Abstract-The COVID-19 pandemic has impacted ongoing clinical trials. We consider particular impacts on noninferiority clinical trials, which aim to show that an investigational treatment is not markedly worse than an existing active control with known benefit. Because interpretation of noninferiority trials requires cross-trial validation involving untestable assumptions, it is vital that they be run to very high standards. The COVID-19 pandemic has introduced an unexpected impact on clinical trials, with subjects possibly missing treatment or assessments due to unforeseen intercurrent events. The resulting data must be carefully considered to ensure proper statistical inference. Missing data can often, but not always, be considered missing completely at random (MCAR). We discuss ways to ensure validity of the analyses through study conduct and data analysis, with focus on the hypothetical strategy for constructing estimands. We assess various analytic strategies of analyzing longitudinal binary data with dropouts where outcomes may be MCAR or missing at random (MAR). PCNA-I1 purchase Simulations show that certain multiple imputation strategies control the Type I error rate and provide additional power over analysis of observed data when data are MCAR or MAR, with weaker assumptions about the missing data mechanism.The COVID-19 outbreak is impacting clinical trials in many ways, such as patient recruitment, data collection and data analysis. To proceed in this difficult time, the adoption of new technologies and new approaches for conducting clinical trials needs to be accelerated. Simultaneously, regulatory agencies such as the US FDA and EMA have issued guidance to help the pharmaceutical industry conduct clinical trials of medical products during the COVID-19 pandemic. In this article, we will address some statistical issues and operational experiences in the conduction of clinical trials during the COVID-19 pandemic. Specifically, we will share experiences in the applications of remote clinical trials in China. Statistical issues related to protocol modifications caused by COVID-19 will be raised.Abstract-Coronavirus disease 2019 (COVID-19) outbreak has rapidly evolved into a global pandemic. The impact of COVID-19 on patient journeys in oncology represents a new risk to interpretation of trial results and its broad applicability for future clinical practice. We identify key intercurrent events (ICEs) that may occur due to COVID-19 in oncology clinical trials with a focus on time-to-event endpoints and discuss considerations pertaining to the other estimand attributes introduced in the ICH E9 addendum. We propose strategies to handle COVID-19 related ICEs, depending on their relationship with malignancy and treatment and the interpretability of data after them. We argue that the clinical trial objective from a world without COVID-19 pandemic remains valid. The estimand framework provides a common language to discuss the impact of COVID-19 in a structured and transparent manner. This demonstrates that the applicability of the framework may even go beyond what it was initially intended for.Abstract-The COVID-19 pandemic has a global impact on the conduct of clinical trials of medical products. This article discusses implications of the COVID-19 pandemic on clinical research methodology aspects and provides points to consider to assess and mitigate the risk of seriously compromising the integrity and interpretability of clinical trials. The information in this article will support discussions that need to occur cross-functionally on an ongoing basis to "integrate all available knowledge from the ethical, the medical, and the methodological perspective into decision making." This article aims at facilitating (i) risk assessments of the impact of the pandemic on trial integrity and interpretability; (ii) identification of the relevant data and information related to the impact of the pandemic on the trial that needs to be collected; (iii) short-term decision making impacting ongoing trial operations; (iv) ongoing monitoring of the trial conduct until completion, including the possible involvement of data monitoring committees, and adequately documenting all measures taken to secure trial integrity throughout and after the pandemic, and (v) proper analysis and interpretation of the eventual interim or final trial data.Abstract-The COVID-19 pandemic has had and continues to have major impacts on planned and ongoing clinical trials. Its effects on trial data create multiple potential statistical issues. The scale of impact is unprecedented, but when viewed individually, many of the issues are well defined and feasible to address. A number of strategies and recommendations are put forward to assess and address issues related to estimands, missing data, validity and modifications of statistical analysis methods, need for additional analyses, ability to meet objectives and overall trial interpretability.Isotretinoin is a highly efficacious medication for the treatment of acne vulgaris; however, its prescription is subject to the strict requirements of the iPLEDGE restricted distribution program. These requirements have placed significant financial, time, and logistical burdens on patients taking the medication. The stay-at-home ordinances enacted by many states during the 2019 novel coronavirus (COVID-19) global pandemic have accelerated previous trends toward utilization of telehealth and decreased laboratory monitoring in the care of patients on isotretinoin. Recent changes to the iPLEDGE program allowing use of at-home pregnancy tests to meet monthly pregnancy test requirements during the pandemic have increased availability of testing options for patients of child-bearing potential on isotretinoin. The change to use of at-home pregnancy test monitoring as well as long-term trends toward increasing access to isotretinoin through the use of telehealth are discussed.When the COVID-19 pandemic struck the United States in early 2020, few healthcare workers were prepared for what lay ahead. Dermatology nurses, medical assistants, and nurse practitioners experienced rapid changes in the way they conducted their daily practice. This article discusses many of those changes and explores the challenges these healthcare workers faced and continue to face. Almost every aspect of how dermatologic care was delivered prepandemic was affected. Some dermatology nurses, medical assistants, and nurse practitioners were redeployed to COVID-19 testing tents and inpatient hospital units or were asked to perform tasks to help support other healthcare workers. This article explores how clinical practice, dermatology staff, patient care, and education were affected. These changes forced dermatology healthcare workers to be brave, accept risks, and ultimately grow from these experiences.