April 4, 2011 -- As an epidemic of narcotic painkiller abuse raged across America in 2006, researchers at the U.S. Centers for Disease Control and Prevention issued a medical journal report connecting deaths from those drugs to up to a 500 percent increase in prescriptions.
In that same journal, a couple of officials with a little-known group at the University of Wisconsin School of Medicine and Public Health took issue with the paper, issuing their own warning against any attempt to increase regulation of the drugs.
But the article from the UW group did not disclose that over the last decade or so, as this group advocated for greater use of narcotic painkillers, it had received about $2.5 million from companies that make those drugs -- with most of that money paid before they published their arguments defending the use of opioids, as a Journal Sentinel/MedPage Today investigation found.
Read this story on www.medpagetoday.com.
Fueled by a continuous infusion of money from the manufacturers of drugs such as OxyContin, the UW Pain & Policy Studies Group has been a quiet force in the effort to liberalize the way those drugs are prescribed and viewed in the U.S.
UW says the money comes with no strings attached and that the group's goal is to improve pain care and access to opioids worldwide. It says its mission is to "balance" international, national, and state pain policies and to achieve availability of pain medications while minimizing diversion and abuse.
But doctors in the addiction and pain fields say the UW Pain Group pushed a pharmaceutical industry agenda not supported by rigorous science.
"They ... lend credence to positions that benefit pharmaceutical companies and harm the public health," said Andrew Kolodny, MD, an expert on opioid addiction. "The only rational explanation for their mission is that their bread is buttered by big pharma."
The efforts of the UW group helped create a climate that vastly expanded unproven medical use of the often abused drugs, said Kolodny, chairman of psychiatry at the Maimonides Medical Center in New York City.
In addition, a review of records revealed personal financial relationships between drugmakers and two officials with the UW Pain Group. Those include helping a drug company win Food and Drug Administration approval for a new narcotic painkiller and working as speakers or consultants.
The narcotic painkiller industry's funding of the UW Pain Group is a unique twist on the drug and medical device industry's use of medical schools to sell more of its products, sometimes at the expense of patients.
In the past, Journal Sentinel/MedPage Today stories have documented how dozens of UW doctors had hired themselves out as promotional speakers for drug companies or were enriched by lucrative royalty and consulting deals with medical device makers.
At the same time, the medical school itself has pulled in millions of dollars in pharmaceutical industry money to sponsor courses for doctors that critics say have questionable educational value.
On several occasions financial relationships between drug companies and the Group were not disclosed in medical articles co-authored by group scientists, the Journal Sentinel/MedPage Today found.
By far the biggest chunk of money the UW Pain Group got was from Purdue Pharma, which in 2007 was accused by the U.S. Department of Justice of misleading doctors with the fraudulent claim that its narcotic painkiller OxyContin was less addictive, less likely to cause withdrawal, and less subject to abuse than other pain medications. Those claims, the DOJ said, had no basis in proof.
At the time, scores of deaths and an even greater number of addictions were attributed to the drug. The company and three of its executives pleaded guilty to various charges. Fines and restitution payments totaling $635 million were imposed.
Between 2000 and 2010, Purdue paid the UW Pain Group about $1.6 million, according to university records obtained by the Journal Sentinel/MedPage Today through an open records request.
Indeed, the UW Pain Group appears to have played a critical role in rapid growth of Oxycontin.
In 1996, David Joranson, MSSW, who is listed as the founder and distinguished scientist of the group, was vice chairman and co-author of a consensus statement from the American Pain Society and the American Academy of Pain Medicine. The statement suggested that opioids were safe and effective for chronic, noncancer pain and that the risk of addiction was low.
The chairman and co-author of the paper was J. David Haddox, DDS, MD, then a paid speaker for Purdue Pharma, who would become a Purdue Pharma executive three years later.
Critics say there was little evidence supporting the use of opioids for chronic, noncancer pain, both at the time the statement was made and today.
Indeed, doctors in the field say prescribing those drugs long-term for noncancer pain may cause serious problems, including physical dependence, increased pain sensitivity, unintentional overdoses, and death.
A few months before the statement was published, Purdue Pharma's OxyContin received FDA approval for use in the U.S. It sales would skyrocket in the years to come, reaching $3 billion last year, according to data from IMS Health, a drug market research firm.
UW's Joranson, who did not respond to requests to be interviewed, also teamed up with Purdue Pharma's Haddox in 2002 to co-author a paper, warning state medical boards that fears of regulatory scrutiny could harm the efforts to manage pain in the U.S.
The paper, which also was authored by Aaron Gilson, PhD, another UW Pain Group official, made no mention of the money the group was getting from Purdue Pharma and other makers of narcotic pain killers.
UW Pain Group officials declined to be interviewed for this story.
In an emailed response, Lisa Brunette, a UW spokesperson, said the organization's drug industry funding was accepted as unrestricted educational grants and that it did not perform any work for the companies that provided the funding.
Brunette said the organization's mission is to improve the care of patients with pain and to focus on government policies that contribute to untreated pain.
"The medical use of opioid analgesics has been considered, for more than 50 years, as indispensable to the relief of pain and suffering," she said. "The United Nations acknowledged this in 1961, and the executive director of the U.N. Office on Drugs and Crime and the International Narcotics Control Board both reaffirmed this in 2010."
Gilson, who would only respond to questions by email, said he disclosed conflicts of interest "if there was a requirement by the journals" to submit a conflict-of-interest disclosure form. He cited Medscape as an example of articles in which he submitted disclosure forms.
He said he could not remember if disclosure was required for other articles that appeared in publications years ago, but if it was, he submitted the forms.
The Journal Sentinel/Medpage Today investigation found five Medscape articles by Gilson about opioids and pain in which the disclosure section states that Gilson "has disclosed no relevant financial relationships."
"Authors don't control how any journal or website chooses to present information in their publication," Gilson wrote in an email response.
Katherine Hahn, a spokesperson for WebMD, the parent of Medscape, said Gilson disclosed that he received personal income from drug companies in other articles he wrote for Medscape. She said she is not sure why it was not disclosed in the five articles.
In addition, he said the personal income he received from drug companies was appropriately declared to the university.
Purdue Pharma's Haddox said it was "very jaundiced" to think Purdue Pharma was giving the UW Pain Group money to take positions that would allow the company to sell more of its drugs.
While their work may have helped increase sales of Purdue Pharma drugs, that was not the intent of the funding, he said.
"They are trying to promote balanced access to pain care, including the use of opioids," he said. "We believe in the work they are doing."
Not only has the UW Pain Group hauled in pharmaceutical industry money, but on more than a dozen occasions over about 10 years Joranson and Gilson were paid by drugmakers or organizations connected with them to give talks, author papers, or to work in other capacities.
That includes work Joranson did for DesignWrite, a New Jersey medical communications firm that was investigated by a U.S. Senate committee for its involvement in ghostwriting doctor education material that put a rosy spin on hormone therapy drugs, even after the drugs were found to cause breast cancer and also were linked to heart disease, blood clots, and dementia. Joranson was not involved in the hormone therapy articles.
In addition, UW Pain Group scientist Gilson personally was paid between $10,000 and $20,000 in 2008 to help Cephalon, a company that makes narcotic painkillers, obtain FDA approval for a new drug.
The five days of work he did for that money included attending an FDA approval hearing as a consultant on behalf of the company.
Between 2000 and 2004, Cephalon also paid $25,000 to the UW Pain Group.
Like Purdue Pharma, Cephalon has been the target of a U.S. Justice Department investigation involving narcotic pain killers.
In 2008, it settled an investigation of off-label marketing of three of its drugs, including Actiq, a powerful painkilling product manufactured as a lollipop with the drug fentanyl.
The drug was approved for use only by cancer patients who no longer were getting pain relief from morphine-based drugs.
But Cephalon allegedly promoted the drug for noncancer patients with conditions ranging from migraines to injuries. It also promoted Actiq for use in patients who were not opioid-tolerant and for whom it could have been life-threatening.
"These are potentially harmful drugs that were being peddled as if they were, in the case of Actiq, actual lollipops instead of a potent pain medication intended for a specific class of patients," according to a statement from the U.S. attorney's office that handled the case. Cephalon agreed to pay a $425 million penalty.
Advocacy for Opioids
Throughout the 1990s, pain specialists, including researchers at the UW Pain Group, helped change the prevailing view about the use of opioid analgesics, arguing that the risk of addiction to the drugs should not prevent their use in treating long-term, noncancer pain.
The UW Pain Group's work has included chastising states with its annual "report cards" on policies restricting use of narcotic painkillers; writing medical articles supporting use of the drugs; and attempting to influence the Drug Enforcement Administration and the FDA about pain policy.
In 2008, the UW Pain Group wrote to DEA about the agency's proposed electronic prescribing system for controlled substances. It warned that the system likely would "create a cumbersome and overly strict system" that would be "an enormous burden of oversight for practitioners and pharmacies."
In 2009, the group warned the FDA that a moratorium on long-acting narcotic painkillers could hurt patients.
The drugs have been widely abused, creating a serious public health crisis and causing the FDA to reconsider its policy on the drugs.
Among the restrictions being considered were a temporary moratorium on prescribing the drugs and a ban on OxyContin.
Throughout the 1990s and 2000s as doctors became more willing to prescribe opioid analgesics for chronic conditions such as back pain, headache, and fibromyalgia, prescriptions soared though there are serious doubts about whether the drugs actually are beneficial for such conditions.
The UW Pain Group played an important role in liberalizing use of the drugs, said Jane Ballantyne, MD, a professor of anesthesiology and pain medicine at the University of Washington.
"The drug companies have commandeered the good intentions of people like the Wisconsin group," she said. "Part of the way they (drug companies) are so effective is they pick the message and the messenger."
But the concept of treating chronic pain with opioids was flawed, she said.
And it became an agenda based on philosophical grounds, not sound science, she said.
Doctors say it was believed that if the drugs were good for treating pain in terminal cancer patients, they also would be beneficial for people with chronic conditions such as back pain. But rigorous studies proving this have not been done.
The drugs became so common that in 2007, 700 milligrams of morphine or its equivalent were prescribed, on average, for everyone in the country.
That's enough to give every man, woman, and child round-the-clock dosing of Vicodin for three weeks.
America now is facing a prescription drug overdose epidemic.
Unintentional overdose deaths from opioid analgesics grew from 2,901 in 1999 to 11,499 in 2007, by far eclipsing deaths from heroin and cocaine combined. Opioid deaths follow a track that is almost identical to the growth in sales of the drugs. In addition, an estimated 1.9 million people abused the drugs or had dependence problems between 2007 and 2009.
Pain specialists say that a major portion of the abuse and overdose problems have been in people using the drugs for nonmedical purposes.
A lesser percentage of those cases have been in people who became dependent on the drugs after being put on them by a doctor for medical purposes.
In addition, there may be a considerable percentage of people who started out using the drugs for medical reasons and then began abusing the drugs after obtaining them by illegitimate means, doctors say.
Pain experts say the quality of research supporting use of the drugs for long-term, noncancer pain is low, and there is concern that the drugs may cause harm, including dependence and addiction.
"People have gotten a little cavalier about things," said Roger Chou, MD, an associate professor of medicine at Oregon Health & Science University. "A good portion of patients on opioids probably should not have been started on them. There are a lot of people who could be taken off these medications."
Chou said OxyContin is one such drug that was marketed as being safer and not causing withdrawal.
"It turns out, that was not the case," he said.
Chou said the UW Pain Group clearly has staked a position that narcotic painkillers are appropriate for chronic pain.
"How much of that is influenced by Pharma or that they believe it, I can't really say," Chou said.
Either way, he said, there is a legitimate argument that they should not be taking money from the companies that make the drugs.
Consider one of the more influential papers written by UW Pain Group researchers, a 2000 study in the journal JAMA.
In that paper, Joranson, Gilson and two other UW authors assured doctors around the country that increasing prescriptions of narcotic painkillers were not contributing to drug abuse problems in America.
But the article, which looked at reports of abuse between 1990 and 1996, left out important data on one of the most common and most abused opioid pain killers, hydrocodone, including big increases in abuse reports for it in the years 1997 and 1998.
The hydrocodone data for 1997 and 1998 was available when the JAMA article was published in 2000, said Len Paulozzi, MD, MPH, a physician and medical epidemiologist with the U.S. Centers for Disease Control and Prevention.
"I don't have a good understanding of why they made those choices (to omit the hydrocodone data)," said Paulozzi, who points out the missing JAMA data in his slide presentation on America's prescription drug overdose epidemic.
In his email to the newspaper, Gilson said and the other authors of the JAMA article explained in the article that they didn't include hyrdocodone because it was a "lower classification drug", which was not indicated for severe pain.
The 1996 data was the latest that was available to them, Gilson added.
Paulozzi said he believes the reassuring JAMA article had an influence on the prescribing habits of doctors.
Changing those habits will be difficult, doctors say.
But a group known as the Physicians for Responsible Opioid Prescribing now is trying undue the damage.
The task, however, is daunting because the opioid train has left the station.
"It's not an easy thing to turn around," said Ballantyne, of the University of Washington.
Kristina Fiore of MedPage Today and Ben Poston of the Milwaukee Journal Sentinel staff also contributed to this report.