EU-PEARL is developing methodologies and tools to enable the scale-up of platform trials across Europe, and potentially worldwide. These include innovative Information and Communication Technology (ICT) methods and platform specifications to support platform trial queries using federated hospital real-world data. In this article, the authors describe the tools being developed and how these will pave the way for legal, ethical, and technological systematic access to standardised quality data across hospital networks to enable patient count -matching them to protocol eligibility criteria- and to facilitate recruitment.
Article written by Dipak Kalra (i~HD), Nadir Ammour (Sanofi) and Susana Kalko (VHIR).
In a platform trial, multiple drug compounds from more than one pharmaceutical company or academic organisation to treat a specific disease, are tested simultaneously in a single overarching clinical trial. The main advantage of platform trials is that they require only a single control arm (or group), thereby limiting the number of patients who will need to take a placebo or standard of care treatment. This is especially valuable in rare diseases where patients are scarce, and more generally in areas such as paediatric trials. A second benefit is that it is possible to discontinue a treatment group that is demonstrably less favourable compared to the others during a trial and to shift those patients to the more promising treatment arms. Moreover, in platform trials the standard of care arm can be used as a longitudinal natural disease history arm.
EU-PEARL is developing resources such as master protocol templates, statistical analysis methodologies, legal frameworks and checklists, data management guidance, data protection, and data sharing guidelines and templates, to facilitate and streamline the design and conduct of platform trials.
Optimising recruitment of eligible patients
One important enabler of platform trials, although also an enabler for other kinds of clinical trial, is the ability to determine the approximate number of patients who might be eligible based on the inclusion and exclusion criteria, as defined in the master protocol and its separate study arms, so that the eligibility criteria can be adjusted to inform the study design and decisions around investigational site selection and estimated recruitment numbers. This can be undertaken through queries on the hospital Electronic Health Record (EHR) systems to count the number of matching patients, without extracting any patient-level details. A complementary facilitation of platform trials is the ability for hospitals to rapidly identify the number of potential suitable patients so that all patients who would potentially be interested and eligible could be considered and invited into the trial.
We are developing Information and Communication Technology (ICT) methods and computable platform specifications to interconnect multiple hospital EHR systems and support platform trial feasibility queries using clinical real-world data.
We have been developing a battery of these Information and Communication Technology (ICT) methods and computable platform specifications to support platform trial feasibility queries using hospital real-world data. This will enable us to leverage EU- PEARL’s access to disease-specific longitudinal natural history cohorts, as pools of candidate trial patients for potentially rapid future recruitment.
Paving the way for EHR hospital federated data sharing
One critical success factor for the discovery of relevant patients is the quality of hospital EHR data. We have developed an eSource readiness survey that can be used by hospitals to self-assess their EHR system maturity and capability, and the quality of the EHR data. This is a unique survey developed following desk research and with formalised (Delphi style) input from pharma and hospital partners.
We have developed an eSource readiness survey that can be used by hospitals to self-assess their EHR system maturity and capability, and the quality of the EHR data, as the basis from which to discover and quantify potentially eligible patients.
New-generation ICT platforms will be required to interconnect multiple hospital EHR systems, initially with protocol designers and later with Electronic Data Capture (EDC) systems, so that hospital EHR data can be remotely queried using a federated architecture. It is important that EU-PEARL helps to guide the ICT ecosystem on the platform trial functionality that is needed by such products and also the quality criteria, especially the trustworthiness criteria, that these platforms must meet.
It is important that EU-PEARL helps to guide the ICT ecosystem on the platform trial functionality that is needed by such products and also the quality criteria, especially the trustworthiness criteria, that these platforms must meet.
We are therefore developing the functional requirements, building on prior work of the Electronic Health Record for Clinical Research (EHR4CR) and Electronic Health Record towards Electronic Data Capture systems (EHR2EDC) projects, which aimed to enable the collection of and access to clinical data from existing EHRs to improve the efficiency of research, so that ICT developers can embed those functions into their federated platform products. This will be a novel specification within our field. In parallel, we are developing a certification process to verify the robustness of these platform products, especially in relation to data protection, which we know is a concern of hospitals when making their data available through such products.
Moving forward in four disease areas
We are working with our four disease teams to specify the data items required for performing these remote queries, by examining the frequent eligibility criteria in each disease and defining the kinds of query criteria that are likely to help case-find such patients in broad terms, recognising that each specific trial protocol will introduce some unique criteria. This is being undertaken in collaboration with the Innovative Medicines Initiative (IMI) European Health Data & Evidence Network (EHDEN) project, using Observational Medical Outcomes Partnership (OMOP) and Observational Health Data Sciences and Informatics (OHDSI) tools, through overlapping partners and also partners with technological expertise in EU-PEARL.
We will be establishing a post-project network of excellence for hospitals that have the ambition to be more platform trial capable, to support them with improvements in making the best use of their EHR systems and improving their data quality culture, so that they can play a stronger role in supporting the future scale-up of platform clinical trials across Europe.
We are developing data quality rules for the key eligibility criteria in each disease so that we can help hospitals accurately discover the quality of their data for these critical items, and to improve that quality if they find deficiencies. We will be establishing a post-project network of excellence for hospitals that have the ambition to be more platform trial capable, to support them with improvements in making the best use of their EHR systems and improving their data quality culture, so that they can play a stronger role in supporting the future scale-up of platform clinical trials across Europe.
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