Top FDA official overrules staff to approve gene therapy that failed trial
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Is he a political appointee? If not, I don’t see why he’s doing this unless he stands to benefit financially in some way.
If he is a political appointee, well I guess he’s just continuing the trend of undermining experts because vibes/zeitgeist/whatever
If he is a political appointee, well I guess he’s just continuing the trend of undermining experts because vibes/zeitgeist/whatever
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Mixed feelings on FDA approvals for these rare conditions. I know someone who was in a drug trial, that totally helped them. The trial failed though, because it is almost impossible to get diagnosed for that condition early enough for that experimental treatment to be effective. Since it failed, if they ever need the treatment again, there is only one country in the world you can get it, Italy.
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Bribery of some kind or another does seem like obvious reason for approval against the counsel of all the experts.
Suitcase full of cash, luxury vacations to party with judge Thomas, honey trap with or without blackmail, future job offer for him or his kin, ....?
Suitcase full of cash, luxury vacations to party with judge Thomas, honey trap with or without blackmail, future job offer for him or his kin, ....?
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Ladies and gentlemen, the system works. To make these fuckers a lot of money, I mean, obviously it doesn't work to keep us healthy.
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Captain Dunsel
Smack-Fu Master, in training
Finally, someone who fully understands and supports the strength of anecdotal evidence!
Why do science when we have ad hoc observations?
Science only serves to give snake oil a bad name.
/s
Why do science when we have ad hoc observations?
Science only serves to give snake oil a bad name.
/s
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What are these "secondary" and "exploratory" end points? As pseudo mentioned - drugs for these rare diseases are hard to come by and given the rarity of the conditions are pretty hard to get real sample sizes for. If one of my loved ones had this condition - and there was even a 10% chance of a drug making a difference I'd want the option.
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You mean, like not actually treating the underlying disease? Being useless in a phase III trial seems to suggest that negative side effect or contraindications are the least of this drugs problems.
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There may be a subpopulation that does respond to the drug. That isn't an uncommon result in clinical trials, people metabolize drugs differently after all. But that would suggest the next step was a more refined trial, not a blanket approval.
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Since the trial showed nothing, you approve nothing until there is unambiguous evidence of effectiveness and perhaps delve into the flaws of the trial, and you get into the nuances and details from there.
Or, if you're the FDA, you hand-wave everything and engage in some theatrics to make it look like you know what you're doing and care about integrity and have done due diligence. And years later when people complain, you minimize or deny, demonize them, and defend the hole in which the industry and you have dug for everyone. Same as any other industry or institution. 'Murica.
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Maybe revolving door between FDA and therapeutic companies? The last thing you want to do is piss off the customer; either the ones who sell the therapies or the ones who need the therapies. Makes for poor career prospects.
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The primary endpoint is usually something like “cure” or “survival”. For complex diseases you might not necessarily achieve that during the trial but you might see signs of improvement—maybe an increase in quality of life, or some medical test indicates that something is changing or improving. These are the secondary and exploratory endpoints. A therapy might be approved based on those because it’s presumably doing something, so the drug might eventually work or perhaps it buys patients time until a better therapy comes out.
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Anytime you're tweaking the DNA of a body's cells there's a risk of causing cancer. This happened with some earlier gene therapy approaches.
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Demolition of the FDA's authority on these decisions will lead to insurance companies asserting that FDA approval doesn't mean a therapy or drug works. They will feel free to deny coverage for them.
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As someone directly affected by a disease that’s on the spectrum of Becker/Duchenne muscular dystrophy… the drug itself is a miniaturized version of the dystrophin gene which is huge so the full gene cannot fit into a typical virus vector. (As for my mobility, I am no longer ambulatory since I was 16 and I’ve noticed the progression of my disease very prevalently)
The improvements in function are mixed and deemed not statistically significant, I am not disputing that. However, the actual study does show that the gene in question does have increased expression. At this point, we are looking for any sliver of hope at all for stabilizing our condition… so to be honest, even the improved gene expression is a layer of hope. And it’s entirely possible it takes time to develop enough dystrophin that can significantly alter the course of the disease and the trial won’t capture it.
And not to mention, as the disease is a spectrum between Becker and Duchenne, based in the different mutations to the dystrophin gene, it is entirely possible the therapy can help at least pause the progression of the disease.
The science done may only capture a limited set of data on a complex condition.
The improvements in function are mixed and deemed not statistically significant, I am not disputing that. However, the actual study does show that the gene in question does have increased expression. At this point, we are looking for any sliver of hope at all for stabilizing our condition… so to be honest, even the improved gene expression is a layer of hope. And it’s entirely possible it takes time to develop enough dystrophin that can significantly alter the course of the disease and the trial won’t capture it.
And not to mention, as the disease is a spectrum between Becker and Duchenne, based in the different mutations to the dystrophin gene, it is entirely possible the therapy can help at least pause the progression of the disease.
The science done may only capture a limited set of data on a complex condition.
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If a trial is appropriately designed and the selection process keeps the two groups as consistent as possible with regard to enrollment criteria, the chances of this are very low. A placebo arm in a properly controlled trial won't ever show dramatic improvement, as your doing nothing to treat the problem.
Pain trials often see the most significant placebo effect (30-40% effectiveness in some trials). This is likely due to the fact that pain is highly individual, subjective, and extremely difficult to objectively assess. The "placebo effect" can be powerful in pain trials as if you believe your are being treated for pain, the psychological belief is a positive factor, and improved mood and well-being has a very strong effect on our perception of pain.
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I fail to understand why an agency like the FDA, with all it's experts and clinical review teams, has policies that allow an individual to say "thanks for your input, but I think you're all wrong, I'll just do my own thing". The whole point of the broad review with many experts is to ensure assessments are scientifically sound and minimize the chance of individual bias tainting the decision.
They may need to rewrite some of their own rules to be an effective agency.
They may need to rewrite some of their own rules to be an effective agency.
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We shouldn't be approving medicines or therapies that don't pass trials. Period.
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Is it literally just one guy who decides whether drugs are approved or denied at the FDA? That can't possibly be right, can it?
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Its relative. They are looking for improvements above and beyond the placebo group. If both groups got better perhaps environmental exposures changed. Maybe you conducted the study in a time of year the disease in question trends down. So 100 units of improvement /100 units of improvement is still equal to 1, no association.
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My view is the trial was flawed to begin with by excluding non-ambulatory patients. Just because they are not ambulatory does not mean their condition cannot be improved and stabilized. They needed to look at whether it improves the conditions of folks who are in more dire situations.
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Unfortunately I think many government agencies are set up to give ultimate authority to some elected or appointed official, under the theory that they are accountable to the electorate unlike professional staff (e.g. the so-called "unelected bureaucrats"). Of course, as we've seen numerous times with the FDA now, what really happens is that they prioritize good feels over sound science with predictably bad results.
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Even if this therapy eventually proves useful, he's doing the obviously wrong thing by approving it broadly instead of sending it back for further study. It's just obviously, textbook wrong. Everyone who knows anything in the field are calling him out for being ass-backwards. And yet... it just happens anyway? How the hell does that work?
If he claimed white wine spritzers cured Lupus, and demanded this to be approved as a treatment, would the FDA just go ahead and do that?
If he claimed white wine spritzers cured Lupus, and demanded this to be approved as a treatment, would the FDA just go ahead and do that?
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Found this talk by Marks that I think sheds some light on where he's coming from:
View: https://youtu.be/jt3CNgsCXAk
View: https://youtu.be/jt3CNgsCXAk
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Gobsmacking to me is the mere fact that this individual even has the power to veto expert review boards. It makes a mockery of such boards if the personal opinion of the director is sufficient to override them. In a properly structured agency this should not be admissible imo.
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Ah Derek Lowe. I used to have his blog Things I Won't Work With in my RSS reader. It appears to be defunct, and redirects to the home page. It looks like he discontinued the series a while ago. It's hard to notice when a low volume news feed goes dry. :-(
I'm an Electrical/Computer engineer, so I'm only lightly versed in chemistry. But it was an amusing read in an area I don't get much exposure. That's where I first learned of his beloved FOOF.
I'm an Electrical/Computer engineer, so I'm only lightly versed in chemistry. But it was an amusing read in an area I don't get much exposure. That's where I first learned of his beloved FOOF.
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