Sick kids, desperate parents, and the battle for experimental drugs | Hacker News Reader

Sick kids, desperate parents, and the battle for experimental drugs

bostonglobe.com

46 pointsMz14 comments

"Even some of the drugs showing early promise and that are fast-tracked for approval by the FDA end up failing."

Which is the problem. Most new drugs don't work. Some work in some animals but not in humans. Some have side effects in humans. Some seem to work at first, but the effect doesn't last. Some have long-term side effects. Some are harmful to some part of the population. That's why so much clinical testing is required to find the ones that do work.

The gold standard of clinical testing is "better off 10 years later". Drugs have made it all the way to approval and later been pulled because they failed that test.

I agree completely. The other side of this is: I, or my kid, is doomed anyway, so what have I got to lose? I guess the answer is: individually, maybe not a lot. (One of my favorite Futurama jokes: "Look, do you want false hope or not?")

But collectively, we all lose with shoddy medicine and bad science. Relax standards far enough and you're back to the era of shamans, leeches, or patent tonic charlatans. Which, if you read something like Ben Goldacre's Bad Pharma, it feels like we aren't too far from right now.

That's what scares me about the parents the article describes. They are exactly the sort of people who would gladly help dismantle RCTs and try to return drug and medical treatment development to a pre-scientific process. The usage of RCTs is already fragile and threatened - I remember during the Ebola outbreak, there was a ton of pressure to use limited supplies of Zmapp on patients as fast as possible and the suggestions to make the most of the opportunity by allocating scarce doses via lottery were, as far as I know, ignored. That in a situation where it was vital to know as soon as possible whether we had a useful Ebola treatment or not in case it went pandemic!

If you're evaluating something for use to keep healthy people healthy, then sure, you want to know they'll still be healthy after 10 years and not afflicted by some terrible long-term side effect. The potential downside of taking it may outweigh the downside of not taking it.

On the other hand, if you're evaluating something to keep people from dying, then "not dead" is sufficient in the short-term while continuing to watch for long-term effects. The downside of taking it cannot possibly outweigh the downside of not taking it. (Assuming some reasonable baseline expectation that it treats the condition it intends to treat.)

It is hard to imagine a less ethical or moral action than preventing a terminally ill person from trying drugs that offer some hope.

One of the big impediments against more companies engaging in compassionate use is required adverse event reporting to the FDA. To my knowledge (clinicians / clinical research specialists please correct me here if I'm wrong) companies are required to report any adverse events experienced by patients granted early access to a drug under compassionate use. Any adverse event reported may make it harder for them to bring a drug to market. In addition, it is very difficult for companies to screen these patients or guarantee that they are adhering to regimens as they would in a clinical trial. This biases companies against providing the drugs, even though many would want to. In my opinion, the FDA should drop this requirement and allow for universal access to medications for terminal patients under compassionate use.

As I understand it, when you hear a long list of possible side effects ("nausea, vomiting, upset stomach..."), that's derived from those same trials; if a thousand people try it, and two report those symptoms, they go on the list. (I don't know the actual threshold below which you can discount it as unrelated, but I'd be surprised if it was the same as a threshold for statistical significance, and I'd be somewhat surprised if there's any effort to seek causation.)

Patient information leaflets in the UK classify side-effects by frequency reported in clinical trials and, I think, yellow card reports.

"Very common" affects 1 user in 10

"Common" affects 1 to 10 users in 100

"Uncommon" affects 1 to 10 users in 1,000

"Rare" affects 1 to 10 users in 10,000

"Very rare" affects less than 1 user in 10,000

"Not known" cannot be estimated from available data.

This says nothing about the severity of the side effect.

What's the advantage of stopping reporting of adverse events? Doesn't that just make it easier for dangerous / ineffective (but fantastically expensive) drugs to come to market?

In very sick patients (those generally filing for compassionate use) it's sometimes difficult to pin down whether the drug actually caused a problem or death. Were the patients properly adherent? Did they have comorbidities? Were they simply too sick and died?

A few deaths might cause the FDA to order additional trials which may actually not be necessary, to the tune of millions of dollars. If you were a company that spent years and hundreds of millions trying to bring a product to market, would you want to take that risk?

In addition (adding on to my comment below), companies don't want the FDA to try to use the outcomes of patients taking the drug for compassionate use as a metric of efficacy before a proper phase 2 or 3 clinical trial has been run, for the exact same reasons.

This seems like a simple equation to me. The kid needs to be without further recourse, and the drug company needs to be indemnified. After that, what's wrong with it? A last ditch effort is better than no effort, at least in the hearts of the parents that are about to suffer the worst fate that can befall a human being - losing a child.

(I know it's not "simple.")

You've basically got it, except if you have a ton of super sick people taking the drugs it can mess up the results (when you're that close to death all kids of unrelated stuff starts shutting down).

If you allow the drug companies to omit those people from the results, that can be exploited. Drug companies could give risky drugs to a bunch of really sick people and then use those results to tailor the real trial to try to hide side effects. The point of "report everything" is they can't monkey around with the experiments.

Artificially expensive cures against rare diseases. Company blackmailing the government to pay:

http://www.standaard.be/tag/medicijnen-voor-viktor (Dutch)

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