After the Boles mistrial (Boles will be retried next month), this is the first actual jury verdict in Merck's favor. Here's the AP Newswires reportage:
. . . .Merck today said a unanimous federal court jury in New York found in its favor in the Maley v. Merck case, rejecting the claims of a plaintiff who blamed her dental and jaw-related problems on her Fosamax® use.
"We believe the company acted properly," said Christy Jones of Butler, Snow, O'Mara, Stevens & Cannada PLLC, outside counsel for Merck. “Unfortunately, the plaintiff had multiple medical conditions that cause people to develop the jaw and dental problems she claims she has, regardless of whether they were taking Fosamax. . . ."
Oddly enough (a la a Six Degrees story), Christy Jones was once was my lawyer, in a large corporate defense case. She is a very able lawyer.
The one other Fosamax® bellweather case (Fleming) failed to reach the jury, on peculiarites largely unique to that plaintiff.
5 comments:
It amazes me that this standard defense claim is so effective, i.e. underlying, contributary conditions.
Of course that's exactly who you expect toxicities to show up in.
For example if a person has a history of chronic viral hepatitis it's even more important that they stay away from booze than someone who doesn't.
Instead companies design their studies to exclude exactly the people who are most likely to have problems due to underlying conditions as they don't want it to show up in labeling and effect sales.
Then when exactly those type of people have problems they claim immunity.
To me if you wanted to do things ethically you would include the patients at risk, monitor closely and get an idea of how risky your drug is. Then label it so that even patients with underlying conditions who might really need it can make an informed decision with their physicians, and then monitor for emerging problems.
(As we say in medicine to make a diagnosis you need a high index of suspicion.)
That to me would likely absolve companies. Instead everything possible is done to minimize warnings (as someone from a major company said to me but that will drop sales by 10%) and then do everything possible to delay detection, labeling, and then paying any compensation.
Salmon
Sadly, based on my prior experiences, I have to agree with your candid, and depressing assessment, here Salmon.
Thanks.
Namaste
I understand where Salmon is coming from but, I wonder if his expression of doing things 'ethically' by including those at risk is really accurate.
If you don't know the risks-you cannot properly inform the patient (and this raises another question/issue-what is proper consent). So, to include patients with underlying conditions (outside of disease entity you're studying) isn't really ethical.
This is not just a pharma issue-it is a general underlying problem in any aspect of medicine.
But that's exactly the case with every drug study. We don't know the risks.
Phase I - First in Human. We don't know the risks. Although we might have clues from animal data or other basic pharmacology.
This is also true for every preapproval study at every stage. Instead we slowly increase the number of people exposed as we gain more experience. Sometimes people die in these studies. Plus virtually everyone in phase I studies are healthy volunteers so there's absolutely no expectation of benefit. Yet there is an expectation of some harm. So how is that ethical except that we're looking to prevent a greater harm.
The informed consents are deemed valid because even if we don't know what the risks are we say that the purpose of the study is to determine risks and death is always a possibility.
We study drugs in phase III in a relatively healthy (except for the disease under study) and SMALL population, i.e. ~ 1000 patients, and only 500 for 6 months and 100 for 1 year at the lowest approved dose.
Then we put these drugs on the market and promote likely crazy. Thus they can be used in hundreds of thousands of people in short order. Most of whom the populations in the phase III studies are not reflective of and so extrapolation of effects are not valid. We simply hope for the best.
Most drugs that are taken off the market for killing people are due to either cardiovascular toxicity or hepatotoxicity. With hepatotoxicity we typically have indications from the chemical structure or possibly earlier. .
Let's take psych drugs and I won't use asenapine this time although it's a valid example as it causes dose and time dependent hepatotoxicity.
Duloxetine (Cymbalta - Lilly) is a prime example. It's a naphthyl which is converted to naphthol in stomack acid (hepatotoxic as well as many other toxicities) and so Lilly enteric coated it. So they clearly knew what problems to expect.
Many psych patients are IV drug abusers or alcoholics. Also patients with mania become hypersexual I've had patients in the hospital have 20 sex partners between admission and our getting getting the results of the VDRL (syphyllis test) back. So many of these patients in the general population are likely to have HIV, EBV, or Hepatitis and are at much higher risk of liver damage.
Doesn't it make more sense to include some of these patients in the phase III studies and monitor them closely and stop the drug so we can label the risks appropriately than to just throw the drug out there and let a ton of people die or endstage liver disease. Which is a truly horrible illness. (I've seen drugs that have caused likely 1000's of cases of liver toxicity the first year they were on the market).
No companies would rather remain totally silent on the issue so it won't effect sales and then when someone does eventually put 2+2 together fight it. Plus who's going to pay attention to a psych patient or look into their death anyway. But we're giving these drugs to the elderly in nursing homes simply to shut them up and to kids in adult dosages long term and they're beign promoted and used for so many things off-lable that there's no evidence they work for or in some cases we know they don't work for.
Where is the informed consent there?
No. I believe it's ethical to expose a few people to potential predictable risks and monitor closely so you can appropriately warn others. Whereas keeping your mouth shut when you suspect something and then exposing huge numbers to lethal risks that no one is looking for and likely to be caught too late is unethical.
Salmon
I want to emphasis that many toxicities e.g. Vioxx/Bextra, hepatotoxicity are dose and time related. We know that these drugs and psych drugs absolutely will be used chronically. Yet the ICH safety study and approval requirements are based on lowest approved dose. Even though we know that doses will be pushed and marketing will make sure of that. Plus it's only 500 people for 6 months and 100 for 1 year.
Now it takes about 3 times as many people to see 1 person with a side effect. So with 100 people for 1 year if you see 1 death the best you can say is that the drug doesn't kill more than 3% of relatively healthy people within a year. Yet we know from psych studies (look at the Summary Basis of Approvals) that typically there's around 25-30 deaths in a development program for an antipsychotic. So that's possibly a 10% death rate due to drug. Plus as we know from asenapine and other psych drugs the denominator of 2500 is largely based on short phase I studies of a few days, and acute studies of 6 weeks in schizophrenia and 3 weeks in bipolar. So you need to actually adjust the denominator. So if the deaths are occurring between 6 months and 1 year then the true denominator may be only 200 or 300 people. With 25 deaths you therefore can only rule out a death rate of maybe over 35%. Then if you look at longer and longer exposure periods the rates may continue to go up.
I don't know about you, but it scares me to think of all the fail old people in nursing homes being placed on these things just to make them sleep. (Some nursing homes it's close to 100%).
Doping these old people up takes less staff and besides there's always someone waiting to get in.
So who's going to question if grandma dies?
What about little kids. They're much healthier than adults so maybe they won't die as readily but if they go on these drug at 5 or 6 when they reach school and are being diagnosed with ADHD or bipolar for as the labeling for ADHD drugs now say 'think bipolar if they get irritable'. We know most of these kids are being diagnosed and medicated by teachers, family, and pediatricians, and if you do go to a child psychiatrist they're being taught to think of themselves as psychopharmacologists (HA!). Being able to legally prescribe something and regurgitating skewed information you've been told does not make you a psychopharmacologist.
Besides what kid with ADHD doesn't get really irritable at times.
So what happens to them when they're 20 or 25 or 30?
Go look at the FDA documents on the pediatric use of these drugs from the AC meeting last June.
When Seroquel was given to kids for 'bipolar' (half of whom were still on stimulants for ADHD). Their heart rates and BP shot up through the roof and didn't come down. Yet we know that the degree of elevation in BP is directly correlated with death.
So will we be seeing a lot of these kids keeling over dead when they're young adults and leaving behind families of their own?
Salmon
Post a Comment