ENHANCE E-Mail Exchange: Dear John, John, and...Rick
Today, the WSJ Health Blog provides access to an entire thread of e-mails sent during July 2007 (~3 months after Carrie Smith Cox sold $28 million worth of SP stock) between the ENHANCE study's primary investigator John Kastelein, MD, PhD, and SP's John Strony, MD (IMPROVE-IT study director), and Enrico Veltri, MD (ENHANCE study director)—all of whom express their various frustrations with the protracted examination of the ENHANCE study data. The thread is the original courtesy of SP, in its attempt to provide balance to the excerpted Kastelein e-mails provided by Senator Grassley. The Pathophilia blog, given its love of chronology (chronophilia?), provides an abridged, interpretive version of the e-mail exchange in temporal sequence. One lesson from the publication of the thread: Be careful who you dis in professional e-mails.
07/06/07, Kastelein to Strony: While on vacation, Kastelein is awfully pissed to learn (presumably from an e-mail sent by Strony) that SP has decided not to present the ENHANCE study results at the upcoming scientific sessions of the AHA in November—especially without consulting Kastelein first. (The deadline for abstract submission was June 1, and that for late-breaking clinical trials was June 29.) Kastelein threatens to terminate his collaboration with the company and to "take appropriate steps" to contact the editors of "major journals" and the FDA—the ultimate, but vague, "Dear John" letter (hey, literally and figuratively) of any academic PI.
07/06/07: Strony responds to Kastelein with a somewhat conciliatory e-mail, indicating his best efforts to contact Kastelein by other means and explaining the decision by SP and Merck execs to hold on the submission of the ENHANCE study results to the AHA. Strony itemizes a number of problems with the processing of the ENHANCE data: The primary, carotid data are undergoing a "query process," and the consolidation of the data into a "commercially available, validated system" from scattered sources (eg, various computers, laptops) chewed up weeks. In addition, the auditing of the image database was stalled, when 150 "extraneous image values" were identified in a particular batch. Strony also advises that SP's standard operating procedures forbid the "locking and relocking" (presumably the unblinding and reblinding) of any database. He concedes that ENHANCE is the "trial from hell."
07/07/07: Still miffed and frustrated, Kastelein responds to Strony and cc's Veltri (aka Rick), indicating that Merck had cleared Kastelein to say publicly that the ENHANCE results would be presented at the AHA. Fearing the perception of colluding with SP to hide or manipulate the ENHANCE data with dilatory tactics, Kastelein writes, "[Y]ou will be seen as a company that tries to hide something and I will be perceived as being in bed with you."
07/09/07: Veltri now writes back, explaining to Kastelein that the decision to delay the presentation of the ENHANCE study results was essentially his (and that of his Merck counterpart, Elizabeth Stoner, MD [who has since left Merck]), so that the quality of the data could be ensured. Veltri reminds Kastelein that they've had a discussion about data-quality issues before and chastises, "I do not see what you are raging about," with respect to Kastelein's threat to contact journal editors and the FDA. Veltri also essentially reinforces Strony's explanation for the delayed processing of the ENHANCE data to ensure integrity: "[W]e must work together to complete the outstanding database cleanup and readings in a rigorous manner and not short cut for the sake of presentation." However, Veltri doesn't discount the possibility of submitting the ENHANCE data, if available, for the AHA meeting, even after the "late-breaker" deadline.
07/13/07: Not entirely appeased, Kastelein responds to Veltri (and cc's Strony) by reiterating his frustration and lack of control over the ENHANCE study. He also expresses dissatisfaction with several study consultants, including Gene Bond (presumably M. Gene Bond, PhD), and adds that he is "constantly under pressure" from Merck (not SP, notably) to plan activities before, during, and after the AHA meeting.
