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FDA Worried Drug Was Risky; Now Reports of Deaths Spark Concern (cnn.com)
Blake Ellis and Melanie Hicken, writing for CNN: Two years ago, Brendan Tyne pleaded with the Food and Drug Administration to approve a drug that he was hopeful could finally bring his mother some peace. She could no longer move without assistance and had fallen victim to the debilitating and frightening psychosis that haunts many people with Parkinson's disease. "She thinks there are people in the house and animals are trying to get her," he told an FDA advisory committee. He believed that a new medication called Nuplazid, made by San Diego-based Acadia Pharmaceuticals, was the answer.
Nuplazid's review was being expedited because it had been designated a "breakthrough therapy" -- meaning that it demonstrated "substantial improvement" in patients with serious or life-threatening diseases compared to treatments already on the market. Congress created this designation in 2012 in an effort to speed up the FDA's approval process, which has long been criticized for being too slow. Around 200 drugs have been granted this designation since its creation. [...] The committee voted 12-2 and recommended that the FDA approve Nuplazid for the treatment of Parkinson's disease psychosis based on a six-week study of about 200 patients. It hit the market in June 2016. As caregivers and family members rushed to get their loved ones on it, sales climbed to roughly $125 million in 2017
[...] In November, an analysis released by a nonprofit health care organization, the Institute for Safe Medication Practices, warned that 244 deaths had been reported to the FDA between the drug's launch and March 2017. [...] Since the institute released its analysis, FDA data shows that the number of reported deaths has risen to more than 700. As of last June, Nuplazid was the only medication listed as "suspect" in at least 500 of the death reports.
Nuplazid's review was being expedited because it had been designated a "breakthrough therapy" -- meaning that it demonstrated "substantial improvement" in patients with serious or life-threatening diseases compared to treatments already on the market. Congress created this designation in 2012 in an effort to speed up the FDA's approval process, which has long been criticized for being too slow. Around 200 drugs have been granted this designation since its creation. [...] The committee voted 12-2 and recommended that the FDA approve Nuplazid for the treatment of Parkinson's disease psychosis based on a six-week study of about 200 patients. It hit the market in June 2016. As caregivers and family members rushed to get their loved ones on it, sales climbed to roughly $125 million in 2017
[...] In November, an analysis released by a nonprofit health care organization, the Institute for Safe Medication Practices, warned that 244 deaths had been reported to the FDA between the drug's launch and March 2017. [...] Since the institute released its analysis, FDA data shows that the number of reported deaths has risen to more than 700. As of last June, Nuplazid was the only medication listed as "suspect" in at least 500 of the death reports.
Some you win some you lose, that's what a risk is.
It's a catch 22. The FDA usual process is slow and plodding but results in medications and medical procedures which are generally safe and effective by reducing as much risk as possible. However it takes a LONG time to perform all the necessary studies and clinical trials and critically ill patients die while they wait.
The catch is that if you are trying to get approval for a novel medication that saves lives of the critically ill, how do you justify the delay needed to do all the safety and effectiveness studies? People will die if you don't try, but you might also kill and/or cure. What to do?
"File to fit, pound to insert, paint to match" - Aircraft Maintenance 101
Like surgery and other non-drug therapies, sometimes the risk of death - even if very high - is a good gamble vs. the near-certainty of a poor quality of life.
The key is knowing the risks and taking marketing out of the equation so patients, doctors, and caretakers/family members can make a truly informed, sober choice.
Those people were critically ill anyway. Are we sure the deaths are caused by the medicine directly and not by the critical situation those people were already in?
Paranoid delusions which keep an elderly person miserable, disabled, and disconnected disabled from everyone (even families)?
Or a small chance a Parkinsons sufferer might die or have a radical improvement?
You can't have it both, sign a waiver before treatment and move on. Save and enjoy the few who are able to make it. Mourn and cherish the memories of those who didn't.
Adults understand that life is about risk management. Even if all 700 deaths are attributable to the drug (highly unlikely) many people will take that risk to avoid living with Parkinson's/psychosis.
One can be too cautious or not cautious enough. The FDA is far too cautious, to the extent that current estimates are that the FDA regulations have resulted in as many avoidable deaths as two Nazi Holocausts: http://www.ruwart.com/FDA/prot...
Not every disease can be neatly solved and not every precaution is warranted. For America, deadly government-imposed regulations are a worse evil than patient choice (hopefully made with their physician) both by the philosophy and by the statistics. It shouldn't be surprising in the light of the Socialist Calculation Problem (from an information theory perspective) that freedom works better than being "managed" like livestock.
My God, it's Full of Source!
OUTSIDE_IP=$(dig +short my.ip @outsideip.net)
It's a catch 22. The FDA usual process is slow and plodding but results in medications and medical procedures which are generally safe and effective by reducing as much risk as possible. However it takes a LONG time to perform all the necessary studies and clinical trials and critically ill patients die while they wait.
The catch is that if you are trying to get approval for a novel medication that saves lives of the critically ill, how do you justify the delay needed to do all the safety and effectiveness studies? People will die if you don't try, but you might also kill and/or cure. What to do?
What you should do is put all the responsibility for making a mistake on the bureaucrats responsible for safety protocols, and all the costs associated with those safety protocols should be borne by the drug manufacturers.
In a game-theory sense, that gives you the safest drugs possible within the system.
Then you mandate that no one can go outside this system - no one can decide for themselves whether to take a risk on a non-tested procedure or drug, even if their disease is known to be terminal or completely debilitating.
It's unfortunate that people feel the need to go outside this system. If you follow the hacker community, there are a bunch of projects that could very easily be described as medical devices and experimental procedures. Things like home-built hearing aids, self (by the patient) adjusting glasses, and so on.
Some of these are downright scary.
I suppose it's like any industry. Big, entrenched companies become paralyzed with bureaucracy, and are eventually replaced by small, nimble startups.
I'm sure many Parkinson's patients would prefer a small chance of death for a severe reduction in symptoms. It's a very painful and debilitating disease. I'm not saying that deaths are a good thing, or that it shouldn't be investigated carefully... but sometimes quality of life is more important than not dying.
"I will trust Google to 'do no evil' until the founders no longer run it." Hello Alphabet.
The truth is every one of them could be having quality of life improvements from Marijuana usage (consumed, inhaled, whichever).
There are still people in society however that feel like certain things that they do not agree with (nor ever think about, nor usually are ever exposed to even) should simply be banned.
Because of those people who think that way, a safe drug is made illegal, tons of taxpayer dollars are wasted in a variety of ways (enforcement, prisons, court system load), and more to the point, the same FDA expedites the development of a drug that DOES kill people instead!
Those people killed these people, the FDA killed these people.
Thanks a lot FDA (not!), can I choose to stop sending you tax dollars yet?
Having read the article, the summary misses a crucial point: this drug is being given to people who are very, very sick. The drug manufacturer is in close contact with the families of the people taking this drug. Given that the people taking the drug literally have zero other options, it's honestly not surprising that there is a huge number of people dying whilst on this drug.
The key question is: would they have died anyway?
Yes, the FDA was concerned about rushing this drug to market. Yes, a significant number of the population dies when taking the drug. But there is also zero evidence that the drug caused the deaths.
It's incredibly sad when a loved one dies. Seeing my dad slip away (eg. getting lost in a supermarket he had gone to for 40+ years, talk about me as if I was someone who he had just met) was heartbreaking. I can get a sense of the pain of families who though they were doing the best by getting their loved on on this drug. But life is finite and new treatments carry risk. We learn as much as we can from this and move forwards.
And cry. But that's normal, too.
The original poster provides information from the CNN article that shows deaths. It does not report that (1) the patient population is old, thus prone to death, and (2) that two follow-on studies found no difference in death rate between the drug and placebo. FDA is monitoring the reports of deaths, but unless someone does the science to find out whether the deaths of these old people are unusual you risk denying the patient population that benefits from the drug the relief from their disease.
It is good that the medical community is being made aware of the adverse event reports. Doctors and patients (or their guardians) should know this information in making a personal decision.This is not a drug category with good options as shown by the breakthrough drug designation.
Just let people use pot!
I know, right! The last 25 years have been brutal!
It's a catch 22. The FDA usual process is slow and plodding but results in medications and medical procedures which are generally safe and effective by reducing as much risk as possible. However it takes a LONG time to perform all the necessary studies and clinical trials and critically ill patients die while they wait. The catch is that if you are trying to get approval for a novel medication that saves lives of the critically ill, how do you justify the delay needed to do all the safety and effectiveness studies? People will die if you don't try, but you might also kill and/or cure. What to do?
What you should do is put all the responsibility for making a mistake on the bureaucrats responsible for safety protocols, and all the costs associated with those safety protocols should be borne by the drug manufacturers.
You do realize that higher the penalty you put on making a mistake, the result is that the people responsible for safety protocols will become more risk adverse, and no drug will ever get approved, right?
That's the only way to get 100% certainty of never making a mistake in approving a drug: making sure you never approve a drug.
The FDA receives notifications of patient deaths all the time. The patient was taking a drug for hair loss when he walked in front of a bus and got killed? It may be reported.
I know people who work for the FDA and deal with reports like these. It is a complex and never certain statistical task trying to interpret all this data.
DAFUQ?!?!?!
You just spent an entire post advocating a literally stifling bureaucracy in charge of a huge portion of health care, and now you say that won't work?
Whoosh...
The catch is that if you are trying to get approval for a novel medication that saves lives of the critically ill, how do you justify the delay needed to do all the safety and effectiveness studies?
We need to understand the effects of a range of dosages and what sort of patients are helped and which are not. Yes some patients will be harmed while we take the time to study safety and effectiveness but MORE patients will be harmed if we don't take the time to study safety and effectiveness. Merely knowing that a drug can help some patients isn't sufficient. We need to know what the range of safe and effective dosages are, what patient populations are helped, what the range of expected outcomes are, and why the treatment is effective. The goal of clinical trials isn't to save any specific patient though we'll do that if we can. The goal is to save the most possible patients.
It's a cold hard truth about medicine that we learn how to save some people's lives by sacrificing others. There is no way around this. Some people are being sacrificed for the greater good. You might be one of them someday.
Just because a drug is dangerous (if it's even the drug causing these deaths) doesn't mean that it's necessarily without use. Given the option what would you choose, 5-10 years of crazy interspersed with moments of clarity or 3-8 years of clarity with a 1 in 100 chance of immediate death? Of course the real question is what are the statistics with this drug, and would the average informed and competent person accept those risks/rewards? And it goes without saying (or at least should) that those who stand to make a fortune on this or any drug should not be the ones putting together those statistics which people rely on to make their informed decision.
What you should do is put all the responsibility for making a mistake on the bureaucrats responsible for safety protocols, and all the costs associated with those safety protocols should be borne by the drug manufacturers.
If you make individuals responsible for mistakes then nobody would be willing to do that job. That's why corporations exist and why governments are usually shielded from liability except in extreme circumstances. Would you take full liability for the actions of your employer even for actions you do not control? Everybody makes mistakes sometimes. Don't make perfect the enemy of good. The system cannot work if individuals have unlimited personal liability.
As for the costs, most of the costs of the studies are borne by the drug manufacturers but we don't actually want them to bear all the costs. You don't want the drug manufacturers paying for the salaries of the regulators because then the regulators become beholden to the drug companies. We have enough problems with regulatory capture as it is.
As a former Serious Adverse Event Co-ordinator for an ethical review board for medical studies (IRB) let me explain what is going on here.
Firstly, the study population will have advanced Parkinson's with psychosis. This is a cohort that is very ill and has a high probability of adverse outcomes.
Secondly, the risk a drug can present is set against the benefit it might provide. So for example if a pain killer offers very mild pain relief, but you're just as likely to have blood clots if you take it, the risks outweigh the benefits. Similarly, if you have a medication that is a breakthrough medication with a high degree of success at attenuating psychosis in people with Parkinsons, a higher level of risk would be considered acceptable.
The clearest example of this is the various chemotherapy drugs. They're absolutely toxic - poisons. They're just not as bad as dying.
So here's where it gets complicated. And it's why I am no longer working in the medical ethics field.
As a Serious Adverse Event co-ordinator, if something bad (the "adverse event") happens to a patient taking a study medication or using a study device, the Principal Investigator has to submit an SAE form to their IRB (Independent Review Board.) So I come in at 9am and find a pile of letters reporting various negative outcomes. I then have to sort them into two piles based on some criteria.
The first pile is ignored. Here's what goes in that pile: Any outcome that was described as a possibility in the Informed Consent document. If the Informed Consent the patient or their representative signed when they joined the study said, "risks include bone necrosis, blindness and death" then if any of those things happen, they don't get reported to the FDA. Instead, I send the PI a form letter saying the Adverse Event was not notifiable.
The next level of filtering is that I then examine the adverse event itself, to make a judgment call of whether the event was "Unlikely" "Possibly" or "Definitely" related to the study medication or device. If it was unlikely or possibly related, the form letter is sent to the PI and the FDA isn't notified.
Only if the outcome ISN'T described in the Informed Consent, AND I determine the event was "definitely" related to the study medication does the FDA ever get to know of the event.
The disheartening thing about this is, and I'll give a real but anonymized example: one study I was SAE for, I would get many, many reports of bone necrosis of the jaw for a cancer medication. People's jaw bones were dying, and they would lose all their teeth in their lower jaw. They often would get infections, and in a few cases they would die. This was all described in the Informed Consent. For this one particular drug, the adverse event happened a lot - at least 30-40% of the cohort was experiencing this. The drug was lifesaving, so a high level of SAEs could be tolerated, BUT there was an existing medication on the market that had this adverse event occur at a much lower level - around 10-15%.
And there was no mechanism for me to give this information to the FDA. There was no way for them to know what the real stats were. Their information collection system was designed to ignore vast swathes of negative outcomes.
The pharma companies know how the system works, so they obviously will try to list any inhibiting adverse events in the documentation. If you read the documentation for approved and released drugs, the same things happen. Everyday drugs have listed side effects that include death all the time. Now you know why.
So, obviously, I don't work in that field any more. It was soul destroying.
The death of the subjects in this case is sort of irrelevant.
The claim the son had made was that this would improve her quality of life since she could no longer move. If this allows people with parkinsons who would otherwise be immobile or have hallucinations/psychosis symptoms relating to their disease reduced, at the expense of a shortened life, then I imagine many people would choose that.
So the real question comes down to: Does this drug provide any of the 'relief of symptoms' that it was claimed to provide, if it did, how long did the subject last while taking the medication, and finally, what was the prognosed expectation of death over the same period with and without the drug?
Parkinsons is a terrible disease that can manifest differently between individuals. Much like the catch all 'dementia' and Alzheimers, once you are confirmed as having it, death is simply a matter of when, not if, and often devolves into one becoming trapped in one's own mind, whether due to lack of control of one's body, psychological barriers either keeping you from moving, or driving you further into your own subconscious, many people becoming trapped there for however long they last. Sometimes external stimulus will get to them, othertimes they will just have good and bad days. In some cases there will just be a steady decline unto death.
Having dealt with this both among family members and friends of the family, I can say that if there was a drug that provided a tangible benefit, even if it shortened their life, it would have been worth it. At the time however nothing was available that provided more than a temporary lull in symptoms, and only if the disease was caught early (which it almost never was.)
Every drug has risks. What the FDA should be doing is evaluating risks vs. benefits for different patient populations, and creating indications for use for such populations. Then, letting the informed patients and their physicians make the call whether to use the drug or not.
Many people with utterly debilitating diseases deserve access to drugs that may be more beneficial to them than the risk posed, and that choice should be up to THEM and their treating physicians. Restricting access to drugs based on "oh but its RISKY!" makes as much sense as banning automobiles because they're risky. FDA is slowly getting better about this, but they're still largely stuck in the backwards mindset of restricting too many drugs based on risk, and condemning too many patients to death and disease. They work too much on the population level and use that data to restrict too many drugs for use on the individual level without considering what is good for individual patients.
Sometimes the FDA gets it wrong, and post-marketing data shows a drug is not actually very beneficial but is very risky (as is probably the case here). However, "fixing" situations like this often entails denying patients with no other options any treatment at all, which is even less ethical than making the decision to deny a treatment at all.
Drug policy is ugly sometimes, but patients deserve a say, ESPECIALLY those with so few or no options. Sick people are sick RIGHT NOW, and the FDA isn't the arbiter of all that is good and right in the drug world.
$0.02
'In Trump's America, you don't get healthcare, healthcare gets you!'
This evil and corrupt agency, the puppet of Big Pharma, makes it illegal for terminally ill people to try potentially life-saving treatments (for their own "safety," of course). It also tells us that lots of over the counter drugs are good but too many eggs will kill you.
The FDA is evil and stupid, and it should be abolished.
Your understanding of "rational behavior" is erroneous. First, emotion is a key component of rational decision making; without emotional involvement, your ability to make rational decisions is severely impaired. Second, government lacks the information to make good decisions for individuals; a 50-50 chance of death from a Parkinson's drug may well be the right choice for an individual even if it isn't the right choice for most sufferers. Third, government isn't composed of rational decision makers, government is composed of people who act in their own self-interest, and you can be certain that their self-interest is not your best interest.
Making tough life and death decisions is part of life, and adults are well prepared to handle it. You want to be like a little kid, with daddy government making all the hard decisions for you "rationally", and what you are actually advocating is a failing totalitarian state.
One can be too cautious or not cautious enough. The FDA is far too cautious, to the extent that current estimates are that the FDA regulations have resulted in as many avoidable deaths as two Nazi Holocausts:
What a bunch of bullshit. The FDA has saved orders of magnitude more people than have died and I think your equating their actions to the holocaust is entirely inappropriate and false. Here is the cold hard fact. Clinical trials only work because some people are sacrificed to save more people in the long run. Yes people will die who theoretically might have been saved but doing so actually costs MORE lives in the long run. There is absolutely no way around this. This process usually takes lots of time and money to do correctly and it is inevitable that some people will suffer and die during the process. While tragic it would be a far greater tragedy to short cut the process to save a few at the expense of many.
Not every disease can be neatly solved and not every precaution is warranted.
Quackery is a real thing. Drug companies can/will/have sold snake oil in a heartbeat if it means more profit. While there are ways to improve speed to market for drugs we cut corners at our peril.
The key question is: would they have died anyway?
The only way to know that is with a properly conducted clinical study. Preferably of the double blind variety if possible. Which makes the whole argument about rushing the drug to market before we know if/when/why/how it works idiotic. We do studies the way we do them for very good reasons which we learned the hard way. It's a tragedy that anyone has to suffer or die but those deaths become wasteful if we do not learn anything from them. The greater tragedy is to have more people die because we lacked the patience and fortitude to see the studies through and look for the evidence.
My mother just died from ALS. Horrible way to die. There are some experimental treatments but she understood that the odds were against her so she enrolled in some studies to help other people. She didn't want to die or suffer but the only way we will ever cure a horrible disease like ALS is if some people willingly sacrifice themselves for the greater good.
The certification for a drug is paid for by the company that wants to manufacture the drug. This creates a huge conflict of interest in those doing the testing of the drug. To mitigate this we add more and more layers of regulation. The regulators though have a conflict of interest. They will rarely be punished for not approving something or for being overly cautious. So the regulation becomes so bloated and slow that actually filling the paperwork for certification becomes a significant cost.
A better approach would be to have the original research publicly funded (which it usually is), then have the national/state/provincial health care providers (or in the US the hospitals and health insurance companies) pay for the certification. We would have to get rid of drug patents and have some sort of international policy to encourage each country to pay a certain percent of their health care budget towards identifying and certifying new drugs. With the right incentives I'm sure we could come up with a system far better than what we have today.
500-700 people sounds terrible on the surface. How many people are taking this drug? 700 out of million no so bad, 700 out of 800 very bad. The article does not give the population of people taking this drug. Not to defend this drug company, I must pointing out you need more data to proclaim this stuff bad. Critical thinking peoples.
At that level of trial, the "IC" criteria aren't ignored, they're already studied. The last trials are all about finding new risks, not the old risks that have already been measured and accepted.
"substantial improvement" in patients with serious or life-threatening diseases compared to treatments already on the market.
Reports of deaths by those on the drug does not necessarily imply a causal relationship.
Their condition is life-threatening, therefore, you administer the drug. If the drug doesn't work then possibly they die. If the drug kills them, then they die.
So how to make sure they responsibly analyze the report and find the reason for complications was caused by the drug, and/or the drug is unreasonably risky or unsafe compared to attempting to live with the condition it treats without the drug?
These people used these drugs being aware of the dangers and lack of review, because they were their last hope. They were used on people as a last ditch effort for people who are already very ill. Overall, allowing people to try more dangerous but promising drugs will save lives by helping getting drugs that do work available faster. Since these people were already in a very critical state its absurd to blame a drug that was their last hope, because they had lost their quality of life already. To move things forward we have to accept some danger and these people accept this danger, knowing the risk, but already are suffering greatly already. Basically, its their own personal choice to take these risks, they should have a right to do so, even if there is danger, so at least they have a fighting chance rather than have to accept their fate.
It was already known from the six-week test involving 200 people that more people on the drug died than people on placebo.
The choices facing the families of people with this fatal disease were (1) let them possibly live a bit longer but while suffering psychosis or (2) risk an earlier death but without suffering psychosis.
Shouldn't the families be allowed to make such a choice rather than have the choice forced upon them by a government bureaucrat?
You're deliberately deceiving us. You're trying to make us believe that the pharmaceutical companies are hiding data, but that's just not true. Your job was oversight for the IRB. The IRB's job is to make sure that the patients had informed consent. They aren't there for total safety; your FDA oversight was doing that. They weren't collecting data and building the report on the trial, the PI was doing that. You lie like a cheap cotton rug.
> if something bad (the "adverse event") happens to a patient taking a study medication or using a study device, the Principal Investigator has to submit an SAE form to their IRB
So the PI is collecting data on the SAE's .... you're trying to convince us that they're not.
> Only if the outcome ISN'T described in the Informed Consent, AND I determine the event was "definitely" related to the study medication does the FDA ever get to know of the event.
You're asserting, without any evidence at all, and in contradiction to federal regulations and our test approval from the FDA, that the ONLY way for the FDA to get data about adverse outcomes is from the IRB. That is a blatant lie. The PI has ethical, contractual and legal obligations to report the adverse outcomes from the trail. The IRB's job is to make sure the PATIENTS were properly informed. The IRB's role here is when the PATIENTS didn't know something. That's when the IRB and the FAA decide whether or not to intervene. Nothing about that process prevents the PI from halting the trial independently, it's just another level of oversight.
Oh, and your basic argument is based on the assumption that KNOWN adverse reactions are new and dangerous and inherently bad. The trial wouldn't have been approved if the previous stages had demonstrated that the KNOWN adverse reactions were unacceptable.
Are you a shill, troll, or idiot?
The patients aren't the prescribers. Or are you saying that Doctors merely surrender to the expectations of their patients. Admitted the crazy American system of allowing Big Pharma to advertise their drugs directly to the public can make a physicians job harder in refusing what isn't good for them, but in the end the professional responsibility remains.
Problem was Parkinson disease. Death removed Parkinson, the cure is efficient
Seriously speaking, if I was trapped in Parkinson, a risky cure with possible death outcome would seem better to me than status quo.
This is where vivisection and the power of Big Pharma gets you. The whole thing is a massive fraud, only a tiny number of drugs actually work and DON'T have dangerous side effects. Drugs are being taken off the market every day, after passing animal experiments, then passing human experiments (AKA 'clinical trials), then getting to market, and then the side effects are found to be so bad, and also possibly the drug is so ineffective that it is taken off the market.
The FDA has been on a tear to get rid of medications used for pain control, even without narcotics. The interesting thing is that most of these meds have been on the market for over 40 years and never caused a problem. Now the FDA feels that if someone can use the drug and overdose, it is a lethal drug that must be taken off the market. Of course, the FDA reasoning for pulling the meds is that it causes heart failure. This crap has to stop if they want to stop the suffering in agony that many elderly patients and accident victims have to go through. And they want us to carry around Narcan for OD patient?
Life is in a state of dynamic equilibrium, it both blows and sucks
The saying :
I've heard references to it pushing 200 years old, and it probably wasn't new then.
Birds are not dinosaur descendants;birds are dinosaurs, for all useful meanings of "birds", "are" and "dinosaurs"