What is safety?: Miracles, benefit-risk assessments, and the "right to try"

Public discourse is full of quick solutions to health care problems like cancer and rare diseases. Among these is Right to Try legislation for experimental therapies. Right to Try legislation is based on the premise that all experimental agents in clinical trials are safe and guaranteed to produce miracles. Unfortunately, this notion is at odds with expert understanding, which indicates that the benefits and risks of drug products can only be understood together and evaluated incrementally and over time. The current manuscript examines why benefit to risk considerations, a lynchpin of the ethical conduct of clinical research since the Nuremberg Code, might be easily elided from public discourse. This paper considers guidelines for regulatory writing, which routinely separate discussions of effectiveness and safety, as a possible source for some confusion. The internationally-accepted ICH M4E (Common Technical Document) guideline published in 2016 now provides additional guidance for composing Benefits and Risks Conclusions, which weigh and consider effectiveness and safety together. Yet fundamental differences in understanding the "safety" of medicinal products continue to exist between experts in biomedicine, politicians, and healthcare activists. Examining differences in the understanding of "safety" between experts and non-experts also may help explain the source for flawed logic about the safety of investigational products in Right To Try narratives. No drug product is 100% safe. Continuing to weigh benefits and risks together is an important intellectual practice necessary to safeguard human health worldwide, and testing clinical safety is the only way to provide meaningful protections to patients. Science, not miracles, can ensure the protection of patients in clinical research as well as clinical practice. Weighing benefits and risks is an essential intellectual act that informs public health. Science, not miracles, can guide this work.