Developing robust common data models to guide safety in medicines in Europe

The European Medicines Agency held a 2 day international workshop in London [11th -12th December 2017] to define the opportunities and challenges around implementation of a common health data model in Europe to support regulatory decision making. The expected outcome of the workshop was agreement of guiding principles for the development of a Common Data Model (CDM) in Europe, including key criteria for validation in the context of regulatory decision-making.

A common data model could help harmonise healthcare data across multiple data sets and provide a mechanism to conduct pan-European studies in a timely manner to address regulatory questions. At the same time, applying a common model to European data has multiple challenges. The meeting brought together regulators with academia, data holders and the pharmaceutical industry.

Sessions included talks from experts from North America (FDA, Harvard, Duke, Georgia Tech ...) and the European region (Erasmus, Utrecht, CBG-MEB, EMA ...) discussing lessons learned and current challenges in very large current clinical data resources, regulatory verification and related issues. Common data model case studies considered included Sentinel – the Harvard-based FDA system for accessing patient data from 16 health data partners across the USA and CNODES (the Canadian Network for Operational Drug Effect Studies) which can access data on 100 million patients – a similar scale to Sentinel.

The U.S. Food and Drug Administration's (FDA) Sentinel Initiative is a long term approach which uses a common health data model to improve the FDA’s ability to identify and explore safety issues for medical products. Sentinel actively surveys pre-existing electronic healthcare data from multiple sources.

Consistent themes included ensuring the relevance of evolving common data models to health policy, keeping timelines as short as practical, interoperability, consent and related ethical issues (data custodians, patient data protection and privacy), and careful internal and external validation of clinical definitions, data, software and analytical models.

From the perspective of health professionals, policy makers, regulators and the public, key questions included whether clinical outcomes from common data models are generalisable or only relevant to specific sub-populations based on geography, genetics, demographics and/or complex co-morbidity.  In the era of precision medicine there is the clear need is to avoid “right” answers from the wrong clinical populations and “wrong” answers from the right populations.

Further key points considered included: what is the cost of developing and maintaining validated CDMs; who should pay; whether updating existing databases is a sufficient approach or rather new more robust databases are needed.

See more about the workshop

Impact of decision to move European Medicines Agency to Amsterdam

As one of many consequences of Brexit, following a very close vote by member states on Monday 20th November, Amsterdam has been confirmed as the new home for the European Medicines Agency. On current plans, the EMA will be operating in Amsterdam from April 2019, following a likely shadow hosting of the EMA there for some months before the formal date for completing the move of the agency.

The EMA's Patients and Consumers Working Party annual meeting

Meantime the EMA's Patients and Consumers Working Party (PCWP) is holding its annual meeting with all EMA eligible patient/consumer consumer organisations to consider relocation preparedness, patient and consumer involvement in EMA activities, highlights from major EMA committees and updates on pharmacovigilance, information on medicines and future work programmes in 2018 and 2019 for the PCWP and the EMA's Healthcare Professionals Working Party.

Effective medicines have both powerful therapeutic actions as well as the potential for serious unwanted adverse effects. The EMA was founded in 1995 with initial funding from the European Union and the pharmaceutical industry, and further support from EU member states. The European Medicines Agency is concerned with regulation, supply chain and pharmacovigilance for medicines and other advanced therapies for 28 countries across the European Union - from the Baltic countries to Ireland and from Scandinavia to the Balkans and the Mediterranean. All these roles concern balancing benefits and risks when it comes to patient safety with regard to medicines.

The EMA has established mechanisms for involving patients in regulatory assessment: patients’ value perception and value systems. The EMA also has an increasing remit to engage with stakeholder organisations and to improve transparency in its activities for the ~510 million citizens of the European Union. Furthermore the EMA has a major role in educating patients, carers and health care professionals about medicines. There have for example been recent workshops on

• combating antibiotic resistance: a partnership with the European Centre for Disease Control 
• biosimilars
• personalised medicine initiatives
• applying big data to improved regulation of medicines in Europe which raises important questions about clinical utility, quality, accessibility and systems for data mining

There remain many decisions and actions for the coming months needed to ensure continuity of the EMA's business. These involve the smooth relocation of the EMA to Amsterdam and either developing systems to retain UK expertise for the EMA or replacing that expertise from other EU member states. For the EMA, priorities include:

• minimising the impact on staff of the move to maximise staff retention
• maintaining capacity to continue the work of the EMA 
• the resulting need to prioritise EMA core and planned further activities
• continuing productive engagement with stakeholder groups: patients, carers, healthcare professionals ...
• maintaining the capacity of the EMA to engage with the public

For the UK, there are pressing questions regarding the future regulation of medicines in the UK post-Brexit, the impact of loss of international influence of UK regulators and other experts on medicines and the impact of loss of biotech and pharmaceutical companies from London to Amsterdam.

The EMA has been based in London for over 20 years. Many staff have strong family and other personal ties in the UK - for example partners' work, children at school, dependent relatives ...  Adapting to a new country is no simple matter. The working language of the EMA is currently English however full integration within Amsterdam will need competency in the native language in the Netherlands. There will also be practical challenges arising from the simultaneous impact of the arrival of up to 800 families on the Amsterdam housing market and schools system.

© Donald Singer 

Safer Big Data for safer medicines?

14-15 November, 2016: The European Medicines Agency invited experts from the European Union and the USA to discuss 5 key perspectives to speak on Big Data at a workshop in London aimed at identifying opportunities from 'Real World and other "Big Data" to improve development of new medicines and surveillance of licensed medicines for safety, risk and effectiveness.

The 5 key 'stakeholder' perspectives? Patients and the public, health professionals, academia, regulators and policy makers, industry (both health sector and software/hardware) and payers (considering a change in strategy to payment for health impact rather than sales, as exemplified by the Health Impact Fund).

A pragmatic definition from Lu and his colleagues states that "Big data analytics (BDA) applications are a new category of software applications that process large amounts of data using scalable parallel processing infrastructure to obtain hidden value." There are many potential applications from planning for public transport flows to using large health record datasets to improve patient safety such as in the US FDA-Harvard Sentinel partnership.

The FAIR principles for Big Data, Finding, Accessing, Interoperability and Reuse of Big Data, have both general and special challenges and potential benefits when applied to healthcare.

For example, in a recent issue of Nature Reviews Cardiology, Rumsfeld and colleagues from Colorado and Boston outline 8 potential applications of big data analytics to improve cardiovascular care, including "predictive modelling for risk and resource use, population management, drug and medical device safety surveillance, disease and treatment heterogeneity, precision medicine and clinical decision support, quality of care and performance measurement, and public health and research applications".

The EMA note: "Rapid developments in technology have led to the generation of vast volumes of data, which have the capability to transform the way the benefit-risk of medicinal products is assessed over their entire life cycle. However, it is recognised there are multiple challenges in the exploitation of these data.

"These range from the fundamental need to establish methods to enable the access to, integration and analysis of heterogeneous datasets to understanding the limitations in its use. Importantly, robust and transparent mechanisms to protect patient confidentiality are key to secure patient trust. It is important for the European Medicines Agency and the European Union medicines regulatory network to gather information on the latest developments in big data from the perspective of all stakeholders in order to identity how and when the multitude of data sources may contribute to medicinal product development, authorisation and post-marketing surveillance."

Some key themes:
- Patrick Ryan on which patients chose which treatments
- Sophie Louveaux discussing new EU regulation of data, meaningful consent and processing sensitive health data
- David Martin addressing challenges in Big Data analytics from FDA and PPP perspectives
- Julian Isla from the Dravet patient charity on making the patient the centre in digital health
- Baroness Helene Hayman on ethics, governance and public confidence
- Ronald Brand from the University of Leiden on informed consent v. opt out
- Nicolas Tatonetti from Columbia University, NY on data mining for medical discovery
- Nico Gaviola from Google on cloud data for safer medicines

See more on key threads and discussion points including on the European Open Science Cloud, new EU General Data Protection Regulations - from May 2018, replacing Directive 95/46, machine-learning for chemogenomics, challenges to implementing applications to precision medicines, access to the OHDSI community, social media to find new adverse drug event signals, FDA case studies using then Sentinel-HMO-Harvard collaboration,  opening access to the 28 EU independent national health care systems and more in due course when talks are made available on the EMA website for public access.

The EMA Launches new PRIority Medicines scheme - PRIME

The European Medicines Agency has today launched the new PRIME (PRIority MEdicines)

scheme to strengthen support for medicines that target an unmet medical need.  

The scheme focuses on medicines that may offer a major therapeutic advantage over existing treatments, or benefit patients with no treatment options. 

 A press release and further information on PRIME have been published on the EMA website, including details of how to apply. 

A dedicated EMA e-mail box has been set up for any queries.

The EMA website

Moving the new Personalized Medicine to the Clinic

I am on the Advisory Board for a conference to be held 13-14 May in San Francisco on Personalized Medicine from the perspectives of regulators, biotech and pharma interest, health service funders and patient users of new and emerging technologies in this area.

Trusted doctor-patient relationships form a long recognized key underpinning basis for ensuring as effective as possible disease prevention and treatment. That relationship needs to be supported by a strong evidence base on clinical and cost-effectiveness and safety in use of medicines and supporting diagnostics and devices.

Thanks to economies arising from progress in gene technology (Moore's Law applied to medicine) and advances for exponential increase in active partners in this field (Metcalfe's Law applied to medicine), costs of genetic, genomic and other technologies to stratify diagnosis and treatment choice are becoming increasingly affordable in clinical practice.

The Summit is a one-day conference that will gather biotechnology and pharmaceutical experts and healthcare stakeholders as keynote speakers and panel discussants on legal, regulatory, funding and other key issues that will promote research and development, growth and effectiveness  in the short to medium term horizon for emergence of personalized medicine for clinical care.

The summit is co-hosted by the Personalized Medicine Coalition and Foley & Lardner LLP and is supported by major academic, clinical and industry patrons Life Technologies, Cancer Treatment Centers of America and the California Institute of Regenerative Medicine.

See the Personalized Medicine Summit website for more on the conference and how to register.

Selected papers from the conference will be published in the international journal Health Policy and Technology.