A real clinical trial to treat psoriasis is used to illustrate the application of the considered exact approaches.The EU is a member of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH), and therefore adopts the ICH Guidelines, including the ICH M3 Guideline on Nonclinical Safety Studies. Following the 2016 incident in France with BIA 10-2474, and in light of the substantial evolvement of how early clinical development has been undertaken during the last 10 years, for example, conducting integrated (FIH) studies that include multiple parts (eg, single ascending doses, multiple ascending doses, food effect), EMA decided to update the existing 2007 FIH guideline. The key revisions to the 2007 guideline, now titled “Guideline on Strategies to Identify and Mitigate Risks for First-in-Human and Early Clinical Trials With Investigational Medicinal Products,” include additional information. The revision reinforces the importance and impact of pharmacologic data, which supports the intended efficacy of the compound, risk assessment, and protocol design. The updates, effective February 2018, are intended to provide additional guidance and clarity for Sponsors developing FIH and early phase clinical research programs, and ultimately support subject safety. At the 2018 DIA Europe Annual Meeting in Basel, Switzerland, European regulators, industry representatives and academics convened a DIAlogue Session on April 17 to discuss how the revised 2017 guideline is being applied, and to establish recommendations for its application. Using two case studies as examples, the session participants discussed the nonclinical and clinical considerations for applying the newly revised recommendations, and interacted with a panel including regulators and industry representatives. The proceedings from this session reflect practical considerations for the implementation of the revised guideline.This paper provides examples of defining estimands in real-world scenarios following ICH E9(R1) guidelines. Detailed discussions on choosing the estimands and estimators can be found in our companion papers. Three scenarios of increasing complexity are illustrated. The first example is a proof-of-concept trial in major depressive disorder where the estimand is chosen to support the sponsor decision on whether to continue development. The second and third examples are confirmatory trials in severe asthma and rheumatoid arthritis respectively. We discuss the intercurrent events expected during each trial and how they can be handled so as to be consistent with the study objectives. The estimands discussed in these examples are not the only acceptable choices for their respective scenarios. The intent is to illustrate the key concepts rather than focus on specific choices. Emphasis is placed on following a study development process where estimands link the study objectives with data collection and analysis in a coherent manner, thereby avoiding disconnect between objectives, estimands, and analyses.BACKGROUND Although great efforts have been made to address delays in new-drug approvals between different regions, little is known regarding drug lag in Korea. We compared drug lag in Korea with that in Japan, which is well known through many previous studies. selleck chemicals llc METHODS We extracted approval information from public data obtained from the regulatory authorities on all new drugs that were listed in both Korea and Japan between 2009 and 2017. Relative drug lag represented the difference between the date of approval in the country of interest and the date of the first global approval. Relative drug lag was measured as median approval lag. Multiple regression models were used to identify the factors associated with drug lag. The factors considered included origin of substance, nationality of manufacturer, original approval date, orphan drug status, and therapeutic class. RESULTS In total, 394 new drugs were approved in both countries between 2009 and 2017. The median approval lag was 28.2 and 54.1 months in Korea and Japan, respectively. Domestic company drugs were associated with longer median approval lag in Korea ([Formula see text]), sensory organ drugs were associated with shorter median approval lag in Japan ([Formula see text]), and orphan drug status was associated with longer duration of drug approval in Japan ([Formula see text]). CONCLUSIONS Notable drug lags were observed in both Korea and Japan, but the lag was shorter in Korea. Inclusion of global clinical trials and existence of prior knowledge in new drug development were critical to reduce drug lag.BACKGROUND To determine the time taken to perform 5 Risk Evaluation and Mitigation Strategy (REMS) tasks across 3 channels for the Celgene REMS programs, with an aim to better understand which channels may minimize REMS administrative burden. METHODS Five mandatory REMS tasks (new prescriber and patient enrollments, prescriber and patient surveys, and pharmacy dispenses) were performed across applicable REMS channels (online portals, telephone interactions with customer care representatives [CCRs], or an interactive voice response [IVR] system). Five REMS representatives, who had ≥1 year of experience as a CCR, simulated the completion of the same set of testing activities across REMS channels. The execution time for each task by channel was measured and averaged across the participating CCRs. RESULTS Using the online portal, less time was taken to enroll a new prescriber (1.3 minutes) and adult male (6.7 minutes), compared to when the CCR channel was used (21.9 and 25.9 minutes, respectively). Similarly, completion of 3 AFRP prescriber surveys, the adult male patient survey, and 5 pharmacy dispenses was faster using the online portals (3.1, 1.3, and 1.7 minutes, respectively) compared to when the CCR (4.9, 1.8, and 3.4 minutes, respectively) and IVR (10.7, 4.0, and 11.3 minutes, respectively) channels were used. CONCLUSION The use of online channels may alleviate some of the REMS burden by reducing the administrative time it takes for prescribers, patients, and pharmacy stakeholders to complete mandatory REMS tasks. More education and awareness of the available efficient channels should be provided to REMS stakeholders.