In Aaron Sorkin’s A Few Good Men, the defense attorney played by Tom Cruise objects to the testimony of a medical examiner, saying he’s “an internist, not a criminologist, and the medical facts here are ultimately inconclusive.” Cruise is overruled, but he shows during cross-examination that the doctor possibly had an ulterior motive for ruling the crime was a murder.
Then the defense makes an error. As Kevin Bacon, playing the prosecutor, is concluding his questioning during recross, another defense attorney, Demi Moore, says, “Your Honor, we renew our objection.” “Overruled.” “The defense strenuously objects.” “The objection of the defense has been heard and overruled. […] The witness is an expert and the court will hear his opinion,” says the judge, giving additional weight to the testimony.
Such is the debate over new draft guidelines released in September by the Centers for Disease Control. They address the prescription of opioids—the family of drugs that includes Vicodin, OxyContin, Percocet, Demerol, morphine, and other drugs that block pain perception in the brain. The guidelines will limit the use of opioids for chronic pain.
Some argue it’s a step to help prevent addiction and overdose promulgated by the misleading marketing tactics of the pharmaceutical industry. Others see it as move by anti-opioid activists and the trial lawyers lobby to hijack the debate. Both sides accuse the other of conflicts of interest.
Discussion of opioid use has become so heated that some sources for this article (not all sources are quoted) feared death threats from activists as a result of their comments to InsideSources.
Dysfunctional, heated politics no longer is the domain of Washington but now defines the medical field, especially in the use of opioids.
Doctors have a limited arsenal for the management of chronic pain. For patients with severe pain, opioids are often the only way to provide patients with the relief to get through their day and fall asleep at night.
But there are serious drawbacks. For long-term, chronic pain, opioids lose their effectiveness over time. It will take a higher and higher dose for a patient to feel relief. Painkiller abuse is deadly. There are 15,000-17,000 deaths per year as a result of prescription painkiller abuse.
Indeed, the pharmaceutical industry is itself partly responsible for the epidemic. According to ProPublica, the industry has paid over $13 billion in fines as a result of U.S. Department of Justice investigations into deceptive marketing. That number comprises a range of drugs, but some of the biggest fines have revolved around painkillers. Pfizer was fined $2.3 billion in 2009 for misleading marketing of the painkiller Bextra. Merck agreed to pay $950 million in 2011 as a result of its marketing for the now-discontinued Vioxx. Specifically in regards to opioids, Purdue Pharma, the maker of OxyContin, was fined $600 million in 2007 for its misbranding of the drug and its risk of addiction. Additionally, three top Purdue executives pled guilty to criminal charges in relation to deceptive marketing.
Concerns over abuse have led some advocates to call for tighter guidelines for doctors to follow, but with few effective alternatives, that could leave many doctors unable to relieve patients’ chronic pain for everything ranging from back problems to fibromyalgia to cancer.
Dr. Daniel Clauw, of the University of Michigan, is considered one of the world’s leading experts in the treatment of fibromyalgia. “I think the CDC guidelines are very reasonable going forward to say this is how opioids should be prescribed, but the problem is there are a whole bunch of people with chronic pain that didn’t have opioids prescribed in this manner,” Clauw told InsideSources. “If you apply those same rules or policies to them, it’s going to cause a tremendous problem, and then people will be left without a class of drugs that is improving their pain.”
Clauw believes there needs to be a two-pronged approach so that those who are benefiting from opioid therapy do not have it taken away. Additionally, part of his research focuses on determining when opioids are useful for the management of chronic pain.
Referring to the Drug Enforcement Administration’s rescheduling of the opioid hydrocodone as a Schedule II narcotic and to the pending CDC guidelines, Clauw says there has been a “trickle-down effect” on the people who had been on the drug and benefiting from it. As the rules grow more onerous, more doctors are choosing not to prescribe opioids or not refill prescriptions even when they may be helpful.
As other doctors and patient advocacy groups review the guidelines, they’re speaking out against the document that they argue has little scientific grounding. The process of writing the guidelines, they say, was tainted by decisions made behind closed doors in consultation with anti-opioid activists and a paid consultant for a law firm, which stands to make substantial gains from pending suits.
On October 1, Christopher Hansen, president of the American Cancer Society Action Network, sent a scathing letter to the CDC questioning the methodology used in drafting the guidelines and noting the lack of transparency and public input. Hansen states: “Our concerns are so serious that we cannot endorse the proposed guidelines in any way and suggest suspending the process until the methodological flaws are corrected and more evidence is available to support prescribing recommendations.”
The National Fibromyalgia & Chronic Pain Association, Hospice and Palliative Nurses Association, American Chronic Pain Association, and a wide range of other patient advocacy groups and healthcare professional organizations have also come forward to denounce the lack of scientific evidence behind the proposed rules and the lack of transparency in writing them.
The methodology CDC employed in writing the guidelines is intended to evaluate the quality of evidence and the emphasis on particular recommendations. But the critics point out that every recommendation in the guidelines, according to the CDC’s own documentation, is based on “very low quality of evidence” or “low quality of evidence.”
While the University of Michigan’s Clauw sees the guidelines as a step in the right direction to address a public health epidemic, he says if the CDC’s rules were applied broadly to all people suffering chronic pain, it would be “catastrophic.” The effect of the rules is likely to take opioids away from people who otherwise have no available course of treatment. He stated that the CDC’s rules could lead to suicides among this group.
Why ‘Guidelines’ Carry the Force of Law
CDC has declined to release full documentation of expert recommendations and research. All public comments have been anonymized. While the federal government requires by law that regulatory agencies provide 30-90 day public comment periods on proposed rules, the CDC offered only 48 hours and did not provide much notice to stakeholders.
CDC offered emailed responses to questions from InsideSources. While the guidelines released are only a draft with no set date for final approval, the agency says, “Expediting the release of these guidelines is driven by one fact: more than 44 Americans will die today from prescription painkiller overdoses. We must get the guidelines into the hands of health care professionals who can help prevent these deaths.” In total, CDC states that it has received 1,200 comments from patients, practitioners, and organizations.
As to why the comments were all anonymous, the agency explains: “CDC redacted all personally identifiable information from comments received to preserve the anonymity of the individual submitting feedback. CDC wanted individuals to feel comfortable and free to share whatever thoughts and opinions they wished. Since we provided comments to peer reviewers and plan to post a summary of comments online, we did not include names or affiliations of persons making comments.”
Peter Pitts of the Center for Medicine in the Public Interest has been one of the most-outspoken critics of the CDC action. Pitts previously served as the Food and Drug Administration’s associate commissioner for external relations. In an interview with InsideSources, he noted that all FDA actions are public and the documentation fully reviewable before the hearing happens. “The complete, 180-degree different approach that CDC took is inexcusable,” says Pitts. “CDC is a government agency. They exist within the same department as FDA. They must play by the same rules.”
CDC has no legal obligation to open the draft guidelines for public comment or fully disclose the research that went into writing the rules. This is part of what has critics so angry. As Hansen explained in his letter: “By legal definition the guideline is not a proposed regulation subject to the Administrative Procedures Act, but clearly the intent of CDC is that the guideline be distributed to and adopted by state public health entities and certifying organizations as if it had the legal authority of a regulation.”
In medicine, there is no central authority that regulates most patient care. The FDA is responsible for approving new drugs, but once it finishes that rigorous and costly process, doctors are not required to follow any specific regulations for prescribing a drug. There is a universe of guidelines that have been adopted by medical groups to advise on proper treatment. Doctors are not required to abide by these, but when they are not followed, doctors and hospitals could be confronted with legal action. Additionally, insurance companies may use guidelines to determine what coverage to provide.
Charles E. Argoff, Professor of Neurology at Albany Medical College and Director of the Comprehensive Pain Center at Albany Medical Center in New York, tells InsideSources that the guidelines threaten to cut patients off from the treatment they need that should be left to the doctor’s judgement. Instead, he explains that insurance companies have already begun to place limits on quantity and duration of treatment for opioids, taking that decision away from medical professionals. Additionally, Argoff cited medical groups that have stopped prescribing opioids to avoid liability.
Another health care provider noted the fear that many pain clinics have of being investigated and shut down. In Ohio, a local pain clinic had been overprescribing. It was raided by police and closed. Its patients have not been welcomed to other pain clinics for fear that triggers an investigation against them. One man with terminal throat cancer has been unable to find any clinics to provide pain relief because he had been a customer at the overprescribing clinic.
While the CDC guidelines may not carry the force of law, they are likely to be central to lawsuits involving opioids because of the, perhaps perceived, authoritative backing of a government agency.
In August, Judge Robert J. Moss of the Orange County, California Superior Court stayed a case of the People of the State of California against several manufacturers of opioids. Plaintiffs say the pharmaceutical company has employed misleading marketing tactics. Moss wrote in his ruling: The plaintiff’s “complaint cites to various treatises and the like showing that the representations made by the defendants are misleading, there is no doubt that defendants’ experts will assert the exact opposite.”
Indeed, in a pending lawsuit filed by the City of Chicago against a similar group of defendants as the California case, six different opioid guidelines documents are cited in a brief from the plaintiff. The lawyers representing Chicago charge that some of those guidelines have been produced by organizations, such as the American Geriatrics Society, which have accepted limited funding from the pharmaceutical industry, thus biasing the recommendations.
The problem for the courts arbitrating such cases is that for all the guidelines objected to by plaintiffs as having received funding from the pharmaceutical industry, the defendants can cite the exact same conflicts of interest, both financial and ideological, for guidelines produced by anti-opioid activists.
In the California case, the judge argues that the courts are not experts in the medical field, and for an issue with so much disagreement over evolving research, it is challenging to reach a decision. “The court does not shrink from its responsibilities to handle complex, convoluted litigation; it handles such matters every day of the week. It does, however, take pause at involving itself in an area which is best left to agencies such as the FDA who are designed to address such issues.”
Indeed, FDA has chosen to avoid action specifically because there is a lack of data. In 2013, responding to a public petition from Physicians for Responsible Opioid Prescribing (PROP), a lobbying group that works to limit opioid use, the FDA agreed with PROP that extended-release opioids should not be used for “moderate to severe,” continuous, around-the-clock pain. FDA changed the labelling to drop “moderate” and indicate the pain should be “severe.” But it also denied the petition’s request to distinguish between cancer and non-cancer pain because of a lack of evidence. It denied a request to list a maximum daily dose or duration of use, both of which are part of the CDC guidelines.
FDA allowed for significant public comment. It looked at the same evidence as the CDC, and it chose to not change its labelling of opioids. Nonetheless, the CDC is a government agency, and its guidelines will likely carry significant weight in a court of law.
The Debate Within the Debate: Who Has a Conflict of Interest?
The CDC guidelines raise questions over why the agency has taken its own action when the FDA has more direct authority on opioid use. Anti-opioid activists, rather than an independent panel representing both sides of the debate, were the driving force behind the CDC guidelines. Additionally, a member of the “Core Expert Group” that helped to author the CDC guidelines had been a paid consultant to the law firm responsible for both the California and Chicago court cases.
CDC has been secretive throughout the drafting of the guidelines, going so far as to refuse to disclose its outside advisors. Those advisors became public from a leaked confidential draft. Critics say the panel is compromised because of its ideological composition and conflicts of interest.
According to critics, chief among those with potential conflicts is Jane Ballantyne, President of PROP. Ballantyne has served as a paid consultant to the law firm Cohen Milstein, which was profiled by the New York Times late last year for its coaxing of state attorneys general to sign contingency agreements allowing the firm to file suit against potential targets it has identified by scouring the news media and public records. In what the Times suggests is a quid pro quo arrangement, the attorneys general receive substantial campaign contributions either right before or after they sign the contingency agreements.
The Times article focused on Cohen Millstein attorney Linda Singer for the success she has had convincing politicians to allow her firm to pursue action on a state or city’s behalf for which, in many cases, the state or city had not even considered pursuing a lawsuit. Singer also happens to be the lead counsel in both the State of California and City of Chicago cases against opioid manufacturers.
While there has been a direct financial relationship between Cohen Milstein and Ballantyne, PROP executive director Andrew Kolodny tells InsideSources that the consulting relationship ended over one year ago, that consulting occurred before Ballantyne became president of PROP, and that relationship was disclosed to the CDC. “We don’t believe there’s any conflict of interest with [Ballantyne] having served as a consultant for Cohen Milstein,” says Kolodny. “It’s actually an alignment of interests in a sense that we believe that pharmaceutical companies have promoted opioids improperly, so we think these suits are valid and they’re important.”
When Kolodny was pressed on why Ballantyne working for a law firm with a financial interest in the guidelines is different than input from doctors with financial ties to pharmaceuticals, he said: “I’m not sure how I would understand that to be a conflict if somebody is an expert and they’re asked for their expertise.”
Kolodny thinks differently about doctors who receive money from pharmaceutical companies. Out of 970,000 doctors in the United States, 606,000 received payments from pharmaceutical companies in 2014, according to data analyzed by ProPublica. During the 17-month period studied, pharmaceutical companies paid about $9.9 billion to doctors, to include research payments, speaking and consulting fees, and licensing. Kolodny sees such financial ties as a fundamental conflict of interest.
Asked whether those on the other side of the debate receive consulting fees because they’re also experts, Kolodny responded, “No. They receive fees because they say the things drug companies like them to say.”
That’s “totally wrong,” explains Dr. Tom Stossel, American Cancer Society Professor of Medicine at Harvard Medical School. He is the author of a new book, Pharmaphobia: How the Conflict of Interest Myth Undermines American Medical Innovation. “Companies want to interact with the best and brightest, not the most gullible.” Conflicts of interest, he explains, are an “alignment of interests” whether that is a law firm or a pharmaceutical company.
PROP, for its part, has not accepted any contributions from law firms, insurance companies, pharmaceutical companies, or medical device manufacturers. Kolodny says their funding comes from those who have been affected by opioid addiction and “passing the hat” among PROP’s board members. PROP exists under Phoenix House, a nonprofit drug & alcohol rehabilitation organization with over 120 programs in ten states, serving 18,000 individuals each year.
Who Shaped the Guidelines?
The greatest concern for critics is not a specific conflict of interest but that the panel itself is heavily biased toward implementing overbearing rules.
There were three contributing authors to the guidelines, two of whom were CDC staff members, plus the 17-member Core Expert Group. According the documentation for the draft guidelines, that group served to “assist in interpreting the evidence and translating the evidence into recommendations.”
The Core Expert Group, according to critics, lacks a true representation of scientific opinion on opioids. PROP holds close ties to the Core Expert Group. Ballantyne and PROP vice president Dr. Gary Franklin were both part of the 17-member advisory panel.
“I’m sure everyone on the committee is an expert, but you need to have a variety of opinions, otherwise why even bother having the meeting in the first place,” said Pitts, whose responsibilities at the FDA included overseeing the formation of FDA’s advisory committees. Referring to PROP’s role in creating the guidelines, Pitts said, “When you basically take one group that is considered the opioid lunatic fringe and allow them to create the basis of your policy almost verbatim is inexcusable. It’s bad policy. It’s bad science. It’s poorly serving the public health.”
InsideSources asked PROP whether it had actively pursued involvement in the Core Expert Group and what role the organization played in encouraging the CDC to write its own guidelines. Kolodny called such accusations a “conspiracy theory.” He says he has seen the accusations online that PROP lobbied the CDC to create these guidelines because the FDA rejected part of their petition. While he’s pleased CDC acted, any claims that PROP lobbied for this are “completely, totally false.”
CDC told InsideSources, “No organization external to CDC or to the Department of Health and Human Services influenced CDC’s decision to develop these guidelines.”
PROP and the CDC do have close connections among staff. PROP’s Kolodny worked under CDC director Tom Frieden when Frieden was commissioner of the New York City Health Department. Perhaps more noteworthy is that CDC’s Division of Unintentional Injury Prevention oversaw the writing of the guidelines. Dr. Leonard Paulozzi, who is the medical epidemiologist for that division of the CDC, appears on PROP letterhead as a board member in its 2012 petition to the FDA. Paulozzi no longer serves on the board, but he did work at the CDC at the time of the petition through the present.
CDC claims “our Core Expert Group comprises a diverse group of subject matter experts – with substantial knowledge on several aspects of opioid prescribing,” but critics believe the choices for the Core Expert Group suggest that CDC set out with the goal of writing tough guidelines.
“You don’t put multiple people on the advisory committee with similar conflicts. That’s just completely nonsensical and contrary to the public interest,” says Pitts. CDC absolutely would have known the views of every Core Expert Group member before inviting them to serve on the panel, according to Pitts, so the panel composition shows they set out with a specific goal in mind, regardless of disagreement within the medical community.
PROP’s Franklin was responsible for writing very similar opioid guidelines in Washington State. In addition to the PROP members, several others have been outspoken about the need to control opioids. Psychiatrist Judith Turner rounds out a strong contingent, along with Ballantyne and Franklin, from the University of Washington. Several panel members treat addiction and emergency room visits resulting from overdoses.
What is distinctly missing from the panel, says Argoff, are any medical professionals actually responsible for treating patients suffering from chronic pain.
Dr. Roger Chou of Oregon Health and Sciences University served both as one of the contributing authors and as a member of the Core Expert Group. In 2009, he was the lead author for opioid guidelines commissioned by the American Pain Society and the American Academy of Pain Medicine that reached conclusions that were significantly more open to prescribing opioids. Research into opioid use has changed little since the 2009 guidelines were written. Chou’s decision to alter course is unclear. He did not respond to a request for an interview.
There are several more moderate members of the Core Expert Group, but Harvard’s Stossel, a resident scholar at the American Enterprise Institute, recognizes potential problems with the panel based on research in behavioral economics. His research indicates that industry connections do not improperly skew medical research. But in the case of the CDC panel, he says there may be a “conformity cascade.” The CDC placed a number of outspoken anti-opioid activists on a panel with only a few moderate members and no pain experts. While vigorous debate can lead to good policy decisions, the Core Expert Group lacked opposing arguments, and a drive to conformity can lead all members to reach conclusions inconsistent with the evidence.
But some don’t believe there is any difference of opinion among experts.
“I don’t think there are two sides to this, and in terms of what medical and pain professionals believe, there is only really one side here,” claims Kolodny. “There’s the medical experts and the leaders in the field, and then there’s the industry and the groups and individuals who take money from them.”
“I think a good way of thinking about this would be climate change,” says Kolodny. “You’re not going to find many experts who study climate change who are going to say there’s no such thing as climate change. And if you did […] they were folks working for industry.”
“I think having individuals who are getting payments from companies that make these products and have a financial stake in seeing aggressive prescribing—I don’t think those individuals should be allowed to participate in writing any type of guidelines,” Kolodny told InsideSources.
Do Only Corporate Ties Bind?
Sally Satel, a lecturer at the Yale School of Medicine who has treated many opioid addicts, says that in selecting a panel to advise guidelines like the CDC’s, you want a team of rivals and representation from all viewpoints, no matter who pays them. She also notes that ideological commitments are often more influential than financial conflicts. “Why do people think only corporate ties are the ones that bind?”
The Annals of Internal Medicine, in its October 6, 2015 issue, presents guidance from an international board on the disclosure and management of conflicts of interest. While “direct financial” interests are easily defined, the article outlines “indirect” conflicts in the areas of academic advancement, clinical revenue streams, community standing, and scientific interest. Examples of such conflicts include “having published on a topic that expresses an opinion on the effectiveness of an intervention,” “gaining clinical income from the recommendation,” “leadership or board or committee memberships,” “involvement with an advocacy group,” and “personal convictions.”
While excluding those with conflicts of interest may be the ideal, we live in the real world. As the report notes: “Pluralism of stakeholders is a desirable feature of guideline panels and may reduce the risk of bias resulting from [conflicts] and lead to balanced final decisions.”
Much remains unknown about when the CDC plans to finalize its guidelines or whether it may work to find more moderate ground than it has currently staked. But without question, the guidelines will be the subject of debate in billion-dollar court cases, will set standards for coverage by insurance companies, and will change how opioids are prescribed in the United States for both those already treating chronic pain and others who are yet to suffer from it.