The Price of Prescribing
How do “transfers of value” influence your clinical decisions? Welcome to the TOV effect
Thomas V. Johnson | | 9 min read | News
As glaucoma specialists, we often have patients visit our clinics with high eye pressure despite receiving therapeutics. In talking to these patients, we often discover a range of explanations for why people have problems adhering to topical medications. Some have allergies and develop adverse reactions to eye drops, others simply forget. There’s a whole array of literature on barriers to adherence, but we find that the cost of eye drops is a significant factor in patients’ ability to adhere to a therapy. So why are patients often being prescribed higher priced name brands when the lower priced and more affordable generic brands are often just as effective?
On investigating this question, my colleagues and I found that transfers of value (TOV) from makers of prescription glaucoma drops to eye doctors are associated with increased prescription of branded drugs (1).
You would be forgiven for believing that only large TOV affected prescribing habits; however, the median TOV in our study was only US$65 – and even these modest levels of payment were enough to influence the prescription of branded eye drops. Shocked? We were too.
How did we get here? We started by scouring the literature for studies on the TOV effect specifically in ophthalmology; we presumed any findings would translate to our community. But the only papers that we could find were on anti-VEGF administration, with an important confounding factor – the payment and reimbursement structures are based on Medicare Part B, which is a buy-and-bill model. So, in addition to being paid for the procedure of intravitreal injection, the doctors purchase the medicines themselves from pharmaceutical companies, and are then reimbursed for the cost of that medication plus a percentage of what that medication cost. In other words, there is a direct financial incentive for using a more expensive anti-VEGF medication.
Importantly, our work looked at the prescription of prostaglandin analog (PGA) eye drops because it removes the risk of such direct financial incentives confounding the analysis of any association between TOV and choosing to prescribe costlier agents.
A different kind of side effect
I often see new patients who are already on a regimen of glaucoma eye drops. Some struggle month to month to pay for necessary refills, so attempt to ration the medication – taking one drop instead of the necessary two a day to extend their prescription. When we review their medication list, we often find they are being prescribed expensive branded glaucoma medicines. Admittedly, these name brands do play a clinical role in some cases; for example, with preservative-free formulations or formulations with different preservatives or carriers to which the patient is tolerant. For some glaucoma drug classes, on branded options are avilable. But for the vast majority of patients, the relatively inexpensive generic versions of glaucoma eye drops would be just as good at lowering eye pressure as their more expensive counterparts.
Many of these patients have never tried using cheaper drops – probably because they were given expensive eye drops from the start. One reason that is unrelated to TOV but nevertheless interesting is the role played by free samples provided by pharmaceutical companies; increased accessibility leads patients to go for the easy option – and then the patient is more likely to stay on those eye drops.
Evidently, the effect of pharmaceutical company interaction on prescribing is not limited to ophthalmology and optometry; outside of the ophthalmology literature, there are plenty of papers that highlight the influence of the pharmaceutical industry on physician prescribing behavior. The influence is not necessarily generated through TOV (for example, payments, meals, consulting fees) but can instead be the result of exposure to talks and information during CME events or medical research conferences. The more positive anecdotes doctors hear about certain medicines, the more likely they are to prescribe it. And that’s why it’s incumbent upon physicians to delve into the literature and examine the primary data with a critical eye. If clinical trials evaluating the effects of two different eye drops suggest that the benefit of drug A over drug B amounts to an extra half a millimeter of mercury, but drug A will cost the patient significantly more each month, we should question the cost/benefit ratio of drug A for our patients.
View from the vision industry
The whole issue of TOV is highly complex. In general, there is a shared feeling within our community of professionals that a doctor’s primary responsibility is to the patient – we all took the Hippocratic Oath. Doctors want to be objective, and studies have shown that most doctors believe themselves to be objective – acting in the best interests of patients. However, pharmaceutical companies have additional goals and needs, and they are ultimately responsible to their shareholders; the purpose of any corporation is to make money, which raises a potential conflict.
To be clear, I am not saying that physicians should avoid interactions with industry – such interactions are critical for the development of new drugs and devices and for the design and execution of clinical trials, for example. I would even argue that collaborations between physicians and industry are one of the most important factors driving biomedical research forward. But we should be entirely transparent about our interactions – we owe it to our peers and to all patients. And so, at research meetings, in peer-reviewed publications, and in discussions with our patients, disclosing all potential conflicts of interest is the least we can do.
The US government backed the concept of transparency in 2010 by passing the Physician Payments Sunshine Act, which “requires that detailed information about payments and other ‘transfers of value’ worth over $10 from manufacturers of drugs, medical devices and biologics to physicians and teaching hospitals be made available to the public.” (2). Notably, these TOV aren’t always true conflicts of interest; sometimes they’re just perceived or potential. Nevertheless, this requirement for transparency has given rise to the open payments database, accessible via a website, that allows people to find the annual tally of TOV received by any physician licensed in the US. We used this dataset to conduct our study.
There has been some skepticism as to whether small amounts – TOV that are seemingly trivial for a doctor – need to be disclosed in the same way. If you go to a US$40-worth dinner where a drug company is telling you about the latest FDA-approved eye drop, is that relevant enough to be disclosed? According to our work: Absolutely.
We also found regional differences in prescribing habits – an interesting aspect that is echoed in other fields. Using provider ZIP codes, we found clear evidence that some regions in the US had higher rates of prescribing branded versus generic eye drops. The data also showed that doctors within those regions tended to cluster or converge towards certain prescribing habits – but we don’t know why. We also looked at whether providers in urban regions received a different level of TOV compared with those in non-urban regions, but that wasn’t the case. However, the rate of prescribing branded prostaglandin analogues was higher in urban areas than non-urban areas.
How to combat the TOV effect
Exhibiting an unconscious bias towards prescribing certain drugs is clearly not ideal, but there is a simple way to help combat the problem: Awareness – something I hope to raise with our study and this article. There are plenty of studies over the last few years that have shown that engaging with the makers of devices and drugs does influence behavior and prescribing habits. And it happens in a number of interesting contexts; for example, research has shown how presentations on drugs can affect recall and choice of agents for prescriptions later on. Being aware of this effect is crucial.
Importantly, awareness needs to be more than skin deep. Individuals can often recognize a problem, but still be under the impression that they are immune; if you query doctors about how much other people are likely to be influenced by CME or drug company presentations, they tend to assume it is very high. Ask them about their own likelihood of being influenced, and they will say it is very low. These viewpoints may be partly driven by the assumption that only large amounts of TOV influence behavior, and, as these physicians are not receiving significant sums, they don’t contribute to the bigger problem. Interestingly, we did find that around 85 percent of the payments from drug manufacturers went to around 25 percent of the physicians in the database, which appears to support the notion that “The problem is with the ‘other’ 25 percent.” But even when we removed the highest receivers of TOV, the effect on prescribing branded drugs remained.
The fact that even small payments (on average US$65 per year) influence behavior substantiates the impact of our study and the dataset itself – together they suggest that many, many physicians are at risk of prescribing while under the influence of the TOV effect.
In addition to increasing awareness about the TOV effect, I’d like to use this opportunity to remember our obligation to ongoing education. If this article inspires or reminds other physicians to go back to the literature for well-designed studies and quality data to help inform their decision making, I will be delighted. We shouldn’t simply accept summaries from those willing to offer them – especially those with a vested interest.
In short, we must be able to take full responsibility for our prescribing decisions.
I’m a clinician scientist and a glaucoma specialist. I completed my neuroscience training before my medical training through a PhD in Neuroscience at the University of Cambridge, UK, where I was interested in neuroprotection and neuroregeneration of the optic nerve. I’ve been at Johns Hopkins University, Baltimore, Maryland, US, since 2010 – and that’s where I completed medical school, residency, glaucoma fellowship, and chief residency. I’ve been on the faculty for a few years now.
I have several research interests. I primarily run a translational neuroscience lab, where we study retinal ganglion cell transplantation and the development of vision-restoring treatments for glaucoma and other optic neuropathies. I also have a number of clinical research interests that include both remote tonometry for 24-hour IOP monitoring of patients with glaucoma and community-based glaucoma screening.
Andrew M. Nguyen, a medical student at Johns Hopkins, did the vast majority of the analyses and wrote much of the paper, so he deserves a loud shout out and a great deal of credit for this work, which formed part of his medical school training. Nguyen approached me and Jerry Anderson from the School of Public Health about looking at big data and industry effects, and we both mentored him through respective parts of the process.
- AM Nguyen et al., “Association Between Open Payments–Reported Industry Transfers of Value and Prostaglandin Analog Prescribing in the US,” JAMA Ophthalmology, e222757 (2022). PMID: 35900736.
- John Hopkins Medicine, “Sunshine Act,” Available at: https://bit.ly/3Bm3e9A.