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The study estimated the extent to which drug innovations over the past 30 years may have improved outcomes for six diseases.We analyzed six diseases (ischemic heart disease, lung cancer, breast cancer, human immunodeficiency virus [HIV] infection, type 2 diabetes mellitus, and rheumatoid arthritis [RA]) with significant mortality or morbidity for which there have been major drug innovations over the past 30 years. We used U.S. data from the Global Burden of Disease (GBD) database and a patient registry to perform counterfactual time-series analyses predicting the improved health outcomes that may have been associated with major drug innovations. For 5 conditions using data from the GBD study, years of life lost per individual with the condition could have been higher by 17.1% (breast cancer) to 660.6% (HIV infection) in 2017 had the major drug innovations not been introduced. For RA, using patient registry data, patients' functional status could have been 11.5% worse had biological therapies not been introduced.Policies targeting drug prices should be broadened to consider the price and value of all health-care services. The societal importance of the pharmaceutical industry's ability to respond rapidly to emerging diseases should be recognized.

RASSF1A may be the most frequently inactivated tumor suppressor identified in human cancer so far. It is a proapoptotic Ras effector and plays an important role in the apoptotic DNA damage response (DDR). We now show that in addition to DDR regulation, RASSF1A also plays a key role in the DNA repair process itself. We show that RASSF1A forms a DNA damage-regulated complex with the key DNA repair protein xeroderma pigmentosum A (XPA). XPA requires RASSF1A to exert full repair activity, and RASSF1A-deficient cells exhibit an impaired ability to repair DNA. Moreover, a cancer-associated RASSF1A single-nucleotide polymorphism (SNP) variant exhibits differential XPA binding and inhibits DNA repair. The interaction of XPA with other components of the repair complex, such as replication protein A (RPA), is controlled in part by a dynamic acetylation/deacetylation cycle. We found that RASSF1A and its SNP variant differentially regulate XPA protein acetylation, and the SNP variant hyperstabilizes the XPA-RPA70 complex. Thus, we identify two novel functions for RASSF1A in the control of DNA repair and protein acetylation. As RASSF1A modulates both apoptotic DDR and DNA repair, it may play an important and unanticipated role in coordinating the balance between repair and death after DNA damage.