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The United States is a global leader in biomedical research, generating therapeutic breakthroughs that advance the health of the nation and the world. The public and private sectors contribute to this advancement by funding biomedical research and development. The current level of investment in pharmaceutical development in the United States, while substantial, does not always yield desired health outcomes or meet the needs of patients. Public and private funders face a myriad of challenges that affect their funding decisions and hinder the ability of the drug development system to prioritize disease burden and unmet need - often leaving critical gaps in available treatment options. To better understand these gaps, Gates Ventures and the Peterson Center on Healthcare asked the National Academies to examine current challenges and offer strategies and recommendations for improvement. The resulting report emphasizes that current research prioritization does not systematically account for disease burden and unmet needs, and describes how a robust, timely, accessible data system is needed. It also explores the ways in which implementing recommended policy changes could deliver better health outcomes.