US drug marketing: how does promotion correspond with health value?BMJ 2017; 357 doi: https://doi.org/10.1136/bmj.j1855 (Published 02 May 2017) Cite this as: BMJ 2017;357:j1855
- Tyler Greenway, medical student1,
- Joseph S Ross, associate professor of medicine and public health2 3 4
- 1Yale University School of Medicine, New Haven, Connecticut, USA
- 2Section of General Internal Medicine and the Robert Wood Johnson Foundation Clinical Scholars Program, Yale University School of Medicine, New Haven, Connecticut, USA
- 3Department of Health Policy and Management, Yale University School of Public Health
- 4Center for Outcomes Research and Evaluation, Yale–New Haven Hospital
- Correspondence to: J S. Ross
The pharmaceutical industry uses a variety of techniques to promote its products to clinicians, including gifts and free food, advertisements, and detailing by company representatives. Although manufacturers might argue that drug promotion supports physician education, which in turn leads to more informed prescribing, studies have shown that greater contact with drug sales representatives is associated with an increased likelihood of prescribing brand name medications when cheaper alternatives exist.12 More recent studies have shown that payments from drug companies are associated with a greater likelihood of prescribing promoted drugs.345
In the United States, physicians have extensive financial relationships with the drug industry.67 However, since August 2013, the Physician Payments Sunshine Act requires that the industry publicly discloses all payments to physicians of $10 (£8; €9) or more or $100 on aggregate. This legislation led to the creation of the Open Payments Database, which archives all industry payments to individual physicians and teaching hospitals.8
Early analyses of the database show that numerous small gifts can often add up to large sums of money,910 potentially creating powerful incentives for physicians to prescribe selected drugs. Between August 2013 and December 2014, $3.53bn was paid to 681 432 physicians in the US by 1630 pharmaceutical companies to promote numerous drug products. We assessed the health “value” of drugs being most aggressively promoted to physicians to better understand implications of pharmaceutical promotion for patient care.
Assessing drugs’ value
We obtained data on the top promoted drug products from the Open Payments Explorer, created by the non-profit investigative journalism group ProPublica to make the Open Payments database more easily accessible to consumers.11 We identified the 25 drugs associated with the largest total payments to physicians and teaching hospitals from August 2013 to December 2014, including all direct and indirect payments, such as speaker fees for education lectures, consulting fees, and honorariums, as well as payments in kind, such as the value of food and gifts. However, we excluded research payments, royalties, and licensing fees, which are typically not promotional.
Next, we estimated drugs’ value to society. In theory, value to society (as opposed to the manufacturer) depends on the relative effectiveness and safety of the drug, its priority among available therapeutic alternatives, its level of innovation as an advance in therapy, the prevalence of the disease for which it is indicated, the disease’s attributable morbidity and mortality, and the cost to patients and insurers. The ideal drug would be effective, safe, novel, recommended as first line therapy for common diseases causing substantial morbidity and mortality, and affordable. We estimated drug value using five proxy measures of these characteristics, selected to be readily intuitive and reproducible by practising physicians (box 1).
Box 1: Criteria for assessing drugs’ value
Innovation was assessed following a schematic established by the US Food and Drug Administration (FDA).12 Drugs representing new mechanistic pathways in treating indicated diseases were considered first in class. Drugs that provided meaningful advance over previously existing treatments in the same class and received “priority review” status from the FDA were designated advance in class. Drugs that met none of these criteria were considered addition to class.
Effectiveness and safety were assessed by using the ratings systems of the French drug industry watchdog Prescrire International.13 Prescrire employs a robust evaluation process, whereby 10 or more reviewers, physicians, pharmacists, nurses, and dentists with no conflicts of interest who have had 2-3 years of specialised training on drug evaluation, review each drug evaluation for quality control. For drugs for which Prescrire ratings were not available, assessments were extrapolated based on Prescrire statements in materials and guidelines. For instance, many commonly used drugs such as levothyroxine, lisinopril, and metoprolol are recommended in Prescrire guidelines but have no official Prescrire rating.
Generic availability was used as a proxy measure of affordability for patients. We used the Drugs@FDA database to determine whether the drug was generically manufactured in the US or whether there was another generic drug in the same class with comparable clinical value available in the US
Clinical value was also determined by proxy measure, based on whether each drug was on the World Health Organization list of essential medicines for 2015. This list includes drugs that are essential to any basic, fully functional healthcare system, and thus offers a simple metric reflecting both the utility of the drug and the relative prevalence of the disease for which it’s indicated. Drugs containing multiple active ingredients, including asthma combinations and HIV drugs, were considered to be an essential medicine if any of its ingredients were on the WHO list.
First line status, or whether the drug was recommended as a first line treatment for its respective disease, was determined using guidelines accessed through the National Guidelines Clearing House.14 If relevant specialty society guidelines could not be identified, UpToDate, an online, evidence based, peer reviewed clinical decision support resource, was used to determine first line status
We also determined the value top 25 drugs by 2014 US sales and the top 25 most prescribed drugs in the US during 2013, identified from IMSHealth data (2014 data for top prescribed drugs were not available when we did the study).15 A complete list of all included drugs, and how each was categorised, is available in the appendix on bmj.com. We used Fisher exact tests to compare categories of top 25 drugs, calculated using JMP 10.0 (SAS Institute, Cary, NC), using a P value of 0.025 to account for the two comparisons made for each measure.
Assessment of highly promoted products
Table 1⇓ lists the top 25 medicinal products in terms of promotion, sales, and prescribing volume. Among the 25 top promoted products, 24 were treatments and one was used to test for adrenocortical function (HP Acthar) and therefore excluded from our analysis. One of the 25 top selling products was a pneumococcal vaccine, which we also excluded; two other products, pegfilgrastin and filgrastin, were listed as one but considered as distinct products. Only four of the 24 top promoted drugs (17%) were also among the top selling drugs (adalimumab, glatiramer, aripiprazole, and budesonide-formoterol), and none were among the top prescribed drugs.
Table 2⇓ gives the comparison of value for the identified drugs. Top promoted drugs were significantly less likely to be innovative than top selling drugs (8/24 (33%) v 18/25 (72%); relative risk (RR)=0.46, 95% confidence interval (CI) −0.25 to 0.86) but not than top prescribed drugs (13/25 (52%); 0.64, 0.32 to 1.26). Furthermore, top promoted drug were significantly less likely to be rated by Prescrire as possibly helpful or offering an advantage than top prescribed drugs (RR=0.25, 95% CI 0.10 to 0.62), although the difference with top selling drugs was not significant.
Only one of the top promoted drugs was on the WHO essential medicines list, compared with nine top selling drugs (RR=0.12, 95% CI 0.02 to 0.85) and 14 top prescribed drugs (0.07, 95% CI, 0.01 to 0.52). Fewer top promoted drugs were considered first line treatments than top selling drugs and top prescribed drugs but the difference was significant only for top prescribed drugs (0.42, 0.23 to 0.76). Generic equivalents were available for 15 (63%) top promoted drugs, eight (32%) top selling drugs, and all top prescribed drugs (table 2⇑).
Compared with top selling and top prescribed drugs, the most aggressively promoted drugs in the US are less innovative, rated less favourably by Prescrire, and are less likely to be recognised as first line treatments by national guidelines, included on the WHO essential medicines list, and available as a generic. Although not all the differences were significant, and the sample sizes and multiple comparison limit the statistical power, the direction and magnitude of the differences suggest that top selling and top prescribed drugs, not top promoted drugs, were more likely to represent the ideal drug that is effective, safe, affordable, novel, and represents a genuine advance in treating a disease.
This raises concerns about the purpose of pharmaceutical promotion and its influence on patient care. One view is that drug companies don’t need to promote high value drugs. If a genuinely innovative drug becomes available that significantly advances patient care, such as sofosbuvir (a top selling drug), this information might be expected to spread rapidly among clinicians, perhaps through peer reviewed publications and scientific meeting presentations, requiring little active promotion by the manufacturer. Conversely, a “me-too” drug with minimal benefit over previous treatments in a class with generic alternatives, such as rasagiline (a top promoted drug), might need robust promotion to facilitate its use.
Efforts are needed to better evaluate the value of drugs, ensuring that this information is readily available at the point of care so that it can inform clinical decision making, promoting use of higher value medicines. Of course, choice of drug may be influenced by factors other than those we included in our value ratings, such as patient experience of treatment, previous treatment, cost effectiveness, and out-of-pocket costs or health plan costs. Even the existence of a comparable generic therapeutic option may depend on clinical context. For example, apixiban can often be replaced by warfarin, but not in patients who have contraindications to warfarin.
Our list of top promoted drugs accounted only for payments to US physicians and teaching hospitals from August 2013 to December 2014. We did not include other promotional efforts, such as advertising to physicians, direct-to-consumer advertising and disease awareness efforts coordinated with patient advocacy organisations, pharmaceutical detailing to physician offices, or efforts to raise product awareness at professional and scientific meetings that did not include transfers of value such as a meal or gift, or continuing medical education through third parties. Furthermore, US data on payments to physicians from pharmaceutical manufacturers are available only since 2013 and our results may not reflect behaviour before this time or outside the US. However, we expect patterns of promotion to be similar, even if coverage and reimbursement policies differ.
Despite these caveats, our findings suggest that pharmaceutical promotion should be met with healthy scepticism. Clinicians should consider taking steps to limit their exposure to industry promotion, including detailing by company representatives and sponsored educational events.16 They could also consider engaging with “academic detailing” programmes—educational outreach by pharmacists, nurses, and physicians that provides non-commercial, evidence based recommendations about medication choices.17
US physicians receive billions of dollars each year from drug companies as part of drug promotion
Top promoted drugs were less likely than top selling and top prescribed drugs to be effective, safe, affordable, novel, and represent a genuine advance in treating a disease
Clinicians should question the value of drugs being most heavily promoted by pharmaceutical manufacturers before prescribing them
We thank William Fleischman for help in checking the accuracy of the Open Payments data.
Contributors and sources: JSR has studied and reported widely on physicians’ financial relationships with industry and has a long research interest on biases that may distort evidence based practice. This article arose from discussions with TG about potential student research projects. TG and JSR had full access to all of the data in the analysis and take responsibility for the integrity of the data and the accuracy of the data analysis. Both authors contributed to concept and design, analysis and interpretation of data, performing the statistical analysis, as well as the drafting and critical revision of manuscript.
Competing interests: We have read and understood BMJ policy on declaration of interests and declare that JSR receives research support through Yale University from Johnson and Johnson to develop methods of clinical trial data sharing; from Medtronic and the FDA to develop methods for post-market surveillance of medical devices; from FDA to establish a Center for Excellence in Regulatory Science and Innovation; from the Blue Cross Blue Shield Association (BCBSA) to better understand medical technology evidence generation; from the Centers of Medicare and Medicaid Services to develop and maintain performance measures that are used for public reporting; and from the Laura and John Arnold Foundation to support the Collaboration on Research Integrity and Transparency at Yale.
Provenance and peer review: Not commissioned; externally peer reviewed.