I ended up emailing the recipe to a sick friend who had really been hoping for something new. I took my website off the web because I was getting so much shit off of people about "endangering" people's lives with my "quack" remedies. The reality is that my condition is very deadly and doctors do not even try to cure you.

I have gotten so much flack from people over the choices I made and for trying to help people and I am really burned out and reluctant to stick my neck out these days. But it took a lot of years to get there because I felt NOT trying to share what I knew was tantamount to standing idly by and letting people die slow, gruesome deaths unnecessarily. I mean, there is a reason my condition is called a dread disease: because what it does to you is horrifying.

So, while I wish there were other things being researched -- like what nutrition can do, which has had a really dramatic impact on my life -- I also think our current approach to drug approval for really horrible conditions is extraordinarily callous and I do not know how people can sleep nights when they are de facto denying hope to a lot of people who are suffering so terribly. I mean, if you did this to me to extract political information, it would violate the Geneva Convention. But if you do this to me by cavalierly turning your back on me, well, sucks to be me. I should have had the good sense to be born with better genes. Not your problem.

I am somewhat surprised it doesn't result in violent assault at times on someone representing the establishment/system/whatever. Because it really is a hugely hard thing to ask a really sick person to politely accept -- that we should quietly die a gruesome death and not make a stink while you make sure it will not have side effects. For some of us, we would be happy to live long enough to have to suffer the side effects and worry about solving them.

I liked how well rounded and even handed the piece was. But, seriously, for some people, this process amounts to politely torturing us until we die of it while denying us relief. And I wish people making the rules had a better grasp of that. I wish they really understood that. Really and truly.
posted by Michele in California at 5:26 PM on July 15, 2015 [2 favorites]

I think it's less about callousness and covering one's ass (individual or institutional) and more about the fact that training for ethical treatment of human subjects is literally all about Nuremberg and that the Hippocratic oath starts with "primum, non nocere".
(Disclosures: I have cancer, an illness on the critical care insurance Dread Disease List. I am also a medical researcher. I work in Australia so none of my current work is directly regulated by the USFDA but I have collaborators whose work is.)
posted by gingerest at 6:56 PM on July 15, 2015 [1 favorite]

Gingerest, no, it's all about Thalidomide.

Thalidomide was a tranquilizer which was approved for use in Europe, but not in the US because the FDA was dragging its heels. Doctors in Europe started prescribing it to pregnant women, and soon there were a lot of horribly deformed babies.

And the FDA learned a lesson from that -- delay is good. Haste is bad. We will make sure we never have a Thalidomide in the US.

And they have made sure, but the consequence of that policy is to abandon people like me, and the kids who are the subject of this post.
posted by Chocolate Pickle at 8:54 PM on July 15, 2015 [1 favorite]

The push for open access to experimental drugs is being led (and funded) by one right-wing think tank, the Goldwater Foundation, which opposes all FDA regulation.

Make no mistake -- this is a deliberate effort to end the use of science in approving or rejecting drugs.

Does that seem extreme? Look at it this way. The argument is, "people are dying, we must give them a chance to try drugs." But nearly all significant drugs are for potential fatal diseases. (What are the exceptions? Acne, viagra, headaches?) An exception for terminal diseases is a near-universal exception.

Good science requires clinical trials, first to make sure there are no major (disproportionate) side effects, and then for efficacy. It is human nature that anyone facing death will try an experimental drug, no matter how vague the hope or severe the side effects. Clinical trials will be impossible -- why would you take the chance of being in the placebo group, when you can just ask for the real thing? And that is precisely the goal. To eliminate the role of science and regulation.

Companies will then be able to release any drug instantly ("for compassionate reasons") and profit immediately, without the annoying delays to avoid side effects or worthless expense. They won't be liable for deadly side effects because people signed waivers.

"The right to try" is a very alluring slogan, but it's more like "The right to try dangerous and ineffective drugs."
posted by msalt at 12:10 AM on July 16, 2015 [5 favorites]

Chocolate Pickle: Thalidomide was a tranquilizer which was approved for use in Europe, but not in the US because the FDA was dragging its heels. Doctors in Europe started prescribing it to pregnant women, and soon there were a lot of horribly deformed babies.

Just to clarify for anyone who would like more info....

Thalidomide was originally developed as a medicine for respiratory infections. However, researchers also found it to be an anti-emetic (anti-nausea/vomiting) drug. Three years after it was released to market, the German company that developed it started advertising it as an OTC anti-morning sickness medication for pregnant women.

Within a very short time span, between 5000 and 7000 babies were born with teratogenic deformities in Germany. Only 40% survived. Those that did often had severe internal and/or external deformities. "Flipper-like" arms. Missing limbs. Heart / Cardiac deformities. Blindness. Deafness. Intestinal problems. The drug also caused countless miscarriages.

But by then thalidomide had been exported to other countries, marketed as a sedative and anti-morning sickness medication. Somewhere around 10,000 babies were born malformed worldwide. And of those, only 50% survived. But estimates of how many babies died worldwide (including in Germany,) range from ~15,000 to ~80,000.

Canada literally just came to a financial settlement with 92 thalidomide survivors two months ago.

"In Canada, free samples were distributed to doctors between 1959 and 1961 and given to expectant moms even before the drug was approved by federal regulators in April, 1961. By then, strong evidence was already emerging that thalidomide was causing miscarriages and birth defects. Yet the drug, sold under the brand names Kevadon and Talimol, remained in Canadian pharmacies until May, 1962, fully three months after it was banned in England and Germany.

Thalidomide’s Canadian distributor, William S. Merrell Co., made payments to parents who made a fuss, about $10,000 each, to buy their silence. Thanks to national health care, the drug was distributed free to patients."

In hindsight, the FDA was right to drag its heels.

Chocolate Pickle: And the FDA learned a lesson from that -- delay is good. Haste is bad. We will make sure we never have a Thalidomide in the US.

Yes. Also, the FDA wasn't the only regulatory agency (of pharmaceuticals) to learn that lesson. Many did, worldwide. Worth noting that it was public backlash which forced thalidomide off the market in Germany and other countries. Regulators had to be pressured into action. And public backlash and horror over Thalidomide babies and deaths then pushed those same regulatory agencies into more closely scrutinizing and standardizing stage 3 drug testing.
posted by zarq at 6:36 AM on July 16, 2015 [3 favorites]

‘I have some friends who are worse than I am. Are you going to get them on the drug too?’

I swear, sometimes I think we'd all be better off if kids ran the world.
posted by prepmonkey at 7:47 AM on July 16, 2015 [2 favorites]

To try to be more clear about the point I was trying to make: Lung bleeds are really common with my condition. There is a topical inhaled treatment that was being tested for its ability to help prevent lung infections, and some kids got lung bleeds. Rather than saying "okay, if it causes bleeding, discontinue use" or even "this drug is approvef for adults only for the time being", they just denied it entirely.

The current life expectancy for my condition is 37 in the U.S. It accounts for something like half of all pediatric lung transplants and I think a third of adult lung transplants. In order to get listed for transplant, you have to first lose the majority of normal lung function. The mechanism for this loss is repeated infections that eat your lungs away, leaving them with big holes.

So they are de facto denying all people with this condition a means to reduce infection because some of them might get a lung bleed from the treatment. It is cheap, effective and not really a drug. It is a simple sugar. I used to make a chemically similar solution with xylitol and sterile water and nebulized it to help me stay out of the ER and off antibiotics. It was dirt cheap, very effective, and lacked the horrendous side effects of most of the drugs I was on.

This makes a lot more sense to me as a treatment than the strong drugs with horrible side effects that are currently the standard treatment. One of the antibiotics we get prescribed is known to cause tendons to rupture. Another common issue is c. dif. infections, the result of using high levels of antibiotics. Getting c. dif. can result in having your colon surgically removed.

So maiming us with antibiotics is a-okay. But the possibility that some folks will get lung bleeds and maybe should not use this new therapy is a deal killer and no one gets to use it.

I just cannot wrap my brain around that logic. It seems insane to me. I just cannot understand how you make that conclusion if you know anything of substance about CF.
posted by Michele in California at 10:28 AM on July 16, 2015

the drugs in question aren't known to be ineffective and dangerous, they're drugs of unknown or uncertain efficacy and safety.

Sometimes. People use all kinds of ineffective, dangerous remedies. I got an ad for colloidal silver just today. That's why quackery is illegal. Worse yet, people who make money off quack remedies have a direct financial incentive to scare people, confuse the issue and attack and mislead about medically proven medicines. (Joseph Mercola for example).

But either way, the drugs will remain unknown and uncertain unless there are double-blind, controlled studies. And letting all terminal patients take whatever drug they want, will instantly end double-blind controlled studies. That is in fact the goal of the Goldwater Institute.
posted by msalt at 4:27 PM on July 16, 2015 [1 favorite]