Objectives & results

The problem to be solved

The The European Union eHealth Action Plan 2012-2020 - Innovative healthcare for the 21st century notes that information and communication technologies (ICT) applied to health (eHealth) can increase the efficiency, safety and quality of health services, and unlock innovation in health markets. At the EU Member State level, much has already been achieved with respect to unleashing the power and benefits from eHealth applications.

Delivering efficient cross-border healthcare opens up great opportunities for eHealth applications, but also poses specific challenges, like differences in language, alphabets, culture.. The ePrescription pilots implemented as part of the European epSOS project identified the “delivery” problem of medicinal products (MPs) mentioned in a prescription as one in urgent need for a solution: it discovered cases where the identification of the medicinal product (MP), which was noted in a prescription from a given country, was impossible for a pharmacist wanting to dispense it in another country. The pharmacist was unable to select from the pharmaceutical products available in that country the product that matched the prescribed pharmaceutical product. Or, if substitution was permitted, a similar product in line with national regulation.

 

 

Objectives

openMedince addressed both the identification and the substitution challenge. It aimed to reach a global consensus in order to univocally identify and describe unambiguously a medicine, resulting in the delivery of the appropriate medicinal product to a patient at the retail or community pharmacy level in line with national regulations. In detail, this concerned developing respectively identifying:

  • a common data model for prescribed medicines
  • a common vocabulary for unambiguous definition, description, and identification of medicines
  • prevailing national rules and practices of Substitution
  • a roadmap for post-project actions and implementations
  • and to contribute towards
  • the intentions of the MoU signed between the US Department of Health and Human Services (HHS) and the EC on trans-Atlantic eHealth cooperation.

 

 

Process and Activities

Context and earlier work

The work benefited from earlier activities of regulatory agencies and global SDOs. The ISO 11615/11616/11238/11239/11240:2012 standards family on “Health informatics -- Identification of medicinal products [IDMP]” was created with the active engagement of regulatory agencies like the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA), and intense debates in the ISO, HL7, CEN groups that engage in pharmacy standardisation. Meanwhile WHO, which maintains several coding systems including the Anatomical Therapeutic Chemical (ATC) Classification System, collaborates with the International Health Terminology Standards Development Organisation IHTSDO in various harmonisation projects. There is need to bring these activities together, particularly also as EMA requires that medicinal product companies submit data using IDMP since 2016. This is a big change both for EMA and the pharmaceutical industry. On the other hand, it is going to affect the information offered by the European Union Drug Regulating Authorities Pharmaceutical Database (EudraPharm), the database of medicinal products that EMA maintains. The experience of the European epSOS project has also shown that, particularly on the issue of cross-border ePrescription/eDispensation, further standardisation activities are urgently needed.

Univocal identification of medicinal products

The unique contribution of the openMedicine initiative was to develop upon this earlier work, take the epSOS experience into account, identify differences and inconsistencies across already existing standards, and thereby contribute towards harmonisation of global standardisation. As a first step, the project developed a concise conceptual framework to guide its work, based on the interoperability domain framework as depicted in Figure 1 and use case scenarios where the identification of a medicinal product is an issue, including pharmacological and pharmacokinetic attributes, clinical indications and risks to be considered.

 

Figure 1. Interoperability Domains

Source: (c) empirica

Next, the identification and description of pharmaceutical products was addressed, not only for standard pre-packed medicinal products, but also for some special cases like MPs with multi-components, biologics, or special packaging as well as those cases where a prescription for a medicinal product only specifies a cluster or subset of products. Furthermore, investigations were undertaken to clarify what attributes are needed for reverse identification of a medicinal product.

Based and expanding upon epSOS results, new use cases, and reviewing ISO/IDMP standards, the work performed identified a common structure, data elements and semantic assets (vocabulary) for the unambiguous definition, description, and identification of medicinal products (MPs) throughout Europe. Detailed exchanges with and contributions to the eHealth Network activities on revised Guidelines led to concrete solution proposals for rendering cross-border eHealth services (ePrescriptions, ePatient Summaries) safer and more efficient.

Medicinal product substitution at the point of dispensation

Substitution of medicinal products at the point of dispensation is a challenge in a cross-border setting due to widely divergent rules. Across all member states, a survey was undertaken to gather information on and to analyse the handling of concepts and practices of substitution of medicinal products at the point of dispensation. Results highlight the tension between maximising patient safety and maximising the probability that a cross-border prescription can indeed be adequately filled in another country. The analysis of this material helped to develop concrete solution proposals towards harmonisation of rules of substitution across member states.

Recommendations

A set of high level, concrete recommendations and a roadmap for post-project actions and implementations were critically discussed, validated and agreed within the consortium as well as with the plenum of the expert council and various of its members individually.

Horizontal activities

To support the core activities of advancing the rules for unique ID of medicinal products and substitution, key activities of openMedicine concerned the active engagement with external players and stakeholders participating in an expert/advisory capacity, and also involving them as quality reviewers of reports produced as well as multipliers.

A special Expert Council was established. Four meetings were organised, twice at the premises of the European Medicines Agenvcy (EMA) in London, at CEN premises in Brussels, and with FDA at their premises in Washington, D.C. These meetings were attended by experts from Europe, the USA, and Canada.

Experts and the Expert Council also became engaged in rigorous validation of the outcomes achieved, including their ability to indeed solve the gaps and challenges identified, their applicability in daily practice of the players and stakeholders involved, and their contribution to health policy priorities and cross-border health services. All of this was translated into an actionable roadmap for implementation and sustainability, as well as recommendations to policy makers.

Guided by a targeted communication strategy, dissemination and liason undertakings focused on the identified core players and stakeholders, mainly national drug agencies, stakeholders in production, prescription and dispensing of medicinal products, but also health system players and policy makers in Europe and the United States. Collaboration and exchange with related European-level interoperability projects and activities in the context of the EC-USA eHealth Memorandum of Understanding were pursued to create synergies and learn from each other.

Work involved not only the whole project team, but also more than 30 members of the openMedicine Expert Council. This council assembled experts from industry, national healthcare systems and competent authorities, research organisations, representatives of stakeholder associations as well as individual experts, all of whom are also available for individual exchange with the project team for work items for which they had indicated a specific interest and competence, and for the quality review of deliverables. To assure reaching the results foreseen and global impact, close cooperation and coordination of activities with the European Medicines Agency (EMA) and the US Federal Drug Administration (FDA) were also established.

Overall structure of work undertaken

The overall structure of the work undertaken is schematically depicted in Figure 2:

 

Figure 2. Work structure

Key results of openMedicine

Key results of openMedicine concern:

  • A common data model - based and expanding upon epSOS results, new use cases, reviewing ISO/IDMP standards – for prescribed medicinal products. This includes a common structure, data elements and semantic assets (vocabulary) for the unambiguous definition, description, and identification of medicinal products throughout Europe.
  • Detailed and extended discussions with and contributions to the activities of the eHealth Network of member state representatives on their revised Guidelines for ePatient Summaries and ePrescriptions. This led to very concrete solution proposals as well as suggestions of how to later integrate and make use of the ISO IDMP based medicines data base of the European Medicines Agency (EMA), which is still under development.
  • Submission of options to member states involved in the present round of developing cross-border eHealth services in the context of the “Connecting Europe Facility” framework. In close cooperation with the EMA, intermediate solutions for univocally identifying medicinal products in cross-border contexts were submitted, particularly for ePrescribing services, based on the presently available EMA data base, to solve the existing identification challenges.
  • Four Expert Council Meetings with representatives of all major player and stakeholder groups from both sides of the Atlantic, two at the premises of EMA in London, one at CEN facilities in Brussels, and one at the US Federal Drug Administration (FDA) in Washington, DC. These extensive discussions and exchanges served to present intermediate and final output of the openMedicine project, to validate results, and to agree on recommendations for further work.
  • An empirical surveyed across all member states on concepts and practices of substitution of medicinal products at the point of dispensation. This turned out to be an unexpectedly complex issue, which was extensively discussed with various experts, stakeholder associations and national competent authorities at the various regional dissemination meetings and workshops.
  • A set of high level, critical recommendations and a roadmap for post-project actions and implementations. These were critically discussed, validated and agreed within the consortium as well as with the plenum of the expert council. They address not only EMA, FDA and national regulatory bodies, but all core players and stakeholders as well.

Progress beyond the state of the art

openMedicine, through its research, its broad discussions with players and stakeholders, the outcomes of its work and its recommendations has substantially contributed towards the univocal identification of medicinal products in a wide variety of contexts. Solutions based on the ISO IDMP (identification of medicinal products) suite of standards are ready to be implemented by international (like EMA or FDA) and national (member state) regulatory bodies, by producers of medicinal products data bases, and by providers of clinical or pharmacy software.  They will furthermore facilitate cross-border ePrescription services like those under implementation in the context of the Connecting Europe Facility (CEF).

openMedicine has undertaken the first EU-wide survey of national substitution rules and procedures. The analysis of these data allowed to suggest rules and submit recommendations on how to deal with the issue of substitution when presenting a prescription in another country. Furthermore, openMedicine has contributed and helped to improve the next draft of the ePrescription and ePatient Summary Guidelines as developed and ratified by the eHealth Network. It  created awareness for the high relevance of all this work also for the clinical context, particularly for clinical documents and messages concerning the recording and information on medicinal products prescribed and dispensed (like prescription histories, active medication lists). And it has identified a variety of open issues and the need for further progress and alignment of the work of different SDOs in order to progress on the ISO IDMP suite of standards and implementation guides.

The concrete solutions as well as well-grounded recommendations to create these impacts concern:

  • The further development and agreement on a common data model for prescribed medicinal products
  • Identification of a common vocabulary for unambiguous definition, description, and identification of medicinal/pharmaceutical products
  • Rules for the cross-border handling of different practices of substitution in Europe
  • A practical roadmap for post-project implementation of the solutions elaborated.
  • Furthermore, through the involvement of US experts and an expert workshop at the US Federak Drug Administration (FDA), impact was also assured on the intentions of the MoU signed between the US Department of Health and Human Services (HHS) and the EC on trans-Atlantic eHealth cooperation.

Benefits, socio-economic impacts, and wider societal implications

OpenMedicine work and outcomes facilitating and promoting the univocal identification of medicinal products in a wide variety of regulatory and clinical contexts will generate long-term benefits and have wider socio-economic and societal impacts for:

  • Patients: safer (cross-border) healthcare, better access to prescribed medicines abroad, easier identification of prescribed and dispensed medicines in ePatient Summaries, electronic health records, CPOE systems and many other clinical contexts
  • Clinicians: improved reliability, and easier understanding and comprehension of medication records, better access to health data of foreign patients
  • Pharmacists: more reliable identification of medicines specified in a (cross-border) prescription, improved substitution guidance
  • Pharmacovigilance: improved identification of medicinal products in question, faster alignment of reports on adverse drug events (ADEs) related to medicinal products with the same active ingredient(s), but different (generic) brand names
  • Pharmaceutical industry: more efficient submission of information necessary for marketing authorisation of new medicinal products, and of follow-up information on already marketed products
  • Further players like national & international regulators (e.g. EMA, FDA); national/regional pharmaceutical data base producers; performers of clinical trials, particularly when patients in several countries are enrolled.

Dissemination

Results and outcomes of the project were widely disseminated and discussed with key players, stakeholders, thought leaders and multipliers through its Expert Council meetings and the involvement of these experts also in internal discussions and work of the project team; through a variety of regional workshops and dissemination events all across the Union; participation in and presentations at national and international scientific and professional conferences; presentation of openMedicine results at meetings of various standardisation bodies; scientific publications; and through a comprehensive website providing a variety of resources and information related to the topic of this project.

Conclusions

Harmonising the identification of medicines in regulatory processes, in ePrescriptions, eDis-pensation reports as well as in clinical messages, records and decision support systems is a European challenge, particularly also when considering the high quality and safe provision of cross-border health services. It impacts on pharmacovigilance, the tracing of data across the life cycle of a medicinal product, the aggregation of information for public health purposes and many other health domains. And it promises a substantial European added value.

Across the Union, differences in names of medicinal products and active substances, variations in strength and box size prevail, and the availability of a specific medicinal product varies considerably across member states. This situation necessitates substitution of the prescribed product at thre point of dispensation in many instances if a patient is to be timely served in a pharmacy. The EU-wide implementation of ISO IDMP standards as under way by EMA for pharmacovigilance is a route to mitigate many of these problems. However, presently, national ePrescription and medicines data bases are not supporting MPID or PHPID attributes and codes, because at the national level there are few direct benefits from solving cross-border identification and semantic issues.

To fundamentally increase the probability, e.g., that a cross-border ePrescription can indeed be dispensed in another member state, it is mandatory to have the pharmaceutical product identification number (PhPID) available respectively automatically included from national sources or a central EMA data base, in order to identify medicinal products locally available which are equivalent to the one identified in the prescription. This also applies mutatis mutandis to other clinical or regulatory records and contexts.

In the medium term, it will be mandatory to link the EMA IDMP (SPOR) DB with national drug DBs (or use NCPeH procedures) to have identifiers and identifying attributes automatically included into software systems which have to make use of such input for prescribing and other clinical systems. This will also improve and harmonise reporting of adverse drug events and pharmacovigilance.

This requires creating an EU approach to further improve, implement and maintain the EMA SPOR data bases and the supporting coding efforts, thereby also facilitating regulatory processes, and even Big Data applications. A common approach and operating model needs to be developed, including common processes for validation of contents, error mitigation, of linking from central hubs to national and regional levels, updates and mappings to other systems. Harmonisation of prescribing and dispensation practices could be a further focus. A sustainable migration process from the present situation to the ISO IDMP / SPOR adoption should be also addressed.

For cross-border health services, when a prescriber specifies an innovator or generic brand name, or an active substance and further attributes, it must be assured that any local ePrescription system will be able to automatically look up equivalent products available in the dispenser’s country by filtering making use of any coded identifier or the identifying attributes reported in the prescription.

Further work and support is also needed for cooperation across SDOs to integrate and agree on standards for medicinal products, pharmacovigilance, usage of these data in the clinical context, for messaging like ePrescription, eDispensation, in ePatient Summaries, clinical electronic records like EHR systems. This may also include the setting up of cross-border pilots to assess and validate the proposed approach in virtual environments with test data.

Work should also concern an assessment of impacts based on benefits and costs to be anticipated. Such an assessment should not only concern regulatory impacts, impacts on setting global standards and best practice, and impact on clinical data quality and interoperability, but also spill-over effects to pharmaceutical companies, data base producers and competitive advantage of European companies.