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Society makes substantial investments in biomedical research, searching for ways to better human health. The product of this research is principally information published in scientific journals. Continued investment in science relies on society's confidence in the accuracy, honesty, and utility of research results. A recent focus on productivity has dominated the competitive evaluation of scientists, creating incentives to maximize publication numbers, citation counts, and publications in high-impact journals. Some studies have also suggested a decreasing quality in the published literature. The efficiency of society's investments in biomedical research, in terms of improved health outcomes, has not been studied. We show that biomedical research outcomes over the last five decades, as estimated by both life expectancy and New Molecular Entities approved by the Food and Drug Administration, have remained relatively constant despite rising resource inputs and scientific knowledge. Research investments by the National Institutes of Health over this time correlate with publication and author numbers but not with the numerical development of novel therapeutics. We consider several possibilities for the growing input-outcome disparity including the prior elimination of easier research questions, increasing specialization, overreliance on reductionism, a disproportionate emphasis on scientific outputs, and other negative pressures on the scientific enterprise. Monitoring the efficiency of research investments in producing positive societal outcomes may be a useful mechanism for weighing the efficacy of reforms to the scientific enterprise. Understanding the causes of the increasing input-outcome disparity in biomedical research may improve society's confidence in science and provide support for growing future research investments.

Increasing disparities between resource inputs and outcomes, as measured by certain health deliverables, in biomedical research