Tuesday, May 24, 2005

Prove it Prove it and I Still Don’t Believe it.

This time I promised to make a submission to the skeptics circle. I’ve been debating who to victimize? Why, there are more than your fare share of scoundrels, thieves, and con men on the World Wide Web to fill Alcatraz seven times over.

Should I aim my wrath at the herbalists that swindle people’s money without a conscience? How about the homeopaths? How about the world of medicine? Why, I would never consider myself a con man. I’m a physician, trained at providing the best of care, using methods clinically proven to be effective, or am I?

We, as physicians, often discuss how medications should first be proven with appropriately conducted trials. To be more precise, what we mean is a trial conducted by a prospective double blind method. In english, that means the drug is tested over time with neither the physician nor the patient knowing whether they are taking the studied dose or the placebo/medication used for comparison. Thus, the design limits bias. There are a number of other trial designs, but that is another topic for another time. The double blind method is considered to be the most accurate.

But what would you have of a double blind trial that was designed well, limited bias, and showed a significant beneficial clinical correlation favoring a certain new medication. Should doubts continue to linger in a physician's mind or should he/she accept the conclusions as self-evident, absolute truth.

A physician or patient should seek one more critical piece of information, Where did the funding for the research come from?

The pharmaceutical industry now spends more on research in the United States than the National Institute of Health (NIH). Research that is unfavorable to the sponsor- meaning, trials that prove that the drug is less clinically effective, cost effective or safe than other medications used to treat the same condition, can pose very significant financial loss. This pressure may result in biases in trial design, outcome, and reporting of research sponsored by the pharmaceutical industry.

A recent systemic review in BMJ (Free copy available here) found that in research conducted by the pharmaceutical industry systemic bias favors the products which are made by the company funding the research. They found that their results applied across a wide range of disease states, drugs, and drug classes over at least two decades and regardless of the type of research assessed. The authors hypothesized four possible explanations.

First, companies may selectively fund trials on drugs that they consider to be superior to the competition. This is unlikely, since researchers could never predict results of trials in advance.

A second possible explanation could be that positive results could be the consequence of poor quality research conducted by the industry. However, the authors concluded that the research sponsored by drug companies is at least as sound as methods in research funded by other sources.

Other explanations include selecting an appropriate comparator. Often, doses of the medications being compared are not equivalent and a paper by Safer reported that in trials of psychiatric drugs the comparator’s drug is often given in doses outside the usual range or there is a rapid increase in the dose of the comparative drug, thus increasing the likelihood of side effects.

A final explanation suggests that publication bias may explain this finding. Research funded by the industry is less likely to be published than research sponsored by another source. Critically, the studies did not point out whether non-publication applied only to research with non-significant outcomes. The publication of these results would be harmful to the advancement of a new medication.

Most of the Giants (Older, wiser physicians) I know refuse to prescribe any new medication until it’s been on the market for at least 5 years. I believe that sounds like the advice of men who’ve learned their lesson. This brings me to the last and hardest to attain ingredient in making a great physician. Experience is everything!