Of Conflicts of Interest, and Interesting Conflicts

A meditation on the bias, psychopharmacology, and pharma advertising.

The Frontier Psychiatrists is a daily-enough health-themed newsletter. It’s been described as “humor adjacent.” Today’s article is on conflicts of interest—and how conflicted we should be about them.

Before we dive into my favorite topics.. I enjoyed two things that are worth sharing:

First, this article on the novel medicine for schizophrenia, Cobenfy, by

Nils Wendel, MD

is worth a read if you are a prescriber of medicines. It assumes knowledge many patients won’t have, but it is excellent and a good read.

The second is to hype my new favorite healthcare policy and history podcast, “Tradeoffs.” Dan Gorenstein does great work as a reporter, and his three-part history of generic drugs and their shortages proved very educational even to an uber-nerd like your editor-in-chief over here.

Finally, I want to remind my readers that I have an event coming up on January 12 in San Francisco. It's Rapid Acting Mental Health Treatment SF 2025. Get your tickets here.

---

Now, on to highly conflicted feelings about conflicts of interest. This newsletter is very educational, my readers might think, from time to time. This should be allowed to be Continuing Medical Education (CME)! Well, it’s not. And the reason it’s not? CME can not be planned by individuals who participate in “ineligible companies.”

This is one specific flavor of conflict of interest, but there is a hard and fast rule here to grapple with! Thus, it’s our starting point:

The ACCME is committed to ensuring that accredited continuing education (1) presents learners with only accurate, balanced, scientifically justified recommendations, and (2) protects learners from promotion, marketing, and commercial bias.

For the uninitiated, which is likely most of the general public, the Accreditation Council for Continuing Medical Education decides what conflicts of interest can or can not impact the vulnerable learners in their charge. Plenty of organizations—the eligible ones—can offer continuing medical education:

Organizations eligible to be accredited in the ACCME System (eligible organizations) are those whose mission and function are: (1) providing clinical services directly to patients; or (2) the education of healthcare professionals; or (3) serving as fiduciary to patients, the public, or population health; and other organizations that are not otherwise ineligible.

I used to be involved extensively in planning CME for AACAP. I had to resign and wrote an article on the topic then. The reason I had to resign? I called a “compliance concern” on myself after being awarded an R44 NIH grant for the development of a medical device that would, according to the terms of the SBIR program, be commercialized.

What kinds of entities have employees— like yours truly— who are, thusly, ineligible to educate other physicians on literally anything?

This list starts with those working in Pharma… but includes:

• Device manufacturers or distributors

Which meant…me. I was biased now, too!

I was not prohibited from content related to my device and my presumptive commercial bias, promotion, and marketing about that device. I was banned from planning CME about all drugs, devices, or medical conditions. I am entirely out of the planning CME game.

This means that since I am the editor of this newsletter and thus plan it, I am responsible for the publication’s voice because it’s a one-man show on the editorial side. Any education you get can only be incidental. It can’t “count” without additional staff planning other parts of your educational experience for the reading you are doing here to maintain your certification—where you need it.

There is a conflict that I can't avoid, which is that I want you to learn things about health and its care, with a bias towards the novel, better, faster, and safer. This bias would be true and present whether I had funding from the NIH to develop a medical device or not since I got that funding and could no longer plan official continuing medical education. Because of my newfound bias, I became even more engaged with industry. I work more closely with industry across several consulting roles. I am now a consultant, in some cases with an equity stake, in several businesses working on both pharmaceuticals and medical devices. I want these businesses to succeed.

However, it's not the money, although ignoring its biasing effect on me would be foolish. My personal biases made me take those roles in the first place. I’m not just a reporter—I’m a marketer! Even when it’s not compensated? Oh, My!

What about the people who are only reporters? Who are maybe even only educators? I have friends like that! I am speaking of colleagues like Chris Aiken, M.D. He works at the Carlat Report as the editor and chief. He and Danny Carlat, who created the eponymous report, have extremely rigorous standards around the role of industry relationships in those reporting for the Carlat Report. They see their role as keeping psychiatry honest, and given its deeply conflicted relationship as an institution with the industries that have preyed upon it, this stance makes all the sense in the world to me.

As I explained just yesterday in my article about why medical devices can't get paid for but drugs can, drugs make a lot of money. Some of the money that those drugs make pharmaceutical companies use to pay for the advertising of those drugs, both direct consumers and marketing to physicians.

Following the playbook created by Arthur Sackler, MD, who, more than any other person, invented the art of drug advertising in his dual roles as scientist and copywriter, the advertising for psychiatric drugs has focused on things that are appealing to physicians—that is to say, it aims to help us feel sciencey. Take a look at this gem, circa the introduction of Prozac:

Shortly after its FDA approval in 1987 [11], the first Prozac (fluoxetine) ads that appeared in medical journals claimed, “There is considerable evidence that serotonergic function may be reduced in the brains of depressed patients,” introducing Prozac as “a specifically-different antidepressant . . . Its distinctive chemistry means greater specificity.”¹

Keep in mind, as I investigated in the footnote of my article on the drug Prozac, none of this drug's specificity even remotely matters. Subsequent science would reveal that in animals who didn't even have the gene for the serotonin transporter for which it was more specific, they experienced identical effects².

But the sense that we're doing something scientific, the sense that we're doing something medical, the sense that that's worth our time and brain space? That's what Pharma is selling. And they're good at selling it, and we're excited to buy it. They're not selling a drug, per se, they're selling an attitude about a psychopharmacology. That attitude highlights the pseudoscientific virtues of fusing about with medicines instead of spending time understanding our patients.

Although all doctors are trained in the basics of science, not all of us have worked in pharmaceutical drug development, and even fewer have worked in the marketing department. We are not privy to how the sausage is made. We're trained to see patients and to understand basic mechanisms, but we are not prepared to be on the lookout for being constantly scammed. These are sophisticated criminal operations. Remember Neurontin?

The Food and Drug Administration approved Neurontin only as adjunct therapy for seizures, but Parke-Davis (now part of Pfizer) deployed a breathtaking array of covert marketing tactics to persuade doctors to prescribe the drug for all manner of conditions for which there was no evidence of efficacy, from migraines to bipolar disorder. Parke-Davis didn't simply buy neurologists tickets to Hawaii or the Olympics. Its “tactical plan” for Neurontin included “encouraging titration to higher doses through peer-to-peer influence,” capturing the pediatric market by creating a Child Neurology Advisory Board, and recruiting neurologists to present case studies to their peers. It deployed a sophisticated publication strategy along with CME activities as ways of driving off-label prescriptions. As a Parke-Davis executive told his staff, “That's where we need to be holding their hand and whispering in their ear, Neurontin for pain, Neurontin for monotherapy, Neurontin for bipolar, Neurontin for everything.³

There were billions in criminal penalties for that behavior. I don’t believe executives went to jail, however, and the drug was more profitable than the penalties, so I suspect the behavior will continue.

Physicians are simple creatures. We want to be told we are scientists:

One of the most damaging tactics used to market Neurontin was the STEPS seeding trial. Parke-Davis recruited 772 physicians to serve as “investigators” for an uncontrolled, unblinded study ostensibly aimed at studying the efficacy of Neurontin. In fact, the trial was a marketing exercise designed to familiarize the investigators with Neurontin and write more prescriptions.⁴

We need to be told we care. It's also important for us to believe we're beyond reproach, which the following data makes pretty clear is also, itself, a great marketing reality (from 2000):

Of the 446 physicians interviewed, 53.9 percent were visited by pharmaceutical company representatives at least once a day, and 43.5 percent spent 15 minutes or more per day on these visits. With respect to the information delivered by the pharmaceutical company representatives, 67.7 percent of physicians thought it was not reliable, and 62.8 percent reported that it had no effect on their prescription writing. The promotional gifts had little effect on prescriptions for 43.9 percent of physicians, and 80.3 percent reported that these gifts were distributed unequally among doctors according to the drugs they prescribed.⁵

Physicians believe that drug advertising and marketing have no effect on their prescribing, although their colleagues might be influenced. The data, of course, shows that this is a wildly successful practice for pharmaceutical companies, which is why they spend money on it. They're not bad at making tremendous piles of money; physicians are just terrible at knowing how influenceable they are.

The advertising that takes place in medical journals is often inaccurate, on top of other plausible sins:

We identified 264 different advertisements for antihypertensive drugs and 23 different advertisements for lipid-lowering drugs. We recorded at least one reference in 31 advertisements in the antihypertensive group and at least one reference in every seven advertisements in the lipid-lowering group, providing a total of 125 promotional claims with references. We could not retrieve 23 (18%) references from monographic works and non-published data on file. 79 (63%) of the 125 references were from journals with a high impact factor; 84 (82%) of the 102 references retrieved were from randomised clinical trials. In 45 claims (44·1%; 95% CI 34·3–54·3) the promotional statement was not supported by the reference, most frequently because the slogan recommended the drug in a patient group other than that assessed in the study.

Much like the difficulties with the slop cranked out by AI, checking in references turns out to matter, and many drug advertisements are based on references to studies that don't support their claims. Remember that the FDA was fundamentally created to regulate advertising around drugs established to be safe and effective. Still, before the advent of the FDA, there was no meaningful regulation around these claims, and so we got ads like this promising Thorazine, “one of the fundamental drugs in medicine,” could do anything…take a look:

And how about kids with nausea? Yes:

How about alcoholism? Also, apparently, yes:

Or just emotional stress, generally? Yes, also that:

The ads go on and on like this. And to be clear, Thorazine is not indicated for any of those uses. These ads had to be regulated. Of course, after the regulations came into play, literal children of Arthur Sackler, like the team at Purdue for pharmaceuticals, including nitwits like Richard Sackler and David Sackler, manipulated the regulatory process to the best of their abilities to bring us a flood of “safe” opiate medications like OxyContin.

The regulations didn't save us. Great marketers with massive budgets figured out how to play by the rules when it suited them and break the rules when it didn't. Physicians are almost infinitely malleable as long as you understand what makes us tick. It's worth noting that Arthur Sackler and Richard Sackler were both physicians. They understood us because they were us. And they used that understanding to create a marketing paradigm that persists. Focus on things that make us feel Sciency, give us things to debate and think about that don't particularly matter, but get drugs moved off the shelf. And here is where we get to my point, flawed though it may be.

A debate about drugs, as you get without any commercial bias in the pages of the Carlat Report, industry bias or not, is serving the interests of Pharma. If we spend time digging into which drugs to prescribe, we still focus on their reality. We've accepted the thesis that psychiatry is about prescribing medicines.

If only we understood those medicines better, without those bad forms of bias, we would do a better job for our patients!

This is a step toward true—but it also keeps the focus on psychopharmacology. It may change which drug we prescribe, but it doesn't change the fact that we think of ourselves as prescribers of medicines. This is as opposed to physicians, whose job is to heal by any means safe and effective.

What is the most effective way to combat pharmaceutical advertising? I don’t have it around. Perhaps we could spend some time creating ourselves? This is not practical, but it might raise suspicions—the LARP version of this would be a fun medical school class! For regular, everyday doctors, don't let the drug reps in your office, don't watch the ads on TV, don't allow the advertisements in your journals, don't allow the booth at your conference. Still, none of these things are likely to happen tomorrow. The conferences don't occur without industry support for a price we could afford. The journals are wildly profitable businesses in and of themselves — that money comes, in part, from advertising. There are economic realities that any individual physician will be unequipped to push back on.

Do I think Chris Aiken does a better job of informing all of us about the realities of science without the bias of being on the pharmaceutical payroll? Yes. I think that's important. That's why I've invited Chris to join us for the RAMHT conference I am promoting at the beginning of this article that you are reading right now. I invited him to help us keep the conversation honest.

I do suspect, however, that the sense that we're not biased is its own kind of bias. Lack of bias perception is an opiate for physicians. We already believe we're beyond reproach. We are not, by the way:

In 2010, the pharmaceutical industry surpassed the defense industry as the leading defrauder of the federal government…Pharmaceutical companies were forced to pay $19.8 billion in penalties over a 20-year period, with a dramatic upswing coming in the mid-2000s. Although the largest category of penalty was for off-label promotion, that particular violation was just the visible face of a more far-reaching scandal. Thanks to the efforts of whistleblowers, expert witnesses, and investigative reporters, we know that pharmaceutical companies have rigged clinical trials, buried unfavorable results, published ghostwritten journal articles, paid kickbacks to high-prescribers, bullied academic critics, produced fake medical journals, and manipulated treatment guidelines. Without the help of physicians, very little of this could have been accomplished.⁶

That's how Pharma companies were so good at selling us on prescribing OxyContin in the first place. We believe it’s the other guy who is influenced, not us.

The uncomfortable reality is that without tools to heal our patients and without science, it's expensive to create those tools, and we don't have anything at our disposal to ease human suffering. At the same time, medicines, as the only tools that we have to use for the suffering of the mind, is a dangerously biased stance. I'm not necessarily gonna get less suffering just by doing better prescribing. Less biased prescribing of drugs is still prescribing of drug drugs. Sometimes, maybe even most of the time, factors other than pharmacological adjustment might be the best approach.

For people who are struggling with homelessness, we may get them well by getting them a home a lot faster than by getting them the most appropriate prescription. For people exposed to trauma, getting them out of the traumatic situation may be more beneficial than giving them Valium to tolerate it. For people struggling with an existential question, it may be that psychotherapy is the best path forward. And suppose nutritional ketosis has its early evidence in bipolar disorder replicated? In that case, it may be that changing your diet in keeping with human biology’s vicissitudes may be a potent intervention. I've already written about the potency of walking as a treatment for depression. There are so many options beyond oral medicine, and that's a conversation we are having when you share this article.

We all have conflicts of interest. We should disclose them and grapple with them. The most important conflicts, however, are not financial. They are the nexus of ego, the sense that we are beyond influence, and our desire to be helpful to our patients. These biases are unavoidable, exploitable by those whose job it is to do so, and worth endlessly re-examining.

This whole newsletter is unambiguously biased. I try to keep the bias front and center because the authors here frequently have both personal and commercial interests in what they do. I absolutely do. These biases are why I spend the time doing something quixotic, like working as a physician and writing this newsletter daily.

Thanks for reading. A special thank you to my friend Chris Aiken, M.D., for his remarkable work crafting less biased journalism about the tools and science we need to understand our craft as healers.

1. Greenslit NP, Kaptchuk TJ. Antidepressants and advertising: psychopharmaceuticals in crisis. Yale J Biol Med. 2012 Mar;85(1):153-8. Epub 2012 Mar 29. PMID: 22461754; PMCID: PMC3313530.

2. Jaggar M, Banerjee T, Weisstaub N, Gingrich JA, Vaidya VA. 5-HT_2Areceptor loss does not alter acute fluoxetine-induced anxiety and exhibit sex-dependent regulation of cortical immediate early gene expression. Neuronal Signal. 2019 Feb 1;3(1):NS20180205. doi: 10.1042/NS20180205. PMID: 32714597; PMCID: PMC7363295.

3. Landefeld CS, Steinman M. The Neurontin legacy: marketing through misinformation and manipulation. N Engl J Med. 2009;360:103–106. doi: 10.1056/NEJMp0808659.

4. Krumholz SD, Egilman DS, Ross JS. Study of Neurontin: titrate to effect, profile of safety (STEPS) trial: a narrative account of a gabapentin seeding trial. Arch Intern Med. 2011;171:1100–1107. doi: 10.1001/archinternmed.2011.241.

5. Güldal, D., & Şmin, S. (2000). The influences of drug companies' advertising programs on physicians. International Journal of Health Services, 30(3), 585-595.

6. Elliott, C. Relationships between physicians and Pharma: Why physicians should not accept money from the pharmaceutical industry. Neurology: Clinical Practice, 4(2), 164. https://doi.org/10.1212/CPJ.0000000000000012