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Uncover bias in clinical trials: drug research should be objective, but when it's funded by manufacturers, study results are often predictably rosy. Look for biases that taint clinical trials.

Article Excerpt
When physicians make treatment decisions and prescribe medications for patients, they rely on information from clinical trials. The medical community universally believes that data on the clinical effectiveness (1) and toxicity of new drugs, compared with available alternatives, must be available to prescribing physicians--and it must be accurate.

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There is no shortage of medical literature evaluating safety and efficacy claims based on clinical trials. Not as well known is the extensive collection of journal articles and other publications written by members of the medical community specifically attacking clinical trials that are funded by the pharmaceutical industry.

Well-respected physicians have noted that science often is not objective. (2) One medical journal article states:

Emotional investment in particular ideas and personal interest in academic success may lead investigators to overemphasize the importance of their findings and the quality of their work. Even more serious conflicts arise when for-profit organizations, including pharmaceutical companies, provide funds for research and consulting, conduct data management and analyses, and write reports on behalf of the investigators. (3)

A clinical trial typically is designed to evaluate safety or efficacy, but not both. "Efficacy" is not the same as "clinical effectiveness." Efficacy simply refers to any arbitrarily chosen effect, which may or may not be clinically relevant. The World Health Organization defines clinical effectiveness as "the likelihood and extent of desired clinically relevant effects in patients with the specified indication." (4)

Once an article is written about a clinical trial, the results can be published or reported in many ways: peer-reviewed journals, symposium proceedings that are adjunct to journals, and "controlled circulation" publications (so-called throwaway medical journals that pharmaceutical companies give to doctors and libraries for free). Study results can also be presented at medical educational seminars.

A clinical trial published in a medical journal usually contains several parts, each with a specific function. Think of the mnemonic IMRC: introduction, methods, results, and conclusion. (5) Understanding how these studies are organized can help you locate the type of information you need to expose a study's flaws.

The introduction contains a basic clinical background of the study, a review of previous studies, and a primary and secondary hypothesis or scientific theory that the study either proved or disproved.

Methods define the study's patient population, the criteria used to select participants, the study design (such as randomization methods, blinding, and controls), and treatment. The methods section defines the primary and secondary outcomes, subgroup analysis, and surrogate markers. It also provides the statistical reference (type of statistical analysis), confidence intervals, outcome comparisons, and power. [For an explanation of some of these terms, see "Epidemiology in Plain English" on page 34.]

The results section contains a summary of the data collected. It might contain tables, figures, or a written description of the results. It also contains any differences in outcomes based on intention to treat, any treatment effects, and an evaluation of confounding factors and interactions (both of which may introduce bias). Confounding factors can introduce bias when a study trait is associated with a particular outcome but is inappropriately described as causing the outcome.

The conclusion (or discussion) interprets the results, including precision and bias. It should contain the study's limitations and strengths. It should also make suggestions for future research and propose specific hypotheses based on the results.

Flawed methodology

It is well known that a poorly designed study can artificially inflate benefits of a test drug. A double-blind, randomized, placebo-controlled clinical trial (RCT) is generally considered the gold standard of valid methodology in the medical community, although that idea is sometimes challenged. (6) An RCT allocates medications to be tested on subjects at random, so that neither the researcher nor the subject knows who receives a particular test medication.

The basic idea behind random allocation is that it makes different treatment groups within a trial statistically equivalent and eliminates "cognitive bias"--a distortion in the way a person perceives reality. But RCTs are not immune to bias. Medical...