By Marianne Nugent and Jeannie-Marie Skinner
Propelled by the COVID-19 pandemic, a new, shortened route to market uptake for some investigational drugs and devices has leaped into public awareness. Companies considering this avenue must recognize and address multiple strategic considerations and potential negative consequences beyond the obvious attractions of early access to patients. Once implemented, careful communication about these products is key to maintaining credibility and confidence.
During declared public health emergencies, section 564 of the Federal Food, Drug, and Cosmetic Act (FD&C Act) allows the FDA Commissioner to allow use of unapproved medical products, or unapproved uses of approved medical products, where there are no adequate, approved, and available alternatives to address serious or life-threatening diseases. This Emergency Use Authorization (EUA) authority, first employed during the Ebola, MERS, and SARS crises, imposes strict constraints over what can be communicated, to whom communications may be directed, and what must be disclosed. At the same time, however, it significantly reduces the burden of proof (of efficacy and safety), the explicit labeling laws, and the prescription and usage guidelines normally required by FDA and state laws to protect the public. As of this writing, FDA has issued COVID-19-related EUAs for eight drugs or biological therapeutics (and revoked one, for hydroxychloroquine), 26 medical device products, 22 personal protective equipment products, and a staggering 294 in vitro diagnostic products.[i]
Eager as the public is for effective COVID-19 countermeasures, commercializing a product under EUA could cause significant issues for a drug or device company. Foremost among them is growing public concern that public health needs and perceived political pressure may compromise patient health by allowing use of ineffective or unsafe products.
The Global Regulatory Strategy group at Syneos Health is currently helping multiple clients navigate the COVID-19 regulatory process with the FDA, including pre-IND, IND, Expanded Access protocols and EUAs. Dr. Jaime Hernandez, who leads our COVID-19 Accelerator Response Team, navigated the Emergency Use Authorization process at its inception, working on the first-ever EUA (for IV peramivir during the 2009 influenza pandemic). In addition, Peter Pitts, a former Associate FDA Commissioner, continues to engage with key leaders with Operation Warp Speed, the public-private partnership to accelerate the development, production and distribution of COVID-19 vaccines, therapeutics and diagnostics. The Global Regulatory Strategy team combines regulatory, clinical, nonclinical, and CMC expertise; industry experience; and strong leadership.
As this work progresses, several key insights have emerged.
Insight #1: Public health requires public trust. An exceptional degree of transparency must accompany EUA applications and utilizations, so that all stakeholders are fully informed of the risks involved. A vaccine, test, or treatment that is not trusted may be tantamount to having none at all. By definition, EUA is issued on the basis of incomplete scientific controls and without the data sets normally used to establish confidence, which in itself may erode trust among professional and lay audiences. In addition, conflicting statements by health authorities and other sources regarding COVID-19 over the course of the pandemic have led to confusion and polarization among many health consumers. A vital component of exercising the EUA option is open and forthright communication that establishes and maintains trust.
Insight #2: Subsets of the population are skeptical. In addition, vocal sub-populations harbor anti-vaccine and anti-pharma biases that may be amplified by a perceived relaxation in regulatory standards. Pre-existing skepticism among subsets of Americans (including communities of color as well hospitals that may feel pressure to purchase and use experimental COVID treatments) must be considered. Dialog and engagement with these subsets is essential.
Insight #3: Lexicon of efficacy and safety matters. Given the comparative paucity of data supporting EUAs in comparison with non-emergency approvals, the language of efficacy and safety surrounding EUA products must avoid implications of equality with formally-approved agents. How effectiveness is defined / described will be critical – and likely come with many caveats. Language must be clear and offer a compelling (and accurate) benefit/risk profile relative to the pandemic.
Insight #4: The EUA option may close off opportunities to gather vital trial data. Once EUA is approved for an agent, investigators face ethical obligations to inform placebo patients in ongoing trials of the availability of a presumably active agent—breaking the codes that blind the studies against bias. Without a placebo comparator, it may be difficult or impossible to accurate gauge efficacy and tolerability over time.
Insight #5: FDA credibility must be preserved. Messaging must maintain confidence in the imprimatur of the FDA approval, the rationale for Emergency Use Authorization(s) and the role of continued study.
As we prepare clients for evaluating EUA options, we are focusing on message testing, scenario planning, evaluating messenger and validator planning, rollout cascades, among other considerations. As an industry, we will develop ways to forestall potential skepticism and ensure a balanced conversation by, among other steps:
Extraordinary times often call for extraordinary measures, and the COVID-19 pandemic has thrust government health agencies and the industries they regulate into uncharted territory.
We are confident, however, that by leveraging our industry’s experience, experts, and our partnerships, we can overcome any and all issues that may arise.
About the Authors
Marianne Nugent is Managing Director, Commercial Innovation and Solutions at Syneos Health, offering customers of all sizes the broadest and most fully integrated end-to-end commercial capabilities in the industry.
Jeannie-Marie Skinner is a Senior Director in the Global Regulatory Strategy group at Syneos Health, with 30 years of experience in the global pharmaceutical industry including Clinical Research, Project Management and Regulatory Affairs.