Myth: CME isn’t influenced by commercial sponsors
An Interview with Rick Deyo, MD MPH
Dr. Deyo, Professor of Medicine, general internist, researcher and author of the book: Hope or Hype: The Obsession with Medical Advances and the High Cost of False Promises
How do pharmaceutical companies influence continuing education?
Pharmaceutical companies influence continuing education in a wide variety of ways. First of all, they’re very careful about who they pick for speakers; they pick speakers based on what they’ve heard about speakers, or hearing them speak themselves, and have some sense of what their message is. They also carefully monitor what their speakers say, and they can and do disinvite speakers who seem to be giving messages that are unfavorable to a particular product, so that they can certainly influence the speaker. There are subtle things that have come out from court documents over court cases with drug recalls and law suits. So for example, at scientific meetings they might plant a question that would deliberately bring out a particular feature of one of their drugs that they want to highlight, so there are subtle ways that can influence the message that the audience is hearing.
And does the audience know that that person planting a question is a pharmaceutical employee?
Oh no, that’s certainly not known, that the person in the audience has been invited to ask that question, or, or literally planted there to ask the question.
What are ways that you’ve found that these forms can influence us, without us knowing it?
Persuasion?
Yeah. Persuasion.
First of all, these messages can be persuasive because we are only hearing, in some cases, a favorable side of a drug. Certainly when drug representatives talk to us in the office, and, and typically in CME as well, we’re hearing a message that’s been somewhat filtered. We’re likely to hear the strongest features of a product, and likely not to hear the weaker features of a product, and if we choose to ask impertinent questions about side effects or other problems, there’s often a diversionary tactic that takes us on to some other topic. I think the first way is that we’re simply getting a, a one-sided presentation even though there may be the appearance of objectivity and balance, it’s likely to be more one-sided than not.
There are other things that I think are important in terms of influence. Certainly simply the friendship aspect of a drug representative in the office. Certainly the authority of a speaker. Typically these speakers are chosen to be well-known, well-recognized researchers or academicians, and simply, simply having an authoritative figure present this information, I think, lends a voice of persuasion to a discussion about a particular product or group of products.
And when you said “diversionary tactic”, what do you mean by that?
For example, if I ask a question about a particular side effect, a response might be “Well, I don’t know much about that, but I can tell you that our drug has far less sedation than the competitor drug”, so that it’s a, a quick turn of attention to something else. _And I wasn’t even asking about sedation in the first place.
In what ways do the pharmaceutical companies influence research?
Pharmaceutical companies influence research in a wide variety of ways. First of all with their own research, they often design research in a way that, while adhering to many of the principals of sound research, may subtly bias things in favor of their own product. This is most apparent in some studies that have compared antipsychotic drugs, where head-to-head comparisons always favor the sponsor’s product over an alternate, and the alternate’s products always end up being favored over their competitors. The explanation for that probably is subtle features of the design. So, for example, we compare our drug at optimal dosing and optimal adjustments of dosing to a sub-optimal dose of the alternative drug or sub-optimal dose adjustments of the alternative drug. Or we highlight good results, good outcome measures and don’t highlight the outcome measures that are less favorable. We highlight certain side effects when we report that we don’t highlight, or we don’t highlight the less favorable side effects when we report. But there are things that are even more obvious than that. So for example, industry sponsored studies simply might not be reported at all if they come up with unfavorable results and that’s now been well document for antidepressant drugs. If there’s a favorable result we publish it, if there’s an unfavorable result, we don’t publish it. And companies can argue that this is proprietary data, they are under no obligation to publish it. It may be available to the FDA, but isn’t typically available to the medical profession through their usual journal publications and the like. So, so bad news gets buried.
Another strategy is simply to publish good news over and over again. There are some good examples where favorable studies have been published in multiple journals with different authorship -Clearly the same data but no reference to the other publications, putting the impression that there are many studies that favor the new drug when in fact there’s only one. When it comes to university agreements, or agreements with university investigators, many of the contracts that are written specifically indicate that the company can suppress certain information from publications, or choose not to publish information, or delay publication, or all of those things. Those are sometimes features that are written directly into the university industry contracts. Finally, when independent investigators are coming up with answers that are unfavorable or unwanted, they may simply be subject to character attacks and insinuations of incompetence and sort of allegations that go beyond simply scientific argument to try to discredit the findings.
When you mentioned the sub-optimal dose, I mean that just seems like it would be flat out illegal to be that misleading.
Well (laugh) it might seem illegal to do these things, but of course the design of a research study is something that is fairly open-ended. There are many decisions that have to be made. It would be hard to regulate exactly what kinds of comparisons are made. And of course part of the problem with drug trials is that in general a comparison is between new drug and a placebo, which tells us nothing about how the new drug actually compares with older drugs or competitor drugs. So that often that kind of direct comparison simply isn’t available at all.
I think a good example of the way that bad news can be suppressed or, or at least attempts are made to suppress bad news is the story of Bruce Psaty, one of my colleagues at the University of Washington who, early in his career was studying side effects of drugs for treating high blood pressure. Bruce found that one class of drugs, so-called short acting calcium channel blockers, these are drugs like nifedipine, for example, actually were associated with a higher risk of myocardial infarction than other older drugs for treating high blood pressure. When he reported that at a meeting of the American Heart Association, it got a lot of press attention and that led to calls to his medical school dean and calls to the dean of the school of public health suggesting that the work should not be published because it might be erroneous and misleading. It led to a nationwide dear doctor letter that basically argued that the research was flawed and not trustworthy, but was not identified as being sponsored by one of the drug companies. The net result was that Bruce felt like his integrity was being challenged as an investigator and his competence was being challenged. And certainly there were important efforts to prevent the data from actually being published. In the end I think Bruce felt that the negative publicity that resulted actually called more attention to the findings than would have happened otherwise and in a way may have been, subverted the efforts of the pharmaceutical companies to suppress the data because it turned out to be bad PR from their perspective.
The other example is my story but it’s a tough one to relate to a specific product. I was the investigator of a research team that was studying outcomes of treatments for back pain, including back surgery. At the time there was a new device called a pedicle screw that was becoming popular for doing particular type of spine surgery. I was involved with research that suggested that this type of surgery was associated with higher costs and higher complications than other types of back surgery. I was also involved with a guideline effort that suggested that in most cases for patients with acute back pain, specifically back pain for less than three months, you wouldn’t generally consider surgery as a treatment alternative. The combination of those guidelines and the research that we were doing actually led to a tremendous backlash from a professional society, the North American Spine Society, and also from one of the device manufacturers, a company called Soft More Danic, which sought a court injunction to actually block release of the guidelines. It led to a letter writing campaign to Congress that tried to argue that the funding agency, the Federal agency, should actually be eliminated because they were funding shoddy research and biased guidelines. in the end, it turns out that some of the device manufacturers are being investigated today for alleged kickbacks to surgeons. There’s still ongoing controversy about the effectiveness of these devices. But it clearly was an effort to, in that case, suppress unfavorable publicity about a particular procedure and a particular device.
If you want to know more about these incidents, read “Deyo RA, Psaty BM, Simon
G, Wagner EH, Omenn GS. The messenger under attack -- intimidation of researchers
by special-interest groups. N Engl J Med. 1997 Apr 17;336(16):1176-80.”
I think the off-label story is an important one, that is some companies have
now been prosecuted for off-label marketing of drugs. Certainly it’s true that
doctors and other practitioners are free to use approved drugs for purposes
other than the ones that are officially labeled by the FDA. They’re free to
use those drugs, but the companies are not free to advertise those uses. Yet
there is plenty of evidence that in some cases there actually has been direct
effort to market off-label uses of these drugs, which expands the number of
patients that would be eligible for them. In other cases they’re sort of skirting
the edges of that sort of promotion by hiring speakers or hiring communication
companies to produce continuing education that might touch on off-label uses
of these drugs without frankly advertising the off-label uses.
And what would be the problem with that?
The problem with that is that the off-label uses of these drugs are often
not well studied. So that while we know that they have at least some efficacy
for the labeled indications, we usually know very little about their efficacy
or safety for other indications, and in that situation some might argue that
we actually are, in essence, experimenting with our patients but without getting
their consent for that.
Thus it bypasses the whole FDA process.
Bypasses the whole FDA process, bypasses the whole research clinical trial process.
Isn’t the FDA protecting us?
I think there’s a popular perception that the FDA regulation process will protect us from unsafe drugs and assure that drugs are, in fact, effective. Probably the story of Vioxx, which is familiar to most people, is an alert that that’s not necessarily the case. Certainly there are plenty of examples where drugs have been withdrawn after they hit the market, even after they were marketed for several years, as they were in the case of Vioxx. And it’s certainly the case that often new side effects become apparent only after the drug is marketed and thousands, or hundreds of thousands of people are taking the drugs. Then we discover rare or longer term side effects that weren’t apparent by the time these drugs were approved. The other problem with the approval process itself is that these drugs are often not compared to alternative treatments. They’re compared to placebo therapies. So we have the impression that it’s—everything is new—is improved—and yet in some cases it’s quite clear that new products were actually less effective than drugs or devices that were already available to us. But again, we often only learn that after they’ve been on the market for a matter of years because it’s simply not part of the FDA process.
Sounds like something that should be changed.
2.43.35 Sounds like something that should be changed 2.43.36 There’s a lot of discussion about this in Congress right now actually, about the comparative effectiveness, is the term that’s used, and I think wide recognition that we really need much better research that would compare these products head to head.
it’s quite clear that many companies use continuing medical education as part of their marketing plan. 2.48.39 Again, when court documents have been discovered with regard to law suits, it’s quite clear that continuing medical education is a part of the marketing plan for these drugs, and it’s not unusual to get flyers in the mail about a continuing education program regarding a new drug that’s being offered in twenty cities over the next six months, with an invitation to come to those programs. Sometimes they include dinner or a meal, so there’s some enticement to come, and when these campaigns have been so thoughtfully planned that you realize there’s a twenty city tour, in essence, for a particular educational program, it certainly creates the appearance that the speakers have been carefully chosen. While their message may not be directly influenced, it’s quite likely that you’re going to see a more favorable presentation at a company-sponsored program that’s being widely produced. The other way in which we know that these presentations are effected is that the company will often offers to prepare slides for a speaker, and those slides are typically prepared to get across particular messages that are important to the company. So the speaker may actually be using slides that have been prepared for him or her by the company.
Those people are talking. No talking! It’s our studio.
That’s right.
I actually have your slides if there is something that you needed to refer to.
2.50.33 Let me say a couple of things about that. Let’s see. We’ve talked about Vioxx, we’ve talked about uh…okay.
Can you tell me about the Senate committee on finance relative—
In 2007 there was a Senate finance committee report on continuing medical education that described in some detail the magnitude of the industry, and the kinds of influence that they had. That report made it clear that the drug companies spend about a billion dollars a year on continuing education programs and the report argued that it’s unlikely companies would be spending that sum if they didn’t think that it was having an influence over prescribing patterns. That report also commented on the accrediting committee for continuing medical education and their review of company-sponsored CME, noting that approximately a quarter of the programs they reviewed actually were not in compliance with their own regulations regarding industry influence over the continuing education program.
I guess it’s an important point is thatin many case the drug companies are
not directly producing these CME programs, but what they do is they contract
with a so-called medical education and communication company, a MEC, that does
the production. Typically those contracts are wide-ranging, and may include
frank marketing activities, but often include these continuing medical education
programs as well.
The drug company typically conveys to them the kinds of messages they’d like
to get across, and that—the kinds of information they think is important, and
the communication companies try to incorporate that in their materials.
It’s not like they just hired us, and we’re like “Okay, sure.”
Does the person taking the course know that this is necessarily backed by a pharmaceutical company?
I think that it’s often clear that there’s some pharmaceutical company sponsorship, but it’s typically with the …the term that this is sponsored by an educational grant from a particular company. Something that sounds like it’s a bit removed from the marketing department.
Okay. And did you have another question?
If we have time for this, the ways that, looking at the literature, it’s misleading. Can you talk about the way providers canbe mislead by research, that is actually seeding trials?
The idea of seeding—seed trials, or seeding trials, is an interesting and important one. The idea there is that physicians are invited to recruit patients for a research study, typically after the drug has already been marketed, with the argument that this will help the company to learn more about the effectiveness or the safety of the drug. The physicians are typically paid, per patient, to enroll patients in the study, and it appears that in many cases these don’t result in any scientific publications, but may simply be an effort to get physicians interested enough to prescribe the drug and use the drug and gain some experience with it in a way that they’re more likely to continue using it after the “research” project is finished.
That almost seems like one of the other psychological ploys, automatic responses to persuasion.
It’s not so much the reciprocity as it is familiarity. It’s a way of gaining familiarity, and so you feel comfortable prescribing the new drug.
And what did you mean when you said “reciprocity”?
The idea of reciprocity, such an important part of drug detailing, is that I give you a gift, I give you a meal, I do something nice for you, and we naturally feel like we should be nice back. It’s just a human response.
When you give your talk are there—is there something about which people are most shocked?
One thing that we haven’t talked about is the whole role of patient advocacy groups in marketing. There are a substantial number of patient advocacy organizations that clearly get most of their finding from pharmaceutical companies and that often promote as part of their activities the use of particular drugs for a particular condition. So for example there’s a National Sleep Association that gets most of its funding from drug companies that sell sleeping medications, and that company—or that organization does surveys and publicizes the magnitude of the problem of sleep disorders, and things that actually help in indirect ways to promote the use of particular products.
Those are usually billed as though they’re grass roots organizations?
In many cases those organizations appear to be grass roots organizations although
they’ve sometimes been dubbed Astroturf organizations because it’s not real
grass roots, and in fact it’s—it’s clear that in some cases those have been
part of the marketing plan as well.