Monday, November 21, 2011

Some Capsules of Recent Pharma-Related Escapades

I've previously mentioned the Primary Care Medical Abstracts program run by my friends Rick Bukata and Jerry Hoffman, in which subscribers receive a CD each month with commentary on 30 recently published papers from medical journals. Since both Rick and Jerry are concerned about the impact of Pharma marketing on medical science and practice, it's not uncommon for several of the papers each month to address topics of interest to this blog. The October, 2011 issue had an especially impressive bumper crop. Here are capsule summaries of some of the papers.

Who's Marketing the Heck Out of Useless Cholesterol Drugs?

Before statins came along, an older class of drugs, the fibrates, was employed in attempts to lower cholesterol. Recent research has documented thoroughly that these drugs have no place in the medical armamentarium. Yet these authors noted a 117% increase in fibrate prescriptions between 2002 and 2009. Was this because physicians all on their own decided to go back to this old class of drugs? Hardly; the data show that newer brand-name fibrates are selling much better than older generics. So it seems that creative drug marketing has resurrected a class of drugs that should have been sent to the retirement home long ago.

Jackevicius CA, Tu JV, Ross JS, et al. Use of fibrates in the United States and Canada. JAMA 305:1217-1224, March 23/30, 2011

Data Dredging: Which Studies Do It the Most?

Here's a basic rule of statistics and study design--when you do a clinical trial, you are supposed to identify up front a handful of primary endpoints. You announce in advance that these are the outcomes you are going to be looking for to decide if your drug works or not. If you do it this way, and your results reach statistical significance, it's unlikely that any results you find are due to chance. But what if you then go back and look at your data to see if you can't find other associations--such as maybe older patients did better than younger patients, or those taking another drug did worse than those on the one drug only, or whatever? When you start doing these subgroup analyses, then you run a much higher risk of finding spurious associations. The common name for this practice is "data dredging" or "data snooping"-- it's a fishing expedition, not legitimate research.

These authors looked at 469 trials published in the supposedly best medical journals in 2007 to see how often data-dredging happened and what was associated with it. They found that the supposedly better the journal, the more likely data dredging was, and not surprisingly, drug-company-sponsored research was much more likely to engage in data dredging than other research. Also not surprisingly, if the primary outcomes were achieved, then data dredging was at a minimum, but it rose as soon as the primary outcomes failed to achieve statistical significance. In other words, when your study is a flop for your drug, then keep digging until you can find something good to say about the drug anyway.

Sun X, Briel M, Busse JW, et al. The influence of study characteristics on reporting of subgroup analyses in randomized controlled trials: systematic review. BMJ 342:d1569, March 28, 2011.

A Guideline Is a Guideline Is a Guideline--or Not

There's been a highly publicized difference of opinion over whether kids aged 2-10 need to be screened for cholesterol. Recently the American Academy of Pediatrics issued a guideline that said yes; but all along the U.S. Preventive Services Task Force has said no. In this paper members of the USPSTF fire back at the AAP. The USPSTF folks list a number of criteria that they use in writing their guidelines for preventive screening. They use a standardized approach to evidence and reject studies that are of poor quality. They rigorously exclude anyone with financial conflicts of interest from guideline-writing. They insist on using the actual evidence rather than relying on other previous guidelines that may not have been rigorously based. They also make public exactly who served on the guideline panel. The AAP guideline committee, these authors note, followed none of these criteria.

Grossman DC, Moyer VA, Melnyk BM, et al. The anatomy of a US Preventive Services Task Force recommendation: lipid screening for children and adolescents. Archives of Pediatrics and Adolescent Medicine 165:205-10, March 2011.

A Debate on Antidepressants

Finally, the British Journal of General Practice featured a pro-con debate over prescribing antidepressant drugs. Middleton and Moncrieff start off by noting that authoritative national guidelines suggesting that drugs be restricted to moderate-to-severe depression seem to have had little impact on profligate prescribing. They summarize recent research (as we have previously reviewed in this blog) that most antidepressants are nearly indistinguishable from placebo in their effectiveness, and that the theory that depression is fundamentally a disease of chemical imbalance in the brain has been vastly overblown. They conclude that since most of the good done by antidepressants seems to be a form of placebo effect, which relies on forming a strong therapeutic relationship with the patient and showing that one takes the patient's problem seriously, cognitive-behavioral psychotherapy is an excellent alternative to drug treatment and should be more widely used.

In reply, Anderson and Haddad basically change the subject and accuse Middleton and Moncrieff of saying a number of things that they don't say. From their doubting the serotonin theory of depression, Anderson and Haddad assume their opponents are guilty of mind-body dualism and dismiss entirely the role of neurotransmitters in mood. Responding to the claim that antidepressants show very little difference from placebo, Anderson and Haddad pounce on the fact that they show some difference from placebo and therefore the placebo effect cannot explain all of what they do. Anderson and Haddad then say, "[F]or individual patients who will not or cannot engage in other approaches, shouldn't this evidence allow at least a consideration of a trial of antidepressants?" This makes them appear reasonable and moderate and their opponents dogmatic, though Middleton and Moncrieff are far from ruling out antidepressant use in every case. Anderson and Haddad then add that psychological therapy will be a failure if you go to a lousy therapist--neatly ignoring all the evidence of the serious risks of antidepressants, in order to focus on the purported risks of psychotherapy!

Of these two sets of authors, one acknowledges receiving financial support from manufacturers of antidepressants. I'll let you guess which.

Middleton H, Moncrieff J. "They won't do any harm and might do some good": time to think again on the use of antidepressants? British Journal of General Practice 61:47-49, January 2011.

Anderson IM, Haddad PM. Prescribing antidepressants for depression: time to be dimensional and inclusive. British Journal of General Practice 61:50-52, January 2011.

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