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Elevated blood pressure increases the risk of adverse cardiovascular events and death. Accordingly, characterizing the off-target blood pressure effects of drugs is an important component of regulatory benefit-risk assessment and post-marketing clinical decision-making. The U.S. Food and Drug Administration (FDA) released draft guidance in May 2018 outlining these considerations and seeking discussion regarding opportunities to improve or reassess methods and analytical techniques to measure and interpret the pressor effects of drugs. Toward this effort, the Duke-Margolis Center for Health Policy-under a cooperative agreement with the FDA-convened a public workshop to bring the stakeholder community together to discuss these opportunities. The following are summary statements and recommendations discussed at the workshop to improve blood pressure assessment throughout the product lifecycle, from development and regulatory review to clinical care.

This White Paper provides a summary of presentations and discussions at a Cardiovascular Safety Outcome Trials Think Tank cosponsored by the Cardiac Safety Research Consortium, the US Food and Drug Administration, and the American College of Cardiology, held at American College of Cardiology's Heart House, Washington, DC, on February 19, 2014. Studies to assess cardiovascular (CV) risk of a new drug are sometimes requested by regulators to resolve ambiguous safety signals seen during its development or among other members of its class. Think Tank participants thought that important considerations in undertaking such studies were as follows: (1) plausibility-how likely it is that a possible signal indicating risk is real, based on strength of evidence, and/or whether a plausible mechanism of action for potential CV harm has been identified; (2) relevance-what relative and absolute CV risk would need to be excluded to determine that the drug had an acceptable benefit-to-risk balance for its use in the intended patient population; and (3) how plausibility and relevance influence the timing and approach to further safety assessment., (Copyright © 2015 Elsevier Inc. All rights reserved.)

This white paper provides a summary of presentations and discussions at a cardiovascular (CV) end point adjudication think tank cosponsored by the Cardiac Safety Research Committee and the US Food and Drug Administration (FDA) that was convened at the FDA's White Oak headquarters on November 6, 2013. Attention was focused on the lack of clarity concerning the need for end point adjudication in both CV and non-CV trials: there is currently an absence of widely accepted academic or industry standards and a definitive regulatory policy on how best to structure and use clinical end point committees (CECs). This meeting therefore provided a forum for leaders in the fields of CV clinical trials and CV safety to develop a foundation of initial best practice recommendations for use in future CEC charters. Attendees included representatives from pharmaceutical companies, regulatory agencies, end point adjudication specialist groups, clinical research organizations, and active, academically based adjudicators. The manuscript presents recommendations from the think tank regarding when CV end point adjudication should be considered in trials conducted by cardiologists and by noncardiologists as well as detailing key issues in the composition of a CEC and its charter. In addition, it presents several recommended best practices for the establishment and operation of CECs. The science underlying CV event adjudication is evolving, and suggestions for additional areas of research will be needed to continue to advance this science. This manuscript does not constitute regulatory guidance., (Copyright © 2014 Elsevier Inc. All rights reserved.)