The coronavirus pandemic has brought public attention to the steps required to produce valid scientific clinical research in drug development. Traditional ethical principles that guide clinical research remain the guiding compass for physicians, patients, public health officials, investigators, drug developers and the public. Accelerating the process of delivering safe and effective treatments and vaccines against COVID-19 is a moral imperative. The apparent clash between the regulated system of phased randomized clinical trials and urgent public health need requires leveraging innovation with ethical scientific rigor. We reflect on the Belmont principles of autonomy, beneficence and justice as the pandemic unfolds, and illustrate the role of innovative clinical trial designs in alleviating pandemic challenges. Our discussion highlights selected types of innovative trial design and correlates them with ethical parameters and public health benefits. Details are provided for platform trials and other innovative designs such as basket and umbrella trials, designs leveraging external data sources, multi-stage seamless trials, preplanned control arm data sharing between larger trials, and higher order systems of linked trials coordinated more broadly between individual trials and phases of development, recently introduced conceptually as "PIPELINEs. " ARTICLE HISTORY

This article reports the consensus recommendations of a working group that was convened at the end of a 4-year research project funded by the National Institutes of Health that examined 280 cases of egregious ethical violations in medical practice. The group reviewed data from the parent project, as well as other research on sexual abuse of patients, criminal prescribing of controlled substances, and unnecessary invasive procedures that were prosecuted as fraud. The working group embraced the goals of making such violations significantly less frequent and, when they do occur, identifying them sooner and taking necessary steps to ensure they are not repeated. Following review of data and previously published recommendations, the working group developed 10 recommendations that provide a starting point to meet these goals. Recommendations address leadership, oversight, tracking, disciplinary actions, education of patients, partnerships with law enforcement, further research and related matters. The working group recognized the need for further refinement of the recommendations to ensure feasibility and appropriate balance between protection of patients and fairness to physicians. While full implementation of appropriate measures will require time and study, we believe it is urgent to take visible actions to acknowledge and address the problem at hand.

United States regulations for the protection of human research subjects prescribe parameters for documentation of valid informed consent, which include the stipulation that the process be in a “language understandable to the subject.” While significant energy has been devoted to improving the readability of consent documents, supplemental educational tools, and nuanced measurements of individual decisional capacity, there is little guidance about how to best meet the informational needs of adults with decisional capacity who do not speak English. This article reviews the institutional review board policies from the twenty‐one research centers that received the most funding from the National Institutes of Health in 2018 and compares their guidelines for obtaining informed consent from non‐English speakers. Inconsistent practices suggest the need for more assertive federal direction on what parameters constitute valid consent for this population. These practices also indicate a reluctance to directly engage the ethical underpinnings of consent policies for non‐English speakers.

Background Traditional clinical trials require tests and procedures that are administered in centralized clinical research sites, which are beyond the standard of care that patients receive for their rare and chronic diseases. The limited number of rare disease patients scattered around the world makes it particularly challenging to recruit participants and conduct these traditional clinical trials. Main body Participating in clinical research can be burdensome, especially for children, the elderly, physically and cognitively impaired individuals who require transportation and caregiver assistance, or patients who live in remote locations or cannot afford transportation. In recent years, there is an increasing need to consider Decentralized Clinical Trials (DCT) as a participant-centric approach that uses new technologies and innovative procedures for interaction with participants in the comfort of their home. Conclusion This paper discusses the planning and conduct of DCTs, which can increase the quality of trials with a specific focus on rare diseases.

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