Wednesday, May 06, 2009

Plavix, Proton Pump Inhibitors, and Data Mining

This morning I was privy to a study that will be released in tandum with this blog post (I was sworn to secrecy by the PR firm that gave me a heads up about the results of the trial until 1:30 CST today). It's about another Medco pharmacy study that demonstrated inhibition of the platelet inhibitor clopidogrel (Plavix) with most of the currently-available proton pump inhibitors on the market: pantoprazole (Protonix), esomeprazole (Nexium), omeprazole (Prilosec), and lansoprazole (Prevacid). It seems they data-mined their pharmacy databases and looked for a combined endpoint (subtext: beware of data mining for "combined" endpoints - individual endpoints might not be as bad as the study suggests) compared the incidence of MI in people taking clopidogrel and proton pump inhibitors to people taking clopidogrel alone, and a higher incidence of myocardial infarction was found.

As background, here's how the study was performed (from MedCo's press release (pdf)):
The Clopidogrel Outcomes Study investigated medical and pharmacy claims data of 16,690 patients who
were taking clopidogrel following a stent procedure and tracked the study subjects (editors note: using pharmacy and medical claims data) for a 12-month period from 2005 to 2006. The study compared a group of 6,828 patients who were concurrently taking a PPI and clopidogrel to a group of 9,862 patients who were only taking clopidogrel. When PPIs were examined individually, all of the associations were highly statistically significant.
No prospective data, mind you, but the results were "highly statistically significant."

Now, is this evidenced-based medicine or correlationally-based medicine? Not that these data might not be important. But when we use medical claims data to guide medical treatment recommendations, as Medco seems to be suggesting, we tread on a potentially very slippery slope. For instance, the presence of "myocardial infarction" on a medical insurance claim may be there to assure payment for services rendered, rather than to identify a new heart attack. As such, claims data are notoriously poor at conclusively identifying clinical endpoints. Should physicians change patient's medication regimens based solely on datamining studies like this? Or would prospective randomized trials be more appropriate to make treatment recommendations? Can the claim that this interaction "increased hosptial costs by 40%" (as their press release claims) be substantiated? Or is this a means of marketing Medco's services to their clients, the largest of which might become the federal government?

It is interesting to note the rush to datamining as the United States implements rationing policies in the name of "personalized medicine." But we only have to harken back to the days of PVC suppression in my field where we thought that reducing PVC's must inherently be helpful at reducing sudden death risk. These assumptions started on the basis of correlational analysis. Only though a carefully-designed prospective, randomized trial (the CAST Trial) did we find the opposite was true: that antiarrhythmic medications designed to suppress PVC's actually increased mortality.

While general correlations are helpful to identify areas for future study, we have to be cautious not to leap to full blown treatment recommendations based on retrospective correlational studies derived from database mining alone.



Anonymous said...

A claim like theirs, based on their study design, suggests one or both of the following:
1. This is a marketing ploy
2. They have no idea what they are doing.
Evidence-based medicine should not be practiced with retrospective claims data as its "base." Period.

Rogue Medic said...

I consider CAST to be possibly the most important medical study we have. One reason is that it was not stopped at the first hint of adverse outcomes. Studies are stopped early, but then do not convince doctors to not use those treatments, because those data do not apply to my patients. While stopping the study early may be safer for some study participants, the result is that more patients will probably receive the potentially dangerous treatment.

How did they find more patients taking clopidogrel without a proton pump inhibitor than those taking clopidogrel with a proton pump inhibitor?

Would these patients be better off taking coumadin with all of its problems?

I like their certainty about this effect - use of PPI therapy in conjunction with clopidogrel increases related hospital costs by at least 38 percent.

at least 38 percent - There could not possibly be less than a 38% increase in costs.

less than 38% - Impossible.

less than 38% - Inconceivable.

I suppose they have a 100% confidence interval.

Sarah said...

Thank you for this blog post on ppi's. There was a recent release of a Canadian study that prompted the powers that be to release info prior to publication due to public health concerns. No peer review=hysteria over nothing! Following the questions and revisions to that "study" has been a comedy of errors. They miscalculated some of the math, excluded and or included parameters that could effect data, and lumped certain ppi's as bad while only giving data on 2:4 listed and proclaimed Protonix as the only safe ppi to use with plavix. However, in their own data there was no statistical significance in the difference between "bad" and "safe". Furthermore, they recommended certain h2s despite knowledge of metabolic pathway interactions far more significant than the "bad" ppi's. So the "payor" in this case "Canadian " govt warns perhaps no ppis should be used unless they are protonix? Then in the us we have several studies that are all data mining sponsored by payors that don't publish all of the data but many have done posters. So the exact numbers and subjects in each ppi analyzed is unavailable. You have "medco" asking pharmacists to get PTs to switch to h2. Ofcourse there are bonus $ and incentives to pharm to make such efforts. Ppi's the largest most expensive chronic use class of drugs and payors are conducting studies in the name of "patient concern"! Hogwash! I often wonder why insurance companies aren't required to do the strictest of studies themselves and then gain peer review publishing and then FDA approval prior to discontinuing payment for certain drugs or issuing "warning" letters to drs and pts. Don't even get me started on their incentives to pharmacy. Insurance is the single most profitable and uncontrolled "healthcare" provider in the US! My insurance agent went to Hawaii 3 times last year! Poor thing! In the south we have a saying for idiots that drive us crazy but we are to polite to be direct. It goes like this "well bless your heart!" To the authors of such studies and the payors that funded them I say "well bless your heart- you must be so proud of such intellect displayed so proudly on those posters!". I'm off to have a mint julep now!