Free Speech, Fraud And Clinical Trial Statistics

Two months ago, the feds excluded W. Scott Harkonen from doing business with various federal healthcare programs such as Medicare and Medicaid. Why? The former InterMune ceo was sentenced earlier this year for wire fraud in connection with disseminating false and misleading statements about the results of a clinical trial for a drug calledActimmune.

Specifically, he was convicted in a September 2009 trial after being accused of making up details about how effective Actimmune was in combating a fatal lung disease, idiopathic pulmonary fibrosis, or IPF. And those details were trumpeted in a 2002 press release that was at the heart of the case (read here and here). The clinical trial failed, but the press release stated a sub-analysis showed the drug helped IPF patients live longer, prompting docs to write scrips even though Actimmune wasn’t approved for that disease.

Now, though, Harkonen is appealing and, at the very least, wants a new trial. But in their brief filed with a federal appeals court late last month, his lawyers are attempting to turn his case into yet another alleged instance in which the First Amendment and commercial speech - as practiced by a pharmaceutical company - have been trampled by federal prosecution.

"In prosecuting this case, the government crossed a line into criminalizing scientific opinions that it never has been permitted to cross," his lawyers write. "More than a century ago, the Supreme Court held that the federal fraud statutes do not permit the government to prosecute individuals for expressing scientific opinions about which reasonable minds can differ."

To the feds, the crime was fairly straightforward. Harkonen, they argued, orchestrated a scheme to widen the market for Actimmune in a way that deceived doctors and investors. And the feds argued that he did so by manipulating the interpretation of a sub-group analysis from the clinical trial in order to show the drug offered a significant survival benefit. The trial failed to meet its primary endpoint of progression-free survival and the FDA was not persuaded to offer approval for IPF (read the indictment here).

To Harkonen and his lawyers, however, their legal case is more subtle and hinges on a willingness to look beyond strict statistical significance in order to recognize perceived value in scientific debate over study results. Specifically, they point to the extent to which the feds relied upon the so-called 'p value,' a key probability measurement, in arguing that Harkonen distorted the results for his own ends.

The brief goes into further detail, but basically, his lawyers maintain the feds overstated the virtues of relying on the p-value to discuss the full spectrum of benefits that were parsed from the clinical trial. In their view, the sub-group analysis clearly offered an additional way to assess the benefit that Actimmune offered, and this approach constituted a legitimate scientific difference of opinion.

An "overemphasis on statistical significance may cause clinically important differences to be incorrectly denoted as nonsignificant and ignored," they wrote. And in their argument, his lawyers cited another case in which the feds, in the form of a friend-of-the-court brief, had maintained that statistical significance was not viewed as the be-all and end-all in determining substantial evidence for real-world effects and material claims. This other case involved Matrixx Initiatives, which was sued for allegedly concealing side effect reports that its over-the-counter cold med caused people to lose their sense of smell. Last spring, the US Supreme Court ruled Matrixx was incorrect to insist that only statistically significant adverse events are required to be reported to shareholders, and allowed investors to proceed with a long-simmering securities fraud claim (back story).

Consequently, the lawyers for Harkonen maintain the feds wrongfully prosecuted him for "expressing a scientific opinion about clinical study results with which the government disagreed," even though the feds conceded the statistics cited in the controversial press release were not in dispute. They argue there was no fraud or intent to deceive, but merely a differing view of clinical trial analyses (you can read the brief here and an amicus filing in his support from PhRMA here).

And so a central issue here, of course, is whether the court will view Harkonen's actions as fraudulent, which would not be free speech or commercial speech that is protected by the First Amendment. This is only the latest instance, by the way, in which the pharmaceutical industry has somehow argued that free speech rights for disseminating various sorts of information are being unfairly restricted.

In an unrelated case, Par Pharmaceutical filed a lawsuit contending that its ability to convey “truthful” information to physicians is protected by the First Amendment, yet is thwarted by agency regulations governing off-label promotion (see here). That suit was filed in the wake of a ruling last June by the US Supreme Court, striking down a controversial Vermont law that restricted the sale of prescription drug info identifying prescribers and patients for commercial marketing purposes.

Meanwhile, Harkonen, who was InterMune ceo from 1998 until 2003, was sentenced last April to three years’ probation, six months of home confinement, a $20,000 fine and 200 hours of community service.

free speech pic thx to newtown graffiti on flickr