In head-to-head trials of two drugs, the one deemed better appears to depend largely on who is funding the study, according to an analysis of nearly 200 statin-drug comparisons carried out between 1999 and 2005.

UCSF researchers examined 192 published results of trials comparing one cholesterol-lowering statin drug to another, or to a non-statin drug.

Their findings found that two links stood out. If the reported results favored the test drug, the trial was about 20 times more likely to be funded by the maker of the statin rather than the comparison drug company. Even more striking, they say, if the conclusions or interpretation of the drug trial – which reflect the impressions of the trial investigators — favored the test drug, the trial was about 35 times more likely to be funded by the maker of that drug rather than the comparison drug.

The analysis found that about half of the trials were funded by industry, and about a third did not disclose any funding source. Among those declaring industry funding, about one fifth explained the role of the sponsor, such as data analysis, or writing and preparing the manuscript. Trials with no disclosed funding sources were less likely to have conclusions favoring the test drug, compared to trials with industry funding, the researchers report.

The researchers note that a number of factors can result in the drug trial results favoring the trial drug’s sponsor. Drug companies could selectively fund trials on drugs that are likely to produce a statistically significant result, the researchers explain. This can be accomplished, they say, by selecting non-equivalent doses of drugs for testing. Also, sponsors may choose not to report results that don’t favor the drugs they sell. Or, they may report positive results in more than one journal, skewing the number of positive articles about their drug.

In addition, almost half of the trials lacked adequate blinding – assuring that study scientists don’t know which drug the patients were taking until the end of the trial. Blinding is considered of paramount importance in clinical trials. The researchers found that those studies with adequate blinding were less likely to report results favoring the test drug. This finding was independent of who funded the study – in other words, funding source was a stronger predictor of outcome than blinding, but both had independent effects on outcome.

The most important weakness found in most of the trials was a lack of clinical measures of outcome, such as heart attacks or mortality — considered better indicators in trial design than less direct measures such as lipid levels.

“The lack of true clinical outcome measures in these direct head-to-head comparisons of drugs is disappointing because the studies don’t give us the best information we need to choose one statin over another,” Bero says.

*Co-authors of the study are Peter Bacchetti, PhD, professor of epidemiology, and Kirby Lee, PharmD, assistant professor of clinical pharmacy, both of UCSF; and Fieke Oostvogel, University of Leiden, Netherlands.