Ethics: October 2009 Archives

The recent publication of commercial payments to physicians allows anyone to compare these data with information disclosed by the very same physicians. And that's just what a few orthopedic surgeons systematically did. Their analysis of their colleagues' disclosures, or lack thereof, is available in the latest issue of the NEJM.

The authors compared online reports of payments in 2007 from the 5 major prosthetic-joint companies (Biomet, DePuy, Smith and Nephew, Stryker, and Zimmer)* with payments voluntarily disclosed by physician participants at the annual meeting of the American Academy of Orthopedic Surgeons (AAOS).

Their findings:

• About one quarter of the commercial payments in 2007 (344/1347) were made to physicians who were AAOS meeting presenters, committee members, or board members in 2008.
• 146 (42%) of these payments exceeded $100,000 (each); 135 (39%) ranged from $10,000 to $100,000; and 63 (18%) were less than $10,000. (From Figure 2, it appears that close to 40 payments exceeded $1 million each.)
• In most cases, payments were made directly to physicians (78% of payments) and were directly related to the presentation topic (70% of payments).
• The overall disclosure rate was 71% (245/344 payments)—meaning that nearly 30% of payments to orthopedic surgeons were not voluntarily disclosed, despite the fact that the meeting's disclosure instructions were broad.**
• Compliance with disclosure was somewhat higher for direct payments (79%) and was substantially lower for indirect payments (50%). (An indirect payment is made through another company or organization—for instance, a medical-education communications company, or MECC.)
• The total amount of undisclosed direct payments (n = 43) exceeded $4 million; the total amount of undisclosed indirect payments (n = 16) exceeded $7 million.
• Payments were more likely to be disclosed if they exceeded $10,000, were given to an individual physician, or included in-kind support.
• Reasons for nondisclosure (from those few nondisclosing, surveyed physicians who responded) included 1) the payment was unrelated to the presentation topic; 2) the disclosure requirements were misunderstood; or 3) the disclosure was incorrectly printed.

* The companies' publication of physician payments in 2007 was required as part of a DoJ settlement.

** The meeting participant was directed to make a disclosure "if he or she has received something of value from a commercial company or institution, which relates directly or indirectly to the subject of their presentation."

A warning to pharma execs who are inclined to bury missed primary endpoints of clinical trials in press releases: You are personally at risk of federal indictment and conviction. No more hiding behind the company shield.

Case in point: Scott Harkonen

The former CEO of InterMune, was found guilty of wire fraud last week in a San Francisco federal court, reported the DoJ in a September 29 statement.* As a result, Harkonen faces up to $250,000 in fines and 20 years in prison. The jury-trial conviction relates primarily to a press release issued by InterMune on August 28, 2002, and reportedly at Harkonen's direction. 

The InterMune press release in question (reprinted here) claimed, in blatant up-front fashion, that the company's drug Actimmune (interferon gamma-1b) improved overall survival in a phase 3 study of patients with mild-moderate idiopathic pulmonary fibrosis (IPF). However, the trial results failed to show a statistical difference in progression-free survival, the trial's primary endpoint, between Actimmune and standard corticosteroid treatment. News of the missed primary endpoint was buried in the first paragraph of InterMune's press release and overshadowed by follow-up praise for the trial results provided by Harkonen and the study's lead investigator, Ganesh Raghu.

In January 2004, Raghu and his scientific colleagues published the results of the same trial in the NEJM. There the peer-reviewed data failed to show that Actimmune significantly improved progression-free survival, pulmonary function, or quality of life. Later that year, the DoJ launched an investigation of InterMune and its promotion of Actimmune for the off-label indication of IPF. The investigation culminated in InterMune paying a $37-million settlement to the government in October of 2006 (for a detailed timeline of InterMune's troubles, go here).** Harkonen was separately indicted by the DoJ in March of last year.

Harkonen resigned from InterMune in June 2003 and is currently President and CEO of Comentis, a San Francisco-based biotech. Notably, in his legal defense, Harkonen claimed that the InterMune press release should be protected by the free-speech clause of the First Amendment. Harkonen argued that he was engaging in "scientific debate"; the judge, however, failed to buy the argument, possibly because she found the press-release statements to be misleading.

* Harkonen was simultaneously acquitted of a misbranding charge.

** In 2007, the clinical investigation of Actimmune in IPF was abandoned by InterMune after interim results of another phase 3 trial showed no survival benefit with drug. InterMune is currently investigating pirfenidone in IPF.