Modeling

One of the harsh realities of preparing for an event that has not happened in almost 80 years—the detonation of a nuclear device in an urban area—is the striking lack of preparedness for this kind of high-impact incident. To help address this very important gap, this issue includes a modeling paper featuring hybrid triage approaches for predicting realistic estimates from improvised nuclear device (IND) detonation scenarios (Iyer et al.). Nuclear triage, or the selection and sorting of patients in the unique and very resource-limited environment that would be expected for an IND and other nuclear emergency scenarios, would be particularly demanding and require a subsequent hybrid triage design, which is discussed here. The relative capabilities (and limitations) of the current state-of-the-art predictive models, especially those from the acknowledged leaders in the field within the federal government at the U.S. Department of Health and Human Services/Administration for Strategic Preparedness and Response (HHS/ASPR) and the Defense Threat Reduction Agency (DTRA), are also reviewed (Cliffer et al.). The assessment of medical countermeasures (MCMs) for a radiological or especially a nuclear incident benefits from estimates of mechanical, thermal burn, and radiation injuries, as has been done in models developed at NIAID and HHS/ASPR, which are also discussed. Further, DTRA estimates of injury from ionizing radiation combined with mechanical trauma and/or thermal burns, including effects on physical capabilities, have been incorporated into models projecting the population consequences of nuclear detonations. In addition, operational practices such as triage and allocation of resources for treatment are discussed in the context of how best to inform decisions and practices using public health response modeling. The critical features of shielding, survival, and survivor behavior (e.g., sheltering and evacuation) are covered in this review of the strategic use of modeling to prepare for and respond to the demanding environments produced by radiological and nuclear mass casualty incidents.

CONOPS

Norm initiated a working group termed “The Solutions Lab” within ASPR/HHS to explore ways in which federal planning and guidance could better foster effective and efficient nuclear detonation response. He recognized the difference between planning guidance (what to do) and a strategy (how to do it) and developed actionable approaches to improve our Nation’s nuclear preparedness, including scarce resources triage protocols, cytokine and evacuation priorities, and the Exposure And Symptom Triage (EAST) tool. A key factor in radiological preparedness requires a rapid initial sorting between the individuals exposed to radiation and the worried-well, especially in situations of scarce resources. As a forward thinker, Norm initiated a think-tank (BIG BEN) to develop a blueprint for integrating relevant national capabilities to provide emergency biodosimetry assistance in civilian populations following a radiological or nuclear incident. Although the initial efforts floundered, the NIAID has advanced the creation of a Biodosimetry Assessment Network Group (BANG) to establish a collaborative public/private partnership and engage its membership to address emergency preparedness, response, and recovery. Also desired was promotion of strategic relationships between network members to encourage resource sharing, engaging with stakeholders to utilize recommended tools and support training exercises, and advancing bioinformatics and machine learning approaches to integrate and utilize the network data for managing emergency situations (Satyamitra et al.).

With the exponential growth of artificial intelligence (AI) and Machine Learning (ML) technologies, there are unique opportunities for use of AI in radiological incidents. A structured framework for AI/ML tool selection and deployment, ethical considerations of deploying advanced technologies in critical public safety scenarios, and real-world applications in damage assessment and medical response can be integrated to improve preparedness, responsiveness, and resilience in radiological or nuclear incidents (Gill et al.). As evidenced by the move to more comprehensive modeling, nuclear emergency CONOPS protocols have evolved considerably over the past 2 decades, and there has been a shift from prioritizing medical treatment for patients with burns and injuries to initiating growth factor treatment initiation soon after radiation exposure to rescue the affected populations (Loelius et al.). This is further supported by the FDA approval of multiple MCMs to mitigate the hematologic effects of radiation injury, which are discussed in this issue.

Medical Preparedness (Coordination)

In the wake of a radiological or nuclear incident, it is expected that there will be routine and intense coordination between authorities at all levels of government—from local, state, and tribal groups through national federal government and even international effort. These interactions cannot just be put into place at the moment that a disaster occurs; they must be established and tested long before an incident; the communication and actions must be practiced to the point that they are instinctive for all parties involved in the response. To that end, potential roadblocks to smooth and consistent communication across disparate agencies have been identified and are discussed within this special issue by Dallas et al. The National Alliance for Radiation Readiness (NARR) has been assembled and is expected to play a key role in ensuring U.S. readiness for a radiation public health emergency. NARR is made up of subject matter experts from 29 national groups, who are focused on training, building response capabilities, and communication. James et al. provide a drill-down on the expertise represented within the group and details on how these individuals would contribute in the wake of a radiation mass casualty occurrence. U.S. Government and private sector representatives have identified and designated Chemical, Biological, Radiological, Nuclear, and Explosive (CBRNE) Medical Operations Science Support Experts (CMOSSE) to serve as key professionals with extensive backgrounds and competencies in technical and strategic response planning who can advise U.S. Government decision authorities on how to proceed in managing post-incident activities. Special consideration is given to the need for this group of assembled experts to represent a wide experience in managing medical needs of large populations during disasters (including natural events like weather-related catastrophes and biological-related epidemics), and also to have diplomatic experience and communication skills.

Medical Preparedness (Healthcare)

The manuscript on preparedness in our health care system discusses the responsibilities and resilience of health care systems in responding to nuclear and radiological emergencies (Chao et al.). It emphasizes the importance of pre-incident preparedness, immediate response strategies, and long-term care, highlighting collaboration between local, state, and federal agencies. Key aspects include specialized training, resource allocation, triage protocols, and the role of networks like the Radiation Injury Treatment Network (RITN) in managing mass casualties. The document also outlines national response frameworks, hospital preparedness, and the integration of military and civilian resources. Long-term care considerations include psychological support, cancer monitoring, and chronic health management. The overall focus is on enhancing health care system’s readiness through structured planning, infrastructure resilience, and coordinated emergency response efforts. Another publication, a scoping review by Hockaday et al., evaluated current literature on health care and public health preparedness for radiological and nuclear disasters. A systematic search identified 96 relevant articles, which were analyzed across 7 key themes. The findings highlight gaps in disaster readiness, including deficiencies in preventive measures, hospital preparedness, training, regional collaboration, communication, and infrastructure support. The review underscores the challenges of modern health care systems in addressing radiological emergencies and identifies key challenges and solutions to enhance public safety and response capabilities, which can hopefully be addressed by the continued efforts of the RITN.

Medical Countermeasures

Since the early 2000s, many advancements have been made to improve medical preparedness for a radiological or nuclear incident. The U.S. Government has provided critical support to the development of products to diagnose, mitigate, and treat the health effects of radiation injury. In this issue, DiCarlo et al. describe MCMs and devices that have been approved by the FDA to treat radiation injury or are under advanced development for that indication. These products are the result of a collaborative, whole-of-government approach along the entire development pipeline, from basic research through advanced development, and demonstrate the value of critical public-private partnerships. The FDA’s approval of multiple colony-stimulating factors (CSFs) for the treatment of hematopoietic acute radiation syndrome (H-ARS) presents a major leap forward for our nation’s medical preparedness over the past decade. A systematic review by Chang et al. characterizes the evidence of the efficacy of these CSFs, including filgrastim, pegfilgrastim, sargramostim, and romiplostim, to treat H-ARS during a nuclear or radiological emergency. Data from studies included in the review demonstrate an overall survival benefit for these FDA-approved products when treatment is started 24 hours after radiation exposure; however, data are limited for efficacy of CSFs when treatment is started beyond 24 hours. This review presents evidence to inform and direct future clinical guidance for administering these life-saving medical countermeasures following a nuclear detonation. Despite these important advances in medical preparedness, key challenges persist, such as the difficulties presented by rising antimicrobial resistance. Antimicrobial-resistant infections are expected to contribute to morbidity and mortality from a nuclear detonation, as well as difficult-to-treat fungal infections. Modeling by Phipps et al. estimates the impact of this concern on our nation’s medical preparedness, which could result in a significant number of casualties at risk of treatment failure due to antibiotic-resistant infections.

Regulatory Affairs

A key aspect of guaranteeing that, should an incident unfold, the U.S. Government is prepared to protect its citizens from harm and save lives is working closely across different agencies in a “one-government” approach. To that end, multiple funding and research-associated organizations have established strong connections with various review divisions and centers within the FDA, including the Center for Biologics Evaluation and Research (CBER), the Center for Drug Evaluation and Research (CDER), and the Center for Devices and Radiological Health (CDRH). These divisions within the FDA are responsible for the approval, licensure, and clearance of products that are being developed in the radiation emergency medicine research space. In 2002, the FDA developed the Animal Rule licensure pathway (21 CFR 314 subpart I for drugs and 21 CFR 601 subpart H for biological products), which is to be used when “human challenge studies (exposing people to the threat agent) would not be ethical and human efficacy studies after an accidental or hostile exposure to the threat agent have not been feasible.”Footnote ^a However, it is not enough to just understand this unique pathway and seek FDA concurrence on candidate products and devices. It is also important to carry out continued research on already approved products, such that their emergency use will yield maximum impact. Homer et al. reviewed aspects of advanced development and procurement, such as animal models, polypharmacy, repurposing of approved products from the clinic, and details concerning challenges and successes in getting other products licensed. They also considered the advent of artificial intelligence and how it might be harnessed to help plan regulatory development of future therapeutic interventions that will need to be approved for emergency use.

Norm’s Lasting Impact

As a distinguished cancer specialist and researcher, Norm embodied a passion for addressing global health disparities to all of his roles from being on the faculty as a Radiation Oncologist at Stanford, as Chair of the Joint Center for Radiation Oncology at Harvard, as Associate Director of the Radiation Research Program at the U.S. National Cancer Institute, as Senior Medical Advisor to the U.S. Government Office of the Assistant Secretary for Preparedness and Response, and as co-founder and Senior Scientific Officer for the International Cancer Expert Corps (Pistenmaa et al.). His overall impact, however, is difficult to account for adequately, even if one focuses only on his work as NCI’s Radiation Research Program (RRP) leader. His programmatic leadership helped the RRP develop health equity programs addressing Native American access to optimal cancer care, evaluation of hadron therapy biology, radiation biology, reproducibility and rigor, foundational molecular biology of the tumor and normal tissue caused by radiation therapy dynamically, and global health and security issues (Buchsbaum et al.).