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

Electronic health records; Platform trialsRegistros médicos electrónicos; Pruebas de plataformaRegistres mèdics electrònics; Proves de plataformaObjective 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.“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.

Les voies de réparation de l’ADN comme source de marqueurs prédictifs dans le cancer de l’ovaire

Dans cette thèse, nous avons cherché à explorer les voies de réparation de l’ADN comme source de marqueurs prédictifs dans le cancer de l’ovaire. Le cancer de l'ovaire est une maladie gynécologique à forte mortalité affectant les femmes du monde entier. Depuis la découverte des mutations BRCA comme marqueurs prédictifs de la réponse au traitement à base de platine et aux thérapeutiques anti-Poly(ADP-ribose) polymérase, des améliorations ont pu être apportées pour les femmes porteuses de cette mutation ou présentant plus largement un profil déficient dans la voie de recombinaison homologue (HRD). Cependant 50% des patientes restent à ce jour soumises à la prise en charge classique du cancer de l’ovaire. Dans la recherche de biomarqueurs, la découverte des patientes présentant un profil HRD a permis de mettre en avant qu’au-delà de l’identification de mutations individuelles signatures de la déficience d’une des voies de la réparation de l’ADN, l’approche par profils fonctionnels (déficients ou compétents de certaines voies) pouvait apporter une information prédictive de la thérapeutique

Odor generation patterns during different operational composting stages of anaerobically digested sewage sludge

International audienceThis study aimed to evaluate the global patterns of odor generation and odorant composition for different operational stages of anaerobically digested sewage sludge (ADS) composting at pilot scale. To this end, gas emissions were sampled and analyzed during storage, forced aeration treatment (active phase), turning process and curing. For each operational stage, odors were monitored by measuring the odor emission rates (OER in OUE h'1 kg'1ADS) through dynamic olfactometry and computing the odor activity values (OAVs) of compounds quantified by analytical methods (i.e., GC/MS). Ammonia and volatile sulfur compounds (VSCs) were the most abundant air pollutants, representing 55.5% and 20.6% of the cumulative mass emitted, respectively. The first eight days of aerobic treatment and the first turning of the compostable mixture were the critical steps for odor generation with OER ranging from 30 to 317 OUE h'1 kg'1ADS. Particularly, the first turning process was responsible for strong odor episodes that were emitted in a short process time (295 OUE h'1 kg'1ADS). Based on the OAVs approach, dimethyl disulfide, dimethyl sulfide, and methanethiol were the predominant odorants along these early operational stages. Odor potential and composition shifted for the middle and later active phase, second turning, and curing stage where OER fluctuated from 0.18 to 12.6 OUE h'1 kg'1ADS, and hydrogen sulfide showed the most substantial odor contribution. A principal component analysis explaining 77% of the variability in odor concentration and OAVs datasets eased the recognition of these odor patterns. © 2019 Elsevier Lt

Loss of parental-specific methylation at the IGF2 locus in human hepatocellular carcinoma

International audienc

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

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.</p

Current state-of-the-art and gaps in platform trials: 10 things you should know, insights from EU-PEARL

Summary: Platform trials bring the promise of making clinical research more efficient and more patient centric. While their use has become more widespread, including their prominent role during the COVID-19 pandemic response, broader adoption of platform trials has been limited by the lack of experience and tools to navigate the critical upfront planning required to launch such collaborative studies. The European Union-Patient-cEntric clinicAl tRial pLatform (EU-PEARL) initiative has produced new methodologies to expand the use of platform trials with an overarching infrastructure and services embedded into Integrated Research Platforms (IRPs), in collaboration with patient representatives and through consultation with U.S. Food and Drug Administration and European Medicines Agency stakeholders. In this narrative review, we discuss the outlook for platform trials in Europe, including challenges related to infrastructure, design, adaptations, data sharing and regulation. Documents derived from the EU-PEARL project, alongside a literature search including PubMed and relevant grey literature (e.g., guidance from regulatory agencies and health technology agencies) were used as sources for a multi-stage collaborative process through which the 10 more important points based on lessons drawn from the EU-PEARL project were developed and summarised as guidance for the setup of platform trials. We conclude that early involvement of critical stakeholder such as regulatory agencies or patients are critical steps in the implementation and later acceptance of platform trials. Addressing these gaps will be critical for attaining the full potential of platform trials for patients. Funding: Innovative Medicines Initiative 2 Joint Undertaking with support from the European Union’s Horizon 2020 research and innovation programme and EFPIA