IDEAS home Printed from https://ideas.repec.org/a/plo/pdig00/0001621.html

Clinical predictive artificial intelligence evaluation: A narrative review of trial designs and practical considerations

Author

Listed:
  • Maxime Fosset
  • Joris Pensier
  • Boris Jung
  • Arjumand Siddiqi
  • Muhammad Mamdani
  • Leo Anthony Celi

Abstract

Artificial intelligence (AI) predictive models demonstrate potential for transforming clinical decision-making across medicine. However, conventional randomized controlled trials (RCTs), the gold standard for evaluating medical interventions, are ill-suited for clinical AI tools due to their static design, lengthy timelines, and inability to accommodate algorithms that evolve and adapt to changing clinical contexts. In this narrative review, we outline the limitations of traditional evaluation frameworks and propose a paradigm shift toward adaptive, iterative, and context-specific assessment methodologies. Evaluating clinical AI in practice requires three interdependent but epistemologically distinct activities: performance monitoring, which tracks the technical characteristics of the deployed model (calibration, discrimination, data drift, alert burden, fairness, workflow fidelity); clinical impact monitoring, which observationally and prospectively tracks whether the initial clinical benefit appears sustained over time; and scientific evidence generation, which produces causal estimates of deployment effects on patient outcomes through pragmatic, adaptive trial designs and causal inference techniques. We propose a predictive-AI-specific framework that links performance monitoring, clinical impact monitoring, evidence generation, causal estimands, and governance of model updates into one coherent decision pathway for clinicians and trialists. We present a governance-driven escalation protocol specifying when monitoring signals should trigger formal evidence generation, a decision pathway mapping signal types (performance or clinical impact) to trial design classifications, and a guide to causal inference methods for clinical AI trials. Drawing from adaptive platform and pragmatic trial designs, we recommend continuous monitoring approaches that prioritize patient-centered outcomes, health equity, and workflow integration over narrow performance metrics, and provide actionable steps to design a clinical AI trial. Successful implementation requires clinician engagement, transparency, and ongoing education regarding AI capabilities and limitations. Within this new evaluation paradigm, predictive AI can progress from a promising technology to reliable clinical tools that improve patient outcomes, support clinical decision-making, and uphold ethical standards in routine practice.

Suggested Citation

  • Maxime Fosset & Joris Pensier & Boris Jung & Arjumand Siddiqi & Muhammad Mamdani & Leo Anthony Celi, 2026. "Clinical predictive artificial intelligence evaluation: A narrative review of trial designs and practical considerations," PLOS Digital Health, Public Library of Science, vol. 5(8), pages 1-20, August.
  • Handle: RePEc:plo:pdig00:0001621
    DOI: 10.1371/journal.pdig.0001621
    as

    Download full text from publisher

    File URL: https://journals.plos.org/digitalhealth/article?id=10.1371/journal.pdig.0001621
    Download Restriction: no

    File URL: https://journals.plos.org/digitalhealth/article/file?id=10.1371/journal.pdig.0001621&type=printable
    Download Restriction: no

    File URL: https://libkey.io/10.1371/journal.pdig.0001621?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Kenneth F Schulz & Douglas G Altman & David Moher & for the CONSORT Group, 2010. "CONSORT 2010 Statement: Updated Guidelines for Reporting Parallel Group Randomised Trials," PLOS Medicine, Public Library of Science, vol. 7(3), pages 1-7, March.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Michael J. Fell & Alexandra Schneiders & David Shipworth, 2019. "Consumer Demand for Blockchain-Enabled Peer-to-Peer Electricity Trading in the United Kingdom: An Online Survey Experiment," Energies, MDPI, vol. 12(20), pages 1-25, October.
    2. Sjöberg Tala, Camilo Alejandro (M.D.), 2025. "ECLIPSE v2.0: A Systematic Falsification Framework with Quantitative Integrity Metrics," MetaArXiv z3fke_v1, Center for Open Science.
    3. Su Keng Tan & Wai Keung Leung & Alexander Tin Hong Tang & Roger A Zwahlen, 2017. "Effects of mandibular setback with or without maxillary advancement osteotomies on pharyngeal airways: An overview of systematic reviews," PLOS ONE, Public Library of Science, vol. 12(10), pages 1-20, October.
    4. Ángel Enrique & Juana Bretón-López & Guadalupe Molinari & Rosa M. Baños & Cristina Botella, 2018. "Efficacy of an adaptation of the Best Possible Self intervention implemented through positive technology: a randomized control trial," Applied Research in Quality of Life, Springer;International Society for Quality-of-Life Studies, vol. 13(3), pages 671-689, September.
    5. Gerben ter Riet & Paula Chesley & Alan G Gross & Lara Siebeling & Patrick Muggensturm & Nadine Heller & Martin Umbehr & Daniela Vollenweider & Tsung Yu & Elie A Akl & Lizzy Brewster & Olaf M Dekkers &, 2013. "All That Glitters Isn't Gold: A Survey on Acknowledgment of Limitations in Biomedical Studies," PLOS ONE, Public Library of Science, vol. 8(11), pages 1-6, November.
    6. Iranzu Mugueta-Aguinaga & Begonya Garcia-Zapirain, 2017. "FRED: Exergame to Prevent Dependence and Functional Deterioration Associated with Ageing. A Pilot Three-Week Randomized Controlled Clinical Trial," IJERPH, MDPI, vol. 14(12), pages 1-18, November.
    7. repec:plo:pone00:0035621 is not listed on IDEAS
    8. Spyridon N Papageorgiou & Georgios N Antonoglou & George K Sándor & Theodore Eliades, 2017. "Randomized clinical trials in orthodontics are rarely registered a priori and often published late or not at all," PLOS ONE, Public Library of Science, vol. 12(8), pages 1-13, August.
    9. Milagros Molero-Zafra & María Teresa Mitjans-Lafont & María Jesús Hernández-Jiménez & Marián Pérez-Marín, 2022. "Psychological Intervention in Women Victims of Childhood Sexual Abuse: An Open Study—Protocol of a Randomized Controlled Clinical Trial Comparing EMDR Psychotherapy and Trauma-Based Cognitive Therapy," IJERPH, MDPI, vol. 19(12), pages 1-16, June.
    10. Eun-Hi Kong & Myoungsuk Kim & Seonho Kim, 2021. "Effects of a Web-Based Educational Program Regarding Physical Restraint Reduction in Long-Term Care Settings on Nursing Students: A Cluster Randomized Controlled Trial," IJERPH, MDPI, vol. 18(13), pages 1-10, June.
    11. Xiaoxuan Gong & Shaowen Tang & Jiangjin Li & Xiwen Zhang & Xiaoyi Tian & Shuren Ma, 2017. "Antithrombotic therapy strategies for atrial fibrillation patients undergoing percutaneous coronary intervention: A systematic review and network meta-analysis," PLOS ONE, Public Library of Science, vol. 12(10), pages 1-13, October.
    12. Stavros Petrou & Oliver Rivero-Arias & Helen Dakin & Louise Longworth & Mark Oppe & Robert Froud & Alastair Gray, 2015. "Preferred Reporting Items for Studies Mapping onto Preference-Based Outcome Measures: The MAPS Statement," Medical Decision Making, , vol. 35(6), pages 1-8, August.
    13. Alexander P. L. Martindale & Carrie D. Llewellyn & Richard O. Visser & Benjamin Ng & Victoria Ngai & Aditya U. Kale & Lavinia Ferrante Ruffano & Robert M. Golub & Gary S. Collins & David Moher & Melis, 2024. "Concordance of randomised controlled trials for artificial intelligence interventions with the CONSORT-AI reporting guidelines," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    14. Juliane Piasseschi de Bernardin Gonçalves & Giancarlo Lucchetti & Paulo Rossi Menezes & Homero Vallada, 2017. "Complementary religious and spiritual interventions in physical health and quality of life: A systematic review of randomized controlled clinical trials," PLOS ONE, Public Library of Science, vol. 12(10), pages 1-21, October.
    15. Jovana Kuzmanovic Pficer & Slobodan Dodic & Vojkan Lazic & Goran Trajkovic & Natasa Milic & Biljana Milicic, 2017. "Occlusal stabilization splint for patients with temporomandibular disorders: Meta-analysis of short and long term effects," PLOS ONE, Public Library of Science, vol. 12(2), pages 1-21, February.
    16. Weißbach Rafael, 2016. "Kommentar zu „Die Interpretation des p-Wertes – Grundsätzliche Missverständnisse“," Journal of Economics and Statistics (Jahrbuecher fuer Nationaloekonomie und Statistik), De Gruyter, vol. 236(5), pages 577-580, October.
    17. repec:plo:pone00:0072546 is not listed on IDEAS
    18. Wendy Hens & Dirk Vissers & Nick Verhaeghe & Jan Gielen & Luc Van Gaal & Jan Taeymans, 2021. "Unsupervised Exercise Training Was Not Found to Improve the Metabolic Health or Phenotype over a 6-Month Dietary Intervention: A Randomised Controlled Trial with an Embedded Economic Analysis," IJERPH, MDPI, vol. 18(15), pages 1-13, July.
    19. repec:plo:pone00:0217134 is not listed on IDEAS
    20. repec:plo:pmed00:1003421 is not listed on IDEAS
    21. Christopher Snyder & Ran Zhuo, 2018. "Sniff Tests as a Screen in the Publication Process: Throwing out the Wheat with the Chaff," NBER Working Papers 25058, National Bureau of Economic Research, Inc.
    22. Maria Giné-Garriga & Carme Martin-Borràs & Anna Puig-Ribera & Carlos Martín-Cantera & Mercè Solà & Antonio Cuesta-Vargas & on behalf of the PPAF Group, 2013. "The Effect of a Physical Activity Program on the Total Number of Primary Care Visits in Inactive Patients: A 15-Month Randomized Controlled Trial," PLOS ONE, Public Library of Science, vol. 8(6), pages 1-8, June.
    23. Clovis Mariano Faggion Jr & Yun-Chun Wu & Moritz Scheidgen & Yu-Kang Tu, 2015. "Effect of Risk of Bias on the Effect Size of Meta-Analytic Estimates in Randomized Controlled Trials in Periodontology and Implant Dentistry," PLOS ONE, Public Library of Science, vol. 10(9), pages 1-9, September.
    24. Salvador Angosto & Jerónimo García-Fernández & Irena Valantine & Moisés Grimaldi-Puyana, 2020. "The Intention to Use Fitness and Physical Activity Apps: A Systematic Review," Sustainability, MDPI, vol. 12(16), pages 1-25, August.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pdig00:0001621. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: digitalhealth (email available below). General contact details of provider: https://journals.plos.org/digitalhealth .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.