Pharmaceutical Companies and Antimicrobial Stewardship: Save Us a Seat
Elizabeth D. Hermsen, PharmD, MBA
The pharmaceutical industry plays an essential role in advancing antimicrobial stewardship and addressing the growing threat of resistant pathogens.
Resistant pathogens are becoming ever more widespread and difficult to treat, with some reports1 suggesting we have already entered a post-antibiotic era. The effects on patients, their families, and societies are devastating: antimicrobial resistance (AMR) threatens our ability to treat common infections in both humans and animals and to benefit from many other achievements of modern medicine.
The importance of access to effective antimicrobials and the need for responsible antimicrobial use, or antimicrobial stewardship (AMS), has been highlighted by the recent coronavirus 2019 (COVID-19) pandemic.
Clinicians around the world are dealing with vulnerable populations suffering from the viral illness and secondary bacterial and/or fungal, and potentially antimicrobial-resistant, infections. As we move through the peri-pandemic stages, AMS is likely to take on increasing importance as a global public health priority.
AMR action plans are being implemented on global2 and national3 levels. In recognition of the interdependence of human, animal, and environmental health (the “One Health” perspective, Fig. 1), these plans encourage multisectoral collaboration, including (but not limited to) governments, agriculture, healthcare providers, and pharmaceutical industry. The pharmaceutical sector’s role in developing new antimicrobials is well recognized, but industry also helps to address AMR by supporting AMS.
Does the pharmaceutical industry’s business model preclude its support of AMS?
Some would say “yes”—but I argue “no”.
The traditional commercial model relies on maximizing profits through sales volume. Although product promotion is a minor driver of actual antibiotic use,4 we know that antimicrobial use is a key driver of AMR. Some companies are experimenting with how to best alter their business model to decouple volume from sales incentives, and some countries5 are implementing ways6 to support such de-linkage.7
For such approaches to be successful, action from pharmaceutical companies and from legislative/regulatory bodies needs to happen in concert—it’s somewhat of a chicken-and-egg debate.
However, even with the current business model, companies that market antimicrobial agents have a social responsibility to support responsible use of these drugs, and investment in AMS also benefits commercial viability. There are four important reasons for this.
First, the responsible use of antimicrobials leads to better patient outcomes, which in turn promotes advocacy for the given product(s).
Second, slowing the development of AMR prolongs the commercial lifespan of a company’s marketed antimicrobial agents.
Third, AMR surveillance can lead to increased awareness of the need for certain antimicrobials based on the observed resistance patterns. This, in turn, can facilitate access to a company’s products where needed most.
And fourth, if patients are succumbing to AMR, they don’t have the opportunity to benefit from medications in other therapeutic areas (eg, oncology, diabetes, etc.) that may also be part of a company’s overall portfolio.
Although not necessarily reflected directly in a company’s bottom line, these benefits are no less important and have the added value of advancing a significant public health priority.
Is the pharmaceutical industry a good AMS partner?
Some would say “no”—but I argue “yes”.
Pharmaceutical companies certainly are not directly responsible for the successful implementation of institution-based AMS programs. However, the expertise and capabilities found within pharmaceutical companies can complement those of other stakeholders when collaborating on multi-sector AMS initiatives.
For example, pharmaceutical companies have employees with a broad range of experience, including but not limited to clinical practice, pharmacoeconomics, epidemiology, health literacy, communications, consumer behavior, market research and analytics, and marketing, along with a large customer network to facilitate best practice sharing.
Global pharmaceutical companies also offer an understanding of both the global and local perspectives and have a worldwide network of institutions with demonstrated ability to conduct clinical studies and surveillance.
The pharmaceutical industry is indeed a good AMS partner.
A recent article8 that I co-authored provided multiple examples of AMS activities that pharma companies can support. As a case study, we used our employer, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (known as MSD outside the USA and Canada), since ours is a globally-operating company marketing antimicrobials and vaccines for humans and animals. A few examples are provided below, grouped into 4 categories:
- Awareness and education: The company has provided a number of independent grants to various non-industry stakeholders to provide education on AMR and AMS, with no direct involvement of the company in content development. Such grants supported a training conference on AMS research methodology,9 development of a comprehensive online AMS resource,10 and creation of a patient engagement educational campaign.11 The company also offers an educational program on reducing infectious disease in livestock12 to reduce the need for antimicrobials in agriculture and supports innovative approaches to improving veterinary medical education13 at universities around the world. Importantly, we ensure our company’s promotional materials encourage responsible prescribing by adhering to the “Star of Stewardship” framework that we developed (Fig. 2).
- Implementation: Merck & Co., Inc. (Kenilworth, NJ, USA) supports implementation of product-agnostic AMS programs worldwide, ensuring that such support is free from commercial influence and that potential conflicts of interest are addressed and disclosed. From an environmental health perspective, the company focuses on minimizing antibiotic discharge from its antibiotic manufacturing facilities.14
- Surveillance and research: Merck & Co., Inc. (Kenilworth, NJ, USA) supports antimicrobial surveillance studies in both human15 and animal16 health. These programs evaluate resistance trends geographically and over time, which can help providers (human health) or food producers (animal health) make decisions based on epidemiological data. The company also funds investigator-initiated research studies, including product-agnostic AMS research.17 The investigators are responsible for data generation, analysis, interpretation, and publication, free from any industry involvement. In line with its commitment to the AMR Industry Declaration,18 our company is also committed to research that aims to assess and abate the environmental impact of antibiotic manufacturing.19 Most recently, our company was one of more than 20 leading biopharmaceutical companies that announced the launch of the AMR Action Fund, a ground-breaking partnership whereby the participating companies will invest nearly $1 billion to bring 2-4 new antibiotics to patients by 2030.20
- Advocacy: Jointly with other (non-industry and industry) stakeholders, the company advocates for policy reforms that support AMS and enable sustainable investment in AMR-relevant innovation. Reimbursement reform and so-called “pull incentives”21 aim to improve patient access to medically necessary and appropriate antibiotics. (Providing the right drug for the right patient is a key characteristic of AMS.) Additionally, our company has partnered with infectious disease societies to call on the FDA and other regulators to include all relevant susceptibility data in the package insert, in order to guide responsible use of novel antibiotics. A foundational aspect of Merck & Co., Inc.’s (Kenilworth, NJ, USA) animal health efforts is advocating for science-based policy. For example, our company helped create and signed on to the “Health for Animals Antibiotics Commitment.”22
The pharmaceutical industry can and should take diverse, impactful actions to support AMS, free from commercial influence. We have the capabilities, capacity, and expertise to be a credible partner. Will you save us a seat at the table?
Figure 1. The One Health partnership to improve human, animal, and environmental health.
Source: CDC. Use of this figure, which is freely available at https://www.cdc.gov/ncezid/pdf/ncezid-2018-accomplishments-H.pdf, does not constitute endorsement or recommendation by the US Government, Department of Health and Human Services, or Centers for Disease Control and Prevention
Figure 2. The “Star of stewardship” principles used at Merck & Co., Inc. (Kenilworth, NJ, USA) to ensure that the company’s antibiotic and antifungal promotional material is supportive of AMS.
Hermsen is an infectious diseases—trained pharmacist who created, implemented, and co-directed a hospital antimicrobial stewardship program for several years before moving to the pharmaceutical industry, where she is now responsible for developing and executing a strategy to advance antimicrobial stewardship globally through education, implementation, research, and advocacy, with a One Health perspective.
The views expressed are those of the author and do not necessarily reflect the position or policy of Merck & Co., Inc., Kenilworth, NJ, USA.
Medical writing assistance was provided by Dominik Wolf, MS, and editorial assistance was provided by Michele McColgan, BA, both of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Potential conflicts of interests
Elizabeth D. Hermsen is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and owns stock or stock options in the Merck & Co., Inc., Kenilworth, NJ, USA.
1. CDC. Antibiotic resistance threats in the United States 2019. https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf. Revised December 2019. Accessed July 31, 2020.2. World Health Organization. Global action plan on antimicrobial resistance. https://www.who.int/antimicrobial-resistance/global-action-plan/en/. Published 2015. Accessed July 31, 2020.3. CDC. U.S. National Action Plan for Combating Antibiotic-Resistant Bacteria (National Action Plan). https://www.cdc.gov/drugresistance/us-activities/national-action-plan.html. Published March 2019. Accessed July 31, 2020.4. The Pew Charitable Trusts. What Drives Inappropriate Antibiotic Use in Outpatient Care? https://www.pewtrusts.org/~/media/assets/2017/06/arp_what_drives_inappropriate_antibiotic_use_in_outpatient_care.pdf. Published June 2017. Accessed July 31, 2020.5. Hillock NT, Merlin TL, Karnon J, Turnidge J, Eliott J. Feasibility of de-linking reimbursement of antimicrobials from sales: the Australian perspective as a qualitative case study. JAC-Antimicrobial Resistance. 2020;2(2)doi:10.1093/jacamr/dlaa0236. Public Health Agency of Sweden. Availability of antibiotics. https://www.folkhalsomyndigheten.se/the-public-health-agency-of-sweden/communicable-disease-control/antibiotics-and-antimicrobial-resistance/availability-of-antibiotics/. Updated March 2020. Accessed July 31, 2020.7. Department of Health and Social Care, gov.UK. Development of new antibiotics encouraged with new pharmaceutical payment system. https://www.gov.uk/government/news/development-of-new-antibiotics-encouraged-with-new-pharmaceutical-payment-system. Published July 2019. Accessed July 31, 2020.8. Hermsen ED, Sibbel RL, Holland S. The role of pharmaceutical companies in antimicrobial stewardship: a case study. Clin Infect Dis. Jul 27 2020;71(3):677-681. doi:10.1093/cid/ciaa0539. The Society for Healthcare Epidemiology of America. 2018 Antimicrobial Stewardship Research Workshop. https://learningce.shea-online.org/content/2018-antimicrobial-stewardship-research-workshop. Accessed July 31, 2020.10. Center for Infectious Disease Research and Policy, University of Minnesota. Antimicrobial Stewardship Project. https://www.cidrap.umn.edu/asp. Accessed July 31, 2020.11. Antibiotics and You. Be an antibiotic hero. http://antibioticsandyou.org/. Accessed July 31, 2020.12. MSD Animal Health. Time to vaccinate. https://www.timetovaccinate.com/. Accessed July 31, 2020.13. Association of American Veterinary Medical Colleges. AAVMC, MSD Animal Health Collaborating on Global Antimicrobial Resistance Project. https://www.aavmc.org/civme/civme-msd-antimicrobial-stewardship-grant-program. Accessed July 31, 2020.14. AMR Industry Alliance. Making antibiotics responsibly. https://www.amrindustryalliance.org/wp-content/uploads/2019/11/Making-antibiotics-responsibly_A-common-manufacturing-framework-to-tackle-AMR.pdf. Accessed July 31, 2020. .15. Morrissey I, Hackel M, Badal R, Bouchillon S, Hawser S, Biedenbach D. A Review of Ten Years of the Study for Monitoring Antimicrobial Resistance Trends (SMART) from 2002 to 2011. Pharmaceuticals (Basel). Nov 01 2013;6(11):1335-46. doi:10.3390/ph611133516. Kansas State University. KSVDL Microbial Surveillance Lab. https://olathe.k-state.edu/research/centers-institutes/microbial-lab/. Updated May 2020. Accessed July 31, 2020.17. Merck & Co., Inc. Investigator Studies Program (MISP): Antimicrobial Stewardship. http://engagezone.msd.com/Antimicrobial_Stewardship.php. Accessed July 31, 2020.18. AMR Industry Alliance. Declaration by the pharmaceutical, biotechnology and diagnostics industries on combating antimicrobial resistance. https://www.amrindustryalliance.org/wp-content/uploads/2017/12/AMR-Industry-Declaration.pdf. Published January 2016. Accessed July 31, 2020.19. Tell J, Caldwell DJ, Haner A, et al. Science-based Targets for Antibiotics in Receiving Waters from Pharmaceutical Manufacturing Operations. Integr Environ Assess Manag. May 2019;15(3):312-319. doi:10.1002/ieam.414120. AMR Action Fund. About us - AMR action fund. https://www.amractionfund.com/about-us/#page-section-0. Accessed July 31, 2020.21. Ardal C, Rottingen JA, Opalska A, Van Hengel AJ, Larsen J. Pull Incentives for Antibacterial Drug Development: An Analysis by the Transatlantic Task Force on Antimicrobial Resistance. Clin Infect Dis. Oct 15 2017;65(8):1378-1382. doi:10.1093/cid/cix52622. Health for Animals. Antibiotic Commitment. https://healthforanimals.org/resources-and-events/antibiotics-commitment.html. Accessed July 31, 2020.