References
Abou Ali, Mohamad, Fadi Dornaika, and Jinan Charafeddine. 2026.
“Agentic AI: A Comprehensive Survey of Architectures,
Applications, and Future Directions.” Artificial Intelligence
Review 59: 11. https://doi.org/10.1007/s10462-025-11422-4.
Agresti, Alan. 2010. Analysis of Ordinal Categorical Data. 2nd
ed. Wiley. https://doi.org/10.1002/9780470594001.
Almirall, Daniel, Inbal Nahum-Shani, Nancy E. Sherwood, and Susan A.
Murphy. 2014. “Introduction to SMART Designs for the
Development of Adaptive Interventions: With Application to Weight Loss
Research.” Translational Behavioral Medicine 4 (3):
260–74. https://doi.org/10.1007/s13142-014-0265-0.
Amershi, Saleema, Dan Weld, Mihaela Vorvoreanu, Adam Fourney, Besmira
Nushi, Penny Collisson, Jina Suh, et al. 2019. “Guidelines for
Human-AI Interaction.” In Proceedings of the 2019 CHI
Conference on Human Factors in Computing Systems, 1–13. https://doi.org/10.1145/3290605.3300233.
Anagnostopoulos, Chris, David Champagne, Thomas Devenyns, Alex
Devereson, and Heikki Tarkkila. 2023. “How Artificial Intelligence
Can Power Clinical Development.” McKinsey & Company. https://www.mckinsey.com/industries/life-sciences/our-insights/how-artificial-intelligence-can-power-clinical-development.
Andhalkar, Niranjan. 2025. “Phase-by-Phase Clinical Trial Costs
Guide for Sponsors.” ProRelix Research blog. https://prorelixresearch.com/phase-by-phase-clinical-trial-costs-guide/.
Angus, Derek C., Scott Berry, Roger J. Lewis, Farah Al-Beidh, Yaseen
Arabi, Wilma van Bentum-Puijk, Zahra Bhimani, et al. 2020. “The
REMAP-CAP (Randomized Embedded
Multifactorial Adaptive Platform for Community-Acquired
Pneumonia) Study: Rationale and Design.” Annals of the
American Thoracic Society 17 (7): 879–91. https://doi.org/10.1513/AnnalsATS.202003-192SD.
Anthropic. 2025. “Model Context Protocol: Introduction.” https://modelcontextprotocol.io/docs/getting-started/intro.
Armitage, Peter. 1954. “Sequential Tests in Prophylactic and
Therapeutic Trials.” Quarterly Journal of Medicine 23
(91): 255–74.
———. 1960. Sequential Medical Trials. Oxford: Blackwell
Scientific Publications.
Association of Clinical Research Organizations. 2025. “2025
Risk-Based Quality Management (RBQM) Summary Report.” https://www.acrohealth.org/wp-content/uploads/2025/06/ACRO_2025-RBQM-Report_Final-062425.pdf.
Atkinson, A. C. 2002. “The Comparison of Designs for Sequential
Clinical Trials with Covariate Information.” Journal of the
Royal Statistical Society: Series A 165 (2): 349–73. https://doi.org/10.1111/1467-985X.00564.
ATTACC Investigators, ACTIV-4a Investigators, REMAP-CAP Investigators,
Patrick R. Lawler, Ewan C. Goligher, Jeffrey S. Berger, et al. 2021.
“Therapeutic Anticoagulation with Heparin in Noncritically Ill
Patients with Covid-19.” New England Journal of
Medicine 385 (9): 790–802. https://doi.org/10.1056/NEJMoa2105911.
Avorn, Jerry. 2015. “The $2.6 Billion Pill — Methodologic and
Policy Considerations.” New England Journal of Medicine
372 (20): 1877–79. https://doi.org/10.1056/NEJMp1500848.
Babb, James, Andre Rogatko, and Shelemyahu Zacks. 1998. “Cancer
Phase I Clinical Trials: Efficient Dose Escalation with
Overdose Control.” Statistics in Medicine 17 (10):
1103–20. https://doi.org/10.1002/(SICI)1097-0258(19980530)17:10<1103::AID-SIM793>3.0.CO;2-9.
Baiocchi, Michael, Jing Cheng, and Dylan S. Small. 2014.
“Instrumental Variable Methods for Causal Inference.”
Statistics in Medicine 33 (13): 2297–2340. https://doi.org/10.1002/sim.6128.
Ballentine, Carol. 1981. “Taste of Raspberries, Taste of Death:
The 1937 Elixir Sulfanilamide Incident.” FDA Consumer. https://www.fda.gov/files/about%20fda/published/The-Sulfanilamide-Disaster.pdf.
Bartlett, Robert H., Donald W. Roloff, Robert G. Cornell, Arthur F.
Andrews, Patrick W. Dillon, and Joseph B. Zwischenberger. 1985.
“Extracorporeal Circulation in Neonatal Respiratory Failure: A
Prospective Randomized Study.” Pediatrics 76 (4):
479–87. https://doi.org/10.1542/peds.76.4.479.
Beal, Kristy, Juliette Dean, James Chen, Elena Dragaon, Ann Saulino, and
Charles D. Collard. 2004. “Budget Negotiation for
Industry-Sponsored Clinical Trials.” Anesthesia &
Analgesia 99 (1): 173–76. https://doi.org/10.1213/01.ANE.0000122633.97424.76.
Bender, Emily M., Timnit Gebru, Angelina McMillan-Major, and Shmargaret
Shmitchell. 2021. “On the Dangers of Stochastic Parrots: Can
Language Models Be Too Big?” In Proceedings of the 2021 ACM
Conference on Fairness, Accountability, and Transparency, 610–23.
https://doi.org/10.1145/3442188.3445922.
Berkeley Artificial Intelligence Research. 2024. “The Shift from
Models to Compound AI Systems.” https://bair.berkeley.edu/blog/2024/02/18/compound-ai-systems/.
Berry, Donald A. 1989. “Monitoring Accumulating Data in a Clinical
Trial.” Biometrics 45 (4): 1197–1211. https://doi.org/10.2307/2531771.
———. 2012. “Adaptive Clinical Trials in Oncology.”
Nature Reviews Clinical Oncology 9 (4): 199–207. https://doi.org/10.1038/nrclinonc.2011.165.
———. 2025. “Adaptive Bayesian Clinical Trials: The Past, Present,
and Future of Clinical Research.” Journal of Clinical
Medicine 14 (15): 5267. https://doi.org/10.3390/jcm14155267.
Berry, Scott M., Bradley P. Carlin, J. Jack Lee, and Peter Müller. 2010.
Bayesian Adaptive Methods for Clinical Trials. Chapman &
Hall/CRC Biostatistics Series. Boca Raton, FL: CRC Press. https://doi.org/10.1201/EBK1439825488.
Biotechnology Innovation Organization, QLS Advisors, and Informa Pharma
Intelligence. 2021. “Clinical Development Success Rates
2011-2020.” https://go.bio.org/rs/490-EHZ-999/images/ClinicalDevelopmentSuccessRates2011_2020.pdf.
Bor, Jacob, Ellen Moscoe, Portia Mutevedzi, Marie-Louise Newell, and
Till Bärnighausen. 2014. “Regression Discontinuity Designs in
Epidemiology: Causal Inference Without Randomized Trials.”
Epidemiology 25 (5): 729–37. https://doi.org/10.1097/EDE.0000000000000138.
Bretz, Frank, Jose C. Pinheiro, and Michael Branson. 2005.
“Combining Multiple Comparisons and Modeling Techniques in
Dose-Response Studies.” Biometrics 61 (3): 738–48. https://doi.org/10.1111/j.1541-0420.2005.00344.x.
Bronner, Denise. 2024. “Why Site-CRO Relationships
Are so Strained, and How to Fix Them.” Clinical Leader, guest
column. https://www.clinicalleader.com/doc/why-site-cro-relationships-are-so-strained-and-how-to-fix-them-0001.
Budd Haeberlein, Samantha, Paul S. Aisen, Frederik Barkhof, Spyridon
Chalkias, Tianle Chen, Sandra Cohen, Gary Dent, et al. 2022. “Two
Randomized Phase 3 Studies of Aducanumab in Early Alzheimer’s Disease.” Journal of
Prevention of Alzheimer’s Disease 9 (2): 197–210. https://doi.org/10.14283/jpad.2022.30.
Cappello, Franck, Sandeep Madireddy, Robert Underwood, Neil Getty,
Nicholas Lee-Ping Chia, Nesar Ramachandra, et al. 2025. “EAIRA:
Establishing a Methodology for Evaluating AI Models as Scientific
Research Assistants.” arXiv Preprint arXiv:2502.20309.
https://arxiv.org/abs/2502.20309.
Cemri, Mert, Melissa Z. Pan, Shuyi Yang, Lakshya A. Agrawal, Bhavya
Chopra, Rishabh Tiwari, Kurt Keutzer, et al. 2025. “Why Do
Multi-Agent LLM Systems Fail?” arXiv Preprint
arXiv:2503.13657. https://arxiv.org/abs/2503.13657.
Chan, An-Wen, Isabelle Boutron, Sally Hopewell, David Moher, Kenneth F.
Schulz, Gary S. Collins, et al. 2025. “SPIRIT 2025
Statement: Updated Guideline for Protocols of Randomised Trials.”
BMJ 389: e081477. https://doi.org/10.1136/bmj-2024-081477.
Chan, Jun Shern, Neil Chowdhury, Oliver Jaffe, James Aung, Dane
Sherburn, Evan Mays, Giulio Starace, et al. 2024. “MLE-Bench:
Evaluating Machine Learning Agents on Machine Learning
Engineering.” arXiv Preprint arXiv:2410.07095. https://arxiv.org/abs/2410.07095.
Cheng, Yuheng, Ceyao Zhang, Zhengwen Zhang, Xiangrui Meng, Sirui Hong,
Wenhao Li, Zihao Wang, et al. 2024. “Exploring Large Language
Model Based Intelligent Agents: Definitions, Methods, and
Prospects.” arXiv Preprint arXiv:2401.03428. https://arxiv.org/abs/2401.03428.
Clinical Data Interchange Standards Consortium. 2024. “CDISC
Foundational Standards: SDTM, ADaM, and CDASH.” https://www.cdisc.org/standards/foundational.
Clinical Leader. 2024. “Best Practices for Randomization and Trial
Supply Management (RTSM).” https://www.clinicalleader.com/doc/best-practices-for-randomization-and-trial-supply-management-rtsm-0001.
Coart, Elisabeth, Perrine Bamps, Emmanuel Quinaux, Geneviève Sturbois,
Everardo D. Saad, Tomasz Burzykowski, and Marc Buyse. 2023.
“Minimization in Randomized Clinical Trials.”
Statistics in Medicine 42 (28): 5285–5311. https://doi.org/10.1002/sim.9916.
Cohen, Lauren W., Rowena J. Dolor, Mark Weiner, Nadine Zemon, Charles
Bailey, Thomas Carton, Erika Cottrell, et al. 2026.
“PCORnet: 10 Years of Research Innovation.”
Medical Care 64: S185–90. https://doi.org/10.1097/MLR.0000000000002269.
Collins, Gary S. et al. 2024. “TRIPOD+AI Statement: Updated
Guidance for Reporting Clinical Prediction Models That Use Regression or
Machine Learning Methods.” BMJ 385: e078378. https://www.bmj.com/content/385/bmj-2023-078378.
Council for International Organizations of Medical Sciences (CIOMS).
2016. International Ethical Guidelines for Health-Related Research
Involving Humans. Fourth. Geneva: CIOMS. https://cioms.ch/publications/product/international-ethical-guidelines-for-health-related-research-involving-humans/.
Cox, D. R. 1958. Planning of Experiments. New York: John Wiley
& Sons.
———. 1972. “Regression Models and Life-Tables.” Journal
of the Royal Statistical Society: Series B (Methodological) 34 (2):
187–220. https://doi.org/10.1111/j.2517-6161.1972.tb00899.x.
———. 2009. “Randomization in the Design of Experiments.”
International Statistical Review 77 (3): 415–29. https://doi.org/10.1111/j.1751-5823.2009.00084.x.
Dahabreh, Issa J., Sarah E. Robertson, Jon A. Steingrimsson, Elizabeth
A. Stuart, and Miguel A. Hernan. 2020. “Extending Inferences from
a Randomized Trial to a New Target Population.” Statistics in
Medicine 39 (14): 1999–2014. https://doi.org/10.1002/sim.8426.
Dahabreh, Issa J., Sarah E. Robertson, Eric J. Tchetgen Tchetgen,
Elizabeth A. Stuart, and Miguel A. Hernan. 2019. “Generalizing
Causal Inferences from Individuals in Randomized Trials to All
Trial-Eligible Individuals.” Biometrics 75 (2): 685–94.
https://doi.org/10.1111/biom.13009.
Davis, Joshua S., John Turnidge, and Steven Y. C. Tong. 2018. “A
Large Retrospective Cohort Study of Cefazolin Compared with
Flucloxacillin for Methicillin-Susceptible Staphylococcus aureus Bacteraemia.”
International Journal of Antimicrobial Agents 52 (2): 297–300.
https://doi.org/10.1016/j.ijantimicag.2018.02.013.
Deloitte Centre for Health Solutions. 2025. “Be Brave, Be Bold:
Measuring the Return from Pharmaceutical Innovation.” https://www.deloitte.com/content/dam/assets-shared/docs/industries/life-sciences-health-care/2025/deloitte-measuring-return-from-pharmaceutical-innovation-2025.pdf.
———. 2026. “Navigating the GLP-1 Boom: Measuring the
Return from Pharmaceutical Innovation.” https://www.deloitte.com/content/dam/assets-shared/docs/industries/life-sciences-health-care/2026/measuring-the-return-from-pharmaceutical-innovation.pdf.
DeTora, Lisa M., Dikran Toroser, Angela Sykes, Christine Vanderlinden,
Fiona J. Plunkett, Trevor Lane, Eline Hanekamp, et al. 2022. “Good
Publication Practice (GPP) Guidelines for Company-Sponsored Biomedical
Research: 2022 Update.” Annals of Internal Medicine 175
(9): 1298–1304. https://doi.org/10.7326/M22-1460.
Dickerman, Barbra A., Hanna Gerlovin, Arin L. Madenci, Katherine E.
Kurgansky, Brian R. Ferolito, Mariantonia Figueroa Munõz, David R.
Gagnon, et al. 2022. “Comparative Effectiveness of
BNT162b2 and mRNA-1273 Vaccines
in U.S. Veterans.” New England Journal of
Medicine 386 (2): 105–15. https://doi.org/10.1056/NEJMoa2115463.
DiMasi, Joseph A., Henry G. Grabowski, and Ronald W. Hansen. 2016.
“Innovation in the Pharmaceutical Industry: New Estimates of
R&D Costs.” Journal of Health Economics
47: 20–33. https://doi.org/10.1016/j.jhealeco.2016.01.012.
Douze, Matthijs, Alexandr Guzhva, Chengqi Deng, Jeff Johnson, Gergely
Szilvasy, Pierre-Emmanuel Mazaré, Maria Lomeli, Lucas Hosseini, and
Hervé Jégou. 2024. “The Faiss Library.” arXiv Preprint
arXiv:2401.08281. https://arxiv.org/abs/2401.08281.
Duke Center for Virtual Imaging Trials. 2024. “Virtual Imaging
Trials in Medicine 2024 Summit.” https://cvit.duke.edu/vitm24/.
Dyck, Christopher H. van, Chad J. Swanson, Paul Aisen, Randall J.
Bateman, Christopher Chen, Michelle Gee, Michio Kanekiyo, et al. 2023.
“Lecanemab in Early Alzheimer’s Disease.” New England
Journal of Medicine 388 (1): 9–21. https://doi.org/10.1056/NEJMoa2212948.
Echt, Debra S., Philip R. Liebson, L. Brent Mitchell, Robert W. Peters,
Dulce Obias-Manno, Allan H. Barker, Daniel Arensberg, et al. 1991.
“Mortality and Morbidity in Patients Receiving Encainide,
Flecainide, or Placebo: The Cardiac Arrhythmia Suppression
Trial.” New England Journal of Medicine 324 (12):
781–88. https://doi.org/10.1056/NEJM199103213241201.
Efron, Bradley. 1971. “Forcing a Sequential Experiment to Be
Balanced.” Biometrika 58 (3): 403–17. https://doi.org/10.1093/biomet/58.3.403.
EMA Committee for Medicinal Products for Human Use (CHMP). 2014.
“Qualification Opinion of MCP-Mod as an Efficient
Statistical Methodology for Model-Based Design and Analysis of Phase
II Dose Finding Studies Under Model Uncertainty.”
European Medicines Agency. https://www.ema.europa.eu/en/documents/scientific-guideline/qualification-opinion-mcp-mod-efficient-statistical-methodology-model-based-design-analysis-phase-ii_en.pdf.
Emanuel, Ezekiel J., David Wendler, and Christine Grady. 2000.
“What Makes Clinical Research Ethical?” JAMA 283
(20): 2701–11. https://doi.org/10.1001/jama.283.20.2701.
Epperson, Will, Gagan Bansal, Victor Dibia, Adam Fourney, Jack Gerrits,
Erkang Zhu, and Saleema Amershi. 2025. “Interactive Debugging and
Steering of Multi-Agent AI Systems.” arXiv Preprint
arXiv:2503.02068. https://arxiv.org/abs/2503.02068.
Erlinge, David. 2021. “Registry-Based Randomized Clinical Trials
in Cardiology: Opportunities and Challenges.”
REC: Interventional Cardiology 3: 157–60. https://doi.org/10.24875/RECICE.M21000205.
Erlinge, David, Sasha Koul, Peter Eriksson, Fredrik Scherstén, Elmir
Omerovic, Rikard Linder, Olof Petter Östlund, Lars Wallentin, Ole
Fröbert, and Stefan James. 2016. “Bivalirudin Versus Heparin in
Non-ST and ST-Segment Elevation Myocardial
Infarction: A Registry-Based Randomized Clinical Trial in the
SWEDEHEART Registry (the VALIDATE-SWEDEHEART
Trial).” American Heart Journal 175: 36–46. https://doi.org/10.1016/j.ahj.2016.02.007.
Erlinge, David, Elmir Omerovic, Ole Fröbert, Rikard Linder, Mikael
Danielewicz, Mehmet Hamid, Eva Swahn, et al. 2017. “Bivalirudin
Versus Heparin Monotherapy in Myocardial Infarction.” New
England Journal of Medicine 377 (12): 1132–42. https://doi.org/10.1056/NEJMoa1706443.
European Commission. 2011. “EudraLex Volume 4, EU Guidelines for
Good Manufacturing Practice for Medicinal Products for Human and
Veterinary Use, Annex 11: Computerised Systems.” https://health.ec.europa.eu/document/download/e63bde49-af31-4d1d-8a2e-1f3f8e5f6d1c_en.
European Medicines Agency. 2006. “Guideline on Clinical Trials in
Small Populations.” https://www.ema.europa.eu/en/clinical-trials-small-populations-scientific-guideline.
———. 2014a. “Assessment Report: Trulicity (Dulaglutide).”
EMA/CHMP/524604/2014, Procedure
No. EMEA/H/C/002825/0000. https://www.ema.europa.eu/en/documents/assessment-report/trulicity-epar-public-assessment-report_en.pdf.
———. 2014b. “European Medicines Agency Policy on Publication of
Clinical Data for Medicinal Products for Human Use (Policy
0070).” https://www.ema.europa.eu/en/human-regulatory-overview/marketing-authorisation/clinical-data-publication.
———. 2017a. “Guideline on Good Pharmacovigilance Practices
(GVP) Module IX Addendum I:
Methodological Aspects of Signal Detection from Spontaneous Reports of
Suspected Adverse Reactions.” https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-good-pharmacovigilance-practices-gvp-module-ix-addendum-i-methodological-aspects-signal-detection-spontaneous-reports-suspected-adverse-reactions_en.pdf.
———. 2017b. “Guideline on Strategies to Identify and Mitigate
Risks for First-in-Human and Early Clinical Trials with Investigational
Medicinal Products.” EMEA/CHMP/SWP/28367/07 Rev. 1.
https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-strategies-identify-mitigate-risks-first-human-early-clinical-trials-investigational_en.pdf.
———. 2022. “Clinical Trials Regulation (EU) No 536/2014 and
Clinical Trials Information System (CTIS).” https://www.ema.europa.eu/en/human-regulatory/research-development/clinical-trials/clinical-trials-regulation.
———. 2023. “Guideline on Computerised Systems and Electronic Data
in Clinical Trials.” https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/guideline-computerised-systems-and-electronic-data-clinical-trials_en.pdf.
———. 2024a. “ICH E6(R3) Good Clinical Practice Guidelines.”
https://www.ema.europa.eu/en/ich-e6-good-clinical-practice-scientific-guideline.
———. 2024b. “Reflection Paper on the Use of Artificial
Intelligence (AI) in the Lifecycle of Medicinal Products.” https://www.ema.europa.eu/en/documents/scientific-guideline/reflection-paper-use-artificial-intelligence-ai-medicinal-product-lifecycle_en.pdf.
———. 2025. “Draft Concept Paper on the Development of a Reflection
Paper on the Use of External Controls for Evidence Generation in
Regulatory Decision-Making.” https://www.ema.europa.eu/en/documents/scientific-guideline/draft-concept-paper-development-reflection-paper-use-external-controls-evidence-generation-regulatory-decision-making_en.pdf.
———. 2026. “DARWIN EU Data Partners Onboarded in Year
I, II, III, IV, and
V.” https://www.ema.europa.eu/en/documents/other/darwin-eu-data-partners-onboarded-phases-i-ii-iii_en.pdf.
European Medicines Agency, Committee for Medicinal Products for Human
Use (CHMP). 2022. “Qualification Opinion for Prognostic Covariate
Adjustment (PROCOVA).” European Medicines Agency. https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/qualification-opinion-prognostic-covariate-adjustment-procovatm_en.pdf.
European Parliament and Council of the European Union. 2004.
“Regulation (EC) No 726/2004 Laying down Community Procedures for
the Authorisation and Supervision of Medicinal Products for Human and
Veterinary Use and Establishing a European Medicines Agency.” https://eur-lex.europa.eu/eli/reg/2004/726/oj/eng.
———. 2014. “Regulation (EU) No 536/2014 on Clinical Trials on
Medicinal Products for Human Use, and Repealing Directive
2001/20/EC.” https://eur-lex.europa.eu/eli/reg/2014/536/oj/eng.
———. 2024. “Regulation (EU) 2024/1689 Laying down Harmonised Rules
on Artificial Intelligence (Artificial Intelligence Act).” https://eur-lex.europa.eu/eli/reg/2024/1689/oj/eng.
———. 2026. “Regulation (EU) 2026/1744 Amending
Regulations (EU) 2024/1689, (EU) 2018/1139 and
(EU) 2023/1230 as Regards the Simplification of the
Implementation of Harmonised Rules on Artificial Intelligence (Digital
Omnibus on AI).” http://data.europa.eu/eli/reg/2026/1744/oj.
Evans, Scott R., and Dean Follmann. 2016. “Using Outcomes to
Analyze Patients Rather Than Patients to Analyze Outcomes: A Step Toward
Pragmatism in Benefit:risk Evaluation.” Statistics in
Biopharmaceutical Research 8 (4): 386–93. https://doi.org/10.1080/19466315.2016.1207561.
Evans, Scott R., David Rubin, Dean Follmann, Gene Pennello, W. Charles
Huskins, John H. Powers, Jerry Rhorer, et al. 2015. “Desirability
of Outcome Ranking (DOOR) and Response Adjusted for
Duration of Antibiotic Risk (RADAR).” Clinical
Infectious Diseases 61 (5): 800–806. https://doi.org/10.1093/cid/civ495.
Faro Health. 2024. “Faro Health: AI-Powered Protocol
Design.” https://farohealth.com.
Fine, Jason P., and Robert J. Gray. 1999. “A Proportional Hazards
Model for the Subdistribution of a Competing Risk.” Journal
of the American Statistical Association 94 (446): 496–509. https://doi.org/10.1080/01621459.1999.10474144.
Fischl, Margaret A., Douglas D. Richman, Michael H. Grieco, Michael S.
Gottlieb, Paul A. Volberding, Oscar L. Laskin, John M. Leedom, et al.
1987. “The Efficacy of Azidothymidine (AZT) in the
Treatment of Patients with AIDS and
AIDS-Related Complex: A Double-Blind, Placebo-Controlled
Trial.” New England Journal of Medicine 317 (4): 185–91.
https://doi.org/10.1056/NEJM198707233170401.
Fisher, Charles K. 2024. “US FDA Comments on
Unlearn’s PROCOVA Methodology.”
Unlearn.AI blog. https://www.unlearn.ai/blog/us-fda-comments-on-unlearns-procova-methodology.
Fortrea Holdings Inc. 2026. “Fortrea Reports Fourth Quarter and
Full-Year 2025 Results; Issues Full-Year 2026 Guidance.” https://ir.fortrea.com/news-releases/news-release-details/fortrea-reports-fourth-quarter-and-full-year-2025-results-issues.
Fortune Business Insights. 2024. “AI in Clinical Trials Market
Size, Share & Industry Analysis.” https://www.fortunebusinessinsights.com/ai-in-clinical-trials-market-114081.
Freedman, Benjamin. 1987. “Equipoise and the Ethics of Clinical
Research.” New England Journal of Medicine 317 (3):
141–45. https://doi.org/10.1056/NEJM198707163170304.
Friends of Cancer Research. 2023. “Considerations for Leveraging
Real-World Endpoints in Oncology Drug Development.” https://friendsofcancerresearch.org/wp-content/uploads/Considerations_Leveraging_Real-World_Endpoints_Oncology.pdf.
Fröbert, Ole, Bo Lagerqvist, Göran K. Olivecrona, Elmir Omerovic,
Thorarinn Gudnason, Michael Maeng, Mikael Aasa, et al. 2013.
“Thrombus Aspiration During ST-Segment Elevation
Myocardial Infarction.” New England Journal of Medicine
369 (17): 1587–97. https://doi.org/10.1056/NEJMoa1308789.
Garcia, Crystal J., Kevin Haynes, Sean D. Pokorney, Nancy D. Lin, Cheryl
McMahill-Walraven, Vinit Nair, Lauren Parlett, et al. 2020.
“Practical Challenges in the Conduct of Pragmatic Trials Embedded
in Health Plans: Lessons of IMPACT-AFib, an
FDA-Catalyst Trial.” Clinical Trials 17
(4): 360–67. https://doi.org/10.1177/1740774520928426.
Gebru, Timnit, Jamie Morgenstern, Briana Vecchione, Jennifer Wortman
Vaughan, Hanna Wallach, Hal Daumé III, and Kate Crawford. 2021.
“Datasheets for Datasets.” Communications of the
ACM 64 (12): 86–92. https://doi.org/10.1145/3458723.
Getz, Kenneth A. 2008. “Is Investigative Site Feasibility
Feasible?” Applied Clinical Trials. https://www.appliedclinicaltrialsonline.com/view/investigative-site-feasibility-feasible.
———. 2012. “Enrollment Performance: Weighing the
‘Facts’.” Applied Clinical Trials 21 (5).
https://www.appliedclinicaltrialsonline.com/view/enrollment-performance-weighing-facts.
Getz, Kenneth A., Zachary P. Smith, and Marcy Kravet. 2023.
“Protocol Design and Performance Benchmarks by Phase and by
Oncology and Rare Disease Subgroups.” Therapeutic Innovation
& Regulatory Science 57 (1): 49–56. https://doi.org/10.1007/s43441-022-00438-5.
Getz, Kenneth A., Zachary Smith, Emily Botto, Elisabeth Murphy, and
Arnaud Dauchy. 2024. “New Benchmarks on Protocol Amendment
Practices, Trends and Their Impact on Clinical Trial
Performance.” Therapeutic Innovation & Regulatory
Science 58 (3): 539–48. https://doi.org/10.1007/s43441-024-00622-9.
Getz, Kenneth A., Stella Stergiopoulos, Mary Short, Leon Surgeon, Randy
Krauss, Sybrand Pretorius, Julian Desmond, and Derek Dunn. 2016.
“The Impact of Protocol Amendments on Clinical Trial Performance
and Cost.” Therapeutic Innovation & Regulatory
Science 50 (4): 436–41. https://doi.org/10.1177/2168479016632271.
Glickman, Seth W., John G. McHutchison, Eric D. Peterson, Charles B.
Cairns, Robert A. Harrington, Robert M. Califf, and Kevin A. Schulman.
2009. “Ethical and Scientific Implications of the Globalization of
Clinical Research.” New England Journal of Medicine 360
(8): 816–23. https://doi.org/10.1056/NEJMsb0803929.
Goodman, Steven. 2008. “A Dirty Dozen: Twelve P-Value Misconceptions.”
Seminars in Hematology 45 (3): 135–40. https://doi.org/10.1053/j.seminhematol.2008.04.003.
Grand View Research. 2025. “Clinical Trials Support Software
Solutions Market Size, Share & Trends Analysis Report.” https://www.grandviewresearch.com/industry-analysis/clinical-trials-support-software-solutions-market-report.
———. 2026. “Healthcare Contract Research Organization Market
Report, 2026-2033.” https://www.grandviewresearch.com/industry-analysis/healthcare-contract-research-outsourcing-market.
Granholm, Anders, Aksel Karl Georg Jensen, Theis Lange, Anders Perner,
Morten Hylander Møller, and Benjamin Skov Kaas-Hansen. 2025.
“Designing and Evaluating Bayesian Advanced Adaptive Randomised
Clinical Trials: A Practical Guide.” Pharmaceutical
Statistics 24 (6). https://doi.org/10.1002/pst.70042.
Grossi, Giuliana. 2025. “FDA Quietly Removes Draft Guidance on
Diversity in Clinical Trials Following Executive Order on DEI.”
The American Journal of Managed Care (AJMC). https://www.ajmc.com/view/fda-quietly-removes-draft-guidance-on-diversity-in-clinical-trials-following-executive-order-on-dei.
Gu, Ningzhou, Zizi Elsisi, Ryan Suk, and Meng Li. 2024.
“Geographic Disparity in the Distribution of Cancer Clinical
Trials in the United States and the Associated Factors.”
Journal of Managed Care & Specialty Pharmacy 30 (4):
376–85. https://doi.org/10.18553/jmcp.2024.30.4.376.
H1. 2024. “H1: Healthcare Provider Intelligence Platform.”
https://h1.co.
Han, Kiki, Franck Le Deu, Fangning Zhang, and Josie Zhou. 2021.
“The Dawn of China Biopharma Innovation.” https://www.mckinsey.com/industries/life-sciences/our-insights/the-dawn-of-china-biopharma-innovation.
Harris Interactive. 2004. “Most Physicians Do Not Participate in
Clinical Trials Because of Lack of Opportunity, Time, Personnel Support
and Resources.” https://www.biospace.com/b-harris-interactive-b-release-most-physicians-do-not-participate-in-clinical-trials-because-of-lack-of-opportunity-time-personnel-support-and-r.
Health Level Seven International. 2024. “HL7 FHIR Bulk Data Access
(Flat FHIR).” https://hl7.org/fhir/uv/bulkdata/.
Hernán, Miguel A., and James M. Robins. 2016. “Using Big Data to
Emulate a Target Trial When a Randomized Trial Is Not Available.”
American Journal of Epidemiology 183 (8): 758–64. https://doi.org/10.1093/aje/kwv254.
Hobbs, Brian P., Bradley P. Carlin, Sumithra J. Mandrekar, and Daniel J.
Sargent. 2011. “Hierarchical Commensurate and Power Prior Models
for Adaptive Incorporation of Historical Information in Clinical
Trials.” Biometrics 67 (3): 1047–56. https://doi.org/10.1111/j.1541-0420.2011.01564.x.
Hripcsak, George, and David J. Albers. 2013. “Next-Generation
Phenotyping of Electronic Health Records.” Journal of the
American Medical Informatics Association 20 (1): 117–21. https://pmc.ncbi.nlm.nih.gov/articles/PMC3555337/.
Hripcsak, George, Jon D. Duke, Nigam H. Shah, Christian G. Reich,
Vojtech Huser, Martijn J. Schuemie, Marc A. Suchard, et al. 2015.
“Observational Health Data Sciences and Informatics (OHDSI):
Opportunities for Observational Researchers.” Studies in
Health Technology and Informatics. https://pmc.ncbi.nlm.nih.gov/articles/PMC4815923/.
Hu, Feifang, and William F. Rosenberger. 2006. The Theory of
Response-Adaptive Randomization in Clinical Trials. Hoboken, NJ:
John Wiley & Sons. https://doi.org/10.1002/047005588X.
Hudson, Marie, Antonio Avina-Zubieta, Diane Lacaille, Sasha Bernatsky,
Lisa Lix, and Sonia Jean. 2013. “The Validity of Administrative
Data to Identify Hip Fractures Is High: A Systematic Review.”
Journal of Clinical Epidemiology 66 (3): 278–85. https://doi.org/10.1016/j.jclinepi.2012.10.004.
Huey, Ryan W., Goldy C. George, Penny Phillips, Revenda White, Siqing
Fu, Filip Janku, Daniel D. Karp, et al. 2021. “Patient-Reported
Out-of-Pocket Costs and Financial Toxicity During Early-Phase Oncology
Clinical Trials.” The Oncologist 26 (7): 588–96. https://doi.org/10.1002/onco.13767.
Ibrahim, Joseph G., and Ming-Hui Chen. 2000. “Power Prior
Distributions for Regression Models.” Statistical
Science 15 (1): 46–60. https://doi.org/10.1214/ss/1009212673.
ICON plc. 2026. “Annual Report on Form 20-F for the
Fiscal Year Ended December 31, 2025.” https://investor.iconplc.com/static-files/ce9930d9-1163-4cbe-907e-540cb4a46d01.
Industry Standard Research (ISR). 2025. “EDC Benchmarking and
Market Dynamics (6th Edition).” https://isrreports.com/reports/2025-edc-benchmarking/.
International Council for Harmonisation. 1994a. “ICH Harmonised
Tripartite Guideline: Clinical Safety Data Management: Definitions and
Standards for Expedited Reporting E2A.” https://database.ich.org/sites/default/files/E2A_Guideline.pdf.
———. 1994b. “ICH Harmonised Tripartite Guideline: The Extent of
Population Exposure to Assess Clinical Safety for Drugs Intended for
Long-Term Treatment of Non-Life-Threatening Conditions E1.” https://database.ich.org/sites/default/files/E1_Guideline.pdf.
———. 1995. “ICH Harmonised Tripartite Guideline: Structure and
Content of Clinical Study Reports E3.” https://database.ich.org/sites/default/files/E3_Guideline.pdf.
———. 1996. “ICH Harmonised Tripartite Guideline: Guideline for
Good Clinical Practice E6(R1).” https://www.ema.europa.eu/en/documents/scientific-guideline/ich-e6-r1-guideline-good-clinical-practice_en.pdf.
———. 1998a. “ICH Harmonised Tripartite Guideline: Ethnic Factors
in the Acceptability of Foreign Clinical Data E5(R1).” https://www.ema.europa.eu/en/documents/scientific-guideline/ich-e-5-r1-ethnic-factors-acceptability-foreign-clinical-data-step-5_en.pdf.
———. 1998b. “ICH Harmonised Tripartite Guideline: Statistical
Principles for Clinical Trials E9.” https://database.ich.org/sites/default/files/E9_Guideline.pdf.
———. 2010. “ICH Harmonised Tripartite Guideline: Development
Safety Update Report E2F.” https://database.ich.org/sites/default/files/E2F_Guideline.pdf.
———. 2013. “ICH E2B(R3): Electronic Transmission of
Individual Case Safety Reports (ICSRs): Data Elements and Message
Specification.” https://ich.org/page/e2br3-individual-case-safety-report-icsr-specification-and-related-files.
———. 2015. “ICH M8: Electronic Common Technical
Document (eCTD), Version 4.0.” https://www.ich.org/page/ich-electronic-common-technical-document-ectd-v40.
———. 2016a. “ICH E6(R2): Integrated Addendum to ICH
E6(R1) - Guideline for Good Clinical Practice.” https://database.ich.org/sites/default/files/E6_R2_Addendum.pdf.
———. 2016b. “ICH M4: Organisation of the Common Technical Document
for the Registration of Pharmaceuticals for Human Use.” https://www.ich.org/page/ctd.
———. 2017. “ICH Harmonised Guideline: General Principles for
Planning and Design of Multi-Regional Clinical Trials E17.” https://www.ema.europa.eu/en/documents/scientific-guideline/ich-guideline-e17-general-principles-planning-and-design-multi-regional-clinical-trials-step-5-first-version_en.pdf.
———. 2019. “ICH E9(R1): Addendum on Estimands and
Sensitivity Analysis in Clinical Trials to the Guideline on Statistical
Principles for Clinical Trials.” https://database.ich.org/sites/default/files/E9-R1_Step4_Guideline_2019_1203.pdf.
———. 2021. “ICH E8(R1): General Considerations for
Clinical Studies.” https://database.ich.org/sites/default/files/ICH_E8-R1_Guideline_Step4_2021_1006.pdf.
———. 2025a. “E20 Adaptive Designs for Clinical Trials.” https://www.ema.europa.eu/en/ich-e20-adaptive-designs-clinical-trials-scientific-guideline.
———. 2025b. “ICH E6(R3): Guideline for Good Clinical
Practice (GCP).” https://database.ich.org/sites/default/files/ICH_E6%28R3%29_Step4_FinalGuideline_2025_0106.pdf.
———. 2025c. “ICH M11: Clinical Electronic Structured
Harmonised Protocol (CeSHarP).” https://database.ich.org/sites/default/files/ICH_Step4_M11_Final_Guideline_2025_1119.pdf.
IQVIA. 2024a. “Decentralized Clinical Trials Solutions.” https://www.iqvia.com/solutions/research-and-development/decentralized-trials.
———. 2024b. “IQVIA Intelligent eTMF.” https://www.iqvia.com/library/fact-sheets/iqvia-intelligent-etmf.
IQVIA Holdings Inc. 2026. “Annual Report on Form 10-K
for the Fiscal Year Ended December 31, 2025.” https://s201.q4cdn.com/580005511/files/doc_financials/2025/q4/IQV-2025-12-31-10K_Filed-with-exhibits.pdf.
IQVIA Institute for Human Data Science. 2024a. “Global Trends in
R&D 2024: Activity, Productivity, and Enablers.”
https://www.iqvia.com/insights/the-iqvia-institute/reports-and-publications/reports/global-trends-in-r-and-d-2024-activity-productivity-and-enablers.
———. 2024b. “Global Use of Medicines 2024: Outlook to
2028.” https://www.iqvia.com/insights/the-iqvia-institute/reports-and-publications/reports/the-global-use-of-medicines-2024-outlook-to-2028.
———. 2025. “Global Trends in R&D 2025.” https://iqvia.com/insights/the-iqvia-institute/reports-and-publications/reports/global-trends-in-r-and-d-2025.
Jefferson, Tom, Mark Jones, Peter Doshi, Elizabeth A. Spencer, Igho
Onakpoya, and Carl J. Heneghan. 2014. “Oseltamivir for Influenza
in Adults and Children: Systematic Review of Clinical Study Reports and
Summary of Regulatory Comments.” BMJ 348: g2545. https://doi.org/10.1136/bmj.g2545.
Jennison, Christopher, and Bruce W. Turnbull. 2000. Group Sequential
Methods with Applications to Clinical Trials. Boca Raton, FL:
Chapman & Hall/CRC.
———. 2015. “Adaptive Sample Size Modification in Clinical Trials:
Start Small Then Ask for More?” Statistics in Medicine
34 (29): 3793–3810. https://doi.org/10.1002/sim.6575.
Junod, Suzanne White. 2008. “FDA and Clinical Drug
Trials: A Short History.” U.S. Food and Drug Administration. https://www.fda.gov/media/110437/download.
Kaplan, E. L., and Paul Meier. 1958. “Nonparametric Estimation
from Incomplete Observations.” Journal of the American
Statistical Association 53 (282): 457–81. https://doi.org/10.1080/01621459.1958.10501452.
Kapoor, Sayash, Benedikt Stroebl, Zachary S. Siegel, Nitya Nadgir, and
Arvind Narayanan. 2024. “AI Agents That Matter.” arXiv
Preprint arXiv:2407.01502. https://arxiv.org/abs/2407.01502.
Khattab, Omar, Arnav Singhvi, Paridhi Maheshwari, Zhiyuan Zhang, Keshav
Santhanam, Sri Vardhamanan, Saiful Haq, et al. 2023. “DSPy:
Compiling Declarative Language Model Calls into Self-Improving
Pipelines.” arXiv Preprint arXiv:2310.03714. https://arxiv.org/abs/2310.03714.
Kim, Edward S., Roy S. Herbst, Ignacio I. Wistuba, J. Jack Lee, George
R. Blumenschein, Anne Tsao, David J. Stewart, et al. 2011. “The
BATTLE Trial: Personalizing Therapy for Lung
Cancer.” Cancer Discovery 1 (1): 44–53. https://doi.org/10.1158/2159-8274.CD-10-0010.
King, Andrew J., Lisa Higgins, Carly Au, Salim Malakouti, Edvin Music,
Kyle Kalchthaler, et al. 2024. “Automatic Population of the Case
Report Forms for an International Multifactorial Adaptive Platform Trial
Amid the COVID-19 Pandemic.” AMIA Joint Summits
on Translational Science Proceedings 2024: 276–84. https://pmc.ncbi.nlm.nih.gov/articles/PMC11141839/.
Korn, Edward L., and Boris Freidlin. 2011. “Outcome-Adaptive
Randomization: Is It Useful?” Journal of Clinical
Oncology 29 (6): 771–76. https://doi.org/10.1200/JCO.2010.31.1423.
Krams, Michael, Kennedy R. Lees, Werner Hacke, Andrew P. Grieve,
Jean-Marc Orgogozo, and Gary A. Ford. 2003. “Acute Stroke Therapy
by Inhibition of Neutrophils (ASTIN): An Adaptive Dose-Response Study of
UK-279,276 in Acute Ischemic Stroke.” Stroke 34 (11):
2543–48. https://doi.org/10.1161/01.STR.0000092527.33910.89.
Lamberti, Mary Jo, Abigail Dirks, Nicholas Kikuchi, Neha Patel
Cervantes, and Kenneth Getz. 2024. “Benchmarking Site Activation
and Patient Enrollment.” Therapeutic Innovation &
Regulatory Science 58 (4): 696–703. https://doi.org/10.1007/s43441-024-00638-1.
Lan, K. K. Gordon, and David L. DeMets. 1983. “Discrete Sequential
Boundaries for Clinical Trials.” Biometrika 70 (3):
659–63. https://doi.org/10.1093/biomet/70.3.659.
Landgren, Ola, and Sean M. Devlin. 2025. “Minimal Residual Disease
as an Early Endpoint for Accelerated Drug Approval in Myeloma: A
Roadmap.” Blood Cancer Discovery 6 (1): 13–22. https://doi.org/10.1158/2643-3230.BCD-24-0292.
Laranjo, Liliana, Adam G. Dunn, Huong Ly Tong, A. Baki Kocaballi,
Jessica Chen, Rabia Bashir, Didi Surian, et al. 2018.
“Conversational Agents in Healthcare: A Systematic Review.”
Journal of the American Medical Informatics Association 25 (9):
1248–58. https://pmc.ncbi.nlm.nih.gov/articles/PMC6118869/.
Laubenbacher, Reinhard, James P. Sluka, and James A. Glazier. 2021.
“Using Digital Twins in Viral Infection.” Science
371 (6534): 1105–6. https://doi.org/10.1126/science.abf3370.
Lavori, Philip W., and Ree Dawson. 2000. “A Design for Testing
Clinical Strategies: Biased Adaptive Within-Subject
Randomization.” Journal of the Royal Statistical Society:
Series A (Statistics in Society) 163 (1): 29–38. https://doi.org/10.1111/1467-985X.00154.
Le Tourneau, Christophe, J. Jack Lee, and Lillian L. Siu. 2009.
“Dose Escalation Methods in Phase i Cancer Clinical
Trials.” Journal of the National Cancer Institute 101
(10): 708–20. https://doi.org/10.1093/jnci/djp079.
Lewis, Patrick, Ethan Perez, Aleksandra Piktus, Fabio Petroni, Vladimir
Karpukhin, Naman Goyal, Heinrich Küttler, et al. 2020.
“Retrieval-Augmented Generation for Knowledge-Intensive NLP
Tasks.” Advances in Neural Information Processing
Systems 33: 9459–74. https://arxiv.org/abs/2005.11401.
Lin, Ruitao, and Guosheng Yin. 2017. “Bayesian
Optimal Interval Design for Dose Finding in Drug-Combination
Trials.” Statistical Methods in Medical Research 26 (5):
2155–67. https://doi.org/10.1177/0962280215594494.
Lin, Yunzhi, Mumu Zhu, and Zheng Su. 2015. “The Pursuit of
Balance: An Overview of Covariate-Adaptive Randomization Techniques in
Clinical Trials.” Contemporary Clinical Trials 45:
21–25. https://doi.org/10.1016/j.cct.2015.07.011.
Lipsitch, Marc, Eric Tchetgen Tchetgen, and Ted Cohen. 2010.
“Negative Controls: A Tool for Detecting Confounding and Bias in
Observational Studies.” Epidemiology 21 (3): 383–88. https://doi.org/10.1097/EDE.0b013e3181d61eeb.
Liu, Suyu, and Ying Yuan. 2015. “Bayesian Optimal Interval Designs
for Phase I Clinical Trials.” Journal of the
Royal Statistical Society: Series C (Applied Statistics) 64 (3):
507–23. https://doi.org/10.1111/rssc.12089.
Liu, Xiaoxuan et al. 2020. “CONSORT-AI Extension: Reporting
Guidelines for Clinical Trials Evaluating Artificial Intelligence
Interventions.” BMJ 370: m3164. https://www.bmj.com/content/370/bmj.m3164.
Lopez Bernal, Jamie, Nick Andrews, Charlotte Gower, Eileen Gallagher,
Ruth Simmons, Simon Thelwall, Julia Stowe, et al. 2021.
“Effectiveness of Covid-19 Vaccines Against the
B.1.617.2 (Delta) Variant.” New
England Journal of Medicine 385 (7): 585–94. https://doi.org/10.1056/NEJMoa2108891.
Ma, Wei, Ping Li, Li-Xin Zhang, and Feifang Hu. 2024. “A New and
Unified Family of Covariate Adaptive Randomization Procedures and Their
Properties.” Journal of the American Statistical
Association 119 (545): 151–62. https://doi.org/10.1080/01621459.2022.2102986.
MacDougall, James. 2006. “Analysis of Dose-Response Studies:
Emax Model.” In Dose Finding in Drug
Development, edited by Naitee Ting, 127–45. Springer. https://doi.org/10.1007/0-387-33706-7_9.
Mandel, Joshua C., David A. Kreda, Kenneth D. Mandl, Isaac S. Kohane,
and Rachel B. Ramoni. 2016. “SMART on FHIR: A Standards-Based,
Interoperable Apps Platform for Electronic Health Records.”
Journal of the American Medical Informatics Association 23 (5):
899–908. https://pmc.ncbi.nlm.nih.gov/articles/PMC4997036/.
Mander, Adrian P., and Michael J. Sweeting. 2015. “A Product of
Independent Beta Probabilities Dose Escalation Design for Dual-Agent
Phase I Trials.” Statistics in Medicine 34
(8): 1261–76. https://doi.org/10.1002/sim.6434.
Marion, Joe, Elizabeth Lorenzi, Cora Allen-Savietta, Scott Berry, and
Kert Viele. 2025. “Predictive Probabilities Made Simple: A Fast
and Accurate Method for Clinical Trial Decision-Making.”
Statistics in Medicine 44 (13-14): e70120. https://doi.org/10.1002/sim.70120.
MarketsandMarkets. 2024. “Electronic Trial Master File System
Market.” https://www.marketsandmarkets.com/Market-Reports/electronic-trial-master-file-system-market-94357456.html.
Medable. 2024a. “Medable Releases New AI Agent to Automate Trial
Master File Processing.” https://www.biopharmatrend.com/news/medable-releases-new-ai-agent-to-automate-trial-master-file-processing-1447/.
———. 2024b. “Medable: Decentralized Clinical Trial
Platform.” https://www.medable.com.
———. 2026. “Medable Clinical Trial Platform.” https://www.medable.com.
Medicenna Therapeutics Corp. 2020. “Medicenna Provides
MDNA55 rGBM Clinical Program
Update Following Positive End of Phase 2 Meeting with the
U.S. Food and Drug Administration
(FDA).” Press release, October 15, 2020. https://ir.medicenna.com/news-releases/news-release-details/medicenna-provides-mdna55-rgbm-clinical-program-update-following/.
Medicines and Healthcare products Regulatory Agency. 2025. “MHRA
Draft Guideline on the Use of External Control Arms Based on Real-World
Data to Support Regulatory Decisions.” https://www.gov.uk/government/consultations/mhra-draft-guideline-on-the-use-of-external-control-arms-based-on-real-world-data-to-support-regulatory-decisions.
Medidata Solutions. 2020. “Medidata Synthetic Control Arm
Supported by the US Food and Drug Administration
(FDA) for Use in Medicenna Therapeutics, Corp. Phase 3
Registrational Trial in Recurrent Glioblastoma.” Press release
(Business Wire), October 28, 2020. https://www.businesswire.com/news/home/20201028005277/en/Medidata-Synthetic-Control-Arm-Supported-by-the-US-Food-and-Drug-Administration-FDA-for-Use-in-Medicenna-Therapeutics-Corp.-Phase-3-Registrational-Trial-in-Recurrent-Glioblastoma.
———. 2024a. “Everest Group EDC PEAK Matrix Assessment.” https://www.medidata.com/en/everest-group-edc-peak-matrix/.
———. 2024b. “Medidata Rave EDC.” https://www.medidata.com/en/clinical-trial-products/clinical-data-management/edc-systems.
———. 2024c. “Medidata Sensor Cloud: Wearable Sensors.” https://www.medidata.com/en/patient-experience/wearable-sensors/.
———. 2024d. “Medidata Synthetic Control Arm.” https://medidata.com/en/clinical-trial-products/medidata-ai/real-world-data/synthetic-control-arm.
Medpace Holdings, Inc. 2026. “Medpace Holdings, Inc. Reports
Fourth Quarter and Full Year 2025 Results.” https://investor.medpace.com/news-releases/news-release-details/medpace-holdings-inc-reports-fourth-quarter-and-full-year-2025/.
Mehta, Cyrus R., and Stuart J. Pocock. 2011. “Adaptive Increase in
Sample Size When Interim Results Are Promising: A Practical Guide with
Examples.” Statistics in Medicine 30 (28): 3267–84. https://doi.org/10.1002/sim.4102.
Mei, Kai, Xi Zhu, Wujiang Xu, Wenyue Hua, Mingyu Jin, Zelong Li, Shuyuan
Xu, Ruosong Ye, Yingqiang Ge, and Yongfeng Zhang. 2024. “AIOS: LLM
Agent Operating System.” arXiv Preprint
arXiv:2403.16971. https://arxiv.org/abs/2403.16971.
Meinert, Curtis L. 2013. Clinical Trials Handbook: Design and
Conduct. Hoboken, NJ: John Wiley & Sons.
Mello, Michelle M., Brian R. Clarridge, and David M. Studdert. 2005.
“Academic Medical Centers’ Standards for Clinical-Trial Agreements
with Industry.” New England Journal of Medicine 352
(21): 2202–10. https://doi.org/10.1056/NEJMsa044115.
Messeri, Lisa, and M. J. Crockett. 2024. “Artificial Intelligence
and Illusions of Understanding in Scientific Research.”
Nature. https://www.nature.com/articles/s41586-024-07146-0.
Ministry of Health, Labour and Welfare. 2024. “Revision of
Notification on Handling of Submission of Electronic Study Data for New
Drug Applications.” https://www.pmda.go.jp/files/000267942.pdf.
Mitchell, Margaret, Simone Wu, Andrew Zaldivar, Parker Barnes, Lucy
Vasserman, Ben Hutchinson, Elena Spitzer, Inioluwa Deborah Raji, and
Timnit Gebru. 2019. “Model Cards for Model Reporting.” In
Proceedings of the Conference on Fairness, Accountability, and
Transparency, 220–29. https://doi.org/10.1145/3287560.3287596.
Moore, Thomas J., Hanzhe Zhang, Gerard Anderson, and G. Caleb Alexander.
2018. “Estimated Costs of Pivotal Trials for Novel Therapeutic
Agents Approved by the US Food and
Drug Administration, 2015-2016.” JAMA Internal
Medicine 178 (11): 1451–57. https://doi.org/10.1001/jamainternmed.2018.3931.
Murphy, Susan A. 2005. “An Experimental Design for the Development
of Adaptive Treatment Strategies.” Statistics in
Medicine 24 (10): 1455–81. https://doi.org/10.1002/sim.2022.
Muss, Hyman B., Donald A. Berry, Constance T. Cirrincione, Maria
Theodoulou, Ann M. Mauer, Alice B. Kornblith, Ann H. Partridge, et al.
2009. “Adjuvant Chemotherapy in Older Women with Early-Stage
Breast Cancer.” New England Journal of Medicine 360
(20): 2055–65. https://doi.org/10.1056/NEJMoa0810266.
Nahum-Shani, Inbal, Ashkan Ertefaie, Xi Lu, Kevin G. Lynch, James R.
McKay, David W. Oslin, and Daniel Almirall. 2017. “A SMART Data
Analysis Method for Constructing Adaptive Treatment Strategies for
Substance Use Disorders.” Addiction 112 (5): 901–9. https://doi.org/10.1111/add.13743.
National Commission for the Protection of Human Subjects of Biomedical
and Behavioral Research. 1979. “The Belmont Report: Ethical
Principles and Guidelines for the Protection of Human Subjects of
Research.” https://www.hhs.gov/ohrp/regulations-and-policy/belmont-report/read-the-belmont-report/index.html.
National Institute for Health and Care Excellence. 2022.
“NICE Technology Appraisal and Highly Specialised
Technologies Guidance: The Manual.” https://www.nice.org.uk/process/pmg36.
National Institute of Standards and Technology. 2023. “Artificial
Intelligence Risk Management Framework (AI RMF 1.0).” https://www.nist.gov/itl/ai-risk-management-framework.
National Institutes of Health. 2023. “NIH Policy for Data
Management and Sharing.” https://sharing.nih.gov/data-management-and-sharing-policy/about-data-management-and-sharing-policies.
National Library of Medicine. 2024. “NIH Common Data Elements
(CDE) Repository.” https://cde.nlm.nih.gov/.
Neuenschwander, Beat, Michael Branson, and Thomas Gsponer. 2008.
“Critical Aspects of the Bayesian Approach to Phase
I Cancer Trials.” Statistics in Medicine 27
(13): 2420–39. https://doi.org/10.1002/sim.3230.
Neuenschwander, Beat, Gorana Capkun-Niggli, Michael Branson, and David
J. Spiegelhalter. 2010. “Summarizing Historical Information on
Controls in Clinical Trials.” Clinical Trials 7 (1):
5–18. https://doi.org/10.1177/1740774509356002.
NextTrial. 2024. “NextTrial AI: Clinical Trial
Intelligence.” https://www.nexttrial.ai.
Nuremberg Military Tribunal. 1949. “The Nuremberg Code.” https://collections.nlm.nih.gov/catalog/nlm:nlmuid-01130400RX2-mvpart.
O’Brien, Peter C., and Thomas R. Fleming. 1979. “A Multiple
Testing Procedure for Clinical Trials.” Biometrics 35
(3): 549–56. https://doi.org/10.2307/2530245.
O’Hagan, Anthony, John W. Stevens, and Michael J. Campbell. 2005.
“Assurance in Clinical Trial Design.” Pharmaceutical
Statistics 4 (3): 187–201. https://doi.org/10.1002/pst.175.
O’Quigley, John, Margaret Pepe, and Lloyd Fisher. 1990. “Continual
Reassessment Method: A Practical Design for Phase 1 Clinical Trials in
Cancer.” Biometrics 46 (1): 33–48. https://doi.org/10.2307/2531628.
Obermeyer, Ziad, Brian Powers, Christine Vogeli, and Sendhil
Mullainathan. 2019. “Dissecting Racial Bias in an Algorithm Used
to Manage the Health of Populations.” Science 366
(6464): 447–53. https://doi.org/10.1126/science.aax2342.
Octozi. 2024. “Octozi: AI for Clinical Operations.” https://www.octozi.com.
Ogier du Terrail, Jean, Quentin Klopfenstein, Honghao Li, Imke Mayer,
Nicolas Loiseau, Mohammad Hallal, Michael Debouver, Thibault Camalon, et
al. 2025. “FedECA: Federated External Control Arms
for Causal Inference with Time-to-Event Data in Distributed
Settings.” Nature Communications 16 (1): 7496. https://doi.org/10.1038/s41467-025-62525-z.
Overhage, J. Marc, Patrick B. Ryan, Christian G. Reich, Abraham G.
Hartzema, and Paul E. Stang. 2012. “Validation of a Common Data
Model for Active Safety Surveillance Research.” Journal of
the American Medical Informatics Association 19 (1): 54–60. https://doi.org/10.1136/amiajnl-2011-000376.
Pallmann, Philip, Alun W. Bedding, Babak Choodari-Oskooei, Munyaradzi
Dimairo, Laura Flight, Lisa V. Hampson, Jane Holmes, et al. 2018.
“Adaptive Designs in Clinical Trials: Why Use Them, and How to Run
and Report Them.” BMC Medicine 16 (1): 29. https://doi.org/10.1186/s12916-018-1017-7.
PANTHER Trial Investigators. 2024. “PANTHER:
Precision Medicine Adaptive Network Platform Trial in Hypoxaemic Acute
Respiratory Failure.” https://www.panthertrial.org.
Park, John W., Minetta C. Liu, Douglas Yee, Christina Yau, Laura J. van
’t Veer, W. Fraser Symmans, Melissa Paoloni, et al. 2016.
“Adaptive Randomization of Neratinib in Early Breast
Cancer.” New England Journal of Medicine 375 (1): 11–22.
https://doi.org/10.1056/NEJMoa1513750.
Park, Joon Sung, Joseph C. O’Brien, Carrie J. Cai, Meredith Ringel
Morris, Percy Liang, and Michael S. Bernstein. 2023. “Generative
Agents: Interactive Simulacra of Human Behavior.” In
Proceedings of the 36th Annual ACM Symposium on User Interface
Software and Technology (UIST ’23). https://doi.org/10.1145/3586183.3606763.
PCORnet. 2025. “PCORnet Common Data Model
(CDM) Specification, Version 7.0.” https://pcornet.org/wp-content/uploads/2025/05/PCORnet_Common_Data_Model_v70_2025_05_01.pdf.
Pearl, Judea. 2009. Causality: Models, Reasoning, and
Inference. 2nd ed. Cambridge: Cambridge University Press.
Pelham, William E., Gregory A. Fabiano, James G. Waxmonsky, Andrew R.
Greiner, Elizabeth M. Gnagy, et al. 2016. “Treatment Sequencing
for Childhood ADHD: A Multiple-Randomization Study of
Adaptive Medication and Behavioral Interventions.” Journal of
Clinical Child & Adolescent Psychology 45 (4): 396–415. https://doi.org/10.1080/15374416.2015.1105138.
Pharmaceutical Research and Manufacturers of America. 2024. “The
Economic Impact of the u.s. Biopharmaceutical Industry.” https://phrma.org/resource-center/topics/economic-impact/industry-economic-impact.
Phlexglobal. 2024. “Phlexglobal eTMF Software.” https://www.phlexglobal.com/etmf-software.
Pocock, Stuart J. 1977. “Group Sequential Methods in the Design
and Analysis of Clinical Trials.” Biometrika 64 (2):
191–99. https://doi.org/10.1093/biomet/64.2.191.
Pocock, Stuart J., Cono A. Ariti, Timothy J. Collier, and Duolao Wang.
2012. “The Win Ratio: A New Approach to the Analysis of Composite
Endpoints in Clinical Trials Based on Clinical Priorities.”
European Heart Journal 33 (2): 176–82. https://doi.org/10.1093/eurheartj/ehr352.
Pocock, Stuart J., and Richard Simon. 1975. “Sequential Treatment
Assignment with Balancing for Prognostic Factors in the Controlled
Clinical Trial.” Biometrics 31 (1): 103–15. https://doi.org/10.2307/2529712.
Pokorney, Sean D., Noelle Cocoros, Hussein R. Al-Khalidi, Kevin Haynes,
Shuang Li, Sana M. Al-Khatib, et al. 2022. “Effect of Mailing
Educational Material to Patients with Atrial Fibrillation and Their
Clinicians on Use of Oral Anticoagulants: A Randomized Clinical
Trial.” JAMA Network Open 5 (5): e2214321. https://doi.org/10.1001/jamanetworkopen.2022.14321.
Prasad, Vinay, and Sham Mailankody. 2017. “Research and
Development Spending to Bring a Single Cancer Drug to Market and
Revenues After Approval.” JAMA Internal Medicine 177
(11): 1569–75. https://doi.org/10.1001/jamainternmed.2017.3601.
Prasad, Vinay, and Martin A. Makary. 2026. “One Pivotal Trial, the
New Default Option for FDA Approval: Ending the Two-Trial
Dogma.” New England Journal of Medicine 394 (8): 815–17.
https://doi.org/10.1056/NEJMsb2517623.
Proschan, Michael A., and Scott R. Evans. 2020. “Resist the
Temptation of Response-Adaptive Randomization.” Clinical
Infectious Diseases 71 (11): 3002–4. https://doi.org/10.1093/cid/ciaa334.
Quintana, Melanie, Benjamin R. Saville, Matteo Vestrucci, Michelle A.
Detry, Lori Chibnik, Jeremy Shefner, James D. Berry, et al. 2023.
“Design and Statistical Innovations in a Platform Trial for
Amyotrophic Lateral Sclerosis.” Annals of Neurology 94
(3): 547–60. https://doi.org/10.1002/ana.26714.
Rao, Gowtham A. 2026. “The OHDSI Phenotype
Library.” R package and GitHub
repository, version 3.37.0, part of HADES. https://github.com/OHDSI/PhenotypeLibrary.
RECOVERY Collaborative Group, Peter Horby, Wei Shen Lim, Jonathan R.
Emberson, Marion Mafham, Jennifer L. Bell, et al. 2021.
“Dexamethasone in Hospitalized Patients with
Covid-19.” New England Journal of Medicine
384 (8): 693–704. https://doi.org/10.1056/NEJMoa2021436.
Redman, Mary W., Vassiliki A. Papadimitrakopoulou, Glenwood D. Goss, et
al. 2020. “Biomarker-Driven Therapies for Previously Treated
Squamous Non-Small-Cell Lung Cancer (Lung-MAP SWOG S1400): A
Biomarker-Driven Master Protocol.” The Lancet Oncology
21 (12): 1589–1601. https://doi.org/10.1016/S1470-2045(20)30475-7.
REMAP-CAP Investigators, ACTIV-4a Investigators, ATTACC Investigators,
Ewan C. Goligher, Corrinne A. Bradbury, Bryan J. McVerry, et al. 2021.
“Therapeutic Anticoagulation with Heparin in Critically Ill
Patients with Covid-19.” New England Journal of
Medicine 385 (9): 777–89. https://doi.org/10.1056/NEJMoa2103417.
REMAP-CAP Investigators, Anthony C. Gordon, Paul R. Mouncey, Farah
Al-Beidh, Kathryn M. Rowan, Alistair D. Nichol, et al. 2021.
“Interleukin-6 Receptor Antagonists in Critically Ill Patients
with Covid-19.” New England Journal of
Medicine 384 (16): 1491–1502. https://doi.org/10.1056/NEJMoa2100433.
Renfro, Lindsay A., and Daniel J. Sargent. 2017. “Statistical
Controversies in Clinical Research: Basket Trials, Umbrella Trials, and
Other Master Protocols: A Review and Examples.” Annals of
Oncology 28 (1): 34–43. https://doi.org/10.1093/annonc/mdw413.
Ritchie, Craig W., José Luis Molinuevo, Luc Truyen, Andrew Satlin, Serge
Van der Geyten, Simon Lovestone, and EPAD Consortium. 2016.
“Development of Interventions for the Secondary Prevention of
Alzheimer’s Dementia: The European Prevention of Alzheimer’s Dementia (EPAD)
Project.” Lancet Psychiatry 3 (2): 179–86. https://doi.org/10.1016/S2215-0366(15)00454-X.
Rivera, Samantha Cruz et al. 2020. “SPIRIT-AI Extension: Guidance
for Clinical Trial Protocols for Interventions Involving Artificial
Intelligence.” BMJ 370: m3210. https://www.bmj.com/content/370/bmj.m3210.
Robins, James M., Miguel A. Hernán, and Babette Brumback. 2000.
“Marginal Structural Models and Causal Inference in
Epidemiology.” Epidemiology 11 (5): 550–60. https://doi.org/10.1097/00001648-200009000-00011.
Rosenbaum, Paul R., and Donald B. Rubin. 1983. “The Central Role
of the Propensity Score in Observational Studies for Causal
Effects.” Biometrika 70 (1): 41–55. https://doi.org/10.1093/biomet/70.1.41.
Rosenberger, William F., and John M. Lachin. 2016. Randomization in
Clinical Trials: Theory and Practice. 2nd ed. Hoboken, NJ: John
Wiley & Sons.
Ross, Jessica L., Arman Sabbaghi, Run Zhuang, and Daniele Bertolini.
2024. “Enhancing Longitudinal Clinical Trial Efficiency with
Digital Twins and Prognostic Covariate-Adjusted Mixed Models for
Repeated Measures (PROCOVA-MMRM).” arXiv Preprint
arXiv:2404.17576. https://arxiv.org/abs/2404.17576.
Rossouw, Jacques E., Garnet L. Anderson, Ross L. Prentice, Andrea Z.
LaCroix, Charles Kooperberg, Marcia L. Stefanick, Rebecca D. Jackson, et
al. 2002. “Risks and Benefits of Estrogen Plus Progestin in
Healthy Postmenopausal Women: Principal Results from the Women’s Health
Initiative Randomized Controlled Trial.” JAMA 288 (3):
321–33. https://doi.org/10.1001/jama.288.3.321.
Roth, Jonathan. 2022. “Pretest with Caution: Event-Study Estimates
After Testing for Parallel Trends.” American Economic Review:
Insights 4 (3): 305–22. https://doi.org/10.1257/aeri.20210236.
Rubin, Donald B. 1974. “Estimating Causal Effects of Treatments in
Randomized and Nonrandomized Studies.” Journal of Educational
Psychology 66 (5): 688–701. https://doi.org/10.1037/h0037350.
———. 1987. Multiple Imputation for Nonresponse in Surveys. New
York: John Wiley & Sons. https://doi.org/10.1002/9780470316696.
Rush, A. John, Maurizio Fava, Stephen R. Wisniewski, Philip W. Lavori,
Madhukar H. Trivedi, Harold A. Sackeim, Michael E. Thase, et al. 2004.
“Sequenced Treatment Alternatives to Relieve Depression
(STAR*D): Rationale and Design.” Controlled
Clinical Trials 25 (1): 119–42. https://doi.org/10.1016/S0197-2456(03)00112-0.
Rush, A. John, Madhukar H. Trivedi, Stephen R. Wisniewski, Andrew A.
Nierenberg, Jonathan W. Stewart, Diane Warden, George Niederehe, et al.
2006. “Acute and Longer-Term Outcomes in Depressed Outpatients
Requiring One or Several Treatment Steps: A STAR*d Report.”
American Journal of Psychiatry 163 (11): 1905–17. https://doi.org/10.1176/ajp.2006.163.11.1905.
Ryan, Patrick B. 2024. “OHDSI for Real World Evidence
(RWE).” Presentation slides, Observational
Health Data Sciences and Informatics. https://www.ohdsi.org/wp-content/uploads/2024/12/2.-OHDSI-for-Real-World-Evidence-RWE-Patrick-Ryan.pdf.
Saama Technologies. 2024. “Saama: Life Sciences Analytics
Cloud.” https://www.saama.com.
Saleiro, Pedro, Benedict Kuester, Loren Hinkson, Jesse London, Abby
Stevens, Ari Anisfeld, Kit T. Rodolfa, and Rayid Ghani. 2018.
“Aequitas: A Bias and Fairness Audit Toolkit.” arXiv
Preprint arXiv:1811.05577. https://arxiv.org/abs/1811.05577.
Saunders, Stina, Sarah Gregory, Matthew H. S. Clement, Cindy Birck,
Serge Van Der Geyten, and Craig W. Ritchie. 2022. “The European
Prevention of Alzheimer’s Dementia Programme: An Innovative Medicines
Initiative-Funded Partnership to Facilitate Secondary Prevention of
Alzheimer’s Disease Dementia.” Frontiers in Neurology
13: 1051543. https://doi.org/10.3389/fneur.2022.1051543.
Saver, Jeffrey L. 2007. “Novel End Point Analytic Techniques and
Interpreting Shifts Across the Entire Range of Outcome Scales in Acute
Stroke Trials.” Stroke 38 (11): 3055–62. https://doi.org/10.1161/STROKEAHA.107.488536.
Saville, Benjamin R., and Scott M. Berry. 2016. “Efficiencies of
Platform Clinical Trials: A Vision of the Future.” Clinical
Trials 13 (3): 358–66. https://doi.org/10.1177/1740774515626362.
Schulz, Kenneth F. 1995. “Subverting Randomization in Controlled
Trials.” JAMA 274 (18): 1456–58. https://doi.org/10.1001/jama.1995.03530180050029.
Scott, Neil W., Gladys C. McPherson, Craig R. Ramsay, and Marion K.
Campbell. 2002. “The Method of Minimization for Allocation to
Clinical Trials: A Review.” Controlled Clinical Trials
23 (6): 662–74. https://doi.org/10.1016/S0197-2456(02)00242-8.
Sel, Kaan, Andrea Hawkins-Daarud, Anirban Chaudhuri, Deen Osman, Ahmad
Bahai, David Paydarfar, Karen Willcox, Caroline Chung, and Roozbeh
Jafari. 2025. “Survey and Perspective on Verification, Validation,
and Uncertainty Quantification of Digital Twins for Precision
Medicine.” Npj Digital Medicine 8: 40. https://doi.org/10.1038/s41746-025-01447-y.
Sentinel Operations Center. 2025. “An Assessment of the Sentinel
System (2022 to 2024).” U.S. Food and Drug
Administration. https://www.sentinelinitiative.org/sites/default/files/documents/PDUFA-VII-Sentinel-System-Report_An-Assessment-of-the-Sentinel-System_2022-to-2024.pdf.
Sertkaya, Aylin, Hui-Hsing Wong, Amber Jessup, and Trinidad Beleche.
2016. “Key Cost Drivers of Pharmaceutical Clinical Trials in the
United States.” Clinical Trials 13 (2):
117–26. https://doi.org/10.1177/1740774515625964.
Shiryaev, Albert N. 1978. Optimal Stopping Rules. Berlin:
Springer-Verlag.
Shriver, Sharon P., Liora Sahar, Vanhvilai L. Douangchai Wills, Devon V.
Adams, and Mark E. Fleury. 2025. “Assessing Populations with
Access to National Cancer Institute-Funded Sites Using Local
Distance-Based Service Areas.” Journal of Clinical and
Translational Science 9 (1): e218. https://doi.org/10.1017/cts.2025.10148.
Simon, Noah, and Richard Simon. 2013. “Adaptive Enrichment Designs
for Clinical Trials.” Biostatistics 14 (4): 613–25. https://doi.org/10.1093/biostatistics/kxt010.
Smith, Zachary P., Joseph A. DiMasi, and Kenneth A. Getz. 2024.
“New Estimates on the Cost of a Delay Day in Drug
Development.” Therapeutic Innovation & Regulatory
Science 58 (5): 855–62. https://doi.org/10.1007/s43441-024-00667-w.
Smith, Zachary, Joseph A. DiMasi, and Kenneth A. Getz. 2024.
“Quantifying the Value of a Day of Delay in Drug
Development.” White Paper. Tufts Center for the Study of Drug
Development. https://csdd.tufts.edu/sites/default/files/2025-02/Aug2024%20Day%20of%20Delay%20White%20Paper%20Final.pdf.
Society for Clinical Data Management. 2023. “Database
Closure.” Good Clinical Data Management Practices chapter,
Journal of the Society for Clinical Data Management. https://scdm.org/wp-content/uploads/2024/07/Database-Closure.pdf.
Sommer, C., D. Zuccolin, V. Arnera, N. Schmitz, P. Adolfsson, N.
Colombo, R. Gilg, and B. McDowell. 2018. “Building Clinical Trials
Around Patients: Evaluation and Comparison of Decentralized and
Conventional Site Models in Patients with Low Back Pain.”
Contemporary Clinical Trials Communications 11: 120–26. https://doi.org/10.1016/j.conctc.2018.06.008.
Stein, Charles. 1956. “Inadmissibility of the Usual Estimator for
the Mean of a Multivariate Normal Distribution.” In
Proceedings of the Third Berkeley Symposium on Mathematical
Statistics and Probability, 1:197–206. https://www.degruyter.com/document/doi/10.1525/9780520313880-018/html.
Struebing, Alessandria, Chelsea McKibbon, Haoyao Ruan, Emma Mackay,
Natalie Dennis, Russanthy Velummailum, Philip He, et al. 2024.
“Augmenting External Control Arms Using Bayesian Borrowing: A Case
Study in First-Line Non-Small Cell Lung Cancer.” Journal of
Comparative Effectiveness Research 13 (5). https://doi.org/10.57264/cer-2023-0175.
Suissa, Samy. 2008. “Immortal Time Bias in
Pharmacoepidemiology.” American Journal of Epidemiology
167 (4): 492–99. https://doi.org/10.1093/aje/kwm324.
Swanson, Chad J., Yong Zhang, Shobha Dhadda, Jianing Wang, June Kaplow,
Robert Y. K. Lai, Lars Lannfelt, et al. 2021. “A Randomized,
Double-Blind, Phase 2b Proof-of-Concept Clinical Trial in Early Alzheimer’s Disease with Lecanemab, an Anti-aβ Protofibril Antibody.”
Alzheimer’s Research and Therapy 13 (1): 80. https://doi.org/10.1186/s13195-021-00813-8.
Taves, Donald R. 1974. “Minimization: A New Method of Assigning
Patients to Treatment and Control Groups.” Clinical
Pharmacology & Therapeutics 15 (5): 443–53. https://doi.org/10.1002/cpt1974155443.
Thompson, William R. 1933. “On the Likelihood That One Unknown
Probability Exceeds Another in View of the Evidence of Two
Samples.” Biometrika 25 (3/4): 285–94. https://doi.org/10.2307/2332286.
TMF Reference Model Initiative. 2024. “Trial Master File Reference
Model.” https://tmfrefmodel.com/.
Tong, Steven Y. C., Jocelyn Mora, Asha C. Bowen, Matthew P. Cheng, Nick
Daneman, Anna L. Goodman, George S. Heriot, et al. 2022. “The
Staphylococcus aureus Network Adaptive
Platform Trial Protocol: New Tools for an Old Foe.” Clinical
Infectious Diseases 75 (11): 2027–34. https://doi.org/10.1093/cid/ciac476.
Tufts Center for the Study of Drug Development. 2013. “89% of
Trials Meet Enrollment, but Timelines Slip, Half of Sites
Under-Enroll.” Tufts CSDD Impact Report 15(1), January/February
2013. https://csdd.tufts.edu/publications/impact-reports.
———. 2021. “Tufts Center for the Study of Drug Development Impact
Reports.” https://csdd.tufts.edu/publications/impact-reports.
———. 2024. “Clinical Trial Management System Benchmarks.”
https://csdd.tufts.edu/publications/impact-reports.
UK Collaborative ECMO Trial Group. 1996. “UK Collaborative
Randomised Trial of Neonatal Extracorporeal Membrane
Oxygenation.” The Lancet 348 (9020): 75–82. https://doi.org/10.1016/S0140-6736(96)04100-1.
Unger, Joseph M., Barbara L. McAneny, and Raymond U. Osarogiagbon. 2025.
“Cancer in Rural America: Improving Access to Clinical Trials and
Quality of Oncologic Care.” CA: A Cancer Journal for
Clinicians 75 (4): 341–61. https://doi.org/10.3322/caac.70006.
Unger, Joseph M., Adrienne Moseley, Beulah Symington, Mariana
Chavez-MacGregor, Scott D. Ramsey, and Dawn L. Hershman. 2018.
“Geographic Distribution and Survival Outcomes for Rural Patients
with Cancer Treated in Clinical Trials.” JAMA Network
Open 1 (4): e181235. https://doi.org/10.1001/jamanetworkopen.2018.1235.
United States Congress. 1951. “An Act to Amend Section 503(b) of
the Federal Food, Drug, and Cosmetic Act (Durham-Humphrey
Amendment).” https://www.govinfo.gov/content/pkg/STATUTE-65/pdf/STATUTE-65-Pg648.pdf.
———. 1997. “Food and Drug Administration
Modernization Act of 1997.”
———. 2007. “Food and Drug Administration Amendments Act of 2007
(FDAAA), Public Law 110-85, Section 801.” https://clinicaltrials.gov/policy/fdaaa-801-final-rule.
University of North Carolina at Chapel Hill. 2024. “Nuremberg
Code.” https://research.unc.edu/human-research-ethics/resources/ccm3_019064/.
University-Industry Demonstration Partnership. 2014. “Accelerated
Clinical Trial Agreement (ACTA).” https://uidp.org/our-work/acta/.
Unlearn.AI. 2024. “Unlearn.AI: Digital Twins for Clinical
Trials.” https://www.unlearn.ai.
———. 2025. “A Risk-Based Approach for Leveraging AI in Clinical
Trials.” https://www.unlearn.ai/blog/how-unlearn-boosts-trial-power-using-the-fdas-ai-framework.
U.S. Congress. 2022. “Food and Drug Omnibus Reform Act
(FDORA) of 2022.” https://www.fda.gov/regulatory-information/selected-amendments-fdc-act/food-and-drug-omnibus-reform-act-fdora-2022.
U.S. Department of Agriculture. 1937. “Report of the Secretary of
Agriculture on Deaths Due to Elixir Sulfanilamide-Massengill.”
U.S. Department of Health and Human Services. 2024. “45 CFR Part
46: Protection of Human Subjects (Common Rule).” https://www.ecfr.gov/current/title-45/subtitle-A/subchapter-A/part-46.
U.S. Environmental Protection Agency. 2007. “Guidance for
Preparing Standard Operating Procedures (SOPs) (EPA
QA/G-6).” EPA/600/B-07/001. https://www.epa.gov/sites/default/files/2015-06/documents/g6-final.pdf.
U.S. Food and Drug Administration. 1994. “Dose-Response
Information to Support Drug Registration.” U.S. Food and
Drug Administration. https://www.fda.gov/media/71279/download.
———. 2005. “Estimating the Maximum Safe Starting Dose in Initial
Clinical Trials for Therapeutics in Adult Healthy Volunteers.”
Guidance for Industry, Center for Drug Evaluation and Research. https://www.fda.gov/media/72309/download.
———. 2006. “Guidance for Clinical Trial Sponsors: Establishment
and Operation of Clinical Trial Data Monitoring Committees.” https://www.fda.gov/media/75398/download.
———. 2010a. “Adaptive Design Clinical Trials for Drugs and
Biologics: Draft Guidance for Industry.” https://web.archive.org/web/2012/http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM201790.pdf.
———. 2010b. “Guidance for the Use of Bayesian
Statistics in Medical Device Clinical Trials.” U.S. Food
and Drug Administration. https://www.fda.gov/media/71512/download.
———. 2013a. “Electronic Source Data in Clinical Investigations:
Guidance for Industry.” https://www.fda.gov/regulatory-information/search-fda-guidance-documents/electronic-source-data-clinical-investigations.
———. 2013b. “Oversight of Clinical Investigations: A Risk-Based
Approach to Monitoring.” https://www.fda.gov/regulatory-information/search-fda-guidance-documents/oversight-clinical-investigations-risk-based-approach-monitoring.
———. 2014. “Expedited Programs for Serious Conditions – Drugs and
Biologics: Guidance for Industry.” https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-serious-conditions-drugs-and-biologics.
———. 2016. “Use of Electronic Informed Consent in Clinical
Investigations: Questions and Answers.” https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-electronic-informed-consent-clinical-investigations-questions-and-answers.
———. 2018a. “Framework for FDA’s Real-World Evidence
Program.” https://www.fda.gov/media/120060/download.
———. 2018b. “The Drug Development Process.” https://www.fda.gov/patients/learn-about-drug-and-device-approvals/drug-development-process.
———. 2018c. “Use of Electronic Health Record Data in Clinical
Investigations: Guidance for Industry.” https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-electronic-health-record-data-clinical-investigations-guidance-industry.
———. 2018d. “Clinical Trial Endpoints for the Approval of Cancer
Drugs and Biologics.” https://www.fda.gov/media/71195/download.
———. 2019a. “Adaptive Designs for Clinical Trials of Drugs and
Biologics: Guidance for Industry.” https://www.fda.gov/regulatory-information/search-fda-guidance-documents/adaptive-design-clinical-trials-drugs-and-biologics-guidance-industry.
———. 2019b. “Approval Package for Application Number
207103Orig1s008: IBRANCE (Palbociclib).” https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/207103Orig1s008.pdf.
———. 2019c. “Demonstrating Substantial Evidence of Effectiveness
for Human Drug and Biological Products.” U.S. Food and Drug
Administration. https://www.fda.gov/media/133660/download.
———. 2019d. “Enrichment Strategies for Clinical Trials to Support
Approval of Human Drugs and Biological Products.” https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enrichment-strategies-clinical-trials-support-approval-human-drugs-and-biological-products.
———. 2020. “Compliance Program 7348.811: Clinical Investigators
and Sponsor-Investigators.” https://www.fda.gov/media/75927/download.
———. 2021a. “Compliance Program 7348.810: Sponsors and Contract
Research Organizations.” https://www.fda.gov/media/75916/download.
———. 2021b. “Conduct of Clinical Trials of Medical Products During
the COVID-19 Public Health Emergency: Guidance for Industry,
Investigators, and Institutional Review Boards.” https://www.fda.gov/media/137496/download.
———. 2021c. “PDUFA Reauthorization Performance Goals and
Procedures, Fiscal Years 2023 Through 2027.” https://www.fda.gov/media/151712/download.
———. 2021d. “Project Optimus: Reforming the Dose
Optimization and Dose Selection Paradigm in Oncology.” FDA
Oncology Center of Excellence. https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus.
———. 2021e. “Providing Regulatory Submissions in Electronic
Format: Standardized Study Data. Guidance for Industry.” https://www.fda.gov/media/82716/download.
———. 2022. “Master Protocols: Efficient Clinical Trial Design
Strategies to Expedite Development of Oncology Drugs and
Biologics.” U.S. Food and Drug Administration. https://www.fda.gov/media/120721/download.
———. 2023a. “21 CFR Part 11: Electronic Records; Electronic
Signatures.” https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-11.
———. 2023b. “21 CFR Part 50: Protection of Human Subjects.”
https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-50.
———. 2023c. “21 CFR Part 56: Institutional Review Boards.”
https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-56.
———. 2023d. “Benefit-Risk Assessment for New Drug and Biological
Products.” https://www.fda.gov/regulatory-information/search-fda-guidance-documents/benefit-risk-assessment-new-drug-and-biological-products.
———. 2023e. “Considerations for the Design and Conduct of
Externally Controlled Trials for Drug and Biological Products.”
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-design-and-conduct-externally-controlled-trials-drug-and-biological-products.
———. 2023f. “Considerations for the Use of Real-World Data and
Real-World Evidence to Support Regulatory Decision-Making for Drug and
Biological Products.” https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-use-real-world-data-and-real-world-evidence-support-regulatory-decision-making-drug.
———. 2023g. “Digital Health Technologies for Remote Data
Acquisition in Clinical Investigations.” https://www.fda.gov/regulatory-information/search-fda-guidance-documents/digital-health-technologies-remote-data-acquisition-clinical-investigations.
———. 2023h. “Digital Health Technologies for Remote Data
Acquisition in Clinical Investigations: Guidance for Industry,
Investigators, and Other Stakeholders.” https://www.fda.gov/regulatory-information/search-fda-guidance-documents/digital-health-technologies-remote-data-acquisition-clinical-investigations.
———. 2023i. “Patient-Focused Drug Development: Incorporating
Clinical Outcome Assessments into Endpoints for Regulatory
Decision-Making.” https://www.fda.gov/regulatory-information/search-fda-guidance-documents/patient-focused-drug-development-incorporating-clinical-outcome-assessments-endpoints-regulatory.
———. 2023j. “Adjusting for Covariates in Randomized Clinical
Trials for Drugs and Biological Products: Guidance for Industry.”
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/adjusting-covariates-randomized-clinical-trials-drugs-and-biological-products.
———. 2024a. “21 CFR 312.32: IND Safety Reporting.” https://www.ecfr.gov/current/title-21/chapter-I/subchapter-D/part-312/subpart-B/section-312.32.
———. 2024b. “21 CFR Part 312: Investigational New Drug
Application.” https://www.ecfr.gov/current/title-21/chapter-I/subchapter-D/part-312.
———. 2024c. “21 CFR Part 54: Financial Disclosure by Clinical
Investigators.” https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-54.
———. 2024d. “Clinical Pharmacology Guidance Documents.” https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs.
———. 2024e. “Diversity Action Plans to Improve Enrollment of
Participants from Underrepresented Populations in Clinical Studies:
Guidance for Industry.” https://www.fda.gov/regulatory-information/search-fda-guidance-documents/diversity-action-plans-improve-enrollment-participants-underrepresented-populations-clinical-studies.
———. 2024f. “Electronic Systems, Electronic Records, and
Electronic Signatures in Clinical Investigations: Questions and
Answers.” https://www.fda.gov/regulatory-information/search-fda-guidance-documents/electronic-systems-electronic-records-and-electronic-signatures-clinical-investigations-questions.
———. 2024g. “FDA Adverse Event Reporting System (FAERS) Public
Dashboard.” https://www.fda.gov/drugs/drug-approvals-and-databases/fda-adverse-event-reporting-system-faers-database.
———. 2024h. “FDA Organization.” https://www.fda.gov/about-fda/fda-organization.
———. 2024i. “Optimizing the Dosage of Human Prescription Drugs and
Biological Products for the Treatment of Oncologic Diseases.”
Guidance for Industry, Center for Drug Evaluation and Research and
Center for Biologics Evaluation and Research. https://www.fda.gov/media/164555/download.
———. 2024j. “Pharmacokinetics in Patients with Impaired Renal
Function: Study Design, Data Analysis, and Impact on Dosing. Guidance
for Industry.” https://www.fda.gov/media/78573/download.
———. 2024k. “Real-World Data: Assessing Electronic Health Records
and Medical Claims Data to Support Regulatory Decision-Making for Drug
and Biological Products.” https://www.fda.gov/regulatory-information/search-fda-guidance-documents/real-world-data-assessing-electronic-health-records-and-medical-claims-data-support-regulatory.
———. 2024l. “Risk Evaluation and Mitigation Strategies
(REMS).” https://www.fda.gov/drugs/drug-safety-and-availability/risk-evaluation-and-mitigation-strategies-rems.
———. 2024m. “Study Data Technical Conformance Guide.” https://www.fda.gov/regulatory-information/search-fda-guidance-documents/study-data-technical-conformance-guide-technical-specifications-document.
———. 2024n. “Conducting Clinical Trials with Decentralized
Elements.” https://www.fda.gov/regulatory-information/search-fda-guidance-documents/conducting-clinical-trials-decentralized-elements.
———. 2025a. “CDER/CBER Rare Disease Evidence Principles
(RDEP).” https://www.fda.gov/industry/fda-rare-disease-innovation-hub/cdercber-rare-disease-evidence-principles-rdep.
———. 2025b. “Drug Development Tools: Fit-for-Purpose
Initiative.” https://www.fda.gov/drugs/development-approval-process-drugs/drug-development-tools-fit-purpose-initiative.
———. 2025c. “Enhancing Participation in Clinical Trials:
Eligibility Criteria, Enrollment Practices, and Trial Designs.”
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/enhancing-participation-clinical-trials-eligibility-criteria-enrollment-practices-and-trial-designs.
———. 2025d. “FDA Qualifies Total Hip Bone Mineral
Density (BMD) as Surrogate Endpoint for Osteoporosis Drug
Development.” https://www.fda.gov/drugs/drug-safety-and-availability/fda-qualifies-total-hip-bone-mineral-density-bmd-surrogate-endpoint-osteoporosis-drug-development.
———. 2025e. “Pediatric Labeling Changes.” https://www.fda.gov/science-research/pediatrics/pediatric-labeling-changes.
———. 2025f. “Considerations for the Use of Artificial Intelligence
to Support Regulatory Decision-Making for Drug and Biological
Products.” https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-use-artificial-intelligence-support-regulatory-decision-making-drug-and-biological.
———. 2026a. “Demonstrating Substantial Evidence of Effectiveness
for Human Drug and Biological Products.” https://www.fda.gov/regulatory-information/search-fda-guidance-documents/demonstrating-substantial-evidence-effectiveness-human-drug-and-biological-products.
———. 2026b. “FDA Launches New Adverse Event
Look-Up Tool.” https://www.fda.gov/news-events/press-announcements/fda-launches-new-adverse-event-look-tool.
———. 2026c. “Master Protocols for Drug and Biological Product
Development: Guidance for Industry.” https://www.fda.gov/regulatory-information/search-fda-guidance-documents/master-protocols-drug-and-biological-product-development.
———. 2026d. “Prescription Drug User Fee Rates for Fiscal Year
2027.” Federal Register 91 FR 48160, 30 July 2026. https://www.federalregister.gov/documents/2026/07/30/2026-15334/prescription-drug-user-fee-rates-for-fiscal-year-2027.
———. 2026e. “Use of Bayesian Methodology in Clinical
Trials of Drug and Biological Products.” U.S. Food and Drug
Administration. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-bayesian-methodology-clinical-trials-drug-and-biological-products.
U.S. Food and Drug Administration, Oncology Center of Excellence. 2024a.
“Project Orbis.” https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis.
———. 2024b. “Real-Time Oncology Review (RTOR).” https://www.fda.gov/about-fda/oncology-center-excellence/real-time-oncology-review.
U.S. Food and Drug Administration, and European Medicines Agency. 2026.
“Guiding Principles of Good AI Practice in Drug
Development.” https://www.fda.gov/media/189581/download.
U.S. Food and Drug Administration, Health Canada, and UK Medicines and
Healthcare products Regulatory Agency. 2021. “Good Machine
Learning Practice for Medical Device Development: Guiding
Principles.” https://www.fda.gov/medical-devices/software-medical-device-samd/good-machine-learning-practice-medical-device-development-guiding-principles.
US Food and Drug Administration, Center for Biologics Evaluation and
Research. 2022. “Clinical Review Memorandum: REBYOTA
(Fecal Microbiota, Live-jslm),
BLA 125739.” US Food and Drug
Administration. https://www.fda.gov/media/164040/download.
VanderWeele, Tyler J., and Peng Ding. 2017. “Sensitivity Analysis
in Observational Research: Introducing the E-Value.”
Annals of Internal Medicine 167 (4): 268–74. https://doi.org/10.7326/M16-2607.
Veeva Systems. 2024a. “Veeva TMF Intake Agent and Quality Check
Agent.” https://www.veeva.com/resources/tmf-intake-agent-and-quality-check-agent/.
———. 2024b. “Veeva Vault Clinical Suite.” https://www.veeva.com/products/vault-clinical/.
———. 2026. “Veeva eTMF.” https://www.veeva.com/products/veeva-etmf/.
Venkatesh, Kaushik P., Marium M. Raza, and Joseph C. Kvedar. 2022.
“Health Digital Twins as Tools for Precision Medicine:
Considerations for Computation, Implementation, and Regulation.”
Npj Digital Medicine 5: 150. https://doi.org/10.1038/s41746-022-00694-7.
Wagner, John, Andrew M. Dahlem, Lynn D. Hudson, Sharon F. Terry, Russ B.
Altman, C. Taylor Gilliland, Christopher DeFeo, and Christopher P.
Austin. 2018a. “A Dynamic Map for Learning, Communicating,
Navigating and Improving Therapeutic Development.” Nature
Reviews Drug Discovery 17 (2): 150. https://doi.org/10.1038/nrd.2017.217.
———. 2018b. “Application of a Dynamic Map for Learning,
Communicating, Navigating, and Improving Therapeutic
Development.” Clinical and Translational Science 11 (2):
166–74. https://doi.org/10.1111/cts.12531.
Wald, Abraham. 1947. Sequential Analysis. New York: John Wiley
& Sons.
Wang, Haiyun, and Douglas Yee. 2019. “I-SPY 2: A
Neoadjuvant Adaptive Clinical Trial Designed to Improve Outcomes in
High-Risk Breast Cancer.” Current Breast Cancer Reports
11 (4): 303–10. https://doi.org/10.1007/s12609-019-00334-2.
Wang, Lei, Chen Ma, Xueyang Feng, Zeyu Zhang, Hao Yang, Jingsen Zhang,
Zhiyuan Chen, et al. 2024. “A Survey on Large Language Model Based
Autonomous Agents.” Frontiers of Computer Science 18
(6): 186345. https://arxiv.org/abs/2308.11432.
Wang, Zifeng, Junyi Gao, Benjamin Danek, Brandon Theodorou, Ruba Shaik,
Shivashankar Thati, Seunghyun Won, and Jimeng Sun. 2025.
“Compliance and Factuality of Large Language Models for Clinical
Research Document Generation.” Journal of the American
Medical Informatics Association. https://doi.org/10.1093/jamia/ocaf174.
Warraich, Haider J., Troy Tazbaz, and Robert M. Califf. 2025. “FDA
Perspective on the Regulation of Artificial Intelligence in Health Care
and Biomedicine.” JAMA 333 (3): 241–47. https://doi.org/10.1001/jama.2024.21451.
Wasserstein, Ronald L., and Nicole A. Lazar. 2016. “The
ASA Statement on p-Values: Context, Process, and
Purpose.” The American Statistician 70 (2): 129–33. https://doi.org/10.1080/00031305.2016.1154108.
WCG Clinical. 2024. “2024 Clinical Research Site Challenges
Report: Data-Driven Insights on Current Site Challenges and Strategic
Recommendations to Overcome Barriers and Boost Clinical Trial
Efficiency.” https://www.wcgclinical.com/wp-content/uploads/2024/10/WCG_2024_Clinical_Research_Site_Challenges_Report.pdf.
Wei, Jason, Xuezhi Wang, Dale Schuurmans, Maarten Bosma, Brian Ichter,
Fei Xia, Ed Chi, Quoc Le, and Denny Zhou. 2022. “Chain-of-Thought
Prompting Elicits Reasoning in Large Language Models.”
Advances in Neural Information Processing Systems 35: 24824–37.
https://arxiv.org/abs/2201.11903.
Wei, L. J., and S. Durham. 1978. “The Randomized Play-the-Winner
Rule in Medical Trials.” Journal of the American Statistical
Association 73 (364): 840–43. https://doi.org/10.1080/01621459.1978.10480109.
Wenzl, Martin, and Suzannah Chapman. 2019. “Performance-Based
Managed Entry Agreements for New Medicines in OECD
Countries and EU Member States: How They Work and Possible
Improvements Going Forward.” OECD Health Working Paper 115.
Paris: Organisation for Economic Co-operation and
Development. https://doi.org/10.1787/6e5e4c0f-en.
WHO Working Group on the Clinical Characterisation and Management of
COVID-19 infection. 2020. “A Minimal Common Outcome Measure Set
for COVID-19 Clinical Research.” Lancet
Infectious Diseases 20 (8): e192–97. https://doi.org/10.1016/S1473-3099(20)30483-7.
Wong, Chi Heem, Kien Wei Siah, and Andrew W. Lo. 2019. “Estimation
of Clinical Trial Success Rates and Related Parameters.”
Biostatistics 20 (2): 273–86. https://doi.org/10.1093/biostatistics/kxx069.
Woodcock, Janet, and Lisa M. LaVange. 2017. “Master Protocols to
Study Multiple Therapies, Multiple Diseases, or Both.” New
England Journal of Medicine 377 (1): 62–70. https://doi.org/10.1056/NEJMra1510062.
World Health Organization. 2021. “Ethics and Governance of
Artificial Intelligence for Health.” https://iris.who.int/handle/10665/341996.
World Medical Association. 2013. “Declaration of Helsinki: Ethical
Principles for Medical Research Involving Human Subjects.” https://www.wma.net/policies-post/wma-declaration-of-helsinki/.
———. 2025. “World Medical Association Declaration of Helsinki:
Ethical Principles for Medical Research Involving Human
Participants.” JAMA 333 (1): 71–74. https://doi.org/10.1001/jama.2024.21972.
Wu, Qingyun, Gagan Bansal, Jieyu Zhang, Yiran Wu, Beibin Li, Erkang Zhu,
Li Jiang, et al. 2023. “AutoGen: Enabling Next-Gen LLM
Applications via Multi-Agent Conversation.” arXiv Preprint
arXiv:2308.08155. https://arxiv.org/abs/2308.08155.
Xu, Yang, Min Dong, and Xuemei Liu. 2020. “Characteristics and
Trends of Clinical Studies Primarily Sponsored by China in WHO Primary
Registries Between 2009 and 2018: A Cross-Sectional Survey.”
BMJ Open 10 (11): e037262. https://doi.org/10.1136/bmjopen-2020-037262.
Yao, Shunyu, Jeffrey Zhao, Dian Yu, Nan Du, Izhak Shafran, Karthik
Narasimhan, and Yuan Cao. 2023. “ReAct: Synergizing Reasoning and
Acting in Language Models.” International Conference on
Learning Representations. https://arxiv.org/abs/2210.03629.
Yuan, Ying, Kenneth R. Hess, Susan G. Hilsenbeck, and Mark R. Gilbert.
2016. “Bayesian Optimal Interval Design: A Simple and
Well-Performing Design for Phase I Oncology Trials.”
Clinical Cancer Research 22 (17): 4291–301. https://doi.org/10.1158/1078-0432.CCR-16-0592.
Zhou, Xian, Suyu Liu, Edward S. Kim, Roy S. Herbst, and J. Jack Lee.
2008. “Bayesian Adaptive Design for Targeted Therapy Development
in Lung Cancer.” Clinical Trials 5 (3): 181–93. https://doi.org/10.1177/1740774508091815.