Too Important for the Bureaucrats: Rethinking Risk and Regulatory Presumptions in Times of Crisis.

The posture of American regulation of medicine is negative-we assume that a new drug is unsafe and ineffective until it is proven safe and effective.1 This regulatory posture is a heuristic normative principle, a specific instance of the so-called precautionary principle in public health law.2 It is defensible, if debatable, in many ordinary circumstances.3 But like many normative heuristics, this negative posture may compel suboptimal decision-making in emergencies, where context-specific decisions must be made and a range of unique values may apply.

An open science pathway for drug marketing authorization-Registered drug approval.

Florian Naudet and co-authors propose a pathway involving registered criteria for evaluation and approval of new drugs.

An urgent call to raise the bar in oncology.

Important breakthroughs in medical treatments have improved outcomes for patients suffering from several types of cancer. However, many oncological treatments approved by regulatory agencies are of low value and do not contribute significantly to cancer mortality reduction, but lead to unrealistic patient expectations and push even affluent societies to unsustainable health care costs. Several factors that contribute to approvals of low-value oncology treatments are addressed, including issues with clinical trials, bias in reporting, regulatory agency shortcomings and drug pricing. With the COVID-19 pandemic enforcing the elimination of low-value interventions in all fields of medicine, efforts should urgently be made by all involved in cancer care to select only high-value and sustainable interventions. Transformation of medical education, improvement in clinical trial design, quality, conduct and reporting, strict adherence to scientific norms by regulatory agencies and use of value-based scales can all contribute to raising the bar for oncology drug approvals and influence drug pricing and availability.

Emergency use of COVID-19 vaccines recommended by the World Health Organization (WHO) as of June 2021.

In December 2019, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the outbreak of coronavirus disease 2019 (COVID-19), and the resulting pandemic has caused widespread health problems and social and economic disruption. Thus far in 2021, more than 4 million people worldwide have died from COVID-19, so safe and efficacious vaccines are urgently needed to restore normal economic and social activities. According to the official guidance documents of the World Health Organization (WHO), vaccines based on four major strategies including mRNA, adenoviral vectors, inactivated viruses, and recombinant proteins have entered the stage of emergency use authorization and pre-certification evaluation. The current review summarizes these vaccines and it looks ahead to the development of additional COVID-19 vaccines in the future.

Vaccines: Underlying Principles of Design and Testing.

In this paper, we review the key elements that should be considered to take a novel vaccine from the laboratory through to licensure in the modern era. This paper is divided into four sections. First, we discuss the host immune responses that we engage with vaccines. Second, we discuss how in vivo and in vitro studies can inform vaccine design. Third, we discuss different vaccine modalities that have been licensed or are in testing in humans. Last, we overview the basic principles of vaccine approvals. Throughout we provide real-world examples of vaccine development against infectious diseases, including coronavirus disease 2019 (COVID-19).

COVID-19 and the Emerging Regulatory Guidance for Ongoing Clinical Trials in the European Union.

The coronavirus disease 2019 (COVID-19) pandemic and the accompanying control measures have significantly affected clinical trial (CT) conduct, and sponsors have needed to make rapid changes to their CT operations. As a result, regulatory guidance was pivotal during the initial phases of the pandemic. This study aimed to evaluate the regulatory readiness and guidance related to COVID-19 in the European Union (EU). The European Medicines Agency (EMA) and national competent authorities' (NCAs') websites were searched in September and October 2020 for guidances on the management of CTs during the pandemic published from January 2020 onward. "Regulatory readiness" was defined as the number of days from the first European COVID-19 case (January 24, 2020) to the first published guidance by the respective NCA. "Regulatory guidance" was evaluated by coding the guidances for the following predefined operational trial activities important for ongoing CTs: obtaining informed consent, participant information, clinic visits, home health visits, telemedicine visits, self-monitoring, investigational medicinal product (IMP) supply, IMP adherence monitoring, CT monitoring, documentation management, regulatory management, and safety management. Twenty-four of the 27 EU NCAs published country-specific guidance. The time from the first European COVID-19 case to the first published EMA guidance was 56 days and ranged from 47 to 66 days for the first national guidances. Guidance was provided most frequently for regulatory management (24/24), safety management (23/24), documentation management (22/24), and CT monitoring (22/24). The regulatory guidance provided during the pandemic, ensuring participant safety and data integrity, may now be the starting point to innovate future CT conduct.

An Overview Of Vaccine Development, Approval, And Regulation, With Implications For COVID-19.

The Food and Drug Administration (FDA) approves vaccines when their benefits outweigh the risks for their intended use. In this article we review the standard FDA approach to vaccine evaluation, which underpins its current approaches to assessment of vaccines to prevent coronavirus disease 2019 (COVID-19). The FDA has established pathways to accelerate vaccine availability before approval, such as Emergency Use Authorization, and to channel resources to high-priority products and allow more flexibility in the evidence required for approval, including accelerated approval based on surrogate markers of effectiveness. Among the thirty-five new vaccines approved in the US from 2006 through October 2020, about two-thirds of their pivotal trials used the surrogate outcome of immune system response, and only one-third evaluated actual disease incidence. Postapproval safety surveillance of new vaccines, and particularly vaccines receiving expedited approval, is crucial. This has generally been accomplished through such mechanisms as the Centers for Disease Control and Prevention (CDC) and FDA Vaccine Adverse Event Reporting System, the CDC Vaccine Safety Datalink, and the CDC Clinical Immunization Safety Assessment Project. Adverse events detected in this way may lead to changes in a vaccine's recommended use or withdrawal from the market. Regulatory oversight of new vaccines must balance speed with rigor to effectively address the pandemic.

Accelerating regulation in response to COVID-19.

Regulators are finding ways to support the expedited development and distribution of novel coronavirus-related vaccines, tests and treatments. Gary Humphreys reports.

Working Hard or Hardly Working? Regulatory Bottlenecks in Developing a COVID-19 Vaccine.

Vaccine solutions rarely reach the public until after an outbreak abates; an Ebola vaccine was approved 5 years after peak outbreak and SARS, MERS, and Zika vaccines are still in clinical development. Despite massive leaps forward in rapid science, other regulatory bottlenecks are hamstringing the global effort for pandemic vaccines.

Time to Step Up: A Call to Action For the Clinical and Quantitative Pharmacology Community to Accelerate Therapeutics for COVID-19.

The global response to finding therapeutics for coronavirus disease 2019 (COVID-19) is chaotic even if well intentioned. There is an opportunity, but more importantly, an obligation for the global clinical and quantitative pharmacology community to come together and use our state-of-the-art tools and expertise to help society accelerate therapeutics to fight COVID-19. This brief commentary is a call to action and highlights how the global pharmacology community should contribute to the COVID-19 pandemic and prepare for future pandemics.