Electronic health records (EHRs) in clinical research and platform trials: Application of the innovative EHR-based methods developed by EU-PEARL

Giulia Lombardo; Camille Couvert; Melisa Kose; Amina Begum; Cecile Spiertz; Courtney Worrell; Danny Hasselbaink; Eva-Maria Didden; Luca Sforzini; Marija Todorovic; Martine Lewi; Mollie Brown; Morgan Vaterkowski; Nancy Gullet; Nare Amasi-Hartoonian; Nicolas Griffon; Raluca Pais; Sarai Rodriguez Navarro; Andreas Kremer; Christophe Maes; Eng Hooi Tan; Maxim Moinat; Joan Genescà Ferrer; Carmine M Pariante; Dipak Kalra; Nadir Ammour; Susana Kalko

doi:10.1016/j.jbi.2023.104553

Electronic health records (EHRs) in clinical research and platform trials: Application of the innovative EHR-based methods developed by EU-PEARL

Giulia Lombardo, Camille Couvert, Melisa Kose, Amina Begum, Cecile Spiertz, Courtney Worrell, Danny Hasselbaink, Eva-Maria Didden, Luca Sforzini, Marija Todorovic, Martine Lewi, Mollie Brown, Morgan Vaterkowski, Nancy Gullet, Nare Amasi-Hartoonian, Nicolas Griffon, Raluca Pais, Sarai Rodriguez Navarro, Andreas Kremer, Christophe MaesEng Hooi Tan, Maxim Moinat, Joan Genescà Ferrer, Carmine M Pariante, Dipak Kalra, Nadir Ammour, Susana Kalko

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

Abstract

OBJECTIVE: Electronic Health Record (EHR) systems are digital platforms in clinical practice used to collect patients' clinical information related to their health status and represents a useful storage of real-world data. EHRs have a potential role in research studies, in particular, in platform trials. Platform trials are innovative trial designs including multiple trial arms (conducted simultaneously and/or sequentially) on different treatments under a single master protocol. However, the use of EHRs in research comes with important challenges such as incompleteness of records and the need to translate trial eligibility criteria into interoperable queries. In this paper, we aim to review and to describe our proposed innovative methods to tackle some of the most important challenges identified. This work is part of the Innovative Medicines Initiative (IMI) EU Patient-cEntric clinicAl tRial pLatforms (EU-PEARL) project's work package 3 (WP3), whose objective is to deliver tools and guidance for EHR-based protocol feasibility assessment, clinical site selection, and patient pre-screening in platform trials, investing in the building of a data-driven clinical network framework that can execute these complex innovative designs for which feasibility assessments are critically important.

METHODS: ISO standards and relevant references informed a readiness survey, producing 354 criteria with corresponding questions selected and harmonised through a 7-round scoring process (0-1) in stakeholder meetings, with 85% of consensus being the threshold of acceptance for a criterium/question. ATLAS cohort definition and Cohort Diagnostics were mainly used to create the trial feasibility eligibility (I/E) criteria as executable interoperable queries.

RESULTS: The WP3/EU-PEARL group developed a readiness survey (eSurvey) for an efficient selection of clinical sites with suitable EHRs, consisting of yes-or-no questions, and a set-up of interoperable proxy queries using physicians' defined trial criteria. Both actions facilitate recruiting trial participants and alignment between study costs/timelines and data-driven recruitment potential.

CONCLUSION: The eSurvey will help create an archive of clinical sites with mature EHR systems suitable to participate in clinical trials/platform trials, and the interoperable proxy queries of trial eligibility criteria will help identify the number of potential participants. Ultimately, these tools will contribute to the production of EHR-based protocol design.

Original language	English
Article number	104553
Pages (from-to)	104553
Journal	JOURNAL OF BIOMEDICAL INFORMATICS
Volume	148
DOIs	https://doi.org/10.1016/j.jbi.2023.104553
Publication status	Published - 22 Nov 2023

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10.1016/j.jbi.2023.104553

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Lombardo, G., Couvert, C., Kose, M., Begum, A., Spiertz, C., Worrell, C., Hasselbaink, D., Didden, E.-M., Sforzini, L., Todorovic, M., Lewi, M., Brown, M., Vaterkowski, M., Gullet, N., Amasi-Hartoonian, N., Griffon, N., Pais, R., Rodriguez Navarro, S., Kremer, A., ... Kalko, S. (2023). Electronic health records (EHRs) in clinical research and platform trials: Application of the innovative EHR-based methods developed by EU-PEARL. JOURNAL OF BIOMEDICAL INFORMATICS, 148, 104553. Article 104553. https://doi.org/10.1016/j.jbi.2023.104553

@article{601325bb877e4aa496515d36994d3ef9,

title = "Electronic health records (EHRs) in clinical research and platform trials: Application of the innovative EHR-based methods developed by EU-PEARL",

abstract = "OBJECTIVE: Electronic Health Record (EHR) systems are digital platforms in clinical practice used to collect patients' clinical information related to their health status and represents a useful storage of real-world data. EHRs have a potential role in research studies, in particular, in platform trials. Platform trials are innovative trial designs including multiple trial arms (conducted simultaneously and/or sequentially) on different treatments under a single master protocol. However, the use of EHRs in research comes with important challenges such as incompleteness of records and the need to translate trial eligibility criteria into interoperable queries. In this paper, we aim to review and to describe our proposed innovative methods to tackle some of the most important challenges identified. This work is part of the Innovative Medicines Initiative (IMI) EU Patient-cEntric clinicAl tRial pLatforms (EU-PEARL) project's work package 3 (WP3), whose objective is to deliver tools and guidance for EHR-based protocol feasibility assessment, clinical site selection, and patient pre-screening in platform trials, investing in the building of a data-driven clinical network framework that can execute these complex innovative designs for which feasibility assessments are critically important.METHODS: ISO standards and relevant references informed a readiness survey, producing 354 criteria with corresponding questions selected and harmonised through a 7-round scoring process (0-1) in stakeholder meetings, with 85% of consensus being the threshold of acceptance for a criterium/question. ATLAS cohort definition and Cohort Diagnostics were mainly used to create the trial feasibility eligibility (I/E) criteria as executable interoperable queries.RESULTS: The WP3/EU-PEARL group developed a readiness survey (eSurvey) for an efficient selection of clinical sites with suitable EHRs, consisting of yes-or-no questions, and a set-up of interoperable proxy queries using physicians' defined trial criteria. Both actions facilitate recruiting trial participants and alignment between study costs/timelines and data-driven recruitment potential.CONCLUSION: The eSurvey will help create an archive of clinical sites with mature EHR systems suitable to participate in clinical trials/platform trials, and the interoperable proxy queries of trial eligibility criteria will help identify the number of potential participants. Ultimately, these tools will contribute to the production of EHR-based protocol design.",

author = "Giulia Lombardo and Camille Couvert and Melisa Kose and Amina Begum and Cecile Spiertz and Courtney Worrell and Danny Hasselbaink and Eva-Maria Didden and Luca Sforzini and Marija Todorovic and Martine Lewi and Mollie Brown and Morgan Vaterkowski and Nancy Gullet and Nare Amasi-Hartoonian and Nicolas Griffon and Raluca Pais and {Rodriguez Navarro}, Sarai and Andreas Kremer and Christophe Maes and Tan, {Eng Hooi} and Maxim Moinat and Ferrer, {Joan Genesc{\`a}} and Pariante, {Carmine M} and Dipak Kalra and Nadir Ammour and Susana Kalko",

note = "Funding Information: The innovative EHR-based methods have been developed as part of the Innovative Medicines Initiative (IMI) EU Patient-cEntric clinicAl tRial pLatforms (EU-PEARL, http://eu-pearl.eu ). As described by Sforzini et al. [2] , EU-PEARL is a European project funded by the IMI aiming to create a design of an integrated research platform (IRP). The project aims to develop methodologies and tools to support the large-scale uptake of platform trial designs across Europe, and potentially globally. It aims to develop generic approaches but focuses on four major clinical areas of high public health relevance: major depressive disorder (MDD), tuberculosis (TB), non-alcoholic steatohepatitis (NASH), and neurofibromatosis (NF) [13] . During the EU-PEARL General Assembly Meeting, representatives from other well-known running platform trials have been invited to share their experience in setting up their own research platforms, by sharing lessons they learned and the challenges they faced (A Randomised, Embedded, Multi-factorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) [14] , the HEALY Amyotrophic Lateral Sclerosis (ALS) platform trial [15] , and Beat Acute Myeloid Leukemia (AML) platform trial [16] . The Leukaemia and Lymphoma Society leading the Beat AML platform has shared how they are successfully leveraging the data from the EHR to screen trial participants and direct them to the best available sub-study based on their specific information. One of the major advantages of this European project is the presence of various stakeholders within this reality: clinicians, patient representatives, clinical sites, regulators, solution providers, and pharmaceutical companies, with Janssen and Sanofi co-authors representing their perspectives. There is an important cooperation between all work packages (WPs) and, as highlighted by Cowie et al. [17] , the collaboration between different perspectives is an essential step towards the effective use of EHRs in clinical research. Furthermore, a master protocol in each disease-specific area is being developed and may be reported in future publications. Funding Information: “EU-PEARL has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 853966-2. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA and CHILDREN'S TUMOR FOUNDATION, GLOBAL ALLIANCE FOR TB DRUG DEVELOPMENT NON PROFIT ORGANISATION, SPRINGWORKS THERAPEUTICS INC.” Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = nov,

day = "22",

doi = "10.1016/j.jbi.2023.104553",

language = "English",

volume = "148",

pages = "104553",

journal = "JOURNAL OF BIOMEDICAL INFORMATICS",

issn = "1532-0464",

publisher = "ACADEMIC PRESS INC",

}

Lombardo, G, Couvert, C, Kose, M, Begum, A, Spiertz, C, Worrell, C, Hasselbaink, D, Didden, E-M, Sforzini, L, Todorovic, M, Lewi, M, Brown, M, Vaterkowski, M, Gullet, N, Amasi-Hartoonian, N, Griffon, N, Pais, R, Rodriguez Navarro, S, Kremer, A, Maes, C, Tan, EH, Moinat, M, Ferrer, JG, Pariante, CM, Kalra, D, Ammour, N & Kalko, S 2023, 'Electronic health records (EHRs) in clinical research and platform trials: Application of the innovative EHR-based methods developed by EU-PEARL', JOURNAL OF BIOMEDICAL INFORMATICS, vol. 148, 104553, pp. 104553. https://doi.org/10.1016/j.jbi.2023.104553

TY - JOUR

T1 - Electronic health records (EHRs) in clinical research and platform trials

T2 - Application of the innovative EHR-based methods developed by EU-PEARL

AU - Lombardo, Giulia

AU - Couvert, Camille

AU - Kose, Melisa

AU - Begum, Amina

AU - Spiertz, Cecile

AU - Worrell, Courtney

AU - Hasselbaink, Danny

AU - Didden, Eva-Maria

AU - Sforzini, Luca

AU - Todorovic, Marija

AU - Lewi, Martine

AU - Brown, Mollie

AU - Vaterkowski, Morgan

AU - Gullet, Nancy

AU - Amasi-Hartoonian, Nare

AU - Griffon, Nicolas

AU - Pais, Raluca

AU - Rodriguez Navarro, Sarai

AU - Kremer, Andreas

AU - Maes, Christophe

AU - Tan, Eng Hooi

AU - Moinat, Maxim

AU - Ferrer, Joan Genescà

AU - Pariante, Carmine M

AU - Kalra, Dipak

AU - Ammour, Nadir

AU - Kalko, Susana

N1 - Funding Information: The innovative EHR-based methods have been developed as part of the Innovative Medicines Initiative (IMI) EU Patient-cEntric clinicAl tRial pLatforms (EU-PEARL, http://eu-pearl.eu ). As described by Sforzini et al. [2] , EU-PEARL is a European project funded by the IMI aiming to create a design of an integrated research platform (IRP). The project aims to develop methodologies and tools to support the large-scale uptake of platform trial designs across Europe, and potentially globally. It aims to develop generic approaches but focuses on four major clinical areas of high public health relevance: major depressive disorder (MDD), tuberculosis (TB), non-alcoholic steatohepatitis (NASH), and neurofibromatosis (NF) [13] . During the EU-PEARL General Assembly Meeting, representatives from other well-known running platform trials have been invited to share their experience in setting up their own research platforms, by sharing lessons they learned and the challenges they faced (A Randomised, Embedded, Multi-factorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) [14] , the HEALY Amyotrophic Lateral Sclerosis (ALS) platform trial [15] , and Beat Acute Myeloid Leukemia (AML) platform trial [16] . The Leukaemia and Lymphoma Society leading the Beat AML platform has shared how they are successfully leveraging the data from the EHR to screen trial participants and direct them to the best available sub-study based on their specific information. One of the major advantages of this European project is the presence of various stakeholders within this reality: clinicians, patient representatives, clinical sites, regulators, solution providers, and pharmaceutical companies, with Janssen and Sanofi co-authors representing their perspectives. There is an important cooperation between all work packages (WPs) and, as highlighted by Cowie et al. [17] , the collaboration between different perspectives is an essential step towards the effective use of EHRs in clinical research. Furthermore, a master protocol in each disease-specific area is being developed and may be reported in future publications. Funding Information: “EU-PEARL has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 853966-2. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA and CHILDREN'S TUMOR FOUNDATION, GLOBAL ALLIANCE FOR TB DRUG DEVELOPMENT NON PROFIT ORGANISATION, SPRINGWORKS THERAPEUTICS INC.” Publisher Copyright: © 2023 The Authors

PY - 2023/11/22

Y1 - 2023/11/22

N2 - OBJECTIVE: Electronic Health Record (EHR) systems are digital platforms in clinical practice used to collect patients' clinical information related to their health status and represents a useful storage of real-world data. EHRs have a potential role in research studies, in particular, in platform trials. Platform trials are innovative trial designs including multiple trial arms (conducted simultaneously and/or sequentially) on different treatments under a single master protocol. However, the use of EHRs in research comes with important challenges such as incompleteness of records and the need to translate trial eligibility criteria into interoperable queries. In this paper, we aim to review and to describe our proposed innovative methods to tackle some of the most important challenges identified. This work is part of the Innovative Medicines Initiative (IMI) EU Patient-cEntric clinicAl tRial pLatforms (EU-PEARL) project's work package 3 (WP3), whose objective is to deliver tools and guidance for EHR-based protocol feasibility assessment, clinical site selection, and patient pre-screening in platform trials, investing in the building of a data-driven clinical network framework that can execute these complex innovative designs for which feasibility assessments are critically important.METHODS: ISO standards and relevant references informed a readiness survey, producing 354 criteria with corresponding questions selected and harmonised through a 7-round scoring process (0-1) in stakeholder meetings, with 85% of consensus being the threshold of acceptance for a criterium/question. ATLAS cohort definition and Cohort Diagnostics were mainly used to create the trial feasibility eligibility (I/E) criteria as executable interoperable queries.RESULTS: The WP3/EU-PEARL group developed a readiness survey (eSurvey) for an efficient selection of clinical sites with suitable EHRs, consisting of yes-or-no questions, and a set-up of interoperable proxy queries using physicians' defined trial criteria. Both actions facilitate recruiting trial participants and alignment between study costs/timelines and data-driven recruitment potential.CONCLUSION: The eSurvey will help create an archive of clinical sites with mature EHR systems suitable to participate in clinical trials/platform trials, and the interoperable proxy queries of trial eligibility criteria will help identify the number of potential participants. Ultimately, these tools will contribute to the production of EHR-based protocol design.

AB - OBJECTIVE: Electronic Health Record (EHR) systems are digital platforms in clinical practice used to collect patients' clinical information related to their health status and represents a useful storage of real-world data. EHRs have a potential role in research studies, in particular, in platform trials. Platform trials are innovative trial designs including multiple trial arms (conducted simultaneously and/or sequentially) on different treatments under a single master protocol. However, the use of EHRs in research comes with important challenges such as incompleteness of records and the need to translate trial eligibility criteria into interoperable queries. In this paper, we aim to review and to describe our proposed innovative methods to tackle some of the most important challenges identified. This work is part of the Innovative Medicines Initiative (IMI) EU Patient-cEntric clinicAl tRial pLatforms (EU-PEARL) project's work package 3 (WP3), whose objective is to deliver tools and guidance for EHR-based protocol feasibility assessment, clinical site selection, and patient pre-screening in platform trials, investing in the building of a data-driven clinical network framework that can execute these complex innovative designs for which feasibility assessments are critically important.METHODS: ISO standards and relevant references informed a readiness survey, producing 354 criteria with corresponding questions selected and harmonised through a 7-round scoring process (0-1) in stakeholder meetings, with 85% of consensus being the threshold of acceptance for a criterium/question. ATLAS cohort definition and Cohort Diagnostics were mainly used to create the trial feasibility eligibility (I/E) criteria as executable interoperable queries.RESULTS: The WP3/EU-PEARL group developed a readiness survey (eSurvey) for an efficient selection of clinical sites with suitable EHRs, consisting of yes-or-no questions, and a set-up of interoperable proxy queries using physicians' defined trial criteria. Both actions facilitate recruiting trial participants and alignment between study costs/timelines and data-driven recruitment potential.CONCLUSION: The eSurvey will help create an archive of clinical sites with mature EHR systems suitable to participate in clinical trials/platform trials, and the interoperable proxy queries of trial eligibility criteria will help identify the number of potential participants. Ultimately, these tools will contribute to the production of EHR-based protocol design.

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Electronic health records (EHRs) in clinical research and platform trials: Application of the innovative EHR-based methods developed by EU-PEARL

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