The clinical trials puzzle: How network effects limit drug discovery

被引:2
|
作者
Vasan, Kishore [1 ]
Gysi, Deisy Morselli [1 ,2 ,3 ,4 ]
Barabasi, Albert-Laszlo [1 ,3 ,5 ]
机构
[1] Northeastern Univ, Network Sci Inst, Boston, MA 02115 USA
[2] Univ Fed Parana, Dept Stat, Curtiba, Parana, Brazil
[3] Dept Vet Affairs, Boston, MA 02115 USA
[4] Brigham & Womens Hosp, Harvard Med Sch, Dept Med, Boston, MA USA
[5] Cent European Univ, Dept Data & Network Sci, Budapest, Hungary
关键词
RESEARCH-AND-DEVELOPMENT; PHARMACEUTICAL-INDUSTRY; PREDICTION;
D O I
10.1016/j.isci.2023.108361
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The depth of knowledge offered by post-genomic medicine has carried the promise of new drugs, and cures for multiple diseases. To explore the degree to which this capability has materialized, we extract meta-data from 356,403 clinical trials spanning four decades, aiming to offer mechanistic insights into the innovation practices in drug discovery. We find that convention dominates over innovation, as over 96% of the recorded trials focus on previously tested drug targets, and the tested drugs target only 12% of the human interactome. If current patterns persist, it would take 170 years to target all druggable proteins. We uncover two network-based fundamental mechanisms that currently limit target discovery: preferential attachment, leading to the repeated exploration of previously targeted proteins; and local network effects, limiting exploration to proteins interacting with highly explored proteins. We build on these insights to develop a quantitative network-based model to enhance drug discovery in clinical trials.
引用
收藏
页数:17
相关论文
共 50 条
  • [41] THE ISSUE OF SIDE-EFFECTS AND THE BLINDABILITY OF CLINICAL DRUG TRIALS
    KATZ, R
    DEVEAUGHGEISS, J
    AMERICAN JOURNAL OF PSYCHIATRY, 1993, 150 (11): : 1759 - 1760
  • [42] Clinical Trials Network: From Clinical Trials to Practice
    Pappas, Virginia
    JOURNAL OF NUCLEAR MEDICINE, 2015, 56 (02) : 12N - 12N
  • [43] Conflict Discovery and Analysis for Clinical Trials
    MacKellar, Bonnie
    Schweikert, Christina
    PROCEEDINGS OF THE 2017 INTERNATIONAL CONFERENCE ON DIGITAL HEALTH (DH'17), 2017, : 72 - 76
  • [44] Epothilones: From Discovery to Clinical Trials
    Forli, Stefano
    CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2014, 14 (20) : 2312 - 2321
  • [45] Utilization of new technologies in drug trials and discovery
    Cronin, MT
    Pho, M
    Dutta, D
    Frueh, F
    Schwarcz, L
    Brennan, T
    DRUG METABOLISM AND DISPOSITION, 2001, 29 (04) : 586 - 590
  • [46] How clinical trials of myasthenia gravis can inform pre-clinical drug development
    Punga, Anna Rostedt
    Kaminski, Henry J.
    Richman, David P.
    Benatar, Michael
    EXPERIMENTAL NEUROLOGY, 2015, 270 : 78 - 81
  • [47] Racial and Ethnic Composition of Cancer Clinical Drug Trials: How Diverse Are We?
    Dickmann, Leslie J.
    Schutzman, Jennifer L.
    ONCOLOGIST, 2018, 23 (02): : 243 - 246
  • [48] Analysis of clinical drug trials in children compared to clinical drug trials in adults, in Argentina
    Traversi, Laura
    Bolanos, Ricardo
    ARCHIVOS ARGENTINOS DE PEDIATRIA, 2019, 117 (01): : 34 - 40
  • [49] Metabolomics and systems pharmacology: why and how to model the human metabolic network for drug discovery
    Kell, Douglas B.
    Goodacre, Royston
    DRUG DISCOVERY TODAY, 2014, 19 (02) : 171 - 182
  • [50] The Design and Analysis of Multisite Effectiveness Trials: A Decade of Progress in the National Drug Abuse Clinical Trials Network
    Nunes, Edward V.
    AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE, 2011, 37 (05): : 269 - 272