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April 02, 2008

Trust no-one...

...would seem to be the message from three papers published over the past few days in different venues.

First, the NEJM published this past weekend a report showing that using a cholesterol-absorption inhibitor (ezetimibe) in combination with statins reduces LDL below what each drug achieves on its own but, alas, there is no similar additive effect on the progression of atherosclerosis.

Then, JAMA published today that rimonabant, the cannabinoid receptor inhibitor that promotes weight loss, has no effect on the progression of atherosclerosis either, although the authors do warn that more studies are needed before we know for sure if this is the case.

Last, a study in PLoS Medicine published yesterday claims that people with Alzheimer's disease are better off without neuroleptics for the treatment of their psychiatric symptoms. These drugs seem not to have significant beneficial effects to outweigh their side effects.

It would seem that every time we look at a drug using higher-magnification lenses we uncover something to discorage us from its use. At this rate, I don't look forward to a future in which the only thing you can buy safely from a drugstore will be aspirin.

P.S. Who comes up with the names of these clinical trials? ENHANCE and STRADIVARIUS? You must be joking! If only their outcomes were as uplifting as their names...

More on discrimination

One of my colleagues was telling me the other day that we at the journal have a bias in favor of the USA. She was specifically making this comment with regard to our reviewer pool, which is indeed dominated by US-based scientists. But then again, there are many more scientists here than in any other country in the world.

In terms of authors, though, there doesn't seem to be such bias in favor of the US or against any country in particular. Have a look at this graph, which shows the ratio of published to submitted papers as a function of country.

ratios.JPG

Each color represents a year -- from 2007 to 2004, top to bottom. Note that this plot includes papers submitted not only to Nat Med, but it's pooled data from NMed, NNeuro, NGenet, NSMB, NCellBio, NImmunol and NBT. I didn't plot the actual number of submitted papers because, of course, we get our largest number of submissions from the US. But this graph clearly shows that we don't favor the US over, say, Italy or Spain. The graph also shows that countries that have invested heavily in science over the past few years, like Australia, show a steady increase in their ratio of successes over failures. Sure, countries like China and India still have some catching up to do, but they'll get there, trust me.

LatAm stands for Latin America. South Pacific includes Singapore, Hong Kong and Taiwan. Scandinavia includes Sweden, Norway, Denmark and Finland.

March 31, 2008

Smoke and Mirrors

The tobacco industry produces a product that, used as intended, kills millions of people each year. So it seems a lot to ask the industry to assume ethical standards in another of its favorite endeavors—funding scientific research.

The tobacco industry is up to some of its usual antics, as reported by
The New York Times. It seems tobacco money helped fund one of the most controversial studies to recently emerge from The New England Journal of Medicine.

The study concluded that the widespread use of CT scans could prevent 80 percent of lung cancer deaths.

The primary author of the study, Claudia Henschke of Weill Cornell Medical College declared funding through a little-known group, the Foundation for Lung Cancer: Early Detection, Prevention and Treatment. It took an investigative
reporter checking tax records to discover that foundation is actually funded by the parent company of the Liggett group, which manufactures several cigarette brands. Henschke did not reveal the source of the foundation’s money to the journal—what’s more, she helped create the foundation and is its president; the dean of Weill Cornell is a director.

The study’s findings obviously are favorable to the tobacco industry. But they have been controversial in part because early screening can lead to unnecessary procedures for spots on a CT scan that are not an imminent threat to health. A $200 million follow-up trial is now under way at the NCI.

What the tobacco linkage will mean for the validity of the study in the minds of experts remains to be seen—although this quote, from Catherine D. DeAngelis, the editor of The Journal of the American Medical Association, is telling:

I would never publish a paper dealing with lung cancer from a person who had taken money from a tobacco company.

Why so much fuss?

As DeAngelis is undoubtedly aware, the industry’s influence in this study fits into an overall pattern.

Tobacco companies fund research that has the potential to minimize the severe effects of smoking, and they also underwrite unrelated, legitimate, research, to bolster their reputation. It’s also not unusual for tobacco companies to keep their fingerprints away from the research they fund.

Tobacco companies also have a well-documented history of trying to stir up ‘debate’ about the dangers of smoking and second-hand smoke. Their support of research to bolster their arguments helped, for many years,
create public uncertainty about the dangers of tobacco and staved off anti-tobacco legislation. Sowing doubt about generally-accepted science is a tactic that foes of global warming legislation successfully borrowed; indeed, the tobacco industry spawned some of the ‘think tanks’ that now fight against global-warming legislation by supporting industry-friendly scientists.

Manipulating science has been a core tactic of the tobacco industry for years. So it’s not surprising that some schools, such as Harvard’s School of Public Health, have banned tobacco money. The University of California system refused to follow suit, but they have implemented a system of extra scrutiny over research funded by the tobacco industry. Opponents of a ban in California argued that it would constrain ‘academic freedom.’

What do you think? Does the source of funding for the NEJM study throw its findings into doubt? Or is this all a bunch of fuss about nothing?

Finally, is it fair for the editor of the Journal of the American Medical Association to refuse lung cancer papers funded by the tobacco industry?

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