D3.2A – A review of the European clinical trial and data confidentiality legal frameworks

The relationship of regulatory documents and directives to each other and to guidelines was mapped out by reviewing the references made within each document to other relevant documents. This ensures that all relevant documents have been identified. A matrix mapping the regulatory requirements to the corresponding CDMS requirement is provided. It details the regulatory documents which provide either general or specific requirements relating to data, data management and IT systems.

This provides the basis for determining the user requirements for the CDMS for the purpose of system validation. Although there is currently no recognised industry standard for specific CDMS system requirements, the European Clinical Research Infrastructure Network (ECRIN) has developed a standard describing the requirements of GCP-compliant data management in multinational clinical trials. This standard covers both the requirements for the IT infrastructure and computer systems in general, and the requirements for data management applications in clinical trials. International, European and national regulations and guidelines relevant to GCP, data security and IT infrastructures were considered in developing this standard. It therefore provides a set of user requirements for a CDMS which could be used to specify requirements for system validation of CDMS. Standards for CDMS system validation may be higher in some areas of clinical research than others, but will need to be taken into account for the TRANSFoRm project. Where the aim of clinical research is to bring new medicinal products to market, the use of electronic data and computerised systems to produce the data in the marketing application must meet the requirements stipulated by the Regulatory Authorities and so will require CDMS system validation.

The use of electronic source data (eSource data) in clinical trials, where the data are captured in an electronic form rather than on paper is becoming increasing prevalent. There are a wide variety of data that may be generated electronically in the conduct of a clinical trial, such as electronic Case Report Forms (eCRF), laboratory test results, ECGs, X-rays and patient diaries. The ultimate desire is for single data capture and the interoperability of EHR with other systems such as Electronic Data capture (EDC). The current regulatory framework is still focussed on the use of paper source documents and paper-based processes rather than electronic source data and computer systems. However the recently published EMA Reflection paper and draft FDA guidance on eSource documentation are beginning to address this.

Standards for eSource data are being developed, but are driven by different groups. In clinical research CDISC provide the direction. The CDISC eSDI Working Group has identified 12 user requirements that an eSource system must fulfil. In the healthcare sector, where Electronic Health Records (EHRs) are becoming more widely used, there are two organisations providing direction for the certification of EHR systems: Health Level 7 Inc., known as HL7 (an American standards development organization) and EuroRec (European Quality Labelling and Certification of Electronic Health Record), the European Union EHR certification committee. These organisations have jointly developed the Electronic Health Record for Clinical research (EHRCR) User requirements, which relate specifically to computerised EHRs used in Clinical Research and provide the core requirements for EHR systems to meet current regulations and guidance for clinical research.

Compliance with the regulations and guidance for clinical research, combined with the CDISC user requirements for eSource data, as detailed in the EMA Reflection Paper (regarding electronic source data) are necessary for regulatory acceptance of eSource data at present. eSource data taken directly from EHRs represent a greater challenge, since the EHR and system must meet clinical research standards. It is important to note that the European regulators are responding to the increasing use of computerised systems in clinical trials, with the recent issue of the EMA Reflection Paper regarding electronic source data (came into effect August 2010) and a revision to Good Manufacturing Practice Annex 11 regarding computerised systems (to come into operation on 30 June 2011). Annex 11 stipulates validation requirements and Good Clinical Practice (ICH E6 (R1)) requires validation of electronic data processing systems. It can therefore be expected that the regulatory landscape will continue to change for CDMS and electronic source data over the coming years.