The following is a guest post by Kevin Lomangino, one of our story reviewers on HealthNewsReview.org. He is an independent medical journalist and editor who is currently Editor-in-Chief of Clinical Nutrition Insight, a monthly evidence-based newsletter which reviews the scientific literature on nutrition for physicians and dietitians. He tweets as @Klomangino.
Blogger Marilyn Mann has identified what seems to be a very strange set of circumstances surrounding a review article in the journal Reviews in Cardiovascular Medicine (RICM). The article is about a class of drugs called fibrates that are used to treat people with cholesterol problems. Whats unusual is that publication of the article seems to have been paid for by drugmaker Abbott, which also happens to make two fibrate drugs, TriCor and Trilipix.
Marilynn wonders, understandably, why anyone would want to spend their time reading a medical journal that publishes review articles that have such a high level of involvement from a commercial enterprise with a vested interest in the topic.
To that I would add this follow-up: Is it wise to trust the judgment of editors who accept consulting and speaking fees from pharmaceutical companies, then write and edit articles that those companies may have an interest in without disclosing the potential conflict to readers?
I am referring here to the medical editors at RICM Norman Lepor, MD and Peter McCullough, MD. According to ProPublicas Dollars for Docs database, Dr. Lepor is one of Californias top earners when it comes to pharmaceutical company payments, receiving some $187K for speaking, consulting and travel from Eli Lilly, Glaxo Smithkline, Novartis, and Pfizer since 2009. Some of these pharma ties are acknowledged on a disclosure page (click the RICM tab after the link) on the website of RICMs publisher, MedReviews, LLC, but other relationships are not. McCulloughs Dollars for Docs listing is also inconsistent with the RICM disclosure page. These discrepancies raise new questions about the objectivity of the writing in RICM.
Consider a commentary (subscription required for full text of many RICM articles) that Lepor and McCullough coauthored in 2011 about the possible overuse of angioplasty procedures. In that piece, they highlighted the limitations of a study which suggested that many angioplasties performed in non-acute settings may be inappropriate, and they countered that it would be useful to find out why some patients are being inappropriately denied access to angioplasty.
But at the same time that these editors were advocating on behalf of improved access to angioplasty, Eli Lilly, which had paid Lepor about $50K in 2010 and more than $30K in the first quarter of 2011, was heavily marketing its brand new anti-clotting drug called Effient (prasugrel) that is approved specifically for use in patients who undergo angioplasty. More angioplasties might mean more demand for Eli Lillys drug that is designed specifically for these patients. But the article does not alert readers to Dr. Lepors potential conflict of interest.
A disclosure might also have been helpful in articles (see here and here) that Dr. Lepor wrote about the drug ranolazine. Although Lepor discloses on the MedReviews website that he has been a speaker for CV Therapeutics (acquired by Gilead in 2009), which makes ranolazine, there is no mention of this relationship in the text of the articles (presumably the place one would most expect to find an acknowledgment of this relationship). The main points box in one of the articles mentions only benefits of the drug and offers no caveats.
The editors relationships also create the opportunity for less direct, but potentially more insidious commercial bias to be introduced. Was it a coincidence that RICM ran a review article about Eli Lillys new cholesterol-lowering drug, pitavastatin, while Lepor was receiving consulting and speaking fees from the company? Although he didnt write it, Dr. Lepor presumably had a role in shaping the content and shepherding the article to publication. The article concludes that pitavastatin has shown favorable clinical efficacy, a positive safety profile, and encouraging clinical experience in Japan and other parts of Asia.
Keep in mind that Dollars for Docs lists payments only from 12 participating companies since 2009, and so we dont know to what extent other RICM content may be conflicted by relationships with non-disclosing companies. This is one reason we need the mandatory disclosure requirements that are being introduced as part of the health care reform law.
To be clear, I am not suggesting that industry ties invalidate ones opinions or make them unworthy of publication. And Im not suggesting that these conflicts are anything new or even in the same league as some other outrageous conflicts that have been uncovered at medical journals in the recent past. But I do think that there needs to be full disclosure of potential conflicts when they exist, and so its troubling that these editors seem to make an extra effort to downplay possible commercial influence rather than getting it out in the open where readers can judge its significance for themselves.
In the sponsored Abbott review, for example, the journal goes out of its way in the disclaimer to say that no funding was provided to authors. The intent seems to be to reassure readers that the content could not possibly be biasedand the wording may be technically accurate. But as both Howard Brody and Pharmalot have pointed out, a portion of Abbotts payments to MedReviews will most likely end up going to RICM editor and coauthor on the article, Peter A. McCullough, MD, in the form of an editorial stipend.
Similar parsing was done in a 2010 supplement about the use of diagnostic tests in cardiology. McCullough wrote or co-authored several articles that discuss the use of tests made by Alere. The disclosures in those articles say that funding for technical assistance was provided to MedReviews, LLC, by Alere, and again that no funding was provided to authors. Some of the articles noted that Dr. McCullough has no real or apparent conflicts of interest to report.
But the disclosure (again, click on the RICM tab) on the MedReviews website lists McCullough as a speaker and consultant to Alere (the disclosure mentions Biosite, a name the company used up until a merger with Inverness/Alere in June 2010)relationships which presumably involved some type of funding and at least the appearance of a conflict of interest. McCullough seems to have had a relationship with the company going back at least to 2002 (see the disclosures mentioned at the end of this article), and he was giving Alere-sponsored talks shortly before and after the supplements publication in 2009, 2010 and 2011.
In fact, in that same problematic 2011 issue with the controversial article on fibrates, McCullough also coauthored an article about galectin-3, a diagnostic biomarker for which Alere (previously known as Inverness Medical ) is currently developing a commercial test. The paper also mentions assays that Alere is currently marketing for natriurietic peptides and says they greatly aid in the diagnosis, prognosis, and management of heart failurean assertion that some experts would challenge. McCullough again reported in the article that he had no real or apparent conflicts of interest to disclose.
If there are reasonable explanations for these discrepancies, the editors did not take advantage of opportunities offered over the course of several weeks to provide them. Dr. Lepor did not respond to phone and email messages I left for him at his office. And McCulloughs one-sentence emailed response to a query from me was: I have no conflicts of interest to disclose.
I fared slightly better in my attempts to get answers from Jeff Arnold, MedReviewss vice president of sales and marketing, who spoke to me briefly in an initial interview but then didnt call back with additional details that he said he needed more time to research. I told Arnold that I was concerned because I know that editors at some medical journals receive a royalty based on journal sales or income, and that this can create a hidden financial incentive for them to pursue deals like the Abbott sponsorship (which the editors ultimately benefit from through the publishers royalty payment).
Arnold assured me that MedReviews pays McCullough and Lepor a flat editorial fee for their services, and so they would not see a percentage of the Abbott sponsorship in the form of a royalty. He said that Abbott does not advertise in the journal and did not purchase reprints of the article on fibrates. He also said that Abbott did not make changes to the article, and that the only reason they wanted to review the article was to make sure that it contained no off-label claims about the companys products. (One has to wonder, though, if Abbott would have been so hands-off if the article reflected negatively on their products instead of advocating strongly in favor them.)
The disclaimer at the end of the article weve had disclaimers like that for 13 years, Arnold said. We have disclaimers like that on every single one of our articles in full plain view.
Notwithstanding the disconnect between these assertions and the reality of RICMs poor disclosure practices, I do empathize with Arnold. He surely has seen his sales at MedReviews drop in recent years as fewer new drugs are approved and pharmaceutical company promotional budgets are reduced. Its perhaps understandable that, as a sales professional, he would try to push the envelope regarding commercial involvement.
But if Arnold was not in a position to see the problems with placing sponsored articles next to the journals regular content without a bold disclaimer, then surely somebody else at the journal should have been. While there is a long history of sponsored content appearing in supplements to medical journals, the unheralded placement of paid content in the text of a regular issue is unexpected and deceptive. And although some may argue that industry-funded journals like RICM are viewed in the field as not worthy of serious clinical consideration, keep in mind that Abbotts sponsored content is now indexed and accessible internationally via the National Library of Medicine, whose users may not be aware of the articles origins in the medical pulp.
Harlan Krumholz, MD, the Yale cardiologist who first tipped off the blogosphere to this situation, described the problem with the Abbott article to me this way: [RICM] is merely a platform for content paid for by the company and the information is presented in a way that is far from obvious and the content leans heavily toward the product in contrast to a recent AHA statement. It is a promotional piece in a journal that is cited on PubMed and widely distributed as a scientific journal. He said RICMs approach to sponsorship has no place in a Pubmed journal.
I would have to agree. Even my free local weeklyfestooned with advertising as it isalerts readers across the top of each page when articles are part of a paid advertising section. And the text is in a different font than the rest of the issue to make sure there is no confusion.
So the conflicts are right out front when it comes to cleaning ladies, roofers, and restaurants. Is it too much to expect the same level of transparency when the topic is as important as our medical care?