Sales of new anticoagulant drugs are booming, thanks to their convenience -- but thanks also to new guidelines that endorse their use and new risk scale that greatly expands the pool of potential patients.
At the center of both guidelines and risk assessment is Gregory Lip, MD, a British heart doctor with extensive financial ties to the pharmaceutical industry.
For years, Lip has worked as a paid speaker and consultant to companies that make novel (or newer) anticoagulants (NOACs), which are marketed for prevention of stroke in patients with atrial fibrillation as well as for prevention of deep vein thrombosis (DVT).
Inflating the Need?
According to , as many 5.2 million people in the U.S. have atrial fibrillation.
The new drugs were approved by the U.S. Food and Drug Administration beginning in 2010 as alternatives to warfarin, which was approved in 1954. They are billed as more convenient, because they don't require INR testing, nor do they require dietary restrictions.
All anticoagulants, new or old, can cause dangerous bleeding. But unlike warfarin, the NOACs currently have no antidote that can stop the blood loss, creating the potential for dangerous uncontrolled bleeding.
Lip served on influential national treatment guideline panels that have recommended greater use of anticoagulants. He also devised a system for assessing who should get an anticoagulant.
Under that system, the number of Americans deemed in need of an anticoagulant jumped overnight from an estimated 3.7 million to 4.7 million, according to a paper published in May in the journal JAMA Internal Medicine.
Independent experts say the new scale can lead to too many people at lower or intermediate risk for a stroke being put on anticoagulants, which exposes them to bleeding risks.
That scale has been adopted in treatment guidelines issued by four leading medical societies in the U.S. and Europe.
And those societies have received at least $40 million in the last 3 years from companies that make or market the new drugs, a 番茄社区app/Journal Sentinel investigation found.
Guideline Panel$
Independent experts say the financial relationships highlight concerns about the influence of pharmaceutical money on medicine.
"It seems to be a poster child for everything that is wrong with how we create guidelines," said Jerome Hoffman, MD, an emergency medicine physician and emeritus professor of medicine at UCLA, .
A 2012 番茄社区app/Journal Sentinel investigation found panels that created treatment guidelines for conditions treated by the nation's most popular drugs (drugs which accounted for $94 billion in sales in 2012) written by panels dominated by doctors with financial ties to drug companies.
That investigation found that 66% of doctors on 16 guideline panels that listed conflicts had financial ties to drug companies. Nine guidelines were written by panels where more than 80% of doctors had financial ties to drug companies.
Critics have argued the financial relationships can lead to guidelines that make ineffective, costly or potentially harmful recommendations. Drug companies and some doctors counter that those with conflicts often are top experts in their fields and they provide essential insight to such committees.
"Guidelines have the ability to move markets because they powerfully affect how doctors practice medicine," said James Stein, MD, a professor of cardiovascular medicine at the University of Wisconsin School of Medicine and Public Health.
He said it is concerning when any researcher or guideline committee member has personal ties to companies that stand to benefit financially from their recommendations.
"Practice changes should be based, whenever possible, on the unbiased review of unbiased scientific data," he said.
The concern that drug companies hold sway over doctors and medical societies has intensified in recent years as more of the payments became public.
Initially, the payments to doctors were revealed only because a handful of large drug companies got in trouble with the U.S. Justice Department for off-label marketing of their products and as punishment were compelled to make large financial settlements. As part of those settlements, the companies also had to start publicly listing how much they were paying doctors.
Then, beginning in 2013, all drug companies were required to reveal payments made to American doctors under the Affordable Care Act.
Overall, the drug makers spent at least $60 million to target the new drugs to doctors. The money represents travel, food, and speaking fees to American doctors for work related to Eliquis (apixaban), Pradaxa (dabigatran), or Xarelto (rivaroxaban), according to the federal data.
The fourth drug, Savaysa (edoxaban) came on the market earlier this year, so no data are publicly available.
According to those disclosures, companies that market or manufacture anticoagulants Eliquis, Pradaxa, or Xarelto paid nine different committee members at least $400,000 for travel, food, and others fees from August 2013 through 2014, according to the federal Open Payments data.
Six members of two U.S.-based guideline committees were each paid at least $4,000 and as much as $50,000 for consulting related to Eliquis, Pradaxa, or Xarelto.
Doctors in Europe are not subject to the same disclosure requirements as American doctors.
Leveraging Lip
Lip, a professor of cardiovascular medicine at the University of Birmingham in England, would not disclose how much money he has received from companies that make or market the new atrial fibrillation drugs.
He said his work goes back 20 years and predates any of his current relationships with drug companies.
"The conflicts cited do not affect/influence my primary research work in this topic area," he said in an email.
While individuals such as Lip should not be barred from serving on guideline panels, their financial ties can influence that work, even if they were not getting industry money earlier in their career, said Eric Campbell, MD, a professor of medicine at Harvard Medical School.
"Often people deny the negative influence and freely embrace the positive influence; It's magical thinking," said Campbell who studies conflicts of interest in medicine.
While it is not known how much drug company money Lip receives, he has been required to reveal the existence of financial relationships with drug companies in numerous disclosures he made for medical journal articles examined by the 番茄社区app/Journal Sentinel.
In 13 papers published since 2006, Lip listed financial ties to at least 12 different drugmakers, including five companies that market or make the new anticoagulants.
In addition, societies that have put Lip on their guideline panels or adopted his stroke scale have received tens of millions of dollars from companies that market the new drugs:
In 2012, the American College of Chest Physicians issued a guideline for treating atrial fibrillation. Lip served as its senior author.
Kristi Bruno, a spokesperson for the organization, declined to say how much money the organization gets from individual drug companies.
Bang for Bucks
However, companies that co-market Pradaxa, Eliquis, and Xarelto, have been listed on its website as corporate supporters of the organization.
Bayer, which co-markets the anticoagulant Xarelto, also provided funding for the guidelines.
Aside from Lip, four of the other 14 panelists had financial ties to the companies.
Bruno said organizations that provide funding "play no role in the development of our guidelines."
In 2012, the European Society of Cardiology updated its guideline on treating atrial fibrillation, saying that the new anticoagulants were broadly preferable to warfarin.
Recommendations from the European cardiology organization sometimes are followed by doctors in the U.S.
Lip also served on that guideline panel. He and a majority of the other co-authors of the guideline listed personal financial ties to companies that market the new anticoagulants.
In an email, spokeswoman Jacqueline Partarrieu would not disclose how much money the society receives from companies that market the new anticoagulants. However, companies that market all of the new drugs are listed as "industry partners," on the society's website.
She said that the organization receives less than 10% of its total revenue directly from "pharmaceutical and related companies." She said the society openly lists any industry ties and is not influenced by drug companies, but that "medical profession and the pharmaceutical industry can work together when and if it is in the best interest of patients."
In 2014, American Heart Association, American College of Cardiology and the Heart Rhythm Society jointly issued a guideline for treating people with atrial fibrillation. Though Lip did not serve on the panel, the guideline adopted his stroke scale.
Three of the 17 panel members listed financial ties to the companies that manufacture or market the new anticoagulants.
In total, the organizations have received tens of millions of dollars in the last several years from companies that market the new anticoagulants, though officials with all of them said the money did not influence the guideline.
For instance, over the last 3 fiscal years, the AHA received more than $13 million from companies that market NOACs, according to revenue statements on its website.
"We are in the business of saving lives," said Rose Marie Robertson, MD, chief science and medical officer with the association. "We are not in the business of fund raising. The trust of the public is the most critical thing we have."
The American College of Cardiology received more than $25 million from 2012 through 2014 from companies that market the NOACs.
None of that influenced the guideline, Kim Allan Williams, Sr., MD, president of the college, said in a statement.
Meanwhile, the Heart Rhythm Society would not reveal how much it received in total from individual drug companies.
However, one form of its corporate support, a program known as the Infinity Circle, recognizes platinum, gold and silver members.
Between 2012 and 2014, four companies that market the new drugs contributed at least $2.9 million, according to records.
In a statement, John Day, MD, president of the society, said the organization has measures to minimize financial or personal biases of guideline members.
John Fauber is a reporter with the Milwaukee Journal Sentinel. Coulter Jones is a reporter with 番茄社区app. This story was reported as a joint project of the Milwaukee Journal Sentinel and 番茄社区app.