Date of download: 5/31/2016 Copyright © 2016 American Medical Association. All rights reserved. From: The Anatomy of Medical Research: US and International Comparisons JAMA. 2015;313(2): doi: /jama The Anatomy of Medical Research: US and International ComparisonsEMA indicates European Medicines Agency; FDA, US Food and Drug Administration. Figure Legend:

Date of download: 5/31/2016 Copyright © 2016 American Medical Association. All rights reserved. From: The Anatomy of Medical Research: US and International Comparisons JAMA. 2015;313(2): doi: /jama US Funding for Medical Research by Source, Data were calculated according to methods outlined in eTable 1 in the Supplement. ARRA indicates American Recovery and Reinvestment Act. a Data were adjusted to 2012 dollars using the Biomedical Research and Development Price Index. b The National Institutes of Health and other federal sources include stimulus provided by ARRA in 2009 and c Data from and were estimated based on linear regression analysis of industry market share. d Compound annual growth rate (CAGR) supposing that year A is x and year B is y, CAGR = (y/x) {1/(B−A)} −1. The CAGR was calculated separately for 2 different periods with a single overlapping year: and The cut point was chosen at 2004 given the changes seen in funding from the National Institutes of Health in that year. Figure Legend:

Date of download: 5/31/2016 Copyright © 2016 American Medical Association. All rights reserved. From: The Anatomy of Medical Research: US and International Comparisons JAMA. 2015;313(2): doi: /jama Growth in US Funding for Medical Research by Source, Data were calculated according to methods outlined in eTable 1 in the Supplement. a Adjusted to 2012 dollars using the Biomedical Research and Development Price Index. b Compound annual growth rate (CAGR) supposing that year A is x and year B is y, CAGR = (y/x) {1/(B−A)} −1. Figure Legend:

Date of download: 5/31/2016 Copyright © 2016 American Medical Association. All rights reserved. From: The Anatomy of Medical Research: US and International Comparisons JAMA. 2015;313(2): doi: /jama Pharmaceutical Industry Medical Research Funding by Phase of Research, Pharmaceutical industry funding by phase was obtained from Pharmaceutical Research and Manufacturers of America (PhRMA) annual reports, Data were 2 years old at time of publication and include both domestic and international research funding from PhRMA members. a Data were adjusted to 2012 dollars using the Biomedical Research and Development Price Index. b Compound annual growth rate (CAGR) supposing that year A is x and year B is y, CAGR = (y/x) {1/(B−A)} −1. c Uncategorized funding could not be allotted to a single phase of research. Figure Legend:

Date of download: 5/31/2016 Copyright © 2016 American Medical Association. All rights reserved. From: The Anatomy of Medical Research: US and International Comparisons JAMA. 2015;313(2): doi: /jama Compounds in Development for Top 10 Therapeutic Areas, 2013Data for the number of compounds in development were from the Citeline Pharma R&D Annual Review Data for rare diseases were from the Pharmaceutical Research and Manufacturers of America. a Number of compounds in clinical trials or under review by the US Food and Drug Administration. This includes a total of compounds in b Includes all nonimmunological anticancer compounds. c Rare diseases were defined as those affecting or fewer people in the United States. Figure Legend:

Date of download: 5/31/2016 Copyright © 2016 American Medical Association. All rights reserved. From: The Anatomy of Medical Research: US and International Comparisons JAMA. 2015;313(2): doi: /jama US Funding for Health Services Research by Source, AHRQ indicates Agency for Healthcare Research and Quality; NIH, National Institutes of Health. Data were calculated according to methods outlined in eTable 5 in the Supplement. a Adjusted to 2012 dollars using the Biomedical Research and Development Price Index. b Compound annual growth rate (CAGR) supposing that year A is x and year B is y, CAGR = (y/x) {1/(B−A)} −1. c Health services industry includes funding from hospitals, ambulatory health care services, nursing and residential facilities. Health insurance companies were not included. Data may not fully capture the entirety of funding for health services research and quality improvement initiatives for the US health care services industry. d Other federal funding includes the Centers for Disease Control and Prevention, Centers for Medicare & Medicaid Services, Veterans Health Administration, Health Resources and Services Administration, and Patient Centered Outcomes Research Institute (in 2011 only). e Foundation funding includes total giving from the Robert Wood Johnson Foundation, California Endowment, Pew Charitable Trusts, W. K. Kellogg Foundation, and Commonwealth Fund. Figure Legend:

Date of download: 5/31/2016 Copyright © 2016 American Medical Association. All rights reserved. From: The Anatomy of Medical Research: US and International Comparisons JAMA. 2015;313(2): doi: /jama Research and Development Investment Ranking of Industrial Sectors Among US-Based Companies, 2011Research and development expenditures for US-based companies performing research by the industrial sector were obtained from the National Science Foundation. Data include research funds spent both domestically and abroad. Industry revenues were obtained from the National Science Foundation or US Census Bureau based on the availability of data. Revenues and research and development expenditures were matched by industry using North American Industry Classification System codes. a The pharmaceuticals and biotechnology, medical devices, and health care services industries are highlighted in red. b Adjusted to 2012 dollars using the Biomedical Research and Development Price Index. c Health care services industry includes US-based hospitals, ambulatory health care services, and nursing and residential facilities. Figure Legend:

Date of download: 5/31/2016 Copyright © 2016 American Medical Association. All rights reserved. From: The Anatomy of Medical Research: US and International Comparisons JAMA. 2015;313(2): doi: /jama Global Medical Research Funding in Select Countries/Regions, 2011The regions/countries/economies in the analysis include the major countries of North America (United States, Canada), Europe (including the 10 largest European countries in the Organisation for Economic Co-operation and Development), and Asia-Oceania (Australia, China, India, Japan, Singapore, and South Korea). Data for African and South American countries and Russia were not available. Data were calculated according to methods outlined in eTable 6 in the Supplement. a Data were converted to US currency using an average annual exchange rate for the respective year and adjusted to 2012 dollars using the Biomedical Research and Development Price Index. b Public research and development funding included that from government agencies, higher educational institutes, and not-for-profit organizations. c Industry research and development funding included pharmaceutical, biotechnology, and medical device firms. d Compound annual growth rate (CAGR) supposing that year A is x and year B is y, CAGR = (y/x) {1/(B−A)} −1. e Global total for medical research funding includes research and development expenditures from 36 major world countries across 4 continents. f Other Asia includes India, Singapore, and South Korea. Figure Legend:

Date of download: 5/31/2016 Copyright © 2016 American Medical Association. All rights reserved. From: The Anatomy of Medical Research: US and International Comparisons JAMA. 2015;313(2): doi: /jama Top 10 Countries by Size of Science and Technology Workforce, The sizes of national science and technology workforces were obtained from the Organisation for Economic Co-operation and Development. a Workforce size was measured in number of full-time equivalents and includes all science and technology sectors (eg, engineering, physical sciences) in addition to the medical and health sciences. b Compound annual growth rate (CAGR) supposing that year A is x and year B is y, CAGR = (y/x) {1/(B−A)} −1. c Annual growth in China’s science and technology workforce may be underestimated because of a change in reporting methods for China in Figure Legend:

Date of download: 5/31/2016 Copyright © 2016 American Medical Association. All rights reserved. From: The Anatomy of Medical Research: US and International Comparisons JAMA. 2015;313(2): doi: /jama Global Life Science Patent Applications by Country of Origin, The number of patent family applications by country filed was calculated based on data obtained from Thomson Innovation. Only the most recent patent application in a patent family was counted for this analysis. Data are included for all countries available in the Thomson data set. a Life science was defined to include the following categories: analysis of biological materials, medical technology, organic fine chemistry, biotechnology, pharmaceuticals, macromolecular chemistry and polymers, and microstructural and nanotechnology. b Only patent grants, not all patent applications, are counted for Japan, which tends toward patent applications with narrower definitions and therefore much greater numbers relative to the number of patents ultimately granted. Figure Legend:

Date of download: 5/31/2016 Copyright © 2016 American Medical Association. All rights reserved. From: The Anatomy of Medical Research: US and International Comparisons JAMA. 2015;313(2): doi: /jama US Life Science Patent Applications by Country of Origin, The number of patent application families by country was calculated counting the most recent application in family of patents based on data obtained from Thomson Innovation. Data are included for all countries available in the Thomson data set. a Life science was defined to include the following categories: analysis of biological materials, medical technology, organic fine chemistry, biotechnology, pharmaceuticals, macromolecular chemistry and polymers, and microstructural and nanotechnology. Figure Legend:

Date of download: 5/31/2016 Copyright © 2016 American Medical Association. All rights reserved. From: The Anatomy of Medical Research: US and International Comparisons JAMA. 2015;313(2): doi: /jama Highly Valuable US Life Science Patents by Country of Origin, The number of patent application families by country was calculated counting the most recent application in family of patents based on data obtained from Thomson Innovation. Data are included for all countries available in the Thomson data set. a Life science was defined to include the following categories: analysis of biological materials, medical technology, organic fine chemistry, biotechnology, pharmaceuticals, macromolecular chemistry and polymers, and microstructural and nanotechnology. b Top 10% of patents ranked by year using BCG Quality Index. The BCG Quality Index is made up of 3 components; specifically, forward citations of a patent in newer patents adjusted for the patent’s age, the number of patent claims, and the strength of a patent’s backward citations. The components and corresponding weights used by the quality index are a product of proprietary Boston Consultng Group research. Figure Legend:

Date of download: 5/31/2016 Copyright © 2016 American Medical Association. All rights reserved. From: The Anatomy of Medical Research: US and International Comparisons JAMA. 2015;313(2): doi: /jama Medical Research Articles and Citations by Selected Countries/Regions, NA indicates not available. Medical research was defined as the life sciences and psychology, excluding agricultural science. Article counts reported by the National Science Foundation were from the Thomas Reuters Science Citation Index and Social Science Citation Index, classified by year of publication and assigned to countries on the basis of institutional addresses listed on each article. Articles were counted on a fractional basis; ie, for articles with collaborating institutions from multiple countries, each country received fractional credit on the basis of proportion of its participating institutions. Citations were based on a 3-year period with 2-year lag; eg, citations for 2000 are references made in articles in 2000 to articles published in The citation index of highly cited articles was defined as the share of the world’s top 1% cited biomedical research articles divided by the share of the world’s biomedical research articles in the cited year window. a Compound annual growth rate (CAGR) supposing that year A is x and year B is y, CAGR = (y/x) {1/(B−A)} −1. b Other includes the remaining 159 nations of the world within the original database. c Other Asia includes India, Indonesia, Malaysia, Philippines, Singapore, South Korea, Taiwan, and Thailand. d The European Union includes 27 European nations. Figure Legend:

Date of download: 5/31/2016 Copyright © 2016 American Medical Association. All rights reserved. From: The Anatomy of Medical Research: US and International Comparisons JAMA. 2015;313(2): doi: /jama Market Performance of Publicly Traded Life Sciences and Health Care Companies, NYSE indicates New York Stock Exchange. Data on market performance was accessed from Bloomberg market data. Market performance was calculated as the return on investment of US $100 on January 3, 2003, at various future time points. More detail regarding the indexes can be found at Standard & Poor’s Dow Jones and New York Stock Exchange sector classifications. Figure Legend: