FDA Panel: Tighter Standards For Diabetes Drugs
13 CommentsBy Ed Silverman // July 2nd, 2008 // 4:51 pm
An FDA advisory committee voted 14 to 2 that all new diabetes drugs should undergo longer studies to ensure cardiovascular risks aren’t increased, a move that is expected to cost drugmakers untold millions of dollars to conduct additional clinical trials, the Associated Press reports.
The recommendation comes less than a year after the FDA was criticized for its handling of heart risks connected with Glaxo’s widely used Avandia diabetes pill, which was approved in 1999. The agency, however, didn’t add a warning about potential heart risks until last November, the AP notes.
The majority of the panel said drugmakers could begin safety testing, which is expected to take between five and seven years to complete, before they submit drugs to the FDA and finish the studies after their release, the AP adds. But at least one FDA panelist doubted whether the proposed studies would actually uncover heart risks.
“If you wait this amount of time for testing you’re going to be preventing certain drugs from getting out there that may be better than what we already have,” said Eric Felner, a pediatric specialist at Emory University School of Medicine.
If the FDA adopts the recommendation, the development of diabetes drugs would become longer and more expensive, since it can cost tens of millions of dollars to perform long-term studies to track heart problems in thousands of patients, the AP writes. Nearly 24 million Americans have Type 2 diabetes.
The FDA was pressured to reconsider how it approves diabetes medications after a meta-analysis released last year showed Glaxo’s Avandia may increase the risk of heart attacks by 43 percent.
The agency currently approves diabetes drugs based on their ability to lower blood sugar levels, since the condition is characterized by excessive blood sugar. Steven Nissen of the Cleveland Clinic Foundation, who authored the Avandia meta-analysis, said that criteria has little value if drugs also increase heart problems.
The FDA is operating under “the irrational belief that lowering blood sugar using virtually any pharmacological means will produce” better results, he said, and recommended the FDA require drugmakers to prove their drugs don’t have significant heart risks before granting approval. After drugs are available, drugmakers would be required to complete large, multi-year trials to confirm safety.
FDA scientists and outside researchers have warned that saddling drugmakers with additional safety requirements could slow the development of new medications.
“The fallacy here is that we will never know everything we’d like to about a drug before it goes on the market,” Ray Woosley, president of the Critical Path Institute, a non-profit working with the FDA to speed drug development, tells the AP. “If we held up drugs until we did know everything a lot of people would die.”
Approving drugs based on biological measurements, like blood sugar levels in diabetics, is thought to be a promising method for speeding-up drug development because the results can be gathered relatively quickly, the AP writes.
But that approach is under scrutiny, as some lawmakers and medical experts believe the FDA should not approve drugs without evidence they improve more meaningful measures like increasing patients’ life span. The Senate Finance Committee is investigating the FDA’s approval of Avandia and another drug Vytorin, which was also cleared based on biological test results.
The agency approved Vytorin, which is jointly marketed by Merck and Schering-Plough, based on its ability to lower bad cholesterol, which is widely believed to reduce heart attacks and deaths. But as the AP notes, a study released in January showed Vytorin was no more effective at limiting deadly plaque buildup than a low-cost generic drug.
Since then, the FDA has denied approval of another highly anticipated cholesterol drug from Merck, prompting speculation by analysts that the agency is raising approval standards for those medications. The FDA has not said whether such changes are in the works, the AP adds.
Source: The Associated Press
Justice in MI
I often agree with Ray Woosley, but his commentary as quoted here - that anyone is advocating “that we know everything we’d like to know about a drug” before marketing - seems to be a gross disortion of what is being considered here.
Again, it is a question of weighing risks/benefits, scale of impact, alternative therapies and their efficacy/safety, etc. etc. This is a subtle process, to say the least.
The preemptors have been telling us repeatedly how excellent the FDA is at doing precisely this. And that their expertise in such considerations should not be second-guessed.
Am I hearing some folks are say it _is_ OK to “second-guess” the FDA?
If so, who would have the right to do that? In other words, what defines the circle you have to be inside to “second-guess”? (We know that “lay juries” are excluded by those who favor preemption.)
Justice in MI
I’ve been trying to find out who were the sixteen members of the advisory committee who voted. Anyone have a link? Thanks!
CMC guy
JIM there is often a lag on FDA site between draft and final but think following will provide some data for this meeting:
http://www.fda.gov/ohrms/DOCKETS/ac/cder08.html#EndocrinologicMetabolic
Perhaps Woosley’s comments are part hyperbolic however it is true that it is always impossible to learn everything upfront. In order to retain manageable trials One tries to monitor risks/benefits as much as possible but the noise is generally too high thus can not know what is causal relationship. More focused studies (such as I think may be subject here) may or may not be able to provide the true signal. Doing more animal models/studies likewise reach limits.
Ed Silverman
Hi JIM,
Here is the committee roster…
http://www.fda.gov/ohrms/dockets/ac/08/roster/2008-4368r1-FDA-committee.pdf
Cheers
ed
Justice in MI
Thanks CMC Guy and Ed - As will probably not surprise you, I was curious how many of the panelists had ties to cardiology or, in some other way, some potential conflict of interest in voting as they did.
At least as I understand it, they voted 14-2 essentially endorsing the same view that Naissen articulated. In the thread about him, a number of folks ridiculed him personally and suggested that his opinions should be scanned for COIs.
I’m all for scanning. But here are 16 people of whom 14 said, in essence, the same thing. They are mostly endocrinologists (not the sort of people you would think would want to fight the development of diabetes drugs). Plus a statistician, health educator, and one lipids/cardio person.
Anybody think they were “going after” pharma to line their own pockets?
CMC guy
JIM I think your 14-2 endorsement statement may be an over simplification (or reductionism to borrow from Dr. Helm) as need to see the specific questions plus the discussion that took place to understand the vote (questions should be part of meeting package, transcript typically follows in few weeks). Generally these meetings are very narrow so what may appear solid in the context does not consider broader issues of importance. I will generalize myself and say “Ask a scientist if they want more data and invariably expect the answer to be yes”. I don’t have enough info to reach any conclusion you have and would assume people are mostly honorable so your final question lacks substance.
Based on available past information Nissen should require a level of scrutiny as a pharma critic in the same way occurs with pro-pharma people. I don’t know much about his particular COIs but comments I have seen out of him seem more ego enhancing than patient concerns.
Ed Silverman
Hi CMC,
If you go to this link, you can read the COI waiver given Nissen. It doesn’t name specific drugmakers, but you can get an idea…
http://www.fda.gov/ohrms/dockets/ac/08/waivers/2008-4368w1-00-index.htm
ed
Justice in MI
CMC Guy - You are entirely right - to really understand what was being endorsed we need more info. I think that’s why I said somewhere on the Nissen thread that I wasn’t sure _what_ was being recommended (by him). So I plead guilty to reductionism in the absence of knowing more. It’s a good word to use, especially here!
Re: the last bit, I was being “ironic” in a probably indulgent way. I read some of the Nissen thread comments as having their own reductionism - not only that potential COIs should be considered (which I said there I agreed with) - but there was a little trashing going on too. Presumption of guilt, at least as I read it.
is Nissen really a “pharma critic” or at least the opposite of those who are “pro-pharma”? That, too, seems a bit reductionist to me. But I do agree that “ego” does not seem to be one of his deficiencies.
Nathan
So, the way I read it, the new CV risk trials just need to be *started* (not completed) before approval. Is that the way you guys understand it? If so, then this really is just an added cost - not a delay. Also, per the previous comment thread, it seems to apply only to diabetes drugs — not to all drugs for cardiovascular and metabolic disease (as seemed to be implied in the previous article).
Bottom line IMHO: It’s an additional burden for drugmakers, but not as bad as it could be.
CMC guy
Ed I was aware of posting of the Nissen COI waiver but had not taken time to read earlier. The financial stuff is fairly typical of what have seen. Most interesting are comments about his known pharma (& FDA?) criticisms and how he provides an opposing and/or diversity point of view (not sure ever seen so blatantly stated invitee rationale). So for balance of opinions think they should have invited PHARMA’s Tauzin?
Actually I believe I recall reading Nissen has close ties with certain strong anti-pharma Beltway Politicos but not sure who (Grassley?)? Also suggestion has been made he is positioning to become future FDA Commissioner. These would be relevant COIs as underlying motivations that would not be expressed in the waiver letter.
Margaret
If I could vote, I would sure vote for Nissen to become our future FDA Commissioner. Yes, he has an ego, but he also has more than his share of ethics and morality - qualities sorely missing in the industry, medicine, and government.
And, yes. Grassley is THE leading light battling Pharma. Thank heavens for him, at least.
Justice in MI
Obviously, I know what we all mean by the terms, but (again, in the interest of avoiding reductionism!), I think there are very few people who are “against pharma.”
Yes, there are those out there in the world who think that statin is satan spelled backward, who believe it’s all a conspiracy against garlic supplementation, etc.. But here we’re talking about specific policy issues - DTC, preemption, reps, etc. - upon which we have a wide range of views. But I see very few that that the pro/anti pharma dichotomy covers.
The best threads are when we see the range of views within a core consensus about what the issues are and, within whatever differences, learn from other.
Kumbaya.
(And agree with Nathan that we need specifics here about what is being recommended.)
Ed Silverman
Hi CMC,
Sorry for the belated reply. I agree that COI form is standard, but I posted it because folks like to see that sort of thing anyway. I don’t know for a fact that he’s close to Grassley’s staff or others in DC, so I chose not to include that for the obvious reason. Same thing for any aspirations; he’s never confirmed the speculation, or accusation, as it comes across when some discuss it.
Of course, the Cleveland Clinic may benefit when industry conducts tests. But there’s no guarantee what will happen as a result of the commmittee recommendation. I’ll leave that one to others to debate, because I’m sure there will be strong views, given the emotions Nissen generates anytime he’s at the center of the action.
Cheers
ed