Salmon

The facts are we have a possible public health risk (Cancer) without out a clear demonstrable benefit on a clinical outcome. In fact the labeling for Vytorin (it’s available via googling Drugs@fda) clearly states that although Vytorin effects plasma clolesterols, triglycerides, and lipids there is no evidence that this will result in a clinical benefit. In other words these there may not be a cause and effect with clinical outcomes, e.g. heart attacks.

As for ‘accepting that most responsible commentators seek outcomes, or “improvement” data primarily for “me too!” drugs — before granting FDA approval.’

This is not the legal standard that FDA must use. Only that a drug is safe and effective and for a combination product that each drug together provides more oomph than either drug used alone (and is not more dangerous).

Determining whether a drug is safe is a judgment call and safety is perceived relative to the condition and to other drugs for the condition and whether there is evidence that some individuals may benefit from a new drug(s) who clearly don’t benefit from available treatments and that the benefits outweigh the risks.

Presumably when the judgement is close there should be an advisory committee and full discussions are made in public. In truth the advisory committees members are often not given all the information and in some cases the AC meetings are even rigged (personal knowledge).

Although FDA is calling for quantitative risk assessment in guidances, when you look at the references the FDA uses this quantitative assessment refers to the economic impact on the company. It is not what clinicians would think is important which is the marginal improvement relative to the risk, e.g. if 50% of people get a true clinical improvement on drug vs. 30% on placebo (thus only 20% of people taking drug get a benefit, yet 10% of everybody get a lifethreatening side effect within before you even have a chance to determine if the drug is working, thus for every 100 people started on drug 20 will get a benefit but of these 20, 2 (10%) will have a lifethreatening side effect. In addition 80 will have have no benefit and of these 80 8 will have a life threatening side effect. Consequently you get 10 people with lifethreatening side effects for every 2 people getting a benefit.

In addition the way the safety evalutions have been set up by Pharma and the International Conference on Harmonization (which FDA must follow) if side effects are due to long term exposure, e.g. Vioxx and possibly even Vytorin and CA it would only be picked up if the rate is greater than 3.3%, this includes death.

Plus new FDA labeling rules exclude inclusion unless the rate is greater than 5% and is double the placebo rate. Yet with noninferiority trials and the claimed unethical nature of using placebo in long term safety studies it’s impossible to detect or label this with initial approvals under FDA rules. Thus we’re left with epidemiological studies that may or may not be done and will be argued over for years.

Remember all of these rules were implemented with input from pharmaceutical companies and if there was any input from consumers they likely lacked the acumen to realize what was really going on.

Salmon

You are right about statins and doctors grasping them for thier patients since mevacor. Yet at that time (mid 1980s), cholesterol lowering drugs were cumbersome for patients as far as intake and side effects go, and LDL lowering was not in the spotlight then like it is now regarding the correlation between lowering LDL and reducing CV events.

Now, some are suggesting statins have the same status as aspirin as far as taking one for preventitive reasons, regardless of how well your cholesterol level is.

Paul G. — I think there ought to be a disctinction between a novel drug — one which meets an entirely unfilled need — and a “me too!” after the fact offering.

Vytorin is in the latter category; Lipitor: the former.

When statins were first being approved, there was nothing like them. More on this, soon, here:

http://shearlingsplowed.blogspot.com/2008/09/new-england-journal-of-medicine-weighs.html

Adding some other medicine to a statin strikes me as a “me too!” move. To properly frame the debate, we ought to accept that most responsible commentators seek outcomes, or “improvement” data primarily for “me too!” drugs — before granting FDA approval.

Thus, IMO, your concerns seem a little overblown.

As with other new medications, doctors want the evidence before they will conclude anything about a drug.