Steve Nissen Gives The FDA Some Advice
19 CommentsBy Ed Silverman // July 2nd, 2008 // 11:51 am
The FDA’s Endocrinologic and Metabolic Drugs Advisory Committee will conclude today a two-day meeting to decide whether clinical trials to evaluate cardiovascular risks should be undertaken before the meds are approved or after marketing begins and the drugs are used by the population at large
And one non-voting panel member, Steve Nissen of the Cleveland Clinic Foundation, gave a presentation in which he proposed the FDA raised its standards by requiring drugmakers to prove new drugs don’t increase cardiovascular disease, Dow Jones wrote.
“Merely lowering blood glucose levels in diabetes is too simplistic. We must reduce the complications of diabetes, including cardiovascular disease,” Nissen said. “I don’t think it will have a chilling effect but, if we take drugs forward that lower blood sugar but increase the risk of death and heart attack, we haven’t done diabetics any favors.”
The controversial doc suggested that, in addition to requiring more pre-approval studies, drugmakers should have large, long-term studies in place when a drug is approved to monitor whether the medication increases the risk of cardiovascular disease.
The idea is not likely to please pharma, since about 75 percent of all deaths in diabetes patients are a result of cardiovascular disease. Consequently, any move to require more pre-approval studies could slow approval and increase the costs of new diabetes drugs, Dow Jones writes.
Here is a back story with FDA briefing documents and Nissen’s COI waiver form.
Atlex
I certainly hope that Nissen pointed out that as a major researcher in CV disease, he benefits from an increase in CV-related research.
Lisa Van S
Atlex,
And so will many others,.. like the consumer,.. yes?
Vince
To actually have to prove a clinical benefit to patients what a radical idea . Certainly will not improve sales. Then again a drug that increases events really offers a way to increase sales of related drugs sort of the self generating sales machine
Atlex
Lisa,
My point isn’t whether the studies are needed or not. However, when a KOL makes a statement that benefits Pharma, critics immediately go on a witch hunt to prove a COI. When a KOL makes a statement that hurts pharma, no one ever seems to question the motivation or whether there’s a COI.
Atlex
Marilyn Mann
It is not clear to me from reading the press coverage what studies Dr. Nissen thinks should be required preapproval and which could be done postapproval.
Justice in MI
Most agree with last point - I need more particulars.
Nathan
What a way kill some very promising compounds… The addition of 3-6 years of pre-approval clinical trials will shorten the effective patent life of these drugs so much that they either become enormously expensive (multiples of today’s costs) or will simply be discontinued because there will not be enough return-on-investment to make the clinical trials worthwhile.
I agree, Altex. This guy stands to make great gains from any FDA decision requiring additional cardiovascular research. He’s the head of cardiovascular medicine at Cleveland Clinic. The Cleveland Clinic is involved in over 1000 ongoing clinical trials. Guess who pays for those trials? Do you think it’s internal? No — it’s pharmaceutical companies paying the clinic to conduct clinical trials on their products. Steve Nissan and the clinic stand to gain even more clinical trial $$$ if the FDA changes the policy to what he recommends.
Lisa Van S
Atlex,
I guess I am looking at this issue through the eyes of a consumer, safety and full disclosure,… from all sides.
Lisa Van S
Ooops. Even more importantly,… Efficacy!
James
Nathan, surely you wouldn’t impugn the credibility and unbiased viewpoint of Dr. Nissen, would you?
The same man who touted a meta-study to prove a drug was dangerous, even though he had previously discounted the validity of meta-studies as a whole?
The same man who so strongly criticizes industry, yet refuses almost all invitations to speak at and defend his view at industry conferences?
How dare you? ;)
truthman30
hahaha…
Nathan and Atlex….
You have to be joking right?
Dr Nissen has saved many lives with his Avandia warning, he is totally on the side of the consumer, and you guys try to discredit him..
Give credit where credit is due guys…
Marilyn Mann
OK, my information is that he recommended that the preapproval trials be required to show no cardiovascular harm. He also recommended that the companies be required to conduct large post-approval trials with cardiovascular endpoints very soon after approval.
Nathan
That’s a good point Marilyn — maybe my 3-6 year estimate was off. How long would a CV harm test take? 1-2 years? It seems that a pretty large patient population would have to be used. That would be fine for a major therapeutic area (diabetes) but would devastate research in orphan metabolic diseases. Hopefully an exemption would be made based on therapeutic market size.
Marilyn Mann
There are sometimes earlier approvals for orphan diseases.
I don’t know offhand how long these preapproval trials would take. If I find out anything I’ll let you know.
Justice in MI
From the bits and pieces that have come out, it appears that some very senior science people in Merck wanted to do precisely this even before Vioxx was approved, and certainly afterward. They were overridden for a variety of reasons, although - yes VIGOR, et. al., did go forward, as well as AdVANTAGE. While not done to assess CV events, they were certainly being monitored.
Wider point being - as above, this may or may not cause signficiant delay. And it may or may not be something that some comapanies would do anyway.
Meg
I will never forget the FDA’s ADHD hearing when Steve Nissan boldly called for a vote for black box warnings for this array of dangerous drugs for children. The FDA was shocked. SHOCKED! His committee was not supposed to do that but the vote passed 8-7. What a hero (to me). Unfortunately, it was business as usual when the Pediatrics Committee reversed this vote when they met later.
Not too many heroes on the FDA Advisory Committees. As I recall, Dr. Kurt Fuhrberg also spoke out in favor of the warning.
Doc
Pharma hates Nissan, but it takes someone in his position to get real attention to the issues pharma wants to brush under the carpet.
There are a number of agents that work quite well in diabetics, metformin being the major agent with proven CV benefit. Making new agents prove their benefits and/or risks ultimately helps patients.
Go Stevie!!
Justice in MI
As we now know from the thread above, the advisory committee, mostly endocs, voted 14-2 endorsing essentially what Nissen recommended.
Vince
The repeated statement here that Nissen has a lot to gain simply does not hold water. Drug companies are not going to reward a researcher who does not know how to provide the right answer. Read the history of the studies used to get Ketek approved or the NEJM editorial related to Vioxx. With the new trend toward preemption ;how long would dangerous and sometimes lethal drugs unfettered by lawsuits; remain on the market. Nissen is actually stating the old principle “First do no harm”