ESSAYS on the DRUG DISCOVERY INNOVATION SYSTEM By
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ESSAYS ON THE DRUG DISCOVERY INNOVATION SYSTEM by Alfred Sarkissian A Dissertation Submitted to the Graduate Faculty of George Mason University in Partial Fulfillment of The Requirements for the Degree of Doctor of Philosophy Public Policy Committee: _______________________________________ David M. Hart, Chair _______________________________________ Siona Listokin _______________________________________ Naoru Koizumi Ruben Jacobo-Rubio, External Reader _______________________________________ Sita N. Slavov, Program Director _______________________________________ Mark J. Rozell, Dean Date: __________________________________ Fall Semester 2017 George Mason University Fairfax, VA Essays on the Drug Discovery Innovation System A Dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at George Mason University by Alfred Sarkissian Master of Arts Allameh Tabatabai University, 2002 Bachelor of Arts Azad University, 1997 Director: David M. Hart, Professor Department of Public Policy; Schar School of Policy and Government Fall Semester 2017 George Mason University Fairfax, VA Copyright 2017 Alfred Sarkissian All Rights Reserved ii ACKNOWLEDGEMENTS I need to express my deepest gratitude to my committee chair Prof. David M. Hart for his advice, mentorship, and patience in the course of this dissertation and the program. I also owe a sincere appreciation to other committee members Prof. Naoru Koizumi and Prof. Siona Listokin. Prof. Mark Addleson was forthcoming with his time during the field stage of the doctoral program. Special thanks to the administrative staff of the Schar School of Policy and Government. iii TABLE OF CONTENTS Page List of Tables................................................................................................................ vii List of Figures ............................................................................................................. viii List of Equations .............................................................................................................x List of Abbreviations and/or Symbols ............................................................................ xi Abstract ........................................................................................................................ xii Chapter One: Introduction - The Drug Discovery Paradox ...............................................1 1.1 Eroom’s Law ..........................................................................................................1 1.2 Scientific and Technological Advances ..................................................................8 1.3 R&D Management .................................................................................................9 1.4 R&D Spending ..................................................................................................... 12 1.5 Conclusion ........................................................................................................... 15 Chapter Two: Exploring the Drivers of Innovation in the Pharmaceutical Sector - The Impact of Knowledge Recombination ............................................................................ 17 2.1 Introduction .......................................................................................................... 18 2.2 Literature Review ................................................................................................. 19 2.2.1 Role of Science in Pharmaceutical Innovation ................................................ 20 2.2.2 Knowledge Recombination and Innovation .................................................... 26 2.3 Research Question and Hypotheses ...................................................................... 28 2.4 Data ..................................................................................................................... 33 2.5 Methods ............................................................................................................... 36 2.6 Results and Discussion ......................................................................................... 41 2.7 Conclusion ........................................................................................................... 52 Chapter Three: From Bench to Bedside – Determinants of Breakthrough Drug Discovery ...................................................................................................................................... 55 3.1 Introduction .......................................................................................................... 56 3.2 Literature Review ................................................................................................. 59 iv 3.2.1 Theoretical Lens ............................................................................................ 59 3.2.2 Properties of Knowledge ................................................................................ 60 3.2.3 Scope of the Invention ................................................................................... 63 3.2.4 Physical Sources of Knowledge ..................................................................... 64 3.3 Research Question and Hypotheses ...................................................................... 66 3.3.1 Application Breadth or Generality.................................................................. 67 3.3.2 Legal and Technological Scope of the Invention ............................................ 69 3.3.3 Knowledge Recombination Profile ................................................................. 71 3.4 Data ..................................................................................................................... 76 3.5 Methods ............................................................................................................... 84 3.6 Results and Discussion ......................................................................................... 87 3.6.1 Drug Substance Patents .................................................................................. 95 3.6.2 Pre-1995 Knowledge Recombination ............................................................. 98 3.7 Conclusion ......................................................................................................... 100 Chapter Four: Drug Discovery Innovation: A Systemic View ...................................... 103 4.1 Introduction ........................................................................................................ 103 4.2 Conceptual Framework ...................................................................................... 105 4.2.1 Systemic Levels of Analysis ........................................................................ 105 4.2.2 Structural versus Functional Perspectives ..................................................... 110 4.3 Historical Evolution of the Pharmaceutical Sector .............................................. 114 4.4 Institutional Set-up ............................................................................................. 117 4.5 Research Question .............................................................................................. 119 4.6 Data and Methods .............................................................................................. 121 4.6.1 Survey Instrument ........................................................................................ 121 4.6.2 Respondents................................................................................................. 129 4.7 R&D and Innovation Trends............................................................................... 139 4.8 Drivers of Innovation ......................................................................................... 144 4.8.1 Prioritizing Drivers of Innovation: Survey Insights ...................................... 144 4.8.2 Resource Mobilization ................................................................................. 148 4.9 Barriers to Innovation ......................................................................................... 158 4.10 Systemic Failures and Eroom’s Law ................................................................. 165 4.10.1 Lock-in or Path Dependency Failures ......................................................... 165 v 4.10.2 Hard and Soft Intuitional Failure ................................................................ 169 4.10.3 Transition Failures ..................................................................................... 174 4.11 Recommendations and Generalizability of Survey Responses ........................... 175 4.12 Discussion ........................................................................................................ 181 4.13 Conclusion ....................................................................................................... 186 Chapter Five: Conclusion and Policy Implications ....................................................... 189 Appendix A – Chapter Two Supplemental Information................................................ 198 Appendix B – Chapter Three Supplemental Information .............................................. 238 Appendix C – Chapter Four Supplemental Information................................................ 241 References ................................................................................................................... 264 vi LIST OF TABLES Table Page Table 1