Measuring What Matters in Trial Operations: Development and Validation of the Clinical Trial Site Performance Measure

Bozzetti, Mattia; Lo Cascio, Alessio; Napolitano, Daniele; Orgiana, Nicoletta; Mora, Vincenzina; Fiorini, Stefania; Petrucci, Giorgia; Resente, Francesca; Baroni, Irene; Caruso, Rosario; Guberti, Monica

doi:10.3390/jcm14196839

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Open AccessArticle

Measuring What Matters in Trial Operations: Development and Validation of the Clinical Trial Site Performance Measure

by

Mattia Bozzetti

¹

,

Alessio Lo Cascio

²

,

Daniele Napolitano

^3,*

,

Nicoletta Orgiana

^3,*,

Vincenzina Mora

³,

Stefania Fiorini

⁴,

Giorgia Petrucci

⁵,

Francesca Resente

⁶,

Irene Baroni

⁷

,

Rosario Caruso

^7,8,†

and

Monica Guberti

^9,†,‡

on behalf of the Performance Working Goup

¹

Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy

²

Direction of Health Professions, La Maddalena Cancer Center, 90146 Palermo, Italy

³

CEMAD, Fondazione Policlinico Gemelli IRCCS, 00168 Rome, Italy

⁴

Department of Cardiovascular, Neural and Metabolic Sciences, Istituto Auxologico Italiano, IRCSS San Luca Hospital, 20149 Milan, Italy

⁵

Operative Research Unit of Orthopaedic and Trauma Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy

⁶

Department of Oncohematology, Presidio Infantile Regina Margherita, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, 10126 Turin, Italy

⁷

Health Professions Research and Development Unit, IRCSS Policlinico San Donato, 20097 San Donato Milanese, Italy

⁸

Department of Biomedical Sciences for Health, University of Milan, 20141 Milan, Italy

⁹

Allied Health Professions Directorate, Istituto Ortopedico Rizzoli, 40136 Bologna, Italy

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

^‡

Collaborators/Membership of Performance Working Group is provided in Appendix A.

J. Clin. Med. 2025, 14(19), 6839; https://doi.org/10.3390/jcm14196839

Submission received: 2 September 2025 / Revised: 23 September 2025 / Accepted: 25 September 2025 / Published: 26 September 2025

(This article belongs to the Special Issue New Advances in Clinical Epidemiological Research Methods)

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Abstract

Background/Objectives: The execution of clinical trials is increasingly constrained by operational complexity, regulatory requirements, and variability in site performance. These challenges have direct implications for the reliability of trial outcomes. However, standardized methods to evaluate site-level performance remain underdeveloped. This study introduces the Clinical Trial Site Performance Measure (CT-SPM), a novel framework designed to systematically capture site-level operational quality and to provide a scalable short form for routine monitoring. Methods: We conducted a multicenter study across six Italian academic hospitals (January–June 2025). Candidate performance indicators were identified through a systematic review and expert consultation, followed by validation and reduction using advanced statistical approaches, including factor modeling, ROC curve analysis, and nonparametric scaling methods. The CT-SPM was assessed for structural validity, discriminative capacity, and feasibility for use in real-world settings. Results: From 126 potential indicators, 18 were retained and organized into four domains: Participant Retention and Consent, Data Completeness and Timeliness, Adverse Event Reporting, and Protocol Compliance. A bifactor model revealed two higher-order dimensions (participant-facing and data-facing performance), highlighting the multidimensional nature of site operations. A short form comprising four items demonstrated good scalability and sufficient accuracy to identify underperforming sites. Conclusions: The CT-SPM represents an innovative, evidence-based instrument for monitoring trial execution at the site level. By linking methodological rigor with real-world applicability, it offers a practical solution for benchmarking, resource allocation, and regulatory compliance. This approach contributes to advancing clinical research by providing a standardized, data-driven method to evaluate and improve performance across networks.

Keywords: clinical trials; site performance; real-world data; advanced statistical methods; regulatory challenges; operational metrics; quality monitoring; clinical epidemiology; clinical trial site performance measure

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MDPI and ACS Style

Bozzetti, M.; Lo Cascio, A.; Napolitano, D.; Orgiana, N.; Mora, V.; Fiorini, S.; Petrucci, G.; Resente, F.; Baroni, I.; Caruso, R.; et al. Measuring What Matters in Trial Operations: Development and Validation of the Clinical Trial Site Performance Measure. J. Clin. Med. 2025, 14, 6839. https://doi.org/10.3390/jcm14196839

AMA Style

Bozzetti M, Lo Cascio A, Napolitano D, Orgiana N, Mora V, Fiorini S, Petrucci G, Resente F, Baroni I, Caruso R, et al. Measuring What Matters in Trial Operations: Development and Validation of the Clinical Trial Site Performance Measure. Journal of Clinical Medicine. 2025; 14(19):6839. https://doi.org/10.3390/jcm14196839

Chicago/Turabian Style

Bozzetti, Mattia, Alessio Lo Cascio, Daniele Napolitano, Nicoletta Orgiana, Vincenzina Mora, Stefania Fiorini, Giorgia Petrucci, Francesca Resente, Irene Baroni, Rosario Caruso, and et al. 2025. "Measuring What Matters in Trial Operations: Development and Validation of the Clinical Trial Site Performance Measure" Journal of Clinical Medicine 14, no. 19: 6839. https://doi.org/10.3390/jcm14196839

APA Style

Bozzetti, M., Lo Cascio, A., Napolitano, D., Orgiana, N., Mora, V., Fiorini, S., Petrucci, G., Resente, F., Baroni, I., Caruso, R., & Guberti, M., on behalf of the Performance Working Goup. (2025). Measuring What Matters in Trial Operations: Development and Validation of the Clinical Trial Site Performance Measure. Journal of Clinical Medicine, 14(19), 6839. https://doi.org/10.3390/jcm14196839

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