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U.S. v. Harkonen: Should Scientists Worry About Being Prosecuted for How They Interpret Their Research Results?

U.S. v. Harkonen — a case in which Dr. Scott Harkonen, former CEO of InterMune, was convicted of wire fraud based on a press release that discussed clinical trial results for one of InterMune’s drugs – has caused concern that Dr. Harkonen’s conviction means scientists could be subject to prosecution for (mis)interpreting their research results (see here, here, and here).  Dr. Harkonen and others who have voiced these concerns make compelling points—specifically, that scientific debate about the interpretation of research results is commonplace, this debate is critical for medical research, and it must not be chilled.  But are they right to argue that, if the Supreme Court declines to grant Dr. Harkonen’s petition for cert or otherwise allows his conviction to stand, Dr. Harkonen’s conviction puts such scientific debate at risk?  I think the answer is, probably, “no.”

To understand why Dr. Harkonen’s conviction isn’t the death knell of the free exchange of ideas in the scientific community, it’s helpful to understand the background behind Dr. Harkonen’s case.

In 2002, when Dr. Harkonen was the CEO of InterMune, InterMune issued a press release about the results of a phase 3 trial of its FDA-approved drug, Actimmune.  The trial was designed to test Actimmune for a new indication—delaying the progression of idiopathic pulmonary fibrosis (IPF), a rare and fatal disease characterized by progressive scarring of the lungs and generally leading to death within 2-3 years.  See United States v. Harkonen, No. C 08–00164 MHP, 2010 WL 2985257, at *1 (N.D. Cal. July 27, 2010).

After analyses yielded no statistically significant results for any of the trial’s pre-defined endpoints, a series of unblinded post-hoc analyses were conducted.  One of these analyses, conducted at Dr. Harkonen’s request, showed that only 4.8% of trial participants with mild to moderate IPF that received Actimmune (6/126) died during the study, while 16.4% of such participants receiving placebo died (21/128), representing a 70% reduction in mortality.  Although the p value for this result was .004, and statistically significant results are generally considered to be those with a p value less than .05, two biostatisticians, including a former InterMune biostatistician, testified at Dr. Harkonen’s trial that such unblinded post-hoc analyses cannot be considered definitive, and that multiplicity was not controlled for in conducting the post-hoc analyses. (Multiplicity, or the multiple-testing problem, refers to the fact that conducting multiple significance tests with the same data increases the chance that a false positive will occur.)  In other words, that .004 p value was not particularly meaningful.  See id. at *3-8.

Nevertheless, Dr. Harkonen drafted, and InterMune issued, a press release stating that, among other things, the data from the study “demonstrated a survival benefit of Actimmune in IPF” and that Actimmune “reduces mortality by 70% in patients with mild to moderate IPF.”  See id. at *9. (N.B.: the results of the trial were later published in an article in the New England Journal of Medicine that described the results in much more cautious terms, and a follow-up trial specifically designed to study Actimmune in patients with mild to moderate IPF failed to show a benefit of Actimmune when compared to placebo.)

Against this factual background, a Federal jury convicted Dr. Harkonen of wire fraud, which I don’t think scientists should be too worried about. Why?

A wire fraud conviction requires the jury to find that there was a “knowing participation in a scheme to defraud,” and “a specific intent to deceive or defraud.” United States v. Harkonen, 510 F. App’x 633, 636 (9th Cir. Mar. 4, 2013).  This means that Dr. Harkonen was not convicted just because the government did not agree with his interpretation of the clinical trial results.  Instead, he was convicted because a jury found that he intentionally and knowingly sought to defraud someone (presumably, investors) through the statements made in the press release.

And, in this case, there seems to be ample evidence to support to support the jury’s finding—evidence that distinguishes the communication at issue in Dr. Harkonen’s case from the scientific debate that commenters are worried about protecting.  Dr. Harkonen was not a researcher characterizing clinical trial results.  He was the CEO of a biotech company issuing a press release that, ultimately, was intended to communicate information about that company, not scientific information.  Indeed, in addition to describing the clinical trial results, the press release stated that the clinical trial results would “lead to peak sales in the range of $400-$500 million per year, enabling [InterMune] to achieve profitability in 2004 as planned.”  See Harkonen, 2010 WL 2985257, at *13.  Because of his position as CEO, Dr. Harkonen had an obvious financial motive for describing the clinical trial results, which would affect InterMune’s bottom line, in a misleadingly positive light.  In addition, there was testimony at his trial that, among other things, Dr. Harkonen: said he would “cut that data and slice it until [he] got the kind of results [he was] looking for”; departed from InterMune’s usual procedures by preventing clinical and statistical staff at InterMune from seeing the press release before it issued, and; was told by FDA medical officers that they did not believe the data supported the use of Actimmune in IPF patients (which suggests FDA was not likely to approve Actimmune for IPF based on these data, casting doubt on the accuracy of the press release statements about sales).   See Harkonen, 510 F. App’x at 636; Harkonen, 2010 WL 2985257 at *12-13.  In sum, there seems to be a fair amount of evidence that Dr. Harkonen intentionally crafted the press release to be misleading for financial reasons.

I do think the question about where to draw the line between legitimate scientific interpretation and fraud is an interesting one.  But I don’t think this particular set of facts tees up that question well.  It can’t be (at least, I think it shouldn’t be) that merely stating numbers accurately protects a corporate officer from a fraud prosecution, when that corporate officer also omits critical context, describing those numbers in a way that he or she appears to believe is misleading, to improve the company’s bottom line.

A separate question, of course, is whether the Supreme Court will grant Dr. Harkonen’s petition for cert. I would be surprised if the Court agrees to hear Dr. Harkonen’s case because fraudulent speech is not protected by the First Amendment, and it seems unlikely that the Court will want to delve into whether the jury and the District Court correctly determined there was fraud here. (Also worth noting, because Dr. Harkonen was convicted of fraud, this case is distinguishable from the Second Circuit’s Caronia decision—last year’s big off-label promotion case, discussed on CLB’s blog here.)   But I’d be interested to hear what others think.

Patti Zettler

Twitter: @pzettler

6 Responses to “U.S. v. Harkonen: Should Scientists Worry About Being Prosecuted for How They Interpret Their Research Results?”

  1. JD says:

    Engineers can be prosecuted for faulty work, so yes, scientist at a certain level should have to own their decisions and the consequences that may result from faulty science. But, I can also count many reasons why not!

  2. The Harkonen case presents some difficult, complex issues for the Supreme Court. The jury acquitted Dr. Harkonen of misbranding, and the jury’s decision makes the appellate case different from the Caronia case you mentioned. The post-verdict motions and appeals focus on whether accurately stating the data and the p-values can be criminal fraud. The irony is that many federal judges would not exclude an expert witness who would testify under oath to a conclusion based upon much weaker evidence than Dr. Harkonen presented in a press release, and which announced a much fuller discussion at an upcoming scientific conference in a couple of weeks.

    After trial, statisticians Donald Rubin and Steve Goodman (now at Stanford) both filed affidavits in support of Dr. Harkonen, but the trial judge worked hard to uphold the conviction. The trial judge was however hard pressed to find anyone who was harmed by the press release, and she acknowledged that some may have been helped. She sentenced Harkonen to 6 months harm incarceration; the government wanted TEN YEARS in prison. Both sides appealed; and the 9th Circuit affirmed in a cursory opinion. Harkonen has asked the Court to take the case. The government has till next week to submit a brief to argue that the Court should not take the case.

    For more details on the statistical issues, You may want to read an amicus brief in the Supreme Court, in support of granting certiorari, by Professors Kenneth Rothman, Timothy Lash and myself. See http://schachtmanlaw.com/wp-content/uploads/2010/03/KJR-TLL-NAS-Amicus-Brief-in-US-v-Harkonen-090413A.pdf

    NAS

  3. Hank Greely says:

    Thanks to both commenters, especially to Mr. Schachtman, who, as he notes, is part of an amicus brief to the Court on Mr. Harkonen’s behalf. Mr. Schachtman has a long and distinguished career as a lawyer working at the intersection of law and science, including membership in the American Law Institute. I think the brief makes the best case it can, but . . .

    I’d be shocked if the Court granted cert in this case. In this wire fraud case, a jury found Harkonen guilty beyond a reasonable doubt of wire fraud. The unanimous CA 9 panel, which affirmed both the conviction and, against the government’s appeal, the lower than requested sentence, reviewed the sufficiency of the evidence and concluded the jury could reasonably have found that the press release was misleading, that Harkonen knew that it was misleading, and that he had the necessary “specific intent to defraud.” I doubt seriously that the Supreme Court is going to want to review the sufficiency of the evidence to support the jury’s verdict on those points.

    You can find the CA 9 opinion here: http://cdn.ca9.uscourts.gov/datastore/memoranda/2013/03/04/11-10209.pdf

    The amicus brief is interesting, but I note that it consistently paints Harkonen as a scientist, engaged in scientific discourse, albeit through press release. But he was also a CEO and I suspect the press release did not have scientists as its primary audience, but investors and analysts. Which is why I don’t think my scientist friends – when not pumping up their own companies, at least – don’t need to lose sleep over this case.

    I am often wrong about the Supreme Court, but I’d give generous odds that they will deny cert in this case.

    PS I’ve been trying, somehow, in a not inappropriate manner, to link the defendant here with Baron Vladimir Harkonnen from Dune. There’s got to be a good line there some place, but I haven’t found it yet.

  4. Patti Zettler says:

    I second Hank’s thanks for these thoughtful comments. Mr. Schachtman’s amicus brief provides useful information on the statistical issues and makes some good points (for example, citing an NIH press release with similar language to the InterMune press release), but I do think the context of the InterMune press release, and Dr. Harkonen’s position as CEO, are important. The press release seems to have been intended to communicate information about the financial situation of the company, rather than scientific information.

    Also, from a purely pragmatic perspective, I note that the government seems to have had a fair amount of evidence showing Dr. Harkonen’s knowledge and intent to mislead (the conversations with the FDA before the press release was issued, the statements about looking to cut and slice the data, bucking the standard procedures for issuing press releases, etc), which I would guess would not often be present for scientists (or even for corporate officers). Assuming I’m right about that, as a practical matter, I would think researchers don’t have much to be worried about.

  5. [...] Law School, for her doubts that the case will matter to most scientists.  See also Zettle, “U.S. v. Harkonen: Should Scientists Worry About Being Prosecuted for How They Interpret Their Resear…” (Oct. 7, 2013).  If her prediction is correct, then this is a sad commentary on the scientific [...]

  6. D. Mayo says:

    This gives another, telling, perspective on the discussion we’re having on this at my blog; namely he was not really acting as a scientist but as a CEO. http://errorstatistics.com/2013/10/09/bad-statistics-crime-or-free-speech-ii-harkonen-update-phil-stat-law-stock/comment-page-1/#comment-15316

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