An “expert panel” assembled by the National Lipid Association (NLA) is recommending a dramatic expansion in the use of new biomarkers for the diagnosis and management of cardiovascular disease. The recommendations, if widely adopted, would significantly increase not just the use of these diagnostic tests but also lead to much greater use of lipid-lowering drugs. But every member of the panel has extensive ties to industry, and the “consensus conference” that led to publication of the guidelines was funded by an array of diagnostic and drug companies that stand to gain from the new recommendations.
The NLA panel recommends a greatly expanded role for 5 out of 6 new biomarkers– CRP, Lp-PLA2, Apo B, LDL particle number, and Lp(a). (HDL or LDL subfractions did not receive an expanded recommendation.) However, these same biomarkers received a much more critical review in the ACCF/AHA guidelines for cardiovascular risk assessment and in the USPSTF guidelines. The ACCF/AHA guidelines, for example, allow a very modest role for CRP; the other biomarkers are simply not recommended:
Measurement of lipid parameters, including lipoproteins, apolipoproteins, particle size, and density, beyond a standard fasting lipid profile is not recommended for cardiovascular risk assessment in asymptomatic adults.
Panel members, along with the NLA itself, have a dizzying number of industry relationships. The chair of the panel, Michael Davidson, “has received research grants from Abbott Laboratories, Daiichi Sankyo, GlaxoSmithKline, Merck & Co. and Roche… has received consulting fees from Abbott Laboratories, Aegerion Pharmaceuticals, Amgen, AstraZeneca, Atherotech Inc., Daiichi Sankyo, DTC MD, Esperion, GlaxoSmithKline, Intelligent Medical Decisions, Kinemed, LipoScience, Merck & Co, Novo Nordisk, Roche, Sanofi-Aventis, Synarc, Takeda Pharmaceuticals, and Vindico Medical Education…. has received honoraria related to speaking from Abbott Laboratories, GlaxoSmithKline and Merck & Co…. [and] has served on the Board of Directors of DTC MD, Omthera, Professional Evaluation Inc., and Sonogene.”
Chrystie Ballantyne, a co-chair of the panel, has a disclosure list even longer than Davidson’s. Another member of the panel, W. Virgil Brown, is the editor of the Journal of Clinical Lipidology, the NLA journal in which the expert panel appears. He “has received consulting fees from Abbott Laboratories, Amgen, Anthera, Genzyme, Pfizer Inc., LipoScience, and Merck & Co…. [and] has received honoraria related to speaking from Abbott Laboratories, LipoScience, and Merck & Co.”
One of the 17 panel members, James McKenney, had no disclosures in the paper, but this may not tell the entire story. A Pharm.D, McKenney is a former president of the NLA, and a faculty disclosure statement online indicates that McKenney has had extensive ties with industry in the past.
An NLA webpage about the document includes the statement that “contributors to this paper have provided full disclosures and their thoughts on this matter were discussed in advance and the contributors have affirmed that their participation has not been influenced by bias or commercial interest….”
The authors acknowledge financial support to produce the document in the form of “unrestricted grant funding” from 9 companies, all of whom stand to benefit from the changes endorsed by the panel: Abbott Laboratories, Atherotech Diagnostics Laboratory, Berkley Heart Lab, Inc., Boston Heart Diagnostics, diaDexus, Inc., LipoScience, Merck & Co., Inc., and Spectracell Laboratories. After thanking the companies for their support the authors then assert that the document is free from commercial influence:
The NLA would like to thank each company for its support of this endeavor. In accordance with the National Lipid Association Code for Interactions with Companies, the NLA maintained full control over the planning, content, quality, scientific integrity, implementation, and evaluation of the consensus conference and this inflammatory markers and advanced lipoprotein testing consensus document. All related activities are free from commercial influence and bias.
At least one company has already gone ahead and started to use the document to promote its product. Even before the paper had a chance to receive wide distribution, LipoScience, which markets a test that measures LDL particle number (LDL-P), issued a press release announcing the publication, and trumpeting the new indications for its product:
The consensus panel recommends that the use of LDL particle number for initial clinical risk assessment of CVD is reasonable for many patients at intermediate risk, including patients with a family history of coronary heart disease (CHD) and recurrent cardiac events. In addition, LDL particle number should be considered in the risk assessment of selected patients with known CHD or CHD risk equivalent.
The panel also recommends that LDL particle number for on-treatment management of CVD risk is reasonable for many patients at intermediate risk, including patients with coronary heart disease, a CHD risk equivalent and in patients with recurrent cardiac events. LDL particle number should be considered in the management of selected patients with a family history of CHD.
Here’s another question worth asking: how much of the paper did the expert panel actually write? The end of the paper acknowledges “Biofortis-Provident Clinical Research for writing and editorial assistance.” This company has extensive connections with the NLA and the lipid community (some of its current employees were also involved with an Abbott marketing study that was published in the American Journal of Cardiology). In fact, two “non-panel scientists” who are listed as co-authors of the expert panel paper are Kevin C. Maki, PhD and Mary R. Dicklin, PhD. In addition to their numerous other relationships with industry, the disclosures section of the paper states that they receive “salary support from Biofortis.” In fact, they are employees of the company, and a cursory look at Maki’s resume reveals that he is the President and Chief Science Officer of Provident Clinical Research.
Here is how one researcher in this field, who asked not to be identified, analyzed the situation:
Almost every writer has multiple relationships with companies that will benefit from more testing and more drug use. There are the direct relationships, including writers with direct stakes in the companies that do the testing, like Diadexus, which has a test for LpPLA2, and LipoScience and Atherotech, which make lipoprotein tests. But even more insidious are the relationships with pharma companies, since use of these tests broadens the market– ie, tends to increase the number of people eligible for drug treatment. Getting docs to use new tests– be they blood or imaging tests– is a tried and true way to increase drug use.
Also, how were these people chosen? Most have multiple conflicts. Why are they experts? Most (not all) are big pharma players and are not federally funded researchers who performed seminal research on the development of the tests or their evaluation in large epidemiological studies or clinical trials. Many are in private practice and their research experience is participating as a site in a clinical trial. These are the key opinion leaders– ie, experts who become experts through industry backing, getting together, and making an expert panel. To be more pointed, the NLA leaders got together to write a document.
A recent study in BMJ examined the role of conflict of interest in published guidelines for diabetes and cardiovascular disease over the past decade and found numerous problems with the way most organizations manage conflicts of interest on these panels. But, says Mt. Sinai’s Jennifer Neuman, lead author of the study, the NLA paper is an egregious example of these problems:
The Institute of Medicine has made a number of recommendations on how
to manage conflicts of interests on guideline panels in order to limit
potential bias, and the NLA appears to have disregarded most of these
recommendations. This flies in the face of national and international
efforts to improve the credibility of the guideline development