In 2012, a faculty member at a CME activity funded by the company that marketed the nation's top-selling testosterone product told physicians they could safely prescribe testosterone to men with prostate cancer.
This advice was offered despite treatment guidelines -- and the product label itself -- warning that testosterone should not be given to men with prostate cancer.
The same physician who led the online course has participated in at least 19 CME activities since 2010, part of a wave of courses touting the dubious virtues of testosterone treatment -- all bankrolled by companies that manufacture the products.
The testosterone courses are at the forefront of a resurgence in industry-funded continuing medical education courses, a 乌鸦传媒/Milwaukee Journal Sentinel investigation found.
Pharmaceutical and device-maker support of CME programs has ebbed and flowed for the last 40 years beginning with a significant pull-back following Congressional investigations of industry sponsored symposia that were often described as junkets, and again in 2007 and 2009 when a raised questions about aggressive promotion of off-label use under the guise of education.
The CME industry and its certifying body, the Accreditation Council for Continuing Medical Education (ACCME), did initiate a , but today about a quarter of CME income -- $676 million -- comes from industry, with most of that support paid to the medical education companies that create the course curricula, hire the faculty, promote the programs, and track the "learners."
Payments to physicians -- and academic institutions -- are made by those companies, a process that effectively works as an end run that shields those payments from the federally-mandated Open Payments system, which reports pharma payments to physicians. But that will change in 2017 when industry will be required to report these indirect payments to physicians if "they find out the identify of the doctors who spoke or attended the event within a year of the event" -- a less than ironclad requirement, according to
In the interim, these payments to physician faculty comprise the dark money of medicine.
Educating or Converting?
A 乌鸦传媒/Journal Sentinel review of 75 drug industry-funded courses involving testosterone found that the majority of the faculty experts already were on the payroll of drug companies as speakers, consultants, and advisors.
All told, 65 of the courses examined had at least one faculty member who already had worked for the drug company that funded the course or a company that makes or markets testosterone products.
The courses, which are designed to meet state and specialty society CME requirements, are supposed to be free of bias. But some experts question that assumption.
"These companies want to get more money from industry and they're certainly not going to put on a course that doesn't appeal to industry," said , MD, who heads the University of Michigan's clinical and educational conflict of interest committee. "They know where their bread is buttered."
The courses are part of a massive drug-company push over the past 10 years to make testosterone products, which reached $2.1 billion in sales in 2014, a central part of men's health.
Testosterone has been on the market for decades, but until 2000 it was primarily used to treat hypogonadism, a relatively rare condition defined as abnormally low testosterone due to a medical condition, such as genetic problems or damage to the testicles.
But drug companies have exploited a broader definition that includes low testosterone levels that occur due to the natural aging process.
In 2000,. That reached 3.3 million in 2008 and 6.5 million last year -- a more than six-fold increase in prescriptions over the 15-year period, according to data from IMS Health, a drug market research firm.
In many ways, the message of CME courses echoes that of late-night cable TV ads that have highlight "Low T" as a problem for men.
A common theme: millions of middle-aged and older men suffer from untreated low testosterone, leading to a lack of sexual function, energy, mood, and libido, as well as obesity, heart disease, cognitive decline, and even premature death.
But the FDA's approval was not based on the products showing proven benefit in treating cardiovascular disease, cognitive decline, or other conditions related to aging.
Rather, the drugs were approved because they do one thing: boost testosterone to levels found in healthy young men.
Since 2010, testosterone products have been linked to more than 3,900 serious complications, according to a 乌鸦传媒/Journal Sentinel analysis of . Nearly a quarter of those reports involved cardiovascular problems such as heart attacks or blood clots.
The reports include 150 deaths and nearly 2,000 hospitalizations.
In March, the FDA said it was requiring drug companies to change the labels of testosterone products to warn that they are not approved for men with low testosterone due to aging, but since the products are clinically available, doctors are prescribing off-label.
Low T and the Big C
One of the big concerns with testosterone is prostate cancer.
Yet the two were mixed in , which at the time made the nation's top-selling testosterone product, AndroGel.
A review of the online materials for the course, which was led by , found the declaration that testosterone therapy "is no longer ruled out" in men with active, low-grade untreated prostate cancer.
As backup for the claim, the materials show Miner cited two studies, both in which authors had financial ties with companies that marketed testosterone products. One was a single-author review paper; the other involved a study of only 13 men.
The statement is specifically contradicted by the FDA-approved labels for testosterone products, which warn they should not be given to men with known or suspected prostate cancer. And it is contradicted by treatment guidelines established by the Endocrine Society.
Those guidelines say the products should not even be used by men with elevated PSA levels.
When asked about the course, Miner backed away from his statement that testosterone could be given to men with active prostate cancer.
"I don't believe that," said Miner, co-director of the Men's Health Center at Miriam Hospital in Providence, R.I. "If I wrote that, that's inappropriate, because I don't do that. If I wrote that, that's wrong."
He said he gave the medical education company that helped produce the course an outline and that a writer with the company may have written the erroneous statement.
"Perhaps I didn't proof it as well as I should have," he said.
Miner also backed away from another statement included in the course, that he considered a man's testosterone level to be the "best measure" of his overall health.
"That's a loose use of verbiage," he said. "I think it is a good marker. I don't think there is any data that it is the best marker."
Miner noted that while he has urology training, he is not a urologist.
"I'm not probably the ideal person to speak about this," he said.
Among the 75 industry-funded testosterone-related courses reviewed, Miner was listed as a faculty member more often than any single doctor. The review found 20 different CME activities that Miner led since 2010.
In an interview, Miner said he is paid about $2,000 for each one.
Additionally, in 2014 Miner received $20,000 in direct payments from testosterone manufacturers for speaking, travel, and consulting, .
"For many of us who do this teaching, we do so out of passion, not for compensation, though one always wishes to be compensated for their work," Miner said. "I do this work honestly to teach others how to best manage this complex disease state."
As with all CME, the course offered credit for a limited period -- January 2012 through January 2013.
It is unclear how many learners completed the course, which was co-sponsored by New York Medical College and Continuing Education Alliance, a Stamford, Conn., company.
In an email, Eric Van Stone, a vice president of the company, said Miner's erroneous statements either will be revised or taken down from the website.
A spokesperson for Abbott, which funded the course, referred comments on the issue to AbbVie. Abbott had marketed Androgel, but when it spun off its AbbVie business in January 2013, AbbVie took over Androgel.
AbbVie spokeswoman Libby Holman said to ensure that CME providers maintain their independence, the company funds independent, legitimate courses that comply with laws and guidelines.
She said AbbVie does not control or influence the "content, materials, faculty or attendees of CME programs."
But Is It Safe?
The review of the testosterone courses show many have downplayed risks, such as heart attacks, clots, and potential prostate cancer risk.
Yet, the medical literature continues to raise concerns.
- In 2010, involving more than 200 men ages 65 and older was stopped early because of a higher number cardiovascular events, such as heart attacks and chest pain in those getting testosterone, though the number of events was small and may have been due to chance, the authors said.
- A involving 8,700 veterans who had undergone a heart exam found that testosterone therapy was associated with a 29% higher rate of having either a heart attack, stroke, or dying than non-use of testosterone therapy.
- A looked at a database of 55,000 men ages 65 and older and the rate of nonfatal heart attacks within 90 days of getting a prescription for testosterone therapy. It was more than double what was found in the year prior to the prescription.
Meanwhile, Journal of the American Medical Association compared testosterone to a placebo in more than 300 men in their 60s with low to low-normal testosterone levels. It found no improvement in sexual function or health-related quality of life.
The FDA has allowed the new testosterone products on the market based on a short-term surrogate measure, the increase in testosterone levels, rather than the gold standard of a proven clinical measure, such as reduced heart attacks or strokes.
That runs contrary to the approach used with other drugs that are billed as potentially reducing the risk of cardiovascular disease. Drugs that affect such things as blood sugar levels, blood pressure, and cholesterol all have been tested in thousands of people.
In August, citing concerns about cardiovascular safety, the FDA said it would require companies that make testosterone products to conduct a controlled clinical trial.
Such a trial may take years and require 10,000 men, said Steven Nissen, MD, chairman of cardiovascular medicine at the Cleveland Clinic.
"It's going to be big and expensive, but these drugs bring in billions of dollars," Nissen said. "The sooner we start, the sooner we answer it."
He and others point to the case of hormone replacement therapy for women.
Twenty-five years ago, it was thought the treatment would help women ward off cardiovascular disease and other conditions related to aging.
Then a medical bombshell: in the Women's Health Initiative , a study involving 16,000 middle-aged and older women was halted when it showed that hormones actually increased the risk of a heart attack, stroke, dementia, and breast cancer.
Said Nissen of testosterone products: "This is a great experiment with American men as the guinea pigs."
Over the past 3 years, more than 2,500 federal lawsuits have been filed against companies that market testosterone products.
The cases, which have been consolidated in U.S. District Court in Chicago, allege that drug companies knowingly promoted the drugs for unapproved off-label uses.
Mark Hoffman, MD, JD, a Philadelphia attorney and physician who is working on the lawsuits, said the industry-funded testosterone courses are part of an effort to turn a normal physiological process into a medical condition needing treatment.
"They go to physicians and try to set a standard of care that's so far outside the realities of what testosterone is actually about," said Hoffman. "In my view as a physician, it's absolutely egregious."
Jeff Goehring, a 54-year-old Waukesha, Wis., resident, filed a lawsuit in July claiming testosterone caused a stroke that has left him disabled.
In 2009, when he went to his doctor complaining of tiredness, tests showed his testosterone level was low, according to the lawsuit. He was prescribed Androgel. Four days after he started using it, he collapsed on his living room floor from a stroke.
The spokeswoman for AbbVie said the company does not comment on active litigation.
He continues to have trouble using his left arm and leg and has vision and memory problems.
Because he could no longer work and had to pay medical bills, Goehring said he had to sell his company, Jeffy G's Deli & Catering, and several 1960s vintage cars. A mechanic for 25 years, he had rehabbed the collection of cars.
"It just ruined my life," he said of the stroke. "It took the best part of my life away."
A Fine Line, Finely Tuned
While the industry-funded CME courses have not made outright claims that giving men testosterone will reduce adverse outcomes such as heart attacks or dementia, that is the implication in several of them, said James Stein, MD, a professor of cardiovascular medicine at the University of Wisconsin School of Medicine and Public Health.
Stein, who reviewed the content of some of the courses for this story, highlighted two examples of problematic claims:
- A course titled "," offered in 2011 and 2012, said "mounting evidence" has tied low testosterone levels to premature cardiovascular disease, cardiovascular events, and cardiac death, as well as increased risk of dying from all causes.
The material acknowledged that a causal relationship between testosterone and cardiovascular disease has not been proven, but noted: "Despite compelling evidence, many clinicians are not aware of the connections between testosterone, comorbid conditions, and overall health."
The course was funded by three companies that marketed testosterone products: Abbott, Eli Lilly, and Endo Pharmaceuticals.
A spokesman for CogniMed, which handled that activity, said the course is "fully controlled by the faculty" not the drug companies and that participants had "ample time for questions and vigorous discussion" about the science discussed.
- A course titled: "," which was offered to primary care doctors between 2011 and 2013, said the relationship between low testosterone and conditions such as obesity, diabetes, high blood pressure, and Alzheimer's was "an important and dynamic topic for which new data are continuously emerging."
It also said: "Proper treatment may prevent many of the co-morbidities and ameliorate health."
The activity was funded by Eli Lilly. One of the two faculty members also served as a consultant to companies that marketed testosterone products.
Both courses point out associations -- but not causation -- between low testosterone and bad health outcomes, Stein noted.
For instance, it is known that testosterone drops as men age or get heavier.
"All the testosterone level may be is a marker for getting older and fatter," Stein said. "These continuing medical education programs lead doctors to believe that patients with low testosterone have a medical disorder that needs to be treated with a drug when they may be healthy."
Tracking the Grants
Just how many industry-funded testosterone courses have been offered is not known.
The ACCME does not track particular types of courses and only provides overall funding numbers. The 75 courses identified in the 乌鸦传媒/Journal Sentinel analysis likely represent just a fraction of the total.
For instance, Eli Lilly lists medical education . That company alone spent $1.8 million to fund more than 25 testosterone-related courses between 2011 and 2014. It paid as much as $150,000 per course.
Lilly provides grants to a variety of course providers and does not control the content of any activities, company spokesman Mark Taylor said.
"It is possible that the educational programs funded by the company through grants have discussed off-label uses of our products," he said in a statement. "However, it is the company's policy that such content would be determined solely by the grant recipient."
The various testosterone lawsuits, though, allege that Lilly "funneled" money into continuing medical education efforts and claim the company controlled the content of the programs.
Those suits claim the money was "disguised" as educational grants in order to hide Lilly's role and its payments to physician lecturers.
The industry was tarnished in 2007 and 2009, following two U.S. Senate investigations into the practice of drug company funding of continuing medical education courses.
In 2007, that pharmaceutical firms had taken control of the programs to get favorable presentations of their products, grab market share for expensive brand-name drugs, and encourage doctors to write prescriptions for off-label uses.
In a 2009 hearing before the U.S. Senate Committee on Aging, several experts testified that drug company-funded continuing education was being used by the firms to aggressively market their products and contributing to the enormous health care costs in the United States.
At the hearing, a Department of Health and Human Services official testified that every $1 spent on doctor education generated $3.56 in increased revenue for the drug companies.
For doctors, industry funded education represents a sort of necessary evil. Nearly 90% of medical professionals said they believed that such funding introduced bias into the content, according to a 2011 study in the Archives of Internal Medicine.
But only 42% said they were willing to pay increased CME fees to eliminate drug company money.
Amid the scrutiny, industry funding for the doctor education courses dropped from $1.2 billion in 2007 to $830 million in 2010, a 30% decline.
At the same time, Congress moved to crack down on financial conflicts of interest and in 2010 passed a law that mandated disclosure of payments made by drug and medical device companies to doctors beginning in 2013. That became the Open Payments system.
But a 乌鸦传媒/Journal Sentinel analysis shows that as the start date of the Open Payment system grew closer, drug company money started going back into continuing medical education courses -- this time with a twist.
Of the $676 million paid by drug companies to all course providers last year, $311 million went to for-profit medical education companies, a 25% increase from 2011, according to the ACCME.
Testosterone-related courses relied on this approach in dozens of cases, the 乌鸦传媒/Journal Sentinel review found.
Using experts affiliated with academic institutions as course faculty gives an appearance that the information presented is unbiased, said Daniel Carlat, MD, associate clinical professor of psychiatry at Tufts University.
"It looks legitimate and kind of sounds legitimate because a lot of references are being used," said Carlat, "but it takes having a lot of expertise in the topic to realize what you're being fed is a very sophisticated promotional line."
Parker Brown contributed reporting to this story.