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The SARS-CoV-2 pandemic has drastically altered all facets of clinical care and research. Clinical research in hepatology has had a rich tradition in several domains, including the discovery and therapeutic development for diseases such as hepatitis B and C, and studying the natural history of many forms of chronic liver disease. NIH, foundation and industry funding has provided important opportunities to advance the academic careers of young investigators while they strived to make contributions to the field. Instantaneously, however, all non-essential research activities were halted when the pandemic started, forcing those involved in clinical research to re-think their research strategy, including a shift to COVID-19 research while endeavoring to maintain their pre-existing agenda. Strategies to maintain the integrity of ongoing studies, including patient follow up, safety assessments and continuation of investigation products, have included a shift to telemedicine, remote safety laboratory monitoring, and shipping of investigational products to study subjects. As a re-vamp of research is being planned, unique issues that face the research community include maintenance of infrastructure, funding, completion of studies in the pre-determined time frame and the need to re-program career path timelines. Real world databases, biomarker and long term follow up studies, and research involving special groups (children, the homeless and other marginalized populations) are likely to face unique challenges. The implementation of telemedicine has been dramatically accelerated and will serve as a backbone for the future of clinical research. As we move forward, innovation in clinical trial design will be essential for conducting optimized clinical research.