Wednesday, March 17, 2010

Should Sanofi-Aventis Submit an Adverse Event Report Based on "Disgruntled Patient's" Comments to VOICES FB Page?

Sanofi-Aventis (S-A) submitted 14 pages of comments to Docket No. FDA‐2009‐N‐0441 regarding Promotion of FDA‐Regulated Medical Products Using the Internet and Social Media Tools (find it here).

"As part of routine monitoring of online discussions hosted, or with participation, by a company, postings that contain potential adverse event reports should be addressed according to established company policies and procedures for handling and reporting spontaneous adverse event reports according to current FDA regulations," said S-A in its comments. "This includes, when appropriate [my emphasis], to follow-up to obtain the necessary elements needed to report an adverse event."

Considering the problems that S-A is experiencing on its VOICE Facebook page with regard to "disgruntled patient" Shirley Ledlie (see "Disgruntled Patient Shuts Down sanofi-aventis Facebook Page"), I was wondering if it is appropriate for S-A to follow up with her reports of permanent hair loss side effects of the drug Taxotere.

First, what is an adverse event and is what Shirley's reporting an adverse event?

The definition of "adverse event" for both nonprescription drugs and dietary supplements is "any health-related event associated with the use of a [nonprescription or dietary supplement] that is adverse" (see source). This could include any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease, and, more seriously, death.

FDA defines Adverse drug experience as "Any adverse event associated with the use of a drug in humans, whether or not considered drug related, including the following: An adverse event occurring in the course of the use of a drug product in professional practice; an adverse event occurring from drug overdose whether accidental or intentional; an adverse event occurring from drug abuse; an adverse event occurring from drug withdrawal; and any failure of expected pharmacological action." (See here)

Shirley reported hair loss, which is known side effect of Taxotere. Are known side effects, especially those listed in the drug labeling (as is hair loss for Taxotere), considered "reportable" adverse events? I found nothing from searching FDA AE reporting pages to indicate that manufacturers are NOT responsible for reporting adverse events if the event is listed as a side effect in the labeling. Besides, Shirley is reporting permanent hair loss, which is not specifically mentioned in the labeling.

In my opinion, therefore, what Shirley has reported in comments to S-A's VOICE Facebook page is a "potential" adverse event report that requires S-A to follow-up.

Shirley's adverse event also satisfies the FDA' guidance on postmarketing adverse reporting, which S-A cites in its comments to FDA: "Before considering any clinical incident for submission to the FDA in an expedited or periodic safety report, applicants, manufacturers, and licensed manufacturers should have knowledge of the following four dats elements:
  • An identifiable patient;
  • And identifiable reporter;
  • A suspect drug, biological product, or device; and
  • An adverse event or fatal outcome.
S-A has all four data elements in this case. IMHO, therefore, it is appropriate for S-A not only to follow-up with Shirley, but to submit an adverse event report to the FDA. Has it done so? According to Shirley, S-A refuses to speak with her. if that is true, then S-A is not following its own recommendations it suggested in its comments to the FDA.

Does having a disclaimer about adverse events on its FB page mean that S-A does not have to report this adverse event to the FDA?

The disclaimer states: ""This page is not intended as a forum for discussing sanofi-aventis’ or other companies products including the reporting of side effects associated with the use of prescription drugs. As such, Postings that contain product discussions may be removed by sanofi-aventis... If you, or someone you know, have possibly experienced a side effect while taking any sanofi-aventis product, please contact our Drug Safety department at 1-800-633-1610, option 2, or via fax at 1-908-203-7783. You are also encouraged to report negative side effects of prescription drugs to the FDA. To do so, visit or call 1-800-FDA-1088. Postings may be reviewed by sanofi-aventis and may be subject to removal if they are deemed to be inappropriate or inconsistent with the intended use of this site. We reserve the right to block users who violate the terms of use."

S-A suggests the same kind of wording in its comments to FDA, but does NOT say that having such a disclaimer makes it unnecessary for S-A or other drug companies from fulfilling their obligations to report AEs according to FDA law. I think the FDA would agree that it is still necessary to report adverse events found in comments submitted by an identifiable reporter.

In terms of processing AEs on company-owned social media sites, S-A says that "drug sponsors should monitor (through active participation) their own websites for potential adverse events and report according to existing internal standards. It recommends the following monitoring "parameters:"
  1. Development of search terms (product/disease specific) and timeframes
  2. Development of process for identifying and transferring potential adverse events to the company's Pharmacovigilance department
  3. Training monitoring staff (in-house and/or vendor) on the aforementioned process
  4. Training vendors on company standard operating procedures (SOPs) for adverse event reporting
  5. Internal/vendor audits to assess compliance
Has S-A implemented these monitoring parameters? About 26% of pharmaceutical companies may not have any social media adverse event monitoring standard operating procedures according to my recent survey (see "WANTED: Answers to FDA's Questions Regarding Pharma's Use of Social Media" and figure below):

AE Processing


  1. Yes, S-A should report the incident as an adverse event. While the company cannot be certain that Taxotere is the cause of the alleged hair loss (or whether the incident actually happened at all), they should report it.

    While at it, the company should also consider its broader options. The legal standard for defamation is pretty clear and this does seem to fit. The company should file suit against Shirley (or whatever name she's using today) and make her prove her allegations.

  2. Anonymous9:48 AM

    I can't agree with the first part of your statement since we do not know if the drug was responsible for the adverse event. If she was under a combination therapy it could have been any of the other medications as well. Or it could be synergistic. More info needs to be given by the physician, not the patient. Also, permanent alopecia is not part of the MedDra dictionary, perhaps it should be, but it will be difficult to file a report to AERS without a preferred term for this event.
    Also, the second part of your comment is probably not such good advice for S-A. Even if they have a case imagine the PR disaster that would result from such a trial. A big pharma bully suing a cancer survivor who is also the tragic victim of an adverse event that may be linked to your drug... can’t you see the headlines already?

  3. According to FDA, it does not matter if the AE reported by the patient is ACTUALLY due to the drug mentioned. It only requires that the drug be mentioned in connection with the AE. It's up to the FDA to sort out the merits of the claim. I agree that the best AE report originates with the physician. However, more and more reports are coming from patients (see New FDA Data: Adverse Event Reporting Increases Dramatically --

  4. Anonymous12:19 PM

    Hi John,
    Thanks for the link and the information. That certainly clears up a mystery for me. However, it creates another. If one searches the AERS for the HLT alopecias the top drugs identified are not anti-cancer drugs... so does this mean that people don't report AEs that are considered either "obvious" or clearly stated in the label?

  5. That's a good question. The physician may mention "side effects" to expect and patients may report they have had these side effects, but physicians may say these are common and maybe transient, don't worry. Hence, no files an adverse event. The listed side effects may be considered "normal" and not thought of as "adverse events." The connection between known side effects and adverse events is still a bit of a gray area for me.

  6. My comment on suing the patient for unsubstantiated defaming statements was cheeky.

    John, adding to this is the fact that most physicians are reluctant to report perceived adverse events anyway due to the risk of litigation.

  7. How is this handled in advanced countries that have a 1-payer system and universal electronic medical records?

  8. Well that's easy, patients have extremely limited access to recourse in other countries. If you claim harm in the UK under NHS, there is an investigation that can take years. There was a situation of a physician removing the wrong kidney and the patient ultimately died while his case was being reviewed. Patients who claim harm (whether real or fabricated) have a long, tough road to prove their cases. And it's wrong.

    However, the flip side, is that in the U.S. is that it is too easy to make up adverse events and claim damage. In this instance, we have a patient who suffers from a adverse event explicitly described in the PI. The drug was administered by a physician with understanding and the patient accepted with consent. The duration of this event is usual, but it is within the labeling. No, the patient is alleging vast criminal conspiracies (and event sending emails to people commenting on your blog telling them that "I will get what I want.").

  9. Pharm aid - you really dont understand do you.....
    This adverse side effect is NOT mentioned on the PI - if you think it is please tell me were i can read 'permanent hairloss'? My oncologist did NOT know this was a possible side effect. Infact he was part of the team that set up the ongoing survey in NW France (the one that SA are not happy about) because he was so concerned about the numbers that started to be reported around the same time as me.
    Dont know where you are getting my supposed quotes of 'i will get what i want'? not sure what you mean by this. I have said i wont stop shouting about it till i get what i want - i want labeling saying that its a common and frequent side effect (PSA). I am also not alleging vast criminal conspiracies at all, i can back up EVERYTHING i have said. Sanofi know this, why do you think they remain silent.
    So, i really dont know what your problem is pharm aide - you seem quick to judge without knowing any of the facts.
    And as far as them suing me for defam - no chance of that i can assure you.

  10. Anonymous7:17 PM

    I am confused and forgive me if I am missing some facts but where in the Taxotere PI does it say hair loss is temporary?? It does not qualify "alopecia" or "hair loss" as permanent or temporary. The PI states, "Once you have completed all your treatments, hair generally grows back." GENERALLY. I think we all understand that NO guarantee can be made about any medication - whether those guarantees are for the benefits of a medication or the side effects. Is anyone really that naive?? Is this what this world has come to – we have expectations of perfection and guarantees??? While I sympathize with any cancer victim (and I have known many), I have to say I am offended by the characterization of this particular survivor as "disfigured" b/c of hair loss. I would do anything to have my loved ones who lost their fight with cancer back - even bald. This woman is ALIVE and alive for a number of years. I can assure you that when my 31 year old friend was dying from ovarian cancer or when my uncle was dying from his short and torturous fight with pancreatic cancer, the very last thing on their minds was, I wish my hair grew all the way back in. “Disfigured is the child who was burned by a bomb attack or the victim of domestic violence who had acid thrown in her face. Believe me, I have no ties to Sanofi - I don't even know any products they make but it seems that there are more productive ways for this woman to spend her apparently plentiful, free time. How about an effort to raise money for the victims of the earthquake in Haiti, or how about an effort to raise awareness about the lack for clean drinking water for much of the world's population?? I don't want to come off as cold and uncaring b/c I am truly not. Yes, hair loss is not fun, it can be embarrassing, but I think what we all need is a little perspective. SHE IS ALIVE - would this woman have chosen death over a full head of hair? I think not. Thanks for letting say my piece. I won't be posting again.

  11. This chart at the end explaining lot. Thanks for sharing this. I like it.

  12. Anonymous10:27 AM

    It's not just one disgruntled cancer survivor. There are over a hundred of us. Of course, there's no promise that our hair would grow back. GENERALLY grows back. Well for those of us who battled breast cancer but are forced to look at our bald selves in the mirror every day, "generally" isn't good enough. Yes, we're alive. I'm grateful for that. But again, no promise of how long...and with small children, that's another painful reminder of what I've been through. The thing about S-A and Taxotere is this: there's another drug, Taxol, which doesn't cause this permanent alopecia we're dealing with. But we were never told that there was a choice. And what do you think I would have chosen if I'd had a choice? I'm in my early 40s so dealing with permanent alopecial is especially difficult. I have a job in a senior management position. Hard to earn respect when I look like Ben Franklin. We're not mad that Taxotere caused us to experience permanent alopecia...we're mad that we weren't given the choice of the more hair-friendly medication. And why is that? Our oncologists didn't even know. Don't you think they should be made aware of this fact?

  13. Anonymous,

    Thanks for you comments. While I am not knowledgeable regarding the benefits vs risks of one treatment vs another, shame on your oncologist for not knowing or caring enough to offer you a choice!

    It's my understanding that oncologists often make a profit "reselling" these drugs. Obviously, in that case, they have a bested interest in offering patients the drug that gives them the highest profit. I do not know if Taxotere and Taxol differ in this respect.


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