This afternoon Dr. Nissen has been invited to give a talk at a two day hearing of the Endocrine and Metabolic Drugs Advisory Committee designed to “discuss” the role of evaluating cardiovascular disease and/or risk in diabetes drugs. His topic? The need for cardiovascular assessment.
He will make the case that the way to determine whether diabetes drugs prevent or reduce heart attacks is to conduct experiments in which certain people are prevented from taking a drug that will reduce them.
Or will he? Depends on which way the political winds blow and the money is wired.
I as have noted on many occasions, Dr. Nissen uses surrogates – the media – and surrogate measures to get what he craves, exposure and a reputation as some sort of crusader that neither the FDA nor drug companies dare cross. In point of fact, he is mostly best shakedown artist this side of Al Sharpton.
We know that Dr. Nissen never lets science or statistics get in the way of a good soundbyte or payday. Apparently two large studies of diabetics – ACCORD and ADVANCE – which measured whether drastically reducing and controlling glycemic indexes and used reduction of CV risk, as an endpoint are not enough for him. The two large studies used different strategies and drug combinations to get people below a certain A1c level. ACCORD did so more rapidly than ADVANCE. Both used Avandia extensively (ACCORD more so) – and found no reduction in heart attacks. ACCORD had a slight increase in heart attacks but at the end of the day, Avandia was use in combination with other drugs in both studies. Some benefited, some did not. Overall there was no reduction in heart attacks. And there is no evidence that Avandia was associated with either.
www.theheart.org/article/874809.do
So what will even longer and larger clinical trials show? And should such studies, which take years to complete, be a precondition not only of drugs for diabetes but – as that Nobel Prize winning scientist Charles Grassley has noted, for every medicine for every disease?
I am sure Dr. Nissen has a better answer.
And I bet it will be coronary intravascular ultrasonography (IVUS), which involves the insertion of a catheter into the coronary artery in order to measure the size of an atherosclerotic plaque.
IVUS is the "imaging technique that is the hottest and most important right now in anti-atherosclerotic drug development.”
www.pharmaasia.com/article-6017-imagingsharpensdiseaseresearch-Asia.html
Who said that? Dr. Nissen. And who conducts most of the IVUS studies in the US.
Dr. Nissen.
Indeed, Dr. Nissen says that a number of drugs currently in clinical trials are aiming to use imaging as a primary endpoint for registration.
I am sure they are and I wonder who is conducting those trials?
Not that there is anything wrong with tooting your own horn so to speak as long as you don’t seek to infer from ”surrogate measures” studied in Phase I anything conclusive about how the drug will work…..
Nissen regarded the surrogate measures in ENHANCE as unreliable. So why in 2003 did he propose to Merck and Schering-Plough a IVUS study of Vytorin called QUEST: "short for Quantitative Ultrasound Ezetimibe and Simvastatin Trial. Ezetimibe and simvastatin are the generic names for Zetia and Zocor, respectively."
That study, according to Nissen’s Boswell, Matt Herper of Forbes.com, would have been an 800-patient study to see if adding their new cholesterol drug, Zetia, to Merck's cholesterol-lowering blockbuster Zocor can prevent plaque from collecting on the artery wall better than Zocor alone. The patients would be followed for 18 months.
www.forbes.com/2003/11/10/cx_mh_1110merck.html
Merck nixed the study and went with another group and IVUS approach to run what became ENHANCE. Same method, different bank account.
Nissen pounced, saying there was no reason to use Vytorin at all.
But if Nissen, as he most recently claimed, believes in an individual approach to reducing LDL and glycemic levels why ban a drug because it doesn’t work IN GENERAL or because it make aggravate risk because of meta-analysis. Why not promote the Critical Path and more patient specific approaches to life cycle management of drugs including adaptive trials designs and biomarkers. Could that be competition for IVUS perhaps?
Will Nissen promote larger trials that keep important drugs away from people to promote IVUS in favor of a path that target safer more effective therapies using tools other than those he is paid to operate?
It is hard to stay on message when you are trying to stay in the headlines.
Or line your pockets.
