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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.
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.
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.