Considering that thousands of clinical trials are undertaken every year, it's reassuring that the pharmaceutical industry's critics can turn up only a few instances of bad behavior caused by financial conflicts of interest during the last two decades. They repeatedly cite the same handful of cases.
The Tseng Case: In 1985 a young researcher at Harvard Medical School, Scheffer Tseng, published several scientific articles reporting that topical vitamin A ointment could relieve a chronic dry eye condition called keratoconjunctivitis sicca. Tseng rushed to found a company, Spectra Pharmaceutical Services, to produce and distribute the treatment; he and his relatives made more than $1 million by selling stock in the business. Later research showed the ointment was no better than a placebo.
Harvard reacted by instituting some of the country's strictest rules governing university researchers' financial ties to private business. The good news is that Tseng's ineffective ointment caused no harm, so patient health was not compromised.
Until 2002 Tseng was a professor at the University of Miami School of Medicine's Bascom Palmer Eye Institute. He now sits on the boards of directors of three biomedical companies and still receives research grants from the National Institutes of Health.
The Dong Case: In 1987 Betty Dong, a researcher at the University of California at San Francisco, contracted for $250,000 with the U.K.-based Boots Pharmaceutical to compare its thyroid drug, Synthroid, with the cheaper compounds produced by competitors. Synthroid replaces the hormone thyroxine in patients whose thyroids no longer produce enough. Dong found that Synthroid was no more or less effective than the cheaper compounds.
Dong wanted to publish her results in The Journal of the American Medical Association (JAMA), and Boots responded by threatening to sue her. The university initially backed Dong but later withdrew its legal aid after its lawyers found out that, in direct violation of university policy, Dong had signed a research contract stating that "the study results were not to be published or otherwise released without the written consent" of Boots. Turned out the company was afraid that publication of Dong's results might derail the sale of Boots for $1.4 billion to Knoll Pharmaceuticals.
After The Wall Street Journal reported the story, Boots relented, and JAMA published Dong's study a year later. The company was soon hit with several class action lawsuits alleging that it had overcharged patients and insurance companies. Boots eventually settled a patient class action suit for up to $135 million and another suit by 37 state attorneys general for $42 million. As other drug makers eventually would learn, trying to suppress research findings might temporarily protect a company's bottom line, but it costs the firm much more in terms of profits and reputation in the long run.
The Olivieri Case: Treating the inherited blood disorder thalassemia requires repeated transfusions, which lead to a damaging buildup of iron in heart and liver tissue. In the early 1990s, Canadian thalassemia researcher Nancy Olivieri contracted with the pharmaceutical company Apotex to investigate the effectiveness of its chelating compound deferiprone in removing iron from the body.
Olivieri came to believe that deferiprone caused substantial liver damage to some of her research subjects, and she asked the company for support for further research along those lines. The company then showed her results to other researchers who disagreed with her interpretation, and the company decided not to continue to support her research. At that point, Olivieri told Apotex she was going to publish her negative results. The company responded by threatening to sue her.
The threat turned Olivieri into an academic hero. By 1998 her cause was taken up by the editors of JAMA and The New England Journal of Medicine, who publicized the dispute as an egregious example of greedy commercial interests trying to gag a courageous researcher.
So was this a case of a feisty, honest, academic David fighting a greedy, dishonest, commercial Goliath? Not exactly. The legal threats were stupid, but the science has sided with Apotex. More than 50 peer-reviewed studies have now shown that most patients respond well to deferiprone and that it protects them from heart disease caused by iron buildup. The drug is now approved for use in more than 40 countries. The pharmaceutical company was scientifically right, and the scrappy researcher was wrong, but that hardly matters in the ongoing battles over conflicts of interest.
The Gelsinger Case: One of the often-expressed concerns about conflicts of interest is that greedy researchers will harm subjects and patients as they rush treatments to market. One case stands out in this respect. An 18-year-old named Jesse Gelsinger suffered from a genetic disorder, partial ornithine transcarbamylase (OTC) deficiency, that put him in constant danger of building up toxic amounts of ammonia in his blood. In 1999 he volunteered for a gene therapy study at the University of Pennsylvania in which he was injected with cold viruses modified to carry the normal version of the OTC gene.
Shortly after the injections, Gelsinger suffered from a severe immune reaction and died of multiple organ failure. There were a number of irregularities in the trial. Most damningly, the principal investigator, James Wilson, did not disclose that he had a strong personal financial interest in the research. If the treatment had been successful, Wilson would have received stock in Genovo, the company which had the exclusive right to commercialize his discoveries, worth $13.5 million. In 2005 the University of Pennsylvania made a $517,000 settlement with Gelsinger's family.