Led by FDA critic Bart Stupak, 17 members of the House Energy & Commerce Committee wrote a letter to FDA Commish Andy von Eschenbach to ask that the agency withdraw its
recently proposed rule allowing drugmakers to make changes on their product labeling. As they see it, the rule would set a new standard leading to fewer warnings by drugmakers, longer agency reviews and delays in communicating problems to consumers."We have profound concerns with these changes. It is unclear why an agency that is clearly in crisis would seek to limit consumers’ access to information about crucial health and safety risks," the wrote. "....We believe the FDA’s proposed rule directly contradicts this language by reversing a drug manufacturer’s obligation to warn of new risks and hazards and, instead, allowing these companies to claim immunity from liability because they had no duty to warn. This is contrary to congressional intent and to the FDA’s mission to protect the public health." This is the letter.
At issue is preemption. Pharma has been arguing that FDA labeling should trump state court judges and juries because the agency's actions are the final word on safety and effectiveness, which is found in the labeling. And if drugmakers have less latitude to make changes, they can use FDA regs as a defense.
Earlier today, the US Supreme Court left intact a ruling that allows product-liability suits against drugmakers in Michigan to proceed if plaintiffs can show that a drugmaker misrepresented or withheld info from the FDA that would have prevented the agency from approving the drug. A broader preemption case will be heard this fall. You can read about this here.
Besides Stupak, those signing the letter include Gene Green; Lois Capps; Jay Inslee; Jan Schakowsky; Maurice Hinchey; Diana DeGette; Mike Ross; Charlie, Melancon; John Barrow; Eliot Engel; Tammy Baldwin; Anthony Weiner; Michael Doyle; Tom Allen; Hilda Solis; and GK Buttefield. This is the second time that a group of lawmakers has written the FDA to complain about the proposed rule.
11 Comments
Fantastic. Democracy in action as opposed to the special interests in action.
Actually, as a former industry executive I find this very troubling. Skepticism aside, some companies will indeed take progressive action in making changes that address safety. It will be a distinct and real competitive disadvantage because others will not.
Another reason I'm glad to be out of the industry.
The crux of the new language is "reasonable evidence of a _causal_ relationship" for manufacturer-initiated label changes prior to formal FDA approval. The older language spoke of "reasonable evidence of an association" while explicitly stating that "a causal relationship need not be proven."
It may read like a small difference, but it is enormous in its implications. As Ed's post suggests, most claims against manufacturers involve some version of "failure to warn." As Bob suggests, bad actors could very easily hide behind the proposed rule change via the claim that FDA prohibited them from initiating a warning unless there was something approaching evidence of causality - a high bar in the AER business, as we know. There is a spectrum of likelihood that drug/device A is responsible for AE B, and this would ratchet the trigger for reporting up a few notches.
I'm a little torn on this issue -- I understand clearly what Justice and Bob are saying, however the warnings presented on pharmaceuticals these days list SO many possible side effects that its hard to interprit which (if any) side effects pose a real and significant risk. Wouldn't the existing language encourage a company to laundry list essentially every potential side effect with the hope of simply stating "We warned you!" and thereby avoiding a lawsuit?
If you list everything, then when your rep goes to sell your drug against a competitor in the same class, the competitor rep can say, "use our drug, we don't have warnings x,y,z." So there is a downside to listing everything. I don't know which factor - listing everything to cover your butt, or keeping your list brief to look better - works out better economically. Hopefully the law can be written to encourage listing all pertinent warnings/adverse events, and not listing any extra warnings. That system, although easier said than done, would most benefit the patients.
would have guessed that Nathan's suggestion is right - since we know that labels have little impact on rx'ing (with the exception, and only some, of black boxes) - it would seem logical to "pile them on" to cover against liability.
Yet, as I understand it, this usually doesn't happen. Of course, we have the famous case of Merck/Vioxx fighting a stronger label change that they seemed to have believed (based on what has been released) would have really hurt them via Pharmacia-Pfizer/Celebrex. But that is one instance. And, of course, when the label finally did change, they clearly were less liable (as cases went) and sales were not impacted.
That's perhaps a special case. Would be interesting to see how this breaks down across head-to-head blockbusters vs. other categories.
In the spirit of Jack2's comment, we already have the various categories of what is "rare", "very rare," etc., and the grab bag category of what has been reported with no basis to suggest strong association let alone causality. To the extent that labels influence either rx'ers or pts, that system still seems better to me than what has been proposed.
I just can't believe my eyes! The FDA wants to place safety changes to the label in the hands of the pharma companies? Given their past history of not always being forthcoming with such information, this will just make it easier for them to avoid bringing things up. First, it's fine for reps to off-label promote with publications. Now, it's fine to leave safety labels in the hands of pharma. Just what will the FDA be doing? perhaps the pharma companies should be able to bring products to market without review and approval! Maybe we ought to go back to allowing traveling snake-oil salesman going from town to town with their wares on a wagon? No guarantee of efficacy or safety, but I'll sell it to you for a profit anyway. Astounding! Andy needs to go quick before he inflicts any more major damage to the system. Helluva job, Andy!
The rare (eg 1% or less)/very rare (eg 0.1% or less) etc system is gone from the new physcian's labeling rule format. All new drugs will use this format, and many older drugs will switch to it.
As part of the swich, nomenclature changed - now we call them adverse reactions instead of adverse events. The goal is to only include reactions that are really caused by the drug, and not just every bad event experienced by people who happened to be on the drug. Outside of the legal/marketing ramifications of this it should help day-to-day HCPs. Now when adverse event X shows up in patient they can check the label - if it's in the label then switching/discontinuing the drug should help reduce/eliminate the adverse reaction. If it's not in the label it probably isn't a result of the drug. At least that's the goal.
Remember besides the intense legal ramifications of the PI, they are still used some time to advise real healthcare choices for people.
Jack2 - Thanks for this post. Isn't it still true that there is a ten-point scale indicating degree of likeihood that a particular AE was, indeed, caused by the drug.
If so, do you think FDA's proposal will raise the bar for how high a number "qualifies" for label inclusion?
Personally, I experienced an AE from an eyedrop that was not listed on the label. The med had been out for ten years, so it was certainly not common. At the same time, it is an AE listed for one other drug (of five) in this class.
Thanks to an interested med student, working for one of the top opthies in the country, a few other cases were found. Given the relevant pt. histories - how many retrials, impact of stopping, other conditions, etc. - the likelihood was rated at 7 and written up in the Archives of Opthamology. I don't know if it has, or will, appear on a revised label.
What this says to me is that, even with our present system, we are missing a helluva lot, certainly on the labels. I do not think missing more is good policy.
Justice says: "What this says to me is that, even with our present system, we are missing a helluva lot, certainly on the labels. I do not think missing more is good policy."
True -- but before long you'll end up with a 10 page document of possible (mostly unproven) side that may occur upon treatment with the drug. What is to stop my company from listing EVERY possible side effect that it can imagine? As far as I can tell, nothing prevents it. I can't read a current drug label and tell you what side effects are likely to occur and what side effects are just "laundry listings" of theoretical side effects.
Some perspective of the risk needs to be presented. Causation might go too far -- I agree. However, forcing the FDA to make the judgement call on relative risks of side effects seems perfectly logical to me. The FDA must approve claims of benifit before such changes go on the label, so why shouldn't they also approve claims of ill-effect? Isn't this what we fund the agency for? If they don't have enough funds to approve such changes in a timely manner, then its time to increase their funding!
I'm not sure exactly what your referring to in the 10 point system. The old system tried to estimate the frequency of an adverse event from 0.01%-1%. My understanding is that now, someone at the FDA is looking at the AEs and deciding what's reasonable to include. I can think of a few factors they might consider... -How frequent was the AE relative to placebo -How serious was the AE -Do other drugs with a similar mechanism of action cause this AE ...but I don't really know exactly how they decide. I know a bunch of adverse events in our label dropped out when the label switched to PLR format, and I know people in our company didn't specifically advocate for them to come out (or really care - the drug's near the end of it's patent life), but they still came out all the same. There's good and bad to this new label, but without a doubt I think the change makes the labels much more USEABLE for busy docs/pharmacists etc.
20% of my job is answering calls from docs on our drugs. A lot of times they would ask about a given adverse event. In the past, I'd report the incidence, but they still didn't really know what to do (docs know about laundry list too). Now when they call me with a patient experiencing an adverse reaction, and I find that adverse reaction in the label, I can tell them with confidence that it's reasonably likely the drug contributed to the adverse reaction. Then they know to think about changing meds or reducing doses.
All the extra "noise" in the label makes every individual thing in the label less useful. The new label better informs action at the patient label, IMO.
FYI, the new labels contain this statement:
Throughout this section, adverse reactions are reported. Adverse reactions are adverse events that were considered to be reasonably associated with the use of DRUG® (adverse drug reactions) based on the comprehensive assessment of the available adverse event information. A causal association for DRUG® often cannot be reliably established in individual cases. Further, because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.