Transformative drugs, defined as pharmaceuticals that are both innovative and have groundbreaking effects on patient care, are the "holy grail" of drug research and development. The sources of drug innovation are often debated, with pharmaceutical manufacturers arguing that high drug prices support innovative output from their sector. We studied the developmental histories of twenty-six drugs or drug classes approved by the Food and Drug Administration between 1984 and 2009 that were judged by expert physicians to be transformative (in two cases, the first drug in a transformative class was approved before 1984). Most of the twenty-six were first approved early in the study period; only four were approved in 2000 or later. Many were based on discoveries made by academic researchers who were supported by federal government funding. Others were jointly developed in both publicly funded and commercial institutions; the fewest number of drugs had originated solely within pharmaceutical industry research programs. Nine of the twenty-six (35 percent) were repurposed from products developed for other indications, and ten (38 percent) were developed for rare diseases before much broader applicability was found. The insights from these case studies provide an experience-based foundation for policies to encourage the development of future transformative drugs.

Daniel Kramer and colleagues compare strategies for postmarket surveillance of medical devices and discuss ways to improve these systems. Please see later in the article for the Editors' Summary

Specialty drugs are notable among prescription drugs in that they offer the possibility of substantial clinical improvement, come with important risks of adverse events and mortality, can be complex to manufacture or administer, and are usually extremely costly. The Food and Drug Administration (FDA) plays a critical role in ensuring that patients who could benefit from specialty drugs have access to them in a timely fashion. In this article we review the different strategies that the FDA can use to approve and influence the post-approval prescribing of specialty drugs. When specialty drugs show promise in early clinical trials, the FDA can expedite the drugs' availability to patients through expanded access programs and expedited approval pathways that speed regulatory authorization. After approval, to ensure that specialty drugs are directed to the patients who are most likely to benefit from them, the FDA can limit the scope of the drugs' indications, encourage the development of companion diagnostic tests to indicate which patients should receive the drugs, or require that manufacturers subject them to Risk Evaluation and Mitigation Strategies to ensure that their use is appropriately limited to a restricted population that is aware of the drugs' risks and benefits. Implementing these existing regulatory approaches can promote timely patient access to specialty drugs while preventing expensive and potentially inappropriate overuse.

Mass casualty incidents (MCI), particularly involving pediatric patients, are high-risk, low-frequency occurrences that require exceptional emergency arrangements and advanced preparation. In the aftermath of an MCI, it is essential for medical personnel to accurately and promptly triage patients according to their acuity and urgency for care. As first responders bring patients from the field to the hospital, medical personnel are responsible for prompt secondary triage of these patients to appropriately delegate hospital resources. The JumpSTART triage algorithm (a variation of the Simple Triage and Rapid Treatment, or START, triage system) was originally designed for prehospital triage by prehospital providers but can also be used for secondary triage in the emergency department setting. This technical report describes a novel simulation-based curriculum for pediatric emergency medicine residents, fellows, and attendings involving the secondary triage of patients in the aftermath of an MCI in the emergency department. This curriculum highlights the importance of the JumpSTART triage algorithm and how to effectively implement it in the MCI setting.

The prolonged COVID-19 pandemic has created unique and complex challenges in operational and capacity planning for pediatric emergency departments, as initial low pediatric patient volumes gave way to unpredictable patient surges during Delta and Omicron variants. Compounded by widespread hospital supply chain issues, staffing shortages due to infection and attrition, and a concurrent pediatric mental health crisis, the surges have pushed pediatric emergency department leaders to re-examine traditionally defined clinical processes, and adopt innovative operational strategies. This study describes the strategic surge response and lessons learned by 3 major freestanding academic pediatric emergency departments in the western United States to help inform current and future pediatric pandemic preparedness.