My new paper, “P Values on Trial: Selective Reporting of (Best Practice Guides Against) Selective Reporting” is out in Harvard Data Science Review (HDSR). HDSR describes itself as a A Microscopic, Telescopic, and Kaleidoscopic View of Data Science. The editor-in-chief is Xiao-li Meng, a statistician at Harvard. He writes a short blurb on each article in his opening editorial of the issue.
This is a case where reality proves the parody (or maybe, the proof of the parody is in the reality) or something like that. More specifically, Excursion 4 Tour III of my book Statistical Inference as Severe Testing: How to Get Beyond the Statistics Wars (2018, CUP) opens with a parody of a legal case, that of Scott Harkonen (in the parody, his name is Paul Hack). You can read it here. A few months after the book came out, the actual case took a turn that went even a bit beyond what I imagined could transpire in my parody. I got cold feet when it came to naming names in the book, but in this article I do.
Below I paste Meng’s blurb, followed by the start of my article.
Meng’s blurb (his full editorial is here):
P values on Trial (and the Beauty and Beast in a Single Number)
Perhaps there are no statistical concepts or methods that have been used and abused more frequently than statistical significance and the p value. So much so that some journals are starting to recommend authors move away from rigid p value thresholds by which results are classified as significant or insignificant. The American Statistical Association (ASA) also issued a statement on statistical significance and p values in 2016, a unique practice in its nearly 180 years of history. However, the 2016 ASA statement did not settle the matter, but only ignited further debate, as evidenced by the 2019 special issue of The American Statistician. The fascinating account by the eminent philosopher of science Deborah Mayo of how the ASA’s 2016 statement was used in a legal trial should remind all data scientists that what we do or say can have completely unintended consequences, despite our best intentions.
The ASA is a leading professional society of the studies of uncertainty and variabilities. Therefore, the tone and overall approach of its 2016 statement is understandably nuanced and replete with cautionary notes. However, in the case of Scott Harkonen (CEO of InterMune), who was found guilty of misleading the public by reporting a cherry-picked ‘significant p value’ to market the drug Actimmune for unapproved uses, the appeal lawyers cited the ASA Statement’s cautionary note that “a p value without context or other evidence provides limited information,” as compelling new evidence that the scientific theory upon which petitioner’s conviction was based [that of statistical significance testing] is demonstrably false. I doubt the authors of the ASA statement ever anticipated that their warning against the inappropriate use of p value could be turned into arguments for protecting exactly such uses.
To further clarify the ASA’s position, especially in view of some confusions generated by the aforementioned special issue, the ASA recently established a task force on statistical significance (and research replicability) to “develop thoughtful principles and practices that the ASA can endorse and share with scientists and journal editors” within 2020. As a member of the task force, I’m particularly mindful of the message from Mayo’s article, and of the essentially impossible task of summarizing scientific evidence by a single number. As consumers of information, we are all seduced by simplicity, and nothing is simpler than conveying everything through a single number, which renders simplicity on multiple fronts, from communication to decision making. But, again, there is no free lunch. Most problems are just too complex to be summarized by a single number, and concision in this context can exact a considerable cost. The cost could be a great loss of information or validity of the conclusion, which are the central concerns regarding the p value. The cost can also be registered in terms of the tremendous amount of hard work it may take to produce a usable single summary.
P-Values on Trial: Selective Reporting of (Best Practice Guides Against) Selective Reporting
In an attempt to stem the practice of reporting impressive-looking findings based on data dredging and multiple testing, the American Statistical Association’s (ASA) 2016 guide to interpreting p values (Wasserstein & Lazar) warns that engaging in such practices “renders the reported p-values essentially uninterpretable” (pp. 131-132). Yet some argue that the ASA statement actually frees researchers from culpability for failing to report or adjust for data dredging and multiple testing. We illustrate the puzzle by means of a case appealed to the Supreme Court of the United States: that of Scott Harkonen. In 2009, Harkonen was found guilty of issuing a misleading press report on results of a drug advanced by the company of which he was CEO. Downplaying the high p value on the primary endpoint (and 10 secondary points), he reported statistically significant drug benefits had been shown, without mentioning this referred only to a subgroup he identified from ransacking the unblinded data. Nevertheless, Harkonen and his defenders argued that “the conclusions from the ASA Principles are the opposite of the government’s” conclusion that his construal of the data was misleading (Harkonen v. United States, 2018, p. 16). On the face of it, his defenders are selectively reporting on the ASA guide, leaving out its objections to data dredging. However, the ASA guide also points to alternative accounts to which some researchers turn to avoid problems of data dredging and multiple testing. Since some of these accounts give a green light to Harkonen’s construal, a case might be made that the guide, inadvertently or not, frees him from culpability.
Keywords: statistical significance, p values, data dredging, multiple testing, ASA guide to p values, selective reporting
The biggest source of handwringing about statistical inference boils down to the fact it has become very easy to infer claims that have not been subjected to stringent tests. Sifting through reams of data makes it easy to find impressive-looking associations, even if they are spurious. Concern with spurious findings is considered sufficiently serious to have motivated the American Statistical Association (ASA) to issue a guide to stem misinterpretations of p values (Wasserstein & Lazar, 2016; hereafter, ASA guide). Principle 4 of the ASA guide asserts that:
Proper inference requires full reporting and transparency. P-values and related analyses should not be reported selectively. Conducting multiple analyses of the data and reporting only those with certain p-values (typically those passing a significance threshold) renders the reported p-values essentially uninterpretable. (pp. 131–132)
An intriguing example is offered by a legal case that was back in the news in 2018, having made it to the U.S. Supreme Court (Harkonen v. United States, 2018). In 2009, Scott Harkonen (CEO of drug company InterMune) was found guilty of wire fraud for issuing a misleading press report on Phase III results of a drug Actimmune in 2002, successfully pumping up its sales. While Actimmune had already been approved for two rare diseases, it was hoped that the FDA would approve it for a far more prevalent, yet fatal, lung disease (whose treatment would cost patients $50,000 a year). Confronted with a disappointing lack of statistical significance (p = .52) on the primary endpoint—that the drug improves lung function as reflected by progression free survival—and on any of ten prespecified endpoints, Harkonen engaged in postdata dredging on the unblinded data until he unearthed a non-prespecified subgroup with a nominally statistically significant survival benefit. The day after the Food and Drug Administration (FDA) informed him it would not approve the use of the drug on the basis of his post hoc finding, Harkonen issued a press release to doctors and shareholders optimistically reporting Actimmune’s statistically significant survival benefits in the subgroup he identified from ransacking the unblinded data.
What makes the case intriguing is not its offering yet another case of p-hacking, nor that it has found its way more than once to the Supreme Court. Rather, it is because in 2018, Harkonen and his defenders argued that the ASA guide provides “compelling new evidence that the scientific theory upon which petitioner’s conviction was based [that of statistical significance testing] is demonstrably false” (Goodman, 2018, p. 3). His appeal alleges that “the conclusions from the ASA Principles are the opposite of the government’s” charge that his construal of the data was misleading (Harkonen v. United States, 2018, p. 16 ).
Are his defenders merely selectively reporting on the ASA guide, making no mention of Principle 4, with its loud objections to the behavior Harkonen displayed? It is hard to see how one can hold Principle 4 while averring the guide’s principles run counter to the government’s charges against Harkonen. However, if we view the ASA guide in the context of today’s disputes about statistical evidence, things may look topsy turvy. None of the attempts to overturn his conviction succeeded (his sentence had been to a period of house arrest and a fine), but his defenders are given a leg to stand on—wobbly as it is. While the ASA guide does not show that the theory of statistical significance testing ‘is demonstrably false,’ it might be seen to communicate a message that is in tension with itself on one of the most important issues of statistical inference.
Before beginning, some caveats are in order. The legal case was not about which statistical tools to use, but merely whether Harkonen, in his role as CEO, was guilty of intentionally issuing a misleading report to shareholders and doctors. However, clearly, there could be no hint of wrongdoing if it were acceptable to treat post hoc subgroups the same as prespecified endpoints. In order to focus solely on that issue, I put to one side the question whether his press report rises to the level of wire fraud. Lawyer Nathan Schachtman argues that “the judgment in United States v. Harkonen is at odds with the latitude afforded companies in securities fraud cases” even where multiple testing occurs (Schachtman, 2020, p. 48). Not only are the intricacies of legal precedent outside my expertise, the arguments in his defense, at least the ones of interest here, regard only the data interpretation. Moreover, our concern is strictly with whether the ASA guide provides grounds to exonerate Harkonen-like interpretations of data.
I will begin by describing the case in relation to the ASA guide. I then make the case that Harkonen’s defenders mislead by omission of the relevant principle in the guide. I will then reopen my case by revealing statements in the guide that have thus far been omitted from my own analysis. Whether they exonerate Harkonen’s defenders is for you, the jury, to decide.
You can read the full article at HDSR here. The Harkonen case is also discussed on this blog: search Harkonen (and Matrixx).