Supreme Court To Review Adverse Event Disclosure
18 CommentsBy Ed Silverman // June 15th, 2010 // 10:47 am
The failure to disclose adverse events can have all sorts of repercussions. Doctors and patents get alarmed. Regulators get upset (see what the FDA told Pfizer last month). And shareholders get steamed. Now, the US Supreme Court will review a case to determine whether drugmakers must disclose all adverse event reports that may not show statistically significant evidence that a side effect is actually caused by a specific drug.
The case was brought by investors against Matrixx Initiatives, which was sued for allegedly concealing side effect reports that its Zicam cold med caused people to lose their sense of smell, known as anosmia. For its part, Matrixx is challenging an appeals court ruling last fall that reinstated a 2004 shareholder lawsuit alleging the company received at least a dozen AE reports but never disclosed them. The company argues it does not have to disclose AE reports unless these actually show the side effects may be caused by using a drug (see its petition to the Supreme Court).
By withholding the reports, shareholders argue Matrixx unfairly boosted the value of its stock. The Zicam nasal products contain zinc, which the FDA last year warned causes anosmia (see the health advisory), and Matrixx reluctantly recalled its products (see the statement). At the time, the FDA had identified about 120 AE reports and, during a subsequent inspection, found some 800 reports that were never filed with the agency.
In their filing last month in which they hoped to convince the Supreme Court not to review the case, Matrixx shareholders recounted how Matrixx purportedly warned Bruce Jafek, a professor in the department of otolaryngology at the University of Colorado School of Medicine, not to present a poster he and two colleagues prepared for a medical conference Presentation in 2003 that described 10 cases of anosmia linked to Zicam. And several months earlier, Timothy Clarot, Matrixx’s R&D vp, allegedly called Miriam Linschoten of the University of Colorado Health Sciences Center and the Rocky Mountain Taste and Smell Center to discuss a case of anosmia and Zicam, and admitted Matrixx received several other such reports. These took place prior to the class action lawsuit filing.
The shareholders are concerned Matrixx will succeed in obscuring the notion of reporting adverse events and, effectively, obtain a decision that could require drugmakers to report a tidal wave of adverse events, many of which may be irrelevant to a lawsuit. “The broad randomness of typical adverse-event reports is absent (in this case),” the shareholders’ lawyers wrote. “These were specific, identical complaints brought to petitioners’ attention. On those unique facts, the Ninth Circuit correctly ruled that reasonable investors would have wanted to know the undisclosed information before making the decision to buy Matrixx securities.”
Justice in MI
Fascinating case. Obviously, much hinges on the criteria for causality, for which there are likelihood scales, as I understand it.
At the same time, labels routinely list events that occurred in association with a drug’s use in a category which makes clear no causal connection is being suggested or assumed.
Perhaps someone can clarify for me what the causality criteria actually are, particularly re: inclusion on a label. Thanks.
keiner
But likelyhood increases with the number of cases ;-)
Criteria are commonly:
- Is the report consistent (time, route of application) with the reported AE?
- If AE is not irreversible (as for this case): Dechallenge positive? Rechallenge (if ethically justifyable) positive?
- Any other reports for related drugs?
- Very important: A potential mechanism for the potential AE…
Justice in MI
Thanks, keiner. Yes, these are familiar. But I’m still wondering about that category on labels in which events are listed “in association” with the drug’s use which do not meet such criteria. What are the requirements for inclusion in that category?
Betsy Jacobson
Of course all adverse events should be reported. Big Pharma is adept at omitting reports of these events so that they can be approved, and they’ve been doing this for years and years. Everyone knows this, and to permit it to continue to happen, the Supreme Court will be responsible for the deaths of hundreds of thousands of patients every year.
Would that make the Supreme Court murderers?
Josh
That statement makes no sense. AE reports are done for approved drugs…not ones that unapproved.
What does the Supreme Court have to do with it as well? No where is that talked about….
And where are you getting your numbers for deaths associated with AE’s?
keiner
@Justice:
This category is not usual in Europe, so I don’t know :-)
Justice in MI
So it’s clear what I mean, this is from the Lipitor label. In the U.S., at least, most drugs have such a paragraph with the same disclaimers re: frequency and causality.
6.2 Postmarketing Experience
The following adverse reactions have been identified during postapproval
use of LIPITOR. Because these reactions are reported voluntarily from a
population of uncertain size, it is not always possible to reliably estimate
their frequency or establish a causal relationship to drug exposure.
Adverse reactions associated with LIPITOR therapy reported since market
introduction, that are not listed above, regardless of causality assessment,
include the following: anaphylaxis, angioneurotic edema, bullous rashes
(including erythema multiforme, Stevens-Johnson syndrome, and toxic
epidermal necrolysis), rhabdomyolysis, fatigue, tendon rupture, hepatic
failure, dizziness, memory impairment, depression, and peripheral neuropathy.
keiner
No, “postmarketing experience” is not a headline in a European CCDS/SPC. Adverse events are all listed in one section, no matter if evaluated from (premarketing) clinical trials or postmarketing data. Evaluation of incidence is difficult in this case, no question.
But as you can no “earn” such a lot of money from (suspected) adverse drug events, this is usually not a problem here (yet).
keiner
This is the UK-SPC of Lipitor
http://www.medicines.org.uk/EMC/medicine/1424/SPC/Lipitor+10mg%2c+20mg%2c+40mg%2c+80mg+Tablets/
4.8 Undesirable events
There you find some postmarketing information.
There are unspecific things like “vomiting”, “weight gain”, “tinnitus” or “hearing loss”, for which no causal relationship you will be able to proof, based on the few reports to find.
keiner
PS: These findings are sometimes added based on statistical significances for higher incidence compared to placebo, sometimes all reported (harmless) ADRs observed in trials. These things are difficult to decide, need expereinced scientists and largely depend on the culture of legal/pharmacovigilance department of a company…
LILLYK
Your Primary Care Doctor is supposed to monitor your medications. Doctors are not mandated to report errors. Blood Tests do show serious problems from medications—-but doctors are not reporting the side effects—-especially from statins. I am positive that the Supreme Court decison will be the same as the Patient Safety Programs—IN Name Only. Pharma is too Powerful and is protected by politics. Too many Americans are unexpectly dying from medications—but doctors arenot telling the truth. All medication, foods, cosmetics, toothpast, shmpoos have the same chemicals that are in cigarettes.
vallen
I have lost all smell and taste because of this
product and feel it surely should not be still
on the market. Do you know how I feel with no
smell and taste????
Justice in MI
re: Lilly’s comment, yes, pretty much everyone agrees that our Medwatch system is generally a failure, and perhaps 1 in 100 AEs are actually reported.
In the meantime, though, pts can file their own reports with Medwatch and causality does not need to be assumed. A recent NEJM piece suggested that pt-generated reports have shown to be extremely useful in post-marketing surveillance.
Of course, what FDA does with the info, and whether they have the people and technology to do it, becomes the next question. In the question after that is why Congress, year after year, blows hot air at the problem.
keiner
“A recent NEJM piece suggested…” Do you have the Reference at hand? Thank you in advance!
In principle you generate a lot of statistical noise and you have to filter in the end the (potentially) relevant information. The WHO does so at its Centre in Uppsala, but that’s by far not standard technology, yet, I guess.
Jaynesday
I suppose the AE system originally was a good idea. In theory it makes sense. If it was used for the purposes that it was intended and in the way it was intended it would be a good thing. But as is usually the case with regulatory organizations, and especially the FDA, the regulator becomes too close to the regulated and things are neutralized and/or allowed to be ignored.
The AE system is like any database. Unless you report all of the data or unless you insure that all data is valid, none of the data is worth the time it takes to enter it.
I don’t know how much is spent on the current AE system but I propose that it’s all a huge, huge waste of time and money - meant more as a placebo than a corrective measure.
Salient point
Guys-As keiner alludes to above, the European agency does not even always track PM AE’s, let alone add them to the label. There was a post about this very topic here several weeks ago that no one here seemed concerned about.
And yet, when there’s an article about PM AE’s in the US, several people log on & bash FDA. Even though it does track these events & update the label accordingly. And even though this post is not even about FDA, but about a shareholder liability suit re failure to disclose info adverse to stock value.
Unbelievable.
keiner
@salient: No, the regulatory requirements for reporting serious adverse events are world-wide the same. However, the low-quality, hight-frequency patient reports are not handled equally wordl-wide afaik.
The system of Periodic Safety Update Reports for all drug products has been established (in Europe) years ago and if handled correctly it should bring up safety signals on new ADRs properly…
Salient point
keiner-You’re right, I had my facts wrong on this.