Friday, January 29, 2010

Clinical trial research driven by marketing, not evidence

Those of you in the mood for a serious read might want to check out an article in the Journal of Bioethical Inquiry about the way in which many drug companies use their marketing muscle to mislead physicians and consumers about the safety and effectiveness of their products.

This is not news, of course. In recent years, the mainstream media and blogs like this one have spotlighted specific examples where drug companies have achieved blockbuster profits through such smarmy tactics as ghostwriting, the suppression of negative findings, the publication of journal articles that report only positive findings, and paying prominent physicians to convince their peers of the drugs' benefits. Indeed, the illicit marketing campaigns that antidepressant makers like Pfizer, Eli Lilly and GlaxoSmithKline developed to make drugs like Prozac, Paxil and Zoloft look safer and more effective than they really were are the subject of several books, including Side Effects.

What's worthwhile about the article in Bioethical Inquiry is that it makes very clear how widespread this practice of "marketing-based medicine" is and how unreliable our so-called "gold standard" of medical research -- randomized clinical trials -- really is. In too many cases, drug companies, which fund these trials and cherrypick the researchers whose names appear on them, not only ghostwrite the results to hide negative data and overstate the positive. But they also make sure that any truly negative trials never see the light of day. And then once the misleading results are published in supposedly reputable journals, the drug companies use prominent physicians (on their payroll) to market the hell out of them.

In their roundup, the authors, Glen Spielmans and Peter Parry, show how all this worked -- not only with the antidepressant campaigns but also in the way that Eli Lilly and AstraZeneca went about promoting their antipsychotic drugs, Zyprexa and Seroquel and suppressed the drugs' negative side effects to increase market share.

Spielmans and Parry suggest an interesting, if radical, solution: that journals should cease publication of clinical trials, since the much-vaunted process of peer review doesn't seem very effective in weeding out erroneous trial results. Instead, they suggest that trial results could be published in some form of online registry, and that journal articles could focus on the validity of these trial results. Of course, this would deprive the journals of a major source of revenue: reprints of positive trial results (which the drug companies use in their marketing blitzes), as well as lucrative advertising revenue. So don't look for this kind of systematic reform any time soon.

3 comments:

Greg Pawelski said...

I did a paper on taxol and one of the researchers listed in the foot notes of my paper had told me that the study he finally published in the journal Oncology, was rejected by all other American & Europen cancer journals (Journal of Clinical Oncology, Cancer, Annals of Oncology, European Journal of Cancer, International Journal of Cancer) where it had been submitted. The journals were reluctant to publish such a scientific report, simply because taxanes (both taxol and taxotere) were at the time very intensively advertized in these journals.

Less than 20 percent of registered clinical trials of cancer drugs are eventually published in medical journals, according to a review published online by the The Oncologist medical journal.

A search of the National Institutes of Health's ClinicalTrials.gov web site identified 2,028 registered research studies of cancer treatments. Major medical journals require all studies considered for publication be registered at ClinicalTrials.gov or another publicly accessible database.

And a subsequent search of the National Library of Medicine's PubMed database showed that just 17.6 percent of the trials were eventually published in peer-reviewed medical journals.

The publication rate was particularly low for industry-sponsored studies, such as those funded by drugmakers (just 5.9% compared to 59% for studies sponsored by collaborative research networks. Of published studies, nearly two-thirds had positive results in that the treatment worked as hoped. The remaining one-third had negative results like the outcome was disappointing or did not merit further consideration of the tested treatment, they report.

The finding raises concern about publication bias in cancer treatment trials, according to the researchers, Scott Ramsey and John Scoggins of University of Washington and Fred Hutchinson Cancer Research Center in Seattle.

The researchers suspect the rate of negative results is much higher in the studies that have gone unpublished. "It is likely that many unpublished studies contain important information that could influence future research and present practice policy," they wrote.

Of course, we know why a registered trial may not be published, some fail and a researcher may decide the result doesn't enhance knowledge or one's reputation. And some sponsors don't want negative results out there. Same goes for some journal editors.

But "unpublished trials may have special importance in oncology, due to the toxicity and/or expense of many therapies," they wrote. In other words, the knowledge base is incomplete. And who does that help?

Sabina said...

Yesterday I received this newsletter. The first temptation was to laugh. Well, the reality is not so nice.
Want to be a MEDLINE Information Censor? The National Library of Medicine Needs You! (OMNS, Jan 28, 2010) Would you like to dictate what nutritional research people may or may not access? Why not join the NLM's Literature Selection Technical Review Committee? We think a good preparatory step is to take the Medline Censorship Aptitude Test (MED-CENT). Not to worry; it's multiple choice.
First question: Which of the following research papers is NOT indexed by the National Library of Medicine's Medline?
A) Olfactory responses and field attraction of mosquitoes to volatiles from Limburger cheese and human foot odor. (J Vector Ecol, 1998) B) Heated socks maintain toe temperature but not always skin blood flow as mean skin temperature falls. (Aviat Space Environ Med, 2003) C) Jefferson JW, Thompson TD. Rhinotillexomania (nose-picking): psychiatric disorder or habit? (J Clin Psychiatry, 1995) D) Pauling L, Rath M. An orthomolecular theory of human health and disease. (J Orthomolecular Medicine, 1991) Answer: Only choice "D" is not available on Medline.
Let's try another: Which of these studies is NOT indexed by Medline?
A) Psychophysiological responding during script-driven imagery in people reporting abduction by space aliens. (Psychol Sci, 2004) B) The eyebrow frown: a salient social signal. (Emotion, 2002) C) Staring at one side of the face increases blood flow on that side of the face. (Psychophysiology, 2004) D) Rath M, Pauling L. Solution to the puzzle of human cardiovascular disease: Its primary cause is ascorbate deficiency leading to the deposition of lipoprotein(a) and fibrinogen/fibrin in the vascular wall. (J Orthomolecular Medicine, 1991) Answer: "D" is not on Medline. All the rest are.[…]
One last chance, now:
A) How dogs navigate to catch Frisbees. (Psychol. Sci, 2004)
B) Effect on tipping of barman drawing a sun on the bottom of customers' checks. (Psychol Rep, 2000)
C) An objective evaluation of the waterproofing qualities, ease of insertion and comfort of commonly available earplugs. (Clin Otolaryngol, 2004)
D) Hoffer A, Pauling L. Hardin Jones biostatistical analysis of mortality data for a second set of cohorts of cancer patients with a large fraction surviving at the termination of the study and a comparison of survival times of cancer patients receiving large regular oral doses of vitamin C and other nutrients with similar patients not receiving these doses. (J Orthomolecular Medicine, 1993)
Choice "D" is not indexed by Medline. The others are. Yes, they really are. Just type in the title at http://www.ncbi.nlm.nih.gov/pubmed/ or http://www.ncbi.nlm.nih.gov/sites/entrez
If you got all the above items right, you are well qualified to become a member of the NLM's Literature Selection Technical Review Committee, because you can discern what research should and should not be available to the public. […] To personally thank your National Library of Medicine for keeping all this information from the taxpayer: Ms Betsy Humphreys, Deputy Director, NLM email: betsy.humphreys@nih.gov or betsy_humphreys@nlm.nih.gov phone: 301-496-6661
You can also call the NLM Customer Service desk at 1-888-FIND-NLM (1-888-346-3656). Remember to be polite, because, after all, they are the "World's Largest Medical Library." http://www.nlm.nih.gov/nlmhome.html

Michael Kirsch, M.D. said...

Marketing and self-promotion are not limited to the pharmaceutical industry. Hospitals are hawking their wares like retail appliance stores, and some of it is downright shameless. Physician practices advertise regularly, although not quite as crass as hospitals do. The New York Times reported today that a Florida dermatologish is being admonished by the FDA for promoting off label use of a product, when she had a clear conflict of interest. Marketing has permeated the health care system. Caveat emptor. www.MDWhistleblower.blogspot.com