FDA AERS /FDAble site
 

As per a posting by RW several months ago (thanks), I've been able to go on the FDAble site to check adverse reactions reported on drugs:

. . . but when I tried today, I received a new message saying:

"FDable is transitioning to an invitation-only mode. If you are interested in becoming a member, email us at administrator@fdable.com"

Is this something everyone is getting when they go to this site now, or is it only blocking Canadian access? (I've seen that happen before with sites ...)

Also, is anyone a member there now, and if so . . . what is the criteria for membership?

Cherie

I am getting the same message and I am in America.

No, I thought I'd ask here first, since sometimes this is just a "no CANADIANS allowed" thing. :p

Also, I know that RW used that site sometimes, and I was curious if she knew why it had become "invitation only", etc.

I'll probably try to sign up, and see what it says . . . Being Canadian and all, it might kick me out anyway. :D

Cherie

We had a big debate on one of the forums, because someone saw that they could buy cheap, generic Copaxone online at "Canadian Pharmacy" (or Canada Pharmacy ~ something like that). They figured we were scamming Teva by not following the US patent on the drug . . .

Every time any of the Canadians tried to access the site though, we'd get booted out . . . yet all the Americans were insisting they could get through and purchase the product. I guess the site had a block on Canadian IP addresses. :confused:

Turned out that "Canadian Pharmacy" was owned by an American, and operated out of California. :p

I can't watch a my favorite shows online either, like if I miss a Grey's Anatomy episode. Soon as it see's I'm Canadian, it boots me out. :(

.... so I always ask now. :D

http://i12.photobucket.com/albums/a2...adianmouse.gif
Cherie

Sorry Cherie, I just found this post while trying to catch up on the past few days.

The FDAble site is down for a big revamp. He may be going to a pay site, although he might allow limited free access. He's trying to figure that out right now.

He's suffered from some financial people exploiting the site and he put a huge amount of work into it and feels it's time for a change. I'll post more when I have more information.

FDAble/aers
 

Just as an FYI, the site is back up and is public.

-tba

I'm in the midst of adding Q32008 data from AERS which should be complete some time tomorrow.

Thanks so much tba!

Sounds like you are the person to ask questions of, if we don't know how to interpret some information posted there . . . ? :confused:

One thing that has always confused me is when there is one "Case#", with three or four "ISR#'s" assigned to the case.

Is the case# like an individualized "personnel" number for each client/patient, so that ANY time you get a report on a 'person', you source their previously assigned case#?

But when we look at the ISR'#s assigned to an individual case#, sometimes it "appears" that the exact same thing can be reported several times, sometimes on the same event date, but not necessarily. Does that just mean that the same event was reported that many times (from various sources?), or that these are seperate events?

An example would be in the following, under "Case#": 6553717:

http://www.fdable.com/search/aers/ad...y/b8031eda45cb

It shows two similar "ISR #'s" under that case# (person), but in different "Quarters" (one in Q1, and one in Q2), and with only one "Event date" documented .... How would we know if that is the same "event" remitted from two sources, or two seperate events that occurred? :confused:

A better example might be Case# 6551503 (on the same page). Are the four IRS's on that Case# (patient) the same events . . . and how could anyone know that by the report?

Also, where is the legend for the outcomes, like "DE" or "OT"?

Thanks!

Cherie

Hi lady_express_44,

regarding case # vs. ISR...your overall impression is correct.

But just in case you want more detail...think of it this way.

1. Imagine that you take a drug and suffer a HEART ATTACK and are HOSPITALIZED on March 1, 2008.

2. Because of this, you might file an INITIAL adverse event report to the FDA that says something along the lines of "I took Drug X and I had a heart attack and was hospitalized on March 1, 2008."

3. This INITIAL report gets both a Case # **and** an ISR.

4. NOW imagine that 2 days later you died of that heart attack.

5. your spouse or MD or attorney might submit a FOLLOWUP report saying, "and by the way...we had the initial outcome as HOSPITALIZATION, but there's a new outcome of DEATH as well."

6. This FOLLOWUP report (and any other followup reports) gets the same Case #, but it gets a separate ISR #.

So...this is my long-winded way of saying Case # ties together 1 or more reports for the same patient. Each report gets a separate ISR.

Hope that makes sense!

Is the case# like an individualized "personnel" number for each client/patient, so that ANY time you get a report on a 'person', you source their previously assigned case#?
YES!

But when we look at the ISR'#s assigned to an individual case#, sometimes it "appears" that the exact same thing can be reported several times, sometimes on the same event date, but not necessarily. Does that just mean that the same event was reported that many times (from various sources?), or that these are seperate events?

This is a good question, but the answer is not clear as there do not appear to be standardized methods for reporting adverse reactions. I **think** (emphasis on think) that most often, the adverse reactions that are repeated are actually duplications, but that is not necessarily always the case.

It shows two similar "ISR #'s" under that case# (person), but in different "Quarters" (one in Q1, and one in Q2), and with only one "Event date" documented .... How would we know if that is the same "event" remitted from two sources, or two seperate events that occurred? :confused:
Again, the answer isn't clear. In *some* cases, you can probably use common sense to figure out what's going on (e.g., if esophogeal cancer is listed in 2 separate ISRs from the same case, it's likely to simply be a duplication), but this isn't always the case.


Also, where is the legend for the outcomes, like "DE" or "OT"?
DE = Death
OT = Other (i.e. not death, hospitalization, congenital anomaly or "required intervention")
If you click on the column heading labeled "Outcomes", it will pop up a small window that gives you the legend.

Hope that helps.


Best,

-tba

Thanks!

I just tried to access the site and was not able. The site is asking for a user name and password. How does one go about getting one?

Thanks again, tba.

It's too bad there isn't an additional field that ultimately clarifies if events (ISR's) tie together . . . but I suppose that would take a lot of analysis and administration.

Your clarification is appreciated. :)

Cherie

Figured it out! Thanks!!! ;)

Tysabri WIKI
 

Hi Cherie and others,

Hi all,

I thought many of you might be interested in an extension that I've built to the FDAble web-site.

Specifically, it's a WIKI that will hopefully be of use in examining pharma- and drug-related info.

Right now, the only relevant drug listed is tysabri...**

Anyway, if you go to the main FDAble site, the bottom of the page will link to the wiki and then you can simply search for Tysabri to see the relevant info.

I've just begun to consolidate a fair amount of Ty info that is scattered across the web.
**

Thanks for your time.

Best

-tba

Thanks, tba! I'll have a look at that.

Since you are updating Tysabri in particular, I wonder if you plan to be merging the Natalizumab and Tysabri data into one drug file? I understand that there may be several brand names for various drugs, sometimes made by different manufacturers, etc., but in the case of Tysabri/Natalizumab it is ONE drug, made by ONE manufacturer, so why not merge the data?

Do you work for the FDA, tba? If so, I have another question . . .

There are several drugs on the market that have the potential to cause serious risks (like Tysabri, Compath, etc.). In the FDA database, there are several "reports" of patients who "apparently" may have had i.e. PML, yet many of those cases have never been reported in the media/confirmed publically. I have "assumed" this means there was confirmation that that was NOT the cause then . . . :confused:

So . . . are all of the reported cases of "potential" PML cases reported on this site ultimately autopsied/100% screened out for PML? Is that the reason that those cases reported to the FDA were ultimately not "confirmed"?

Also, in the case of Tysabri, is there another formalized reporting method other than this site? I appreciate that this site takes "voluntary" reports, ie. it's up to the doctor/patient/family members to report (or not), but it's my understanding that the Tysabri Risk Plan established a seperate reporting method for adverse events . . . Or is this it?

Thanks again,

Cherie

I have always been warned that Wiki is unreliable for obtaining "facts" about ANY subject, although I have not found this to be the case at all. I love Wiki, personally . . . mostly because it is normally written in layman's terms, but also because it is constantly being verified & updated by MANY sources.

I'm curious if this means that the FDA (US government agency) generally considers this a reliable source of information?

Cherie

I would seriously doubt it. The FDA does serious research on adverse events reported in the AERS before they do anything. Their decisions are based on science and data (lots of it).

it is merged...I was actually just being imprecise by saying "tysabri", when what I actually meant was "tysabri OR natalizumab"

short answer: no. Long answer: no. never. I work in biotechnology.

you are correct in thinking they are "POTENTIAL" cases. Since anyone can file an AE report, the reports themselves span a wide range of 'quality of verification'. I believe the makers of Ty have explicitly stated that while AERS shows a # of suspected PML cases with Ty, there are only a small # that have been confirmed independently.


There may be a separate reporting system (in the U.S.) specifically designed for Ty...I think you are referring to the Touch(tm) risk minimization system. However, anything that goes into Touch should ultimately also makes its way into AERS as well.


I think skepticism is a good rule for any bit of information...and your comfort level may vary depending on the specific source and the specific information.
So far, I am the only person who has added to the wiki and my information has come exclusively from government data...so it's a matter of trusting me...and the US government.
the way that I look at Wikis in general is that they should be a "jumping off point" for additional study. But they *can* be rather informative.

I have no way to say whether the FDA or other agencies consider WIKIs reliable sources of information.
However, I should say that I began making the FDAble last month and someone asked me why I just didn't add information to Wikipedia's entry on Tysabri.
There are a number of reasons for making a different wiki.
0. the idea behind the FDAble WIKI is to aggregate pharma data that is distributed across governmental agencies (e.g. FDA, CDC, clinical trials, USPTO, etc.)
1. wikipedia's goal is to give a narrative about different topics and is generally suited for the layperson. The FDAble wiki is more "data-centric" (less narrative) and more specialized in the type of information dispensed.
2. wikipedia frowns on articles that use many links that lead "outside" of wikipedia (I've tried). FDAble wiki is trying to do the opposite (provide many links that lead outside of the wiki).
3. wikipedia makes it difficult (if not impossible) to add graphical data (e.g. timelines and dynamic maps). FDAble wiki is trying to graphically show the duration of clinical trials and other data.
4. I'll stop there, but there are a few more germane reasons.

Thank you for the feedback!

p.s. I read the other day about a woman with MS who is planning to climb Everest!
pretty impressive considering that you can't get me to climb a chair in my kitchen without a handful of tranquilizers.

Best,

-tba

Cool!

So why is it that when I type in "natalizumab" a seperate database comes up :confused::

http://www.fdable.com/search/aers/ad...y/2fcb1d403a66

Also, do you know why reports for Avonex, Betaseron, etc. all pop up in the database when I request only Tysabri?

http://www.fdable.com/search/aers/ad...y/9eb4fec4b9b6

So, curiousity got the cat . . . why are you responsible for updating the FDAble AERS then? Moonlighting? ;) :p

So are all cases of PML that are reported through AE SENT for independant confirmation then?

It would seem to me that people reporting PML cases shouldn't be doing so willy nilly. They must have some convincing evidence to venture such a "guess". . . :confused:

You might remember when the Crohn's patient died from what was reported as some other condition, and eventually his cause of death was re-evaluated. Not sure how they did this :confused:, but they determined in the end that it was PML. That was before the days when they "looked" for PML, of course, but clearly the dx isn't cut and dry even now.

Do you have any idea what happens when a AE reported PML case is "suspected"? Are all of these cases flagged and sent for independant analysis, or ?

That reminds me, TOUCH is only in the US and about 1/3 (I think) of the patients currently on Tysabri are from outside the US.

Is the AE system only for US reporting too, or does it include all countries?

Yes, I guess it would the the "risk minimization system", but I've not been able to find anything that describes the established procedures for reporting through that system. :confused:


Yeah, I just thought it was interesting to see a government site hook up to Wiki, but that's cool. :)

Do you have MS too? :eek::(

You've been a big help, thanks!

Cherie

The criteria for diagnoses of PML is clear

- Symptoms suggestive of PML
- MRI findings consistent with PML
- JC viral DNA in the CSF

All suspected cases of PML are worked up by BiogenIdec to confirm/rule out PML.

FDAble.com is NOT an FDA or a government site.

It is a private site run by a private person and is in NO way associated with the United States Federal Government or the FDA.

That being said, the amount of work this person (TBA) has put into this site is amazing and MUCH appreciated. It does make it easier to search on adverse events and he is trying to make it even easier by listening to suggestions and adding to his site when he can to make things easier.

Thanks TBA!!!:)

Thanks Riverwild.

I was of the impression that AERS is a government initiative, and that they are somewhat reliant on the integrity of this information to flag safety issues, etc.

It seems that information may be administered through Medwatch, but quarterly reports seem to be accessible through the FDA site. :confused:

http://www.fda.gov/cder/aers/default.htm

So FDAble is another site that presumably provides this same information, in perhaps a more user friendly way? They are getting their information from government endorsed sources though, right?

Cherie

If only it were that simple, Chris.

Apparently there has been approx. one “unconfirmed” case of PML per month reported since the reintroduction of Tysabri, but in every public discussion/corporate Q&A session I've read, Biogen has flatly refused to discuss these cases.

Unfortunately, the neurological symptoms associated to PML may mimic our MS symptoms, and MRI changes (due to PML) may be so subtle that it may be difficult to differentiate PML from MS lesions, without actually doing a biopsy. JC levels may remain below the level of detection at the initiation of a CNS infection, so that even if someone does not initially “prove” to have PML, it doesn’t mean they didn't get it.

There is even some question as to whether one or more of the cases that IS confirmed, actually had/has PML. I just don’t think it is that cut and dry.

It would seem to me, however, that before an adverse event for suspected PML is lodged, the patients’ would have undergone testing, and the results would strongly indicative of PML. Often the cases can not be confirmed (or ruled out) at that point though, so my specific question is “what is the established/required PML confirmation protocol”?

It can take weeks to even months before the JC levels reach detection level for PML, however in the case of patients highly suspected for PML, neurologists are instructed to immediately cease Tysabri and consider treatment with plasma. I trust that they are following this procedure, and chances are this is how “suspected” cases are born in the AE system.

But what then?

It is my understanding that the discretion to cease treatment, use plasma (per the PLEX protocol), as well as for further follow-up with the patient then lies with his physician. But what are the physicians’ expressed responsibilities for follow-up on his patients? Is he mandated to do further testing of JC levels to ultimately confirm/rule out PML?

And, could the use of plasma affect follow-up JC results, often required for confirmation of PML?

What is Biogen’s responsibility in all this? Do they have ultimate responsibility to confirm PML, or does the physician? From what I can tell of the 8-K filings for the European cases, Biogen seemed completely in the dark about the suspected PML cases, up until the point that PML was confirmed by the patient’s physician . . . So, my guess is that perhaps they don’t have any obligation for independent evaluation of every suspected case that is reported.

As far as deaths, what is a physician’s obligation to rule in or out PML for all patients who were on Tysabri? How long might it take to receive these results . . . we still don’t even have confirmation on the cause of death for that US woman who died in early Dec with PML.

What I want to know is what is the specific audit process for suspected cases of PML? Is it the responsibility of the physician to prove PML? Really, what purpose would it serve HIM to do that . . . it’s not like anything at all can be done to treat or manage the disease at that point . . .?

What if the physician doesn’t do follow-up . . . does this just become another case of “unconfirmed PML”? It wouldn’t be good that a physician not do this due diligence . . . but who/what entity is monitoring to ensure they are?

The bottom line is “who’s responsibility is it to thoroughly investigate every reported case of suspected PML”; Biogen’s? The FDA? The physician’s? The patient’s? The patient's lawyer?

I haven’t found documented answers to these questions, but if you have Chris, I would appreciate a link.

Cherie