The Dilemma of Pharmaceutical Promotion Practices: A Conversation with Dr. Aaron Kesselheim

INTERVIEW BY NICO VALLENAS

Aaron Seth Kesselheim, M.D., J.D, M.P.H.Professor of Medicine at Harvard Medical School and a faculty member in the Division of Pharmacoepidemiology and Pharmacoeconomics in the Department of Medicine at Brigham and Women’s Hospital. His research focuses on the effects of intellectual property laws and regulatory policies on pharmaceutical development, the drug approval process, and the costs, availability, and use of prescription drugs both domestically and in resource-poor settings.

Nico Vallenas, who served as Associate Editor at HHPR for the 2019-2020 term, conducted this interview with Dr. Aaron Kesselheim to inquire about how varying tactics of pharmaceutical promotion have serious consequences for public health and the opioid epidemic.

Nico: What interested you in this field concerning pharmaceutical bribery and related subjects?

Dr. Kesselheim: As a professor here at the [Harvard] medical school, I study intersections between laws and policies that affect pharmaceutical use, and evidence-based medicine that end up getting translated into patient outcomes. So, prescription drugs are one of the most important medical interventions that we have in the field. I’m a primary care doctor, and a lot of patients depend on prescription drugs for their care and livelihood. And, making sure that prescription drugs are used in a rational, evidence-based way is extremely important and one of the major factors that contributes to inappropriate use of prescription drugs in the US is pharmaceutical promotion. And we know that from decades of research and experiences that show that pharmaceutical promotion can drive physician prescribing practices in ways that are not consistent with evidence but are consistent with the marketing messages that the pharmaceutical manufacturers bring. I think that because prescription drugs are such an important tool that physicians have and because pharmaceutical promotion is such an important driver of trends in pharmaceutical use … studying pharmaceutical promotion is a really important area of research.

Nico: Delving deeper, could you get into some of the details of when and how these companies use explicit or implicit forms of payment to encourage doctors to make these brand name prescriptions? What would be their specific tactics?

Dr. Kesselheim: Some reviews have found that the pharmaceutical industry in the US spends about 30 or so billion dollars a year on various types of promotion. The primary way that companies promote their drugs is directly to physicians. So, the lion’s share of that $30+ billion dollars is spent on strategies aimed at physicians and other prescribers. Those strategies include the use of detailers, or pharmaceutical sales reps, who visit physicians’ offices and talk to them about the drugs that they use. In a lot of those cases those detailers are trained in marketing principles to ensure that their messages have the maximum impact. There are pharmaceutical companies that put advertisements in materials that doctors read, like their journals. They also disseminate their own leaflets and flyers and advertisements to physicians. Pharmaceutical companies will also use mechanisms to try to enhance the impact of those messages. For example, they may provide food to physicians or they may pay for continuing medical education lectures or credits. They may reach out to physicians and have them come to meetings about the drug and those meetings might be held in fancy hotels, or they may involve other kinds of entertainment activities like concerts or whatever else. They can sometimes hire physicians as speakers as part of a speaker’s bureau to pay them to provide talks about the drug to their peers, and that’s another way pharmaceutical companies develop financial relationships with physicians to both encourage prescription in both in the physicians that they have a financial relationship with and in the people who the physicians talked to. The people who they select for these kinds of speaker’s bureaus and other opportunities are generally people who either prescribe a lot of the product or who they’re trying to encourage to prescribe a lot of the product. Those are some of the more common strategies pharmaceutical companies use to develop financial relationships with physicians that are intended to try to encourage physicians to use the drug that the pharmaceutical company is trying to promote.

Nico: Bouncing off of that, would you say that these practices also occur with generic drugs, or just brand name prescriptions?

Dr. Kesselheim: No, this is limited to brand name drugs. Generic manufacturers do not promote their prescription drugs as a general rule to physicians. The reason they don’t do that is because generic drugs are approved as being interchangeable with the brand name version, and according to various state laws, that are called drug product selection laws, generic drugs are interchangeable at the pharmacy level, when a pharmacist gives a prescription to a patient. There isn’t really any way for physicians to indicate that a particular generic drug needs to be dispensed to a particular patient. ...So there is no financial incentive in those circumstances for them to engage in promotion.

Nico: Would you say that this might interplay with off-label promotion of drugs as well?

Dr. Kesselheim: Off-label promotion is a slightly different set of issues. In general, the current rules in the US are that pharmaceutical manufacturers are only allowed to directly promote drugs for the FDA-approved indication. Now, there are some exceptions to that, so it is not like an airtight rule. So when pharmaceutical manufacturers promote their drugs for non-FDA-approved purposes, or what’s called off-label promotion, that’s supposed to be illegal at least under most circumstances. The reason [off-label promotion] is illegal is because when a drug is FDA-approved, it means that it has gone through a certain minimum level of testing for the drug’s efficacy and safety and the independent experts at the FDA have reviewed those tests to make a determination that for that particular purpose, the drug’s benefits appear to outweigh its risks.Although off-label uses are legal, and physicians prescribe drugs for off-label uses if there are really urgent circumstances, there may not be the same level of evidence supporting them. And pharmaceutical promotion, which is a very strong driver of physicians prescribing practices, can, if directed to off-label uses, lead to substantial public health problems if a lot of physicians end up using drugs that are potentially unsafe or don’t work in an off-label context. Unfortunately, over the last couple of decades, nearly all pharmaceutical manufacturers have engaged in off-label promotion and have been the subject of substantial investigations and civil and criminal fines surpassing 15 or 20 billion dollars because of these illegal practices and because there is such a financial incentive for drug companies to try to expand the market for their products as much as possible. So yes, when drug companies do illegally engage in off-label promotion, they use a lot of the same strategies that they use in “normal” permitted promotion for the FDA-approved drug.

Nico: What would you say are some long-term ramifications of these practices? Could they contribute to overprescription, or the opioid epidemic?

Dr. Kesselheim: There is a lot of evidence out there that pharmaceutical promotion drives physician prescribing practices in ways that are not consistent with the evidence and can lead to overuse of expensive products which leads to excessive health care spending. Also, this can lead to overuse of products in cases where they are not medically recommended which can lead to bad patient outcomes. This is particularly true in the case of off-label promotion. I think that pharmaceutical promotion, particularly after the introduction of oxycontin in the 1990s, was a major contributor to the opioid epidemic.We are now learning that Purdue, in addition to the steps that they took to encourage individual physicians to prescribe oxycontin using the pharmaceutical sales reps and other strategies, also was a substantial investor in pain societies and their attempts to encourage the use of opioids in the management of pain and to set guidelines in which opioids were used in first-line treatment for pain. In this effort to try to encourage oxycontin, and with other companies that came after oxycontin, this was a factor that contributed to the current opioid epidemic we have because of the substantial investment in promotion of these drugs leading to overuse of them.

Nico: In the wake of these findings, what kinds of barriers were put in place to mitigate these practices, and how have pharmaceutical companies responded or tried to sidestep regulations?

Dr. Kesselheim: With the recognition of the effect that pharmaceutical promotion can have on physician prescribing practices in the last few decades, some academic medical centers have worked to try to limit pharmaceutical sales reps’ access to their physicians or have put rules in place about how to negotiate pharmaceutical financial relationships. The open payments database was created about a decade ago now to provide more transparency for physicians’ interactions with pharmaceutical representatives so that patients can have more insight into their physicians’ sources of their financial relationships with pharmaceutical companies. So these have been some of the efforts that have been put in place to try to mitigate the effects of pharmaceutical promotion on physician prescribing practices.

On the other hand, in recent years there have been other efforts that have worked in the other direction to try to expand the effects.For example, various libertarian groups have worked to try to undercut the FDA’s rules relating to off-label drug promotion. Some states have taken action as well. For example, when Massachusetts instituted a ban on certain high-cost meals for prescribers, that ban was subsequently overturned due to lobbying by the pharmaceutical industry and the restaurant lobby. So I think that there have been some efforts to try to have some better local oversight in this area, but at the same time there continue to be efforts to try to undercut those [practices] as well.

Nico: In your personal opinion, what work do you believe still needs to be done, if any at all?

Dr. Kesselheim: There needs to be better recognition among physicians about the effects that pharmaceutical promotion can have on prescribing practices and patient outcomes. I think that we need to reinforce the FDA’s current rules relating to off-label drug promotion and not let them be undercut by misguided court decisions. And, I think that we need to have more resources directed towards ensuring that the promotional materials that are out there are as accurate and fair and well-balanced as possible.

Nico: So one final question to wrap this up. Would like to share any information about current or upcoming research projects of yours?

Dr. Kesselheim: We did a study in which we surveyed physicians about a hypothetical prescription drug and we included either just a description of the on-label use of the product, a description of the off-label use of the product with a disclaimer that the off-label use hadn’t been FDA-approved, and a description of the off-label use of the product with more of a context of the evidence relating to this off-label use and how the off-label use was not supported by the evidence. What we found was that providing physicians with this evidence context was much more effective in limiting prescriptions or proposed prescriptions of the drugs than simply providing pro-forma disclaimers about the product. This was a survey study that we did that’s going to be coming out later this year and I think that what this shows is that providing more high-quality evidence and information to physicians … can help ensure that physicians make optimal prescribing decisions for their patients.

Nico: That is truly fascinating, thank you for sharing. Once again, thank you for taking the time to do this interview and we’ll keep in touch.