Just two weeks ago, there NEJM published an even stronger editorial against FDA preemption in the Jan. 3, 2008 issue. They described the current cases before the Supremes as having “momentous” consequences for patients’ rights and companies accountability. Read the editorial. “Momentous” means cataclysmic.

When the two major medical journals go out of their way to defend what trial lawyers do against FDA preemption, you know you have a “momentous” issue indeed.

- Company sends Medwatch reports but, knowing the limits of ODS resources, camouflages the more serious and less known AEs (that it knows about) behind other AEs that are headlined in reports. Thus, there is “compliance” in letter, but the opposite in intent = essentially leaving FDA to find needle in haystack, what Jerry Avorn of Harvard calls “passive-aggressive compliance.” (There is much delay in reporting also that FDA could - theoretically - take sanctions over, but, in practice, never does.

- Company does its own internal studies which suggest potential problem but does not report results to FDA, or cuts short the study as soon as it “looks like trouble.” This may be harder under FDAAA, but probably not impossible.

- Company reports full data set to FDA but publishes only part of it. CLASS study as published in JAMA is the classic example - the last six months not included. FDA has the data, but not docs (full data set required a FOIA to get). And, of course, FDA has no control over editorial policies of journals.

Of the CLASS episode, FDA’s Bob Temple said, “The hype [caused by published study] probably has more impact than our labelling dos.” Meaning, docs went by what they read in JAMA. Question becomes: Should a company be accountable if it can be shown it _deliberately_ misled HCPs via JAMA even though it reported accurately to FDA?

- Company intimidates researchers, or bribes them, in order to influence research done or not done (I am personally aware of some bribery instances). We hear about the high profile cases, not the ones beyond that. This, of course, is entirely outside the purview of FDA. Ought it be considered a relevant part of a company’s _potential_ accountability for what is, and is not known, about its product? (We’re not talking “vigorous scientific debate” here, we’re talking c-notes in briefcases).

This is a very small sample of some of the issues that arise in civil liability that are essentially not covered by FDA regulation, or covered only partially. A good summary of the impact of this sort of behavior on what we learn about drug safety - that we would never have learned from FDA alone - is in a Commentary by Kesselheim and Avorn that was in JAMA in Jan. 2007. Sorry I don’t have the exact reference in front of me, but the title was something like “The Role of Litigation in Drug Safety.”

The company actually has a broader and deeper understanding (a more complete picture) of safety information about their product as they have data for reported AEs that may show a trend related to safety and/or data from ongoing studies that aren’t reported to the FDA. An HCP (including pharmacist) is supposed to report any AE that is considered to be possibly, probably or definitely related to the product(s) via MedWatch. You run into a couple of problems with this: #1 HCPs don’t utilize the MedWatch reporting system as they should (i.e., if an AE is listed in the PI or is considered a class effect they don’t bother reporting it even though this information is really key for accurate post-market surveillance), they tend to limit reporting to significant events that they are really sure is related to the product; #2 events considered to be odd may not be reported because they don’t see a direct causal relationship even when the event resolves after discontinuation (few docs rechallenge); #3 if the event doesn’t appear to be serious or severe, they tend not to report things they think are nuisance events. Even in clinical trials, I’ve had to fight with investigators to get them to report AEs that they assume aren’t related to study drug or are related to the disease under study or a co-morbidity (they are supposed to report all AEs in studies regardless of relationship to study drug), so you can imagine how hard it is to get them to submit a MedWatch report or even notice events unless they’re so bad and unexpected in a regular clinical setting.

A patient or HCP can report an AE to the company or the FDA’s medwatch number. The company must report the AEs to the FDA. The FDA does not need to (and often does not) report AEs it receives directly from a patient or HCP to the company. So doesn’t the FDA have the only complete picture of reported AEs?

Shouldn’t that leave the FDA in charge of regulating the safety information?

The latest FDA “rule change” is about as naked a power grab as it gets, and perfectly timed to support, no only preemption in general, but the three preemption cases the Supreme Court will hear this term. You’d have to be paranoid _not_ to see the connection!

But Congressional condemnation is not enough. A bill needs to be passed that explicitly says that it is the intent of Congress that FDA compliance complements, but does not fully preempt, state tort liability. That has been the situation for one hundred years (except in my own state).

Congress had a chance to do this as part of FDAAA but they balked to get the bill through. Perhaps that was necessary. But tomorrow is another day.

We’ll see if it is also a different Congress.