Tangle of Interests and Disclosure Omissions Cracks Authors’ Case for Early, Aggressive Treatment
Parallel realities, of sorts, presented themselves last month to medical literature news junkies — which includes a goodly share of the TAG team. Consider this December entry into the public conversation vis-à-vis the recently resurrected “When to start?” debate. Mike Barr reports.
The journal: University of Chicago’s highly esteemed Clinical Infectious Diseases (sister journal to the more well known, Journal of Infectious Diseases or “JID“)
The paper: “The Case for Earlier Treatment of HIV Infection,” a review article which appeared in the December 1, 2004 issue.
The authors: Diane Havlir (formerly of UCSD and now at UCSF), Frank Palella (Northwestern U.), Scott Holmberg (CDC), Ken Lichtenstein (Rose Medical Center, Denver, CO)
The conclusion: With the advent of easier to take, less toxic antiretrovirals, physicians may want to start treating asymptomatic individuals at CD4 cell counts above the currently recommended 350 threshold.
“We note a growing body of evidence suggesting that earlier treatment with newer, better, and safer drugs is associated with improved survival, more effective immune-system improvement, less toxicity and drug intolerance, and other clinical and public health benefits.”
“We think that the issue of toxicity, a frequent reason that clinicians delay therapy, needs reconsideration.”
“The list of novel drugs available for inclusion in ‘salvage’ antiretroviral therapy regimens continues to grow.”
Presented as it was in CID, the weight of the authors’ collective prestige lends an element of credibility to an argument that might otherwise be greeted with a deservedly familiar skepticism. “Have Viread and Reyataz really altered the therapeutic landscape so much that we must now revisit the age old question of when best to start treating asymptomatic individuals? According to these Key Opinion Leaders, it has. But wait, the plot thickens.
The journal’s conflict of interest disclosure policy requires authors to list any financial relationships with drug and diagnostics companies that could be perceived as prejudicial to their judgment. The authors thus complied by submitting the following:
Potential conflict of interests: “FJP has served on speakers’ bureaus for Bristol-Myers Squibb, Gilead Sciences, and Roche Pharmaceuticals. All other authors: no conflicts.”
As a reader, it’s one thing to come across this provocative pitch (access to which was made free to the public and then basically parroted on all but one or two of the HIV Web sites) accompanied by the requisite footnotes indicating if and where the authors might have something to gain from their interpretation of the literature. Dr. Frank Palella (and in a companion editorial commentary, Drs. Brian Boyle and Calvin Cohen, where they “yearn” for the day when all HIV-positive people are on 100% suppressive therapy) is to be recognized for his candor. The larger question is whether it is appropriate for physicians who have been supplementing their income (sums conceivably rising to the low six figures annually) by doing traveling shows on behalf of the makers of Reyataz, Truvada and Fuzeon to be authoring papers where no new data are presented and where no peer-review occurs.
That same candor was missing for two of the paper’s other co-authors. Hadn’t Dr. Diane Havlir, Doug Richman’s UCSD protegée, reported a string of consulting gigs for Tibotec and ViroLogic in Richman’s throw-away journal Topics in HIV Medicine a short while back? No mention of them here. BMS, Gilead, and Glaxo have also been generous to Havlir’s program — a disclosure she was required to make earlier in 2004, but not in CID.
Researchers, understandably, only grudgingly make these details public, regarding quarter-column length financial disclosures as a tad embarrassing. (At the ACTG, FDA AVAC and the PHS guidelines panel, for example, this information, although requested, is treated top secret and carefully guarded in-house.)
Not to be outdone, Dr. Ken Lichtenstein turns out to sit on the advisory boards (a prized post in the pharma consulting world), of BMS, Glaxo and Gilead — as well as a spot on the traveling lecture circuit for Abbott and Merck. None of these was mentioned in the CID article.
One might ask what purpose these essentially voluntary (and easily finessed) disclosure requirements serve if (A) the journals don’t bother to vet them and (B) those potentially in hock up to their stethoscopes (should they ever find time to don one) are allowed to live these double lives and then carry on with business as usual. Mightn’t it be time to give them some teeth? In this particular case, what will it take for reputable journals such as CID to reconsider its position on allowing physicians with these sorts of conflicts of interest to author editorial and review articles — where no new data are presented? The New England Journal and JAMA have had clearly defined restrictions in place for years.
Transparency in these matters is vital, as the guidance and sway of these pharma-funded talking heads exert a powerful and under-appreciated influence on not only the course of AIDS research and drug development efforts but, perhaps more importantly, also on the evolution of clinical care and the long-term well-being of all HIV-positive people struggling to stay alive and well.
On December 12, 2004, the editors of CID posted the following erratum on the CID Web site:
An error appeared in an article in the 1 December 2004 issue of the journal (Holmberg SD, Palella FJ Jr, Lichtenstein KA, Havlir DV. The case for earlier treatment of HIV infection. Clin Infect Dis 2004; 39:1699 704). In the Acknowledgments section, statements regarding potential conflicts of interest were omitted for Diane V. Havlir and Kenneth A. Lichtenstein. The corrected statements are below. The authors regret this error.
Potential conflicts of interest: F.J.P. has served on the speakers’ bureaus for Bristol-Myers Squibb, Gilead Sciences, and Roche Pharmaceuticals. D.V.H. has received grant and research support from BristolMyers Squibb, Gilead, and GlaxoSmithKline. K.A.L serves on advisory boards and speakers’ bureaus for Bristol-Myers Squibb, GlaxoSmithKline, Abbott Laboratories, Gilead, and Merck. S.D.H.: no conflicts.