On MIA Radio this week, MIA’s Gavin Crowell-Williamson interviewed Adriane Fugh-Berman, MD, a professor in the Department of Pharmacology and Physiology and in the Department of Family Medicine at Georgetown University Medical Center (GUMC).
She is the director of PharmedOut, a GUMC research and education project promoting rational prescribing and exposing the effects of pharmaceutical marketing on prescribing practices. Dr. Fugh-Berman leads a team of volunteer professionals that has deeply impacted prescribers’ perceptions of the adverse consequences of industry marketing.
She is interested in physician-industry relationships and is an expert witness in litigation regarding pharmaceutical marketing processes. She was formerly a medical officer in the Contraception and Reproductive Health Branch of the National Institute for Child Health and Human Development.
Dr. Fugh-Berman is the lead author on key articles on physician-industry relationships, including a national survey of industry interactions with family medicine residencies, exposés of how ghostwritten articles in the medical literature are used to sell drugs, an analysis of drug rep tactics, and an explanation of industry publication planning.
She wrote the first chapter on alternative medicine to appear in Harrison’s Principles of Internal Medicine and authored the first clinicians’ reference text on dietary supplements, the 5-Minute Herb and Dietary Supplement Consult, as well as an evidence-based book aimed at consumers, Alternative Medicine: What Works.
In addition to dozens of articles in peer-reviewed literature, Dr. Fugh-Berman coauthored The Truth about Hormone Therapy and co-edited The Teratology Primer. Dr. Fugh-Berman is the former chair of and currently writes a column for the National Women’s Health Network, a consumer advocacy group that takes no money from industry. Dr. Fugh-Berman has appeared on 20/20, the Today Show, and every major news network.
What follows is a transcript of the interview, edited for clarity.
GCW: Thank you for joining me here, Dr. Fugh-Berman, I appreciate you taking the time out of your schedule.
AFB: Thanks for having me, Gavin.
GCW: So we’re here to talk today about your article, Continuing Medical Education and the Marketing of Fentanyl for Breakthrough Pain. But first, can you tell me a little bit about your background and what drove you to do this sort of research?
AFB: Well, I really started off as a women’s health activist even before I went to medical school and have been able to really use the medical degree to expand advocacy in the area of women’s health, but also public health in general.
GCW: It seems to me like a lot of your work is motivated by your passion for studying conflicts of interest in Big Pharma; can you speak to where that specific interest of yours came from?
AFB: Well, it’s really about promoting evidence-based medicine. I’m very interested in people having information about both pharmacologic and non-pharmacologic therapies that are evidence-based and to have that information be free of industry influence. So that’s really what motivates me. And also being against the medicalization of daily life or minor ailments and making sure that when people do use medicine that the benefits are apt to outweigh the risks.
GCW: Yeah, absolutely. Can you tell me a little bit about the founding of PharmedOut? What was the motivation for it, who came together to make it happen?
AFB: Sure. So about 10 years ago, the Attorneys General from all of the states and the District of Columbia took money that they had gotten in a lawsuit against pharmaceutical manufacturers for off-label promotion of a drug called Neurontin. They used that money to fund the education of prescribers and patients on pharmaceutical marketing practices.
So PharmedOut, or Georgetown University Medical Center, got one of these grants. I’d applied for one of these grants and that’s how we started PharmedOut — to educate prescribers about inappropriate pharmaceutical marketing practices. That grant was for two years, but after the grant ran out, everybody who worked on the project was so committed to it that no one left even though no one was getting paid anymore.
It was an unbelievable level of commitment and so we started just raising money from friends and families so that we could keep paying our project manager. And we’ve been able to keep going for the last 10 years based primarily on individual contributions. We have a few other sources of money including a contract for several years from the DC Department of Health to create industry-free continuing education — web-based for doctors, nurses, and pharmacists. So that’s also been one of our sources of income, but we’re primarily still supported by individual donations.
GCW: Wow. That’s amazing. One of the cool things, at least to me, about PharmedOut is that you offer CMEs with no industry ties. Can you speak a little bit to why you find that important?
AFB: Yes. It’s an issue that most people don’t know very much about, but almost all states and almost all physicians in the United States, also nurses and pharmacists, have to do a certain number of hours of continuing education a year. Well, everyone likes free continuing education and most of the free continuing education is funded by pharmaceutical companies and other medical companies and it always has marketing messages in them.
Those marketing messages may be very subtle, but industry-funded continuing education always has marketing messages in them, and PharmedOut is actually the only group in the world that is looking at marketing messages in continuing education.
Education is not regulated in the same way as a promotion. The Food and Drug Administration, for example, does not consider anything educational to be promotional. And in fact, all industry-funded continuing education is in fact promotional even if that promotion is very subtle. So that’s an area that we have created research methods in — to reverse-engineer marketing messages from continuing education.
GCW: In an interview that you did with the Chronicle, you outlined some of the challenges you’ve had getting your studies with PharmedOut published. Can you speak to that a little further?
AFB: Yes, we try to get our studies published in good medical journals, and unfortunately most medical journals get a lot of money, not only from pharmaceutical company advertising but also from the purchase of reprints by pharmaceutical companies. So they’re very loath to publish articles that are critical of pharmaceutical companies or medical device companies, et cetera.
It is actually very difficult for us to get our studies published. Another reason that it’s difficult is that we do a lot of qualitative work and that’s not something that’s easily published in biomedical literature. But we really want to get it into biomedical literature because we want physicians and biomedical researchers to read this and not have it be sort of hidden in the social science literature, which they’ll never see.
GCW: Can you speak to where PharmedOut is right now, what sort of projects you’re working on, and the direction you think or hope you’ll be going?
AFB: We’re doing so much on opioids right now because we’re in the midst of this epidemic, and what people don’t understand is that opioid promotion is still going on. It’s going on internationally, and it’s going on in the US.
Most of the market for opioids is in chronic pain patients. What opioid manufacturers are doing is everything they can to prevent any sort of regulations on doses or duration of opioids; they’re fighting all efforts on this, on every front, and we are fighting back. So we’re doing a lot on opioids.
We’re doing a lot on marketing messages in industry-funded continuing education and we’re also doing a lot on disease invention. There’s nothing to prevent pharmaceutical companies from just creating diseases, or subdividing diseases further. And, of course, they have specific drugs available for each of the diseases that they create. For example, making lots of different flavors of depression so that they can position their particular drug for a particular flavor of depression or a particular flavor of anxiety. This is all done for market positioning and it’s not necessarily helpful for patients. In fact, it can make many people feel ill when really there’s nothing wrong with them, or there’s just a normal human variant of personality, for example.
GCW: Yeah, absolutely. This seems like a good opportunity to lead into this study. Can you first give me a brief outline of the background, methodology and major findings of your study on continuing medical education and the marketing of fentanyl for breakthrough pain?
AFB: Yeah, so we were looking at several conditions that are essentially made up by pharmaceutical companies and one of them is breakthrough pain. They didn’t actually make up the term, but in terms of making it into a disease, that was really an industry invention.
Breakthrough pain refers to when somebody is on opioids for, say, end of life pain and let’s say that they have cancer pain and they’re taking morphine every eight hours and around hour six or seven, they’re in terrible pain. So that’s called breakthrough pain: it’s breaking through the dosing regimen. The way that we would deal with that is to decrease the dosing intervals. So say, okay, we’ll take the morphine every six hours instead of every eight hours, maybe we’ll lower the dose some. So that would be a way of dealing with it.
Well, there were companies that had rapid-acting fentanyl products that only lasted about 45 minutes. Now that can be really useful if somebody’s undergoing a painful dental procedure, for example, or undergoing wound debridement (or cleaning out of a wound), which can be very, very painful. We routinely use opioids to deal with pain in that circumstance but you don’t need the opioid to last very long; that would be a perfect use for rapid-acting fentanyl. But it’s a very limited market when you’re talking about short, painful conditions.
So what Cephalon did, they first had Actiq, which was a fentanyl lollipop. And then when the patent started to run out on the lollipop, they essentially did the lollipop without the stick or a fentanyl lozenge, and then immediately started undermining the lollipop, which then became generic. So they said that, oh, adults don’t want to be seen with a lollipop stick coming out of their mouth. It’s the “stigma of the stick.” The lozenge was much more discreet.
What this company did was to take over the concept of breakthrough pain and describe it as a sort of different kind of pain that should be treated with the short-acting fentanyl. So even when somebody is on a long-acting opioid they should be given bursts of short-acting fentanyl when they had breakthrough pain; well, this is really dangerous.
These submucosal products that are absorbed from under the tongue and from inside the cheek get into the bloodstream much, much faster than taking an oral dose of an opioid. In fact, they get into the bloodstream almost as fast as mainlining or intravenous use of a drug. When something hits you faster, it’s more addictive and that’s definitely true of these fentanyl preparations.
So they were popular, of course, on the street, but by increasing the level of opioid in someone’s body very quickly, they’re also far more dangerous. They were much more apt to cause respiratory depression, especially since they were only approved to treat breakthrough pain in people who are already on opioids. So people already had a background level of opioids and now they’re taking, you know, they’re taking a burst of an even stronger opioid that acts really fast. So that was also quite dangerous and, as I said, this was just something that we could deal with very easily by using good old generic, low-cost morphine, which is an amazing drug because you can use it intravenously, you can use it orally, you can use it sublingually, and because it’s in a liquid, you can titrate the dose sort of endlessly. So morphine is a really great opioid to use.
These fentanyl products were positioned for the treatment of breakthrough pain. In order to position it, the company had to convince physicians that breakthrough pain was a particular kind of pain. Then they also essentially promoted the use of fentanyl for different kinds of pain that weren’t cancer pain, but were pain like low back pain or osteoarthritis for example, or even irritable bowel syndrome or conditions in which it was never appropriate to use opioids.
We wanted to look at, how is breakthrough pain positioned and how is the positioning of opioids sold to physicians. We wanted to compare an industry-funded and a non-industry funded continuing medical education module on breakthrough pain. That didn’t work out very well because we couldn’t find any non-industry funded modules on breakthrough pain, because industry invented breakthrough pain.
There were no non-industry-funded modules on breakthrough pain. We ended up comparing an industry-funded CME activity on breakthrough pain with pain guidelines that were done by an association of pain physicians. That’s what we compared, and we actually randomized participants to either read the industry-funded article or the non-industry-funded article and then we had them take the test from the industry-funded CME activity; there wasn’t a test that was associated with the other article so it wasn’t a perfect comparison, but we couldn’t get a perfect comparison because of the situation.
What was most interesting about our study, I think, is that we also asked people to summarize, what were the main messages that you got out of reading this? What were the take-home messages, what were the “pearls”?
That was really interesting because of course, you can write something in such a way that you take away certain messages or sort of underplay others. What we found is that people who read the industry-funded article, the messages that they came up with were ‘opioids are underused and they should be used more often in pain prevention.’ And they didn’t mention adverse effects.
The ones who read the non-industry funded article on opioids said, ‘opioids are overused and they can cause addiction and death’. So, completely different messages. And so that that was a really important thing to do. The idea, by the way, was given to us by a former drug company executive who said, this is how pharmaceutical companies evaluate whether audiences are taking away the messages that they want them to take away from them because those exact statements are not made in these articles. They’re not made in this continuing medical education.
You can’t say that the industry-funded module never mentioned addiction. It did tend to call it “lack of compliance with the treatment agreement” — they sort of made it seem like a pesky paperwork problem, but you can’t say they didn’t mention it. But you can mention something in such a way that it underplays it, or if you mentioned death, but you mentioned it at the end of a long list of complications that start with constipation and nausea, someone might lose interest before reading the whole list. They go, “oh, constipation, nausea, that’s not so bad.”
When you start an adverse event list with addiction and respiratory depression and death, that would get somebody’s attention more. This is the problem with the continuing education coordinators assessing modules for bias. They don’t actually know what to look for and, in fact, it takes a lot of work to actually be able to reverse engineer marketing messages from these modules. What’s exciting about this study that you’re asking about was that it’s the first randomized controlled trial that I know of where anybody compared an industry-funded and a non-industry-funded module and looked at what the marketing messages are in them.
GCW: Yeah. And I think you’re hinting at this, but I’m just going to ask it outright: I think that some folks would be quick to say, you know, the results to this study are sort of obvious; of course there’s bias in industry-funded CME. Why did you think it was important to do this study despite the ‘obvious’ results that you found?
AFB: Well, this just shows that consumers are smarter than doctors in this way because it’s not at all obvious to doctors. It’s not at all obvious to the offices that accredit continuing education, it’s not at all obvious to regulators about this.
So yeah, it should be obvious. You know, doctors are plenty smart in many different ways, but they’re not good at assessing persuasive writing. They’re not good at recognizing or analyzing sales techniques. They’re not good at social psychology. These are not things that they’re trained in; they’re not things that they’re naturally inclined towards.
People in the financial world say that physicians are very likely to be taken in by financial scams. There is, apparently, a pretty fatal combination of being sort of arrogant and naive at the same time. That makes physicians perhaps more gullible, or more susceptible to certain marketing techniques than even the general population might be.
GCW: I think one of the limitations of this study is that it did run a somewhat small sample size. So given the small sample size, what sort of reasonable implications do you think can be drawn from this study?
AFB: Yeah, it’s definitely a pilot study; this is a study that was done with no funding whatsoever. We’ve been working on doing qualitative analyses of continuing medical education modules on other drugs, and the use of them to establish other diseases. We published an article, for example, looking at marketing messages in establishing hypoactive sexual desire disorder as a real disease, even though we don’t think it’s a real disease.
Yeah, this is a small sample size, but the hope is that some of the techniques that we created could be used to assess other continuing education modules at a later point.
GCW: One of the pieces I found particularly interesting in your study was the concept of manufacturing diseases to sell drugs such as the invention of social anxiety disorder to sell Paxil. Can you explain how you feel breakthrough pain fits that mold, and more broadly, do you feel like opiates, in general, are marketed in this capacity?
AFB: Yeah, so there are different ways that a company can do what they call condition branding a disease, or matching a particular drug with a particular condition. So you might take a condition that already exists and then take a subset of that condition.
For example, antidepressants are also used to treat pain. They can be useful for treating pain, but there was an antidepressant that was put on the market specifically to treat depression and pain. And so their tagline was ‘depression hurts.’ The way that they sold it was, well, do you have patients who are depressed and get headaches? Do you have patients who are depressed and have low back pain? Of course, that’s just about everybody, right? So that was a way of condition branding, the combination of depression and pain, for example.
So, one way to do it is to sub-divide a disease that already exists or to re-name a condition that already exists. For example, erectile dysfunction: we used to call erectile dysfunction impotence, which was sort of a terrible word, but when Pfizer came out with Viagra, or in the years before it came out with Viagra (it was the first and for a while the only treatment out there for this) but they wanted to rename the condition in order to condition brand it and they came up with erectile dysfunction or ED. So that was one way of doing it.
Of course, erectile dysfunction is, no matter what you call it, real and they actually had an effective treatment for it. There’s other diseases that are completely made up or might be taking a particular personality type or a particular life phase and medicalizing it or in some cases just making it up. For example, social anxiety disorder was created to sell a depression and anxiety drug that was late to market. In other words, it was the fifth or sixth or seventh antidepressant out there. Rather than sell it for depression, the company created this concept of social anxiety disorder.
Now, there are people who certainly suffer from social anxiety. There are a number of treatments for it. But they created “Social Anxiety Disorder – SAD”, and condition branded their drug for that particular flavor of anxiety. There are drugs that were condition branded to treat menopause or to treat low testosterone, for example, and the symptoms that were associated with both of these conditions were really just symptoms of aging but were cast as, ‘oh, these are symptoms of hormone deficiency.’ And you need to amp up somebody’s estrogen if they’re a woman, or testosterone if they’re a man. Both of these hormonal treatments have serious adverse effects and don’t actually combat aging.
GCW: I think another one of the major takeaways from this study is that the tools that we currently possess are not adequate to identify this subtle bias that exists in drug marketing. So what do you think you learned from this study about how we can combat that?
AFB: Well, one of the things that we argue for is that education should be completely separate from industry, that industry should not be funding education of physicians or consumers because they’re never going to be objective about it.
That’s also true of assessing their drugs. Industry develops drugs and that’s what they should do, and they test their drugs and that’s what they should do. But in terms of evaluating their drugs in the context of other drugs or other treatments, that’s not something that they should be doing because they’re not going to be objective about it.
I’m hoping with this series of studies and articles that we’ve done or are planning on doing, then we’ll be able to show people that it’s impossible to extract the marketing from education in what industry provides and that it’s better not to try to do that, but simply to ban industry’s involvement in education of either prescribers or consumers. And that the assessment of drugs, the comparative assessment of drugs and nonpharmacologic therapies and other therapies, should be done by neutral bodies.
GCW: It sounds like there’s a lot of intersection between CMEs and a variety of medications. Was there anything specific about the intersection of opioids and continuing medical education that made you particularly interested in studying opioids?
AFB: There are a lot of interesting [opioid-related] things going on now and historically. Several of the things that opioid manufacturers invented are the concept of opiophobia, which refers to physicians who are afraid to prescribe opioids because they were afraid of addicting their patients. That was used as a way to sort of goad physicians into prescribing more opioids, like ‘what are you, a dinosaur?’ You know, ‘you think those opioids are so addictive and really, you have a wrong idea about that’.
Another thing that they invented was the concept of pseudoaddiction. So doctors realized that they were giving their patients opioids and they seem to be expressing addictive behavior. So pharmaceutical companies came up with the concept of pseudoaddiction, which looked exactly like addiction, but was solved by increasing someone’s dose of opioids. So the concept was, oh, this wasn’t an addiction. This was just undertreated pain. You just needed to increase the dose for the patient. Then if their demanding, apparent addictive behavior went away, that shows that it was pseudoaddiction, not addiction.
In fact, there’s no difference between addiction and pseudoaddiction. It was just a term that was created to make physicians feel okay about continuing to prescribe increasing doses of opioids to patients who were clearly addicted.
GCW: I think we’ve hit a lot of the major points of this study. Do you feel like there are any more general takeaways that we haven’t discussed yet?
AFB: Just that it’s very time-consuming and complicated to reverse-engineer marketing messages from not only continuing medical education activities but also educational activities for consumers and testimony that’s provided to state legislators.
There are lots of subtle ways in which pharmaceutical manufacturers are promoting their opioids and promoting other drugs, and that it’s really important to have a high index of suspicion and it’s important to keep industry out of the room when public health concerns are being addressed.
GCW: Now I’m going to jump back a little bit and talk about some of the stuff you were doing before you went to med school. I know you have a history of advocacy before you went down your MD path. How do you feel as though your research and your advocacy have informed one another over the course of your career?
AFB: So it’s important any time one is doing research to be as objective as possible in terms of how a research question is being answered. But what really makes a difference in terms of industry-funded research and non-industry-funded research is what are the questions that are being asked, and it’s really important for us to support non-industry- funded research and to support government-funded research because the government doesn’t have a profit motive in terms of what the results of research are.
Any research that’s done has to be done in as objective a way as possible and so advocacy is separate. Public health advocacy or any kind of advocacy should be separate from research, but certainly, they can each inform each other. One of my frustrations is that often, biomedical researchers will do really great research, but they won’t defend it when it gets attacked by industry.
It’s a tactic for the industry to attack research that it doesn’t like. This really corrupts the scientific process because, in an ideal world, there’s research that’s done, some of it’s good, some of it’s bad, but the bad research gets criticized and falls out of favor and people would stop referring to it. But what’s happening now is that good research is being slammed by industry and industry has really taken over medical discourse and gets to decide what research gets done, how that research is interpreted and how it’s applied.
It’s really important for real researchers to also defend the work that they do and to be aware of when there are industry-funded attacks on their work.
GCW: That’s a really important point. It feels to me oftentimes as though the industry believes itself to be sort of above the scientific process. Thanks for bringing that up. I also understand that you maintain medicinal herb gardens and the Georgetown campus and direct the Urban Herbs projects. Can you tell me about that and how that work intersects with your research and interests in general?
AFB: So that’s really a completely different project of mine. I do maintain gardens on campus that demonstrate a variety of techniques, including permaculture techniques where perennials are emphasized, xericulture techniques in which water-thrifty gardening is emphasized, and ecologic gardening concepts that help pollinators and birds and the environment in general. I also do grow medicinal herbs and also culinary herbs and some small fruits as well in an effort to try and get my very urban students to get some understanding and appreciation of the natural world around them.
Many of my students have never actually plucked a berry off of a bush and put it into their mouth, and that can be a profound experience if you’ve never had it. Or, you know, brewed tea out of something that’s grown on campus. I love it that people will take sprigs of my mint and make it into tea. The gardens are also used by Georgetown Hospital; the nurses bring in patients or sick kids down to the gardens to enjoy them. So that’s really great but I feel like that’s a completely different project.
GCW: Then just to close, if you could imagine us fast forwarding a little bit into the future: in your ideal world, where does the relationship between the pharmaceutical industry and the medical field stand, and how do we get there, more importantly?
AFB: So there is a fiction that pharmaceutical companies and medicine have the best interest of the patients at heart. That’s not actually true; legally and ethically, healthcare providers must represent the best interest of their patients, but legally and ethically, pharmaceutical companies have to represent the best interests of their stockholders. Those are not the same thing at all.
I think it’s really important for medicine, for physicians and nurses and PAs and pharmacists to separate themselves from the pharmaceutical industry and not accept education from them, not accept gifts, not accept funding for conferences, and go back to where we’re actually having the debates about particular therapies and particular treatments within an unbiased environment.
Pharmaceutical companies should make drugs and they should focus on actually creating innovative therapies and not just on marketing therapies that are often mediocre or for which the harms outweigh the benefits. It would be great if pharmaceutical companies could just focus on creating innovative drugs.
GCW: Well, I’m with you there. I think we share that future vision. I want to thank you again for taking the time to chat with me. I really enjoyed our conversation today.
AFB: Sure, so did I. Thanks for having me.