Background - Embracing Narcotics
In the long ago time when I was in medical school, the wisdom was then that narcotics (that is, drugs like morphine or heroin, the latter not legal) should only be used in severe acute pain, like that due to bad trauma or occurring post-operatively, or for the pain of terminal illnesses, like cancer. The reason their use was so restricted was that the drugs were believed to cause frequent adverse effects, from severe constipation, to addiction, to respiratory depression and death.
However, starting in the 1990s, the conventional wisdom changed. Suddenly, the focus was on the under-treatment of chronic, but not malignant pain, and it became permissible, or even preferable, to use potent narcotics for this purpose. Physicians like me who were very conservative in their use of narcotics were chastised for under-treating pain.
The Wall Street Journal article explained how this radical change in approach was apparently engineered by a few key opinion leaders, particularly Dr Russell Portenoy. It opened,
Two decades ago, the prominent New York pain-care specialist drove a movement to help people with chronic pain. He campaigned to rehabilitate a group of painkillers derived from the opium poppy that were long shunned by physicians because of their addictiveness.
Dr. Portenoy's message was wildly successful. Today, drugs containing opioids like Vicodin, OxyContin and Percocet are among the most widely prescribed pharmaceuticals in America.
The article provided graphics showing that per capita prescription narcotic use has more than tripled since 1999,
A Change Driven by Wishful Thinking, not Evidence
Unfortunately, as the article made clear, the radical change that seemed so odd to some of us physicians who were trained before the 1990s was not driven by any good evidence from clinical research.
Per the WSJ,
Because doctors feared they were dangerous and addictive, opioids were long reserved mainly for cancer patients. But Dr. Portenoy argued that they could be also safely be taken for months or years by people suffering from chronic pain. Among the assertions he and his followers made in the 1990s: Less than 1% of opioid users became addicted, the drugs were easy to discontinue and overdoses were extremely rare in pain patients.
However, Dr Portenoy's contention seemed to be based only on a small case-series of patients, lacking any sort of control group, and too small and likely too selective to generalize, particularly to patients with chronic, non-malignant pain.(Portenoy RK, Foley KM. Chronic use of opioid analgesics in non-malignant pain: report of 38 cases. Pain 1986; 25:171-86. This article does not seem to be available online.)
In 1986, at the age of 31, he co-wrote a seminal paper arguing that opioids could also be used in the much larger group of people without cancer who suffered chronic pain. The paper was based on just 38 cases and included several caveats. Nevertheless, it opened the door to much broader prescribing of the drugs for more common complaints such as nerve or back pain.
Dr Portenoy also cited
the statistic that less than 1% of opioid users became addicted.
Today, even proponents of opioid use say that figure was wrong. 'It's obviously crazy to think that only 1% of the population is at risk for opioid addiction,' said Lynn Webster, president-elect of the American Academy of Pain Medicine, one of the publishers of the 1996 statement. 'It's just not true.'
The figure came from a single-paragraph report in the New England Journal of Medicine in 1980 describing hospitalized patients briefly given opioids.
The reference here appears to be a letter to the New England Journal of Medicine ( Porter J, Jick H. Addiction rate in patients treated with narcotics. New England Journal of Medicine 1980; 302:123. Link here.) This was literally one paragraph long, so the methods of the research it reported cannot be rigorously evaluated. In any event, the letter appears to have retrospectively documented an observation of hospitalized patients who were given at least a single dose of narcotics, and thus appears not relevant to the effects of long-term narcotics on patients with chronic pain.
Thus, Dr Portenoy's enthusiasm for aggressive use of narcotics in non-malignant chronic pain was never based on any good evidence from well designed and performed randomized controlled trials with long-term followup that showed that narcotics were safe and effective in this setting. At best, Dr Portenoy's and colleagues' contentions that narcotics should be liberally utilized for such patient were based on wishful thinking, not good evidence.
A Change Driven by Stealth Marketing
The WSJ article documented how Dr Portenoy was a prime mover in what appeared to be deceptive stealth campaigns to market narcotics for chronic, non-malignant pain. Dr Portenoy's 1986 case-series
opened the door to much broader prescribing of the drugs for more common complaints such as nerve or back pain.
Charming and articulate, he became a sought-after public speaker. He argued that opioids are a 'gift from nature' that were being forsaken because of 'opiophobia' among doctors. 'We had to destigmatize these drugs,' said Dr. Portenoy.
He rose to chairman of pain medicine and palliative care at Beth Israel Medical Center in New York. His small office is studded with awards and evidence of his offbeat sense of humor. He prominently displays a magazine mock-up that jokingly dubs him 'The King of Pain.'
At medical conferences, his confident, knowing manner helped smooth the way for his message. Before an audience of government regulators, he once joked that he might tell a patient at low risk of abuse: 'Here, [have] six months of drugs. See you later,' he said, according to a Food and Drug Administration transcript. Amid laughter, he added, 'It's just hyperbole. I don't actually do that.'
Steven Passik, a psychologist who once worked closely with Dr. Portenoy and describes him as his mentor, says their message wasn't based on scientific evidence so much as a zeal to improve patients' lives. 'It had all the makings of a religious movement at the time,' he says. 'It had that kind of a spirit to it.'
So Dr Portenoy became a respected opinion leader. His influence was demonstrated by how he generated disciples
Dr. Portenoy's ideas about opioids reached into mainstream medicine and attracted outspoken advocates. In a 1998 talk in Houston, Alan Spanos, a South Carolina pain specialist, said patients with chronic noncancer pain could be trusted to decide themselves how many painkillers to take without risk of overdose. According to a recording, Dr. Spanos said he understood that a patient would simply 'go to sleep' before stopping breathing. While asleep, he said, the patient 'can't take a dangerous dose. It sounds scary, but as far as I know, nobody anywhere is getting burned by doing it this way.'
Dr Portenoy was affiliated with organized efforts that facilitated the marketing of narcotics for chronic malignant pain. The marketing used clinical practice guidelines to push narcotics
Dr. Portenoy helped write a landmark 1996 consensus statement by two professional pain societies that said there was little risk of addiction or overdose among pain patients.
The campaign enlisted government regulators, and thus seemed to include an element of regulatory capture,
One of Dr. Portenoy's chief complaints was that doctors were reluctant to prescribe opioids because they feared scrutiny by regulators or law enforcement. In the second half of the 1990s, he and his followers campaigned successfully for policies to change that.
In 1998, the Federation of State Medical Boards released a recommended policy reassuring doctors that they wouldn't face regulatory action for prescribing even large amounts of narcotics, as long as it was in the course of medical treatment. In 2004 the group called on state medical boards to make undertreatment of pain punishable for the first time.
This case demonstrated the direct involvement of pharmaceutical companies who sold narcotics,
That policy was drawn up with the help of several people with links to opioid makers, including David Haddox, a senior Purdue Pharma executive then and now. The federation said it received nearly $2 million from opioid makers since 1997. The federation says it derives the majority of its funding from administering medical licensing exams, credential verification, and data services.
A federation-published book outlining the opioid policy was funded by opioid makers including Purdue Pharma, Endo Health Soluttions Inc, and others, with proceeds totaling $280,000 going to the federation. .
The campaign also involved an important hospital accrediting organization
In 2001, the Joint Commission, [JCAHO] which accredits U.S. hospitals, issued new standards telling hospitals to regularly ask patients about pain and to make treating it a priority. The now-familiar pain scale was introduced in many hospitals, with patients being asked to rate their pain from one to 10 and circle a smiling or frowning face.
The Joint Commission published a guide sponsored by Purdue Pharma. 'Some clinicians have inaccurate and exaggerated concerns" about addiction, tolerance and risk of death, the guide said. "This attitude prevails despite the fact there is no evidence that addiction is a significant issue when persons are given opioids for pain control.'
A Change Leading to Personal Enrichment
Meanwhile, Dr Portenoy was personally profiting from his relationships with pharmaceutical companies
Over his career, Dr. Portenoy has disclosed relationships with more than a dozen companies, most of which produce opioid painkillers. 'My viewpoint is that I can have those relationships, they would benefit my educational mission, they benefit in my research mission, and to some extent, they can benefit my own pocketbook, without producing in me any tendency to engage in undue influence or misinformation,' he said.
Dr. Portenoy and Beth Israel declined to provide details of their funding by drug companies. A 2007 fundraising prospectus from Dr. Portenoy's program shows that his program received millions of dollars over the preceding decade in funding from opioid makers including Endo, Abbott Laboratories, Cephalon, Purdue Pharma and Johnson & Johnson.
He currently also appears to be on the advisory boards of Zars Pharma Inc, Relevare Therapeutics, and Cytogel Pharma.
Thus, it seems that Dr Portenoy fit the usual definition of key opinion leader. He was regarded as an authority in his area and his opinions were obviously influential. He was paid by health care corporations with interests in selling their goods or services, in this case, narcotic drugs, and was using his influence to promote individual patient care decisions and policy decisions that facilitated the widespread use of these drugs.
A Change Leading to Sick and Dead Patients
Since the campaign to "destigmatize" narcotics began, the US has seen what many have called an epidemic of narcotic adverse effects. The WSJ article provided graphs showing that narcotic related deaths and hospital admissions both increased more than five times since 1999. As the WSJ put it,
some specialists now question whether the drugs should be prescribed so freely for months or years to people with chronic pain that isn't related to cancer, as Dr. Portenoy proposed 25 years ago. "People lost sight of the fact that these are dangerous drugs that are highly addictive," said Jane Ballantyne, a pain specialist at the University of Washington. She once agreed with Dr. Portenoy and proponents of broad opioid use but now believes they need to be used more selectively.
Dr Portenoy Recants
What is most remarkable about this case is that it seems to be the first in which a highly influential industry paid key opinion leader has publicly had a change of heart.
Now, Dr. Portenoy and other pain doctors who promoted the drugs say they erred by overstating the drugs' benefits and glossing over risks. 'Did I teach about pain management, specifically about opioid therapy, in a way that reflects misinformation? Well, against the standards of 2012, I guess I did,' Dr. Portenoy said in an interview with The Wall Street Journal. 'We didn't know then what we know now.'
I would note there is some sophistry there. There was never good evidence for narcotics' effectiveness or safety for patient with chronic, non-malignant pain.
In fact, Dr Portenoy also admitted that, sort of,
'Data about the effectiveness of opioids does not exist,' Dr. Portenoy said in his recent Journal interview. To get a painkiller approved, companies must prove that it is better at reducing pain than a sugar pill during short trials often lasting less than 12 weeks. 'Do they work for five years, 10 years, 20 years?' Dr. Portenoy said in the Journal interview. 'We're at the level of anecdote.'
Again, it is not that the data that supported the use of the drugs has disappeared, or that new data has been developed that contradicts the old data. There never has been any good data, that is, from well designed and performed randomized controlled trials that demonstrate that the benefits of narcotics outweigh their harms for patients with chronic, non malignant pain. It does not exist now and it never existed.
Dr Portenoy also admitted,
'I gave innumerable lectures in the late 1980s and '90s about addiction that weren't true,' Dr. Portenoy said in a 2010 videotaped interview with a fellow doctor. The Journal reviewed the conversation, much of which is previously unpublished.
In it, Dr. Portenoy said it was 'quite scary' to think how the growth in opioid prescribing driven by people like him had contributed to soaring rates of addiction and overdose deaths. 'Clearly, if I had an inkling of what I know now then, I wouldn't have spoken in the way that I spoke. It was clearly the wrong thing to do,' Dr. Portenoy said in the recording.
So not only did the Wall Street Journal article describe how the overuse of narcotics for chronic, non-malignant pain came from wishful thinking energized by the possibility of corporate and personal profit, it showed how the chief medical cheer leader for these drugs now admits he was wrong.
In summary, it appears that the huge increase in the use of narcotics to treat chronic, non-malignant pain was never based on clear convincing evidence from well-designed studies. At best it was based on irrational enthusiasm and wishful thinking by some very vocal and persuasive advocates. These advocates seemed to become "key opinion leaders," that is, influential people who promoted the use of pharmaceuticals while they were being paid by pharmaceutical companies, and were likely involved in what appears to be systematic stealth marketing campaign by the pharmaceutical companies that make narcotics. These campaigns included production of clinical practice guidelines promoted as authoritative, and enlistment of accrediting organizations and government regulatory agencies.
One particularly disturbing part of this story was the involvement of numerous people and organizations entrusted by society to promote good medical care. It shows how physicians, other health professionals, and the public at large must be very skeptical of vocal advocates of new, aggressive, "innovative" approaches, of clinical practice guidelines even those developed by apparently prestigious professional societies, of accrediting organizations, and of government regulators. That is discouraging, and could lead to the cynical approach of simply not trusting anyone.
I would note, however, that two ways the headlong rush to over-use of narcotics could have been derailed would have been:
- employment of extreme skepticism of people paid by narcotics manufacturers advocating increased use of these drugs, no matter how distinguished, scholarly, or influential these people appear to be. This suggests the need for general skepticism of people with financial relationships with health care corporations pushing the goods or services these corporations provide, or pushing policies that would aid the selling of those goods or services
- a rigorous evidence-based medicine approach, meaning making clinical and policy decisions based on the best evidence found by systematic search from rigorously evaluated clinical research about the benefits and harms of these decisions, informed by patients' values. Such an approach would have revealed there was never any good clinical evidence to support long-term use of narcotics for chronic, non-malignant pain, the particular "innovation" being pushed in this case.
So I would argue that the case of the legal narcotics pushers underlines the need for utmost transparency about conflicts of interest affecting people and organizations that advocate for particular approaches to health care, and to the management of individual patients; continuing movement to bar at least the most egregious conflicts, as per the Institute of Medicine report on the topic (look here); and the need for the very skeptical, rigorous application of true evidence-based medicine approaches.
Finally, I must note that this seems to be the first time that a prominent, highly influential key opinion leader has recanted. Maybe he will write an article entitled "Dr Drug Pusher?" - just joking, but at least one former key opinion leader did write the confessional "Dr Drug Rep." Maybe this is the beginning of a movement toward health care based on logic and evidence rather than wishful thinking, irrational enthusiasm, or ideology, or even worse, on deception or personal enrichment.