The Black Box Warning: Is The FDA Overreacting?
18 CommentsBy Ed Silverman // July 15th, 2008 // 10:43 am
Last week, an FDA advisory committee voted that 11 epilepsy meds can increase the risk of suicide, but voted 14-4 against adding a Black Box about those risks on the drug labeling, something the agency itself suggested several times in the weeks leading to the meeting.
The episode followed a spate of new or revised Black Box warnings - the most serious warning the FDA can recommend a drugmaker place on product labeling - for a host of drugs over the past few years. These include antidepressants, antipsychotics, antibiotics, anemia treatments, ultrasound meds, asthma drugs and diabetes pills (have we forgotten anything? Send us a note).
The recent vote over epilepsy meds prompted speculation that, perhaps, the FDA has become so painfully aware of safety concerns that the Black Box warning is in danger of losing its luster, assuming physicians pay sufficient attention in the first place. Even as calls go out for such warnings on Botox or Singulair, there is chatter that the intended effect of the Black Box is in danger of being diluted.
What do you think?
Should doctors also be targeted for fraud?
- Yes (89%, 180 Votes)
- No (11%, 23 Votes)
Total Voters: 203
Loading ...
Condor
Well, we are often told that consumers pay little attention to these warnings — relying instead on their doctors — is there any data to suggest doctors are OVER-reacting to them?
[Obviously, I voted "No" in the poll.]
Jane
Patients and their families have a right to know if suicide is a side effect of the medications they take. It is really hard to see how the BBW could be diluted when patients are not taking everyone of these medications at one time. There is little regard for the patient here, only the doctors.
Atlex
Jane,
I’m not sure you are focused on the point of Ed’s posting. First, BBWs are not only for suicides, but for a wide variety of untoward effects of medications. Second, they are primarily directed at physicians and not patients. That doesn’t mean that a patient shouldn’t be told about possible side effects; however, the physician is supposed to have enough knolwedge and expertise to properly advise the patient on risk vs. reward. I acknowledge that that discussion does not take place often enough or in enough detail.
Overall, I think Ed is questioning whether or not the FDA’s use of black box warnings is essentially a case of the boy who cried “wolf.” Eventually, the target audience decides not to pay attention. I tend the think that we are reaching that point. There has to be a better way to identify and communicate the risk vs. reward of treatment.
Atlex
B. Martin, MD
Black-box warnings cause much more hand wringing among pharma marketers than they do among prescribing physicians. That said, more black boxes may dilute their intended effect (something slightly less than a skull and crossbones?), but I suspect moreso for consumers than physicians–who are much better equipped to take a very small increase in an absolute risk with the appropriate grain of salt.
Nathan
Does anyone have the numbers of BBWs per year over the last decade? I’ve been scouring the internet for it, but have been unable to find the hard numbers.
Ken Schields
It’s about patient education and, hopefully, health care consumerism.
I am presently going through a serious tendon problem that APPEARS to related to an innocent course of one of the recently black boxed antibiotics.
The problem is education. No one from the pharmaceutical company can give me any information. All they requested was to send my doctor bills. This is not the issue. Getting well is. Side effects are a reality of pharmaceutical intervention. Ongoing research and data gathering must be a responsibility of Big Pharma.
The more black boxes, the more fanfare - hopefully - the more educated the health care consumer AND physician will become.
The most disturbing result of my internet search was to see that the ambulance-chasers are lined up - to help keep our health care costs continue their climb.
Meg
I am almost two for two with atypical antipsychotics and anti-convulsants.
Zyprexa - my son is dead. No warning of any kind at the time (only Lilly knew, hiding their lethal secrets). Death by profound hyperglycemia.
Lamictal - my daughter took this for bipolar depression. No warnings of any kind, from the doctor or Glaxo. Very suicidal/hormonal and in the hospital to taper off. Months of worry.
Zyprexa - off label use for seniors with dementia. Black box warning which no one pays any attention to.
Besides black box warnings, which would have stopped me from having my children go on either of the drugs above, what other remedies are there when Pharma hides lethal side effects and the FDA looks the other way, as do many doctors?
The only remedies I can think of are diet, supplements, fish oil, and a nurturing environment, at least for manic depression.
Jack2
Nathan:
BBWs by Year:
‘03: 21
‘04: 28
‘05: 49
‘06: 58
‘07: 73
I don’t specifically know, but I suspect those numbers refer to products - not novel BBWs. For example, if a class of medications, with 10 members, all get one BBW, that would count as 10 on this list. I don’t know, but I can’t imagine the FDA issued 73 unique BBWs in 07.
Justice in MI
This goes way up the thread to Condor’s question. I, too, would be interested in evidence of docs “over”-reacting to BBWs. The SSRI issues, for example, were primarily publicized through a few high profile cases, studies relevant media attention, etc. Without all that, I doubt a BBW alone would have made much difference.
I have posted my agreement with the dangers of dilution, which we already had even with a few. When whole classes get BB’d without much data, it appears more like FDA CYA than anything else.
Just A Thought
In my opinion the BBWs appear to be moving toward a cover your assism. A ‘Do Something!’ action.
*First the FDA was involved in a CRADA with Pfizer over the manufacturing and quality control of Dilantin (reported two months before the NEW drug was distributed to consumers and which we dug up after the fact).
*Then they offered up that they were not able to review the ridiculously limited study before Pfizer proceeded- but gave approval anyway (under the generics division even though it is still considered a branded drug).
*Then they seemingly ignored the reported AEs.
*Then we started reporting to EVERYONE because we got NO help from Pfizer or the FDA.
*Then they called epileptics depressed overall (many thanks for their contribution toward keeping us well, btw).
*Then they tried to include a BBW for suicidal thoughts and behaviors of epileptics, which incidentally, was based on some pretty small numbers that could probably be found in almost any group. Thankfully it was shot down, but not because of the patients I’ll bet. It would have damaged the industry.
The FDA approved a drug to be changed which is particularly dangerous to change. Do they think we’re making that up? Because there is plenty of evidence about the nature of these drugs which has led to much bustle for new legislation to protect people from being changed to generics. But what, it’s okay for the FDA to allow us to be switched to Pfizer’s new generic Dilantin? Or Pfizer to benefit from this legislation and have protection for their sales so they can have their cake and eat it too?
Interesting but I didn’t see phenytoin on the list of proposed BBW drugs (did I miss it?) even though it is one of the most commonly prescribed epilepsy drugs for epilepsy. Then it is said that the intent of the study was only for epilepsy purposes. I think the phenytoin omission was by design.
Don’t mention Dilantin for the love of God!
While Pfizer is most likely sitting there awaiting the ruling for preemption (the premise being that the drug was reviewed and approved by the FDA) I am waiting to see how hard it will be to make our case exempt from that ruling if it passes. The FDA didn’t handle the approval properly and I am certain that we have plenty of evidence to at least warrant consideration.
Still, it is Pfizer that we hold responsible. They chose not to warn us or our doctors in advance and placed us in a very dangerous situation, and then denied the problem. If the FDA/Pfizer CRADA created an atmosphere toward FDA encouragement of the change then Pfizer can deal with them.
Seriously, what good does a BBW do if the doctors do not know what they are prescribing? In our case the docs were blindsided and many had to be informed by their patients of the change after treating us with Dilantin for decades. It should have been hollered loudly and months in advance (maybe even with some of those TV ad dollars) for our safety. The docs didn’t do anything differently. We endured a lot of eye rolling from misinformed pharmacists. But the evidence does exist and grows daily. People were and are being damaged. A broad statement as to our state of mind does not change that.
Of course this is only my opinion. In case anyone was wondering, I don’t work for anyone, I am simply a patient who was severely wronged.
harpy
Maybe there is more crying of “wolf” because there are a lot more wolves around.
Justice in MI
Touche, Harpy!
Of course, even if there are more wolves, there is a point at which people get wolf fatigue.
Remember the Milgram experiment machine? Maybe we need:
Black Box
Severe Black Box
Extremely Severe Black Box
XXX Black Box XXX - Caution!!!!!!
Fuggedaboudit Box
or not.
Nathan
Here’s an interesting link. (below) This Kaiser study showed that approximately 8% of all prescriptions for “black box medications” are actually written IN VIOLATION of the black box warning! So, you have to ask yourself why:
1) The doctor doesn’t believe / care about the warning
2) The doctor believes that he / she can predict tox better than the FDA.
3) The doctor is so overwhelmed with information that he / she is unaware of the warning.
http://www.kaisernetwork.org/daily_reports/rep_index.cfm?DR_ID=35406
Justice in MI
Thanks, Nathan. I’m frankly surprised the percentage is that low. As one of the few pts who acually reads PIs, I know I’ve been rx’d BB meds many times when other non-BB options were available and equally (or more) medically appropriate - probably more than 8% of the time, particularly if I haven’t used the med before (most typically, an antibiotic and the like).
I suspect that this reflects all your options, just as the rest of the label has been shown to have little impact on rx’ing in a great many instances, particularly in the absence of
a highly publicized study and/or media event related to the drug.
Laurie
“This Kaiser study showed that approximately 8% of all prescriptions for “black box medications” are actually written IN VIOLATION of the black box warning! So, you have to ask yourself why
Sad isn’t it. My experience with researching compliance in prescribing drugs with BB warnings, is that most doc dismiss the warning, or don’t even know about it in the first place. Which begs the question…..where do they get their drug information from?
Jack2
First, I don’t think docs should casually dismiss a BBW, and I don’t think it’s a good thing if docs are ignorant about a BBW, but…
A doc can still prescribe a drug with a BBW, and in a manner that “invokes” the BBW. If the doc could not prescribe the drug under any circumstances in that situation, it would be a contraindication. A BBW is an extra serious warning not a contraindication.
Laurie
“If the doc could not prescribe the drug under any circumstances in that situation, it would be a contraindication. A BBW is an extra serious warning not a contraindication”
I agree completely, but the patient should also be made aware of the potential risk with that specific drug. Some of the BB warnings are problems that most patient would never fathom could be a result of that drug. ie. ruptured tendons from an antibiotic, or increased suicidality from an antidepressant.
Justice in MI
I think we’re all agreeing what would be best in principle. Unfortunately, that seems to have relatively little impact in practice.