Quashed Study Sees Light of Day

Findings suppressed for more than 2 years by a drug company that sponsored the research will finally appear in tomorrow's issue of the Journal of the American Medical Association (JAMA). The report suggests that generic thyroid drugs are as effective as their brand-name counterparts and claims that 8 million Americans could save as much as $365 million a year by switching to the cheaper pills. Beyond the findings, experts say, the paper's long journey to publication reflects the potential pitfalls of commercially sponsored research.

The study was intended to explore why different brands of the thyroid drug levothyroxine, a synthetic version of the hormone thyroxin, seemed to affect patients differently. Boots Pharmaceuticals of Lincolnshire, Illinois, the maker of Synthroid--the oldest synthetic version of the drug--agreed to finance a study by University of California, San Francisco (UCSF), pharmacologist Betty Dong to test Synthroid, another brand called Levoxine, and two generic brands in 22 women whose thyroids were damaged or had been removed. All the women received each drug for 6 weeks at a time in random order, and the researchers measured blood levels of thyroid hormones during the treatment. Dong and her team found that while hormone values fluctuated, there were no significant differences among the four preparations. They concluded that the generic drugs were just as effective for most patients as Synthroid.

When Dong shared the results with Boots officials, they charged that the study had major flaws, wrote JAMA Deputy Editor Drummond Rennie in an accompanying editorial. Although an extensive investigation by UCSF officials in response to Boots's complaints found only minor, easily correctable problems, Rennie says, Boots refused to allow publication of the study. Nevertheless, the researchers submitted their manuscript to JAMA without mentioning the conflict. The journal accepted the paper and scheduled it for publication on 25 January 1995. On 13 January, however, Dong wrote a letter to JAMA withdrawing the manuscript because of what she termed "impending legal action by Boots Pharmaceuticals Inc. against UCSF and their investigators." The contract she had signed with Boots stated that the data could be published only with the company's permission, and UCSF lawyers said they could not defend Dong if she were sued.

Last April, however, The Wall Street Journal ran a front-page article detailing the saga. After the ensuing media storm, Knoll Pharmaceuticals of Mount Olive, New Jersey, which bought Boots in 1995, agreed to let JAMA publish the paper. Company spokesperson Linda Mayer says that although the company still claims the study is flawed, "when The Wall Street Journal article came out a year ago, it took on a life of its own." She says Knoll is "pleased that the study is now published so it can be thoroughly evaluated."

Experts say the results are probably not the final word on the subject. "This is an additional study," says endocrinologist E. Chester Ridgeway of the University of Colorado Medical Center, "that is now in a list of publications, some in favor and some against." But it should give pause to medical researchers contemplating work for industry, says Rennie. "When industry gets in bed with academia, their agendas and their backgrounds are so different that you'd better be damn careful that you don't end up with suppression of unfavorable results or--worse--dangerous results," he says.