P-MEDICINE NEWSLETTERISSUE NO 4 2 no 4 • february 2015 no 4 • february

contents

Editorial 3

Latest Achievements in the p-medicine project 4

How to Ensure GCP-Compliance for p-medicine Tools 6

Predicting Drug Side Effects: Opportunities and Challenges 8

Browse-Directed Search: A Tool for Generating Hypotheses 9

Partners in Depth: Biovista 11

ECRIN and p-medicine 12

ALGA-BC: An interactive empowerment tool for breast cancer patients 14

MyHealthAvatar: A Demonstration of 4d Digital Avatar Infrastructure 15

VPH-Share Makes Impact at VPH2014 in Trondheim 15

Building Policy Recognition for VPH Research 16

p-medicine newsletter 3 editorial by Norbert Graf, p-medicine coordinator

We are fast approaching the end of partner Biovista summarizes the platform will remain. The p-medicine our project now with only six more knowledge gained regarding the partners have agreed to support the months to go. The next half-year will close collaboration of p-medicine development of a legal entity called 2015 no 4 • february be focused on finalising an integrated partners and regulatory bodies, such STaRC: Study, Trial and Research scenario demonstrating all aspects as EMA and FDA. More of Biovista’s Centre that will guarantee that our of the project. All our efforts have interesting work on pages 8-11. fantastic work is continued beyond been put forth to develop tangible the lifetime of p-medicine. scenarios that will convince clinicians At the end of the project we have set to use the p-medicine infrastructure up an infrastructure that will facilitate Of course, these excellent results in their research and their clinical personalized medicine in all aspects, are only possible with a terrific practice. including running more patients consortium. It was and still is in prospective clinical trials using a privilege to work with such Now it’s time to look back. During ObTiMA. We have a legal and ethical exceptional partners and friends the project we have established many framework in place. Data, including in our ambitious p-medicine collaborations. Together with VPH- molecular and imaging data, can be project. This has been and will be Share, we held various meetings, securely stored in a data warehouse the guarantee of our success. It is conferences and a summer school. for further exploitation to gain new beyond words to say how proud and Our main joint activities are related knowledge. Access to biobanking is grateful I am for being part of such to security, semantic interoperability provided. Tools and models will be an endeavour. I am convinced that and running the Oncosimulator in place for decision support. The our mission towards personalized in their infrastructure. Once more ALGA questionnaire enhances patient medicine will help patients in the end. VPH-Share gives an update on their empowerment as a central part of latest activities in this newspaper personalized medicine (see also p. (p. 15). Members of p-medicine 14). The Oncosimulator is able to attended many interfacing meetings simulate response to treatment in not only in Europe but around the nephroblastoma, breast cancer and globe to disseminate our goals ALL. and achievements to a widespread audience including clinicians. In Seeing all our achievements, I am one of our deliverables p-medicine convinced that the p-medicine

Towards a personalized medicine

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latest achievements in the p-medicine project – an interview with gordon mcvie

Now that the end of the project is tissue and the tumor tissue – put put together and the technical people approaching, we have asked Gordon it all together and come up with a got together to create solutions. no 4 • february 2015 no 4 • february McVie from ecancer to give his series of management proposals. personal view on the most important Also, this requires to be translated The core components which are now achievements of the p-medicine into understandable language for the available for usage are: project. patient and the patient needs to be encouraged to question the doctor • A portal for p-medicine Starting off four years ago with a quite and to take part in an equal way in • A workbench for p-medicine disparate group of skilled people, decision making. That’s what we call • A data warehouse i.e. people working on ontology, patient empowerment.” • An ontology annotator, the clinical people, psychologists, first ontology for psychological bioinformaticians, technicians, etc., medicine that we know of these experts have soon learned How has this idea been trans- • Data translation service to speak the same “language” and lated into a precise p-medicine • Privacy protocols started to work together on the product? • ObTiMA, which is a clinical trials subjects of data integration, legal management system and ethical issues of storage of • Biobank access framework so that data, system biology models, tools, Gordon McVie: “The infrastructure you can look at what rare tissues logistics and new ways of data is based around clinical scenarios, are banked and a number of warehousing. in other words the clinicians started European or in fact international off with the questions and there are biobanks By now a clear picture has evolved three groups of patients being looked • Cloud storage infrastructure and this is what Gordon McVie is at (two groups of pediatric oncology, so that all this data can be talking about in an interview filmed that’s Wilms tumor of the kidney and confidentially kept in the cloud and published by ecancer. leukemia, and an adult cancer, the • A whole series of tools for looking very common breast cancer, were at adverse reactions to drugs taken as a model). • And data mining services What is the idea behind • And last but really not least the p-medicine? A number of clinical scenarios were patient empowerment tools”

Gordon McVie: “The idea is that p-medicine will provide a knowledge Video: Gordon McVie sums up the progress discovery platform to manage future clinical research easily for the doctor and understandably for the patient. The entire video is available on ecancer.org and is also prominently featured on the p-medicine website. A patient is now poorly informed about the remarkable progress being made in the whole area of imaging and the whole area of molecular genomics and proteomics and so on. The doctor is bombarded and has sometimes not very much more an idea what to do with all the data than the patient. So the idea would be to put all these masses of data, layers of data, different types together and process it so that the doctor sitting with the patient can press one button and get all the profiles – from the psychological profile to the OBEX profile of the patient’s normal

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Short CV Gordon McVie

Professor Gordon McVie is NCI support, the European New Drug Development widely regarded as a leading Network. international authority in the research and treatment of In the UK he was one of the architects of the Cancer 2015 no 4 • february cancer. Having qualified in the Trials Networks in Scotland, Wales, and England, and 1960ies in science and medicine was a founding member of the National Cancer Research at Edinburgh University, he was Institute appointed Foundation Senior Lecturer at the Cancer Research Professor McVie is the recipient of numerous awards and Campaign oncology unit at the University of Glasgow in has honorary doctorates in science from six universities. 1975. He has served on key committees of AACR and ASCO, and on the boards of the National Cancer Institutes He is currently Senior Consultant to the European Institute of France, Italy, and the Netherlands. He has authored of Oncology, Milan, and is founding editor of ecancer. 350 peer-reviewed articles, and contributed to over 35 org, ecancerpatient.org and ecancerLatinoAmerica- books. online Open Access free websites. His commitment to drug discovery and delivery is He is visiting professor at Kings College London, the evidenced by approximately 240 patents granted to CRC University of Milan and the University of Wales scientists under his leadership, several drugs registered including carboplatin, temozolomide and abiraterone Previously Professor McVie was Chief Executive of the and the foundation of 10 biotechnology companies Cancer Research Campaign (CRC), which, under his based on CRC intellectual property. His clinical interests, aegis, took over seventy molecules from the lab into apart from new drug discovery and chemoprevention, clinical trial. He led CRC into a merger with Imperial are in the management of cancers of the lung, ovary, Cancer Research Fund which formed Cancer Research colon, breast and brain. He is a partner with ecancer in UK, in 2002, and was joint CEO with Sir Paul Nurse. 3 FP7 projects.

Throughout the Eighties, he was Clinical Research He was elected as Fellow of the European Association Director at the National Cancer Institute (NCI) of the for Cancer Science in 2014, and has been secretary of Netherlands. As President of EORTC, he set up the the European Alliance for Personalised Medicine in early present Drug Development Group in Brussels, and with 2013.

A comprehensive infrastruc- The doctor can now get all of that contact ture has been created. What information thanks to a tool called are the benefits for the exter- ALGA tool and the doctor can Prof. Gordon McVie then frame his language and his ecancermedicalscience nal user of this infrastructure? educational pitch to the psychological print-out.“ +44 7785 325 558 Gordon McVie: “Now we are willing to offer to the outside world data Email warehouse access, access to data What is your personal conclu- Website mining, access to a new tools bar sion at the end of the project? working out what a particular individual patient’s understanding of cancer is, understanding of the Gordon McVie: “We have now got the processes involved in management, lab-clinical interface fixed for I think understanding what sort of the first time in any of these types of educational level would be important projects.” in order to handle the information coming from the doctor.

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how to ensure gcp-compliance for p-medicine tools

What means compliance with created for the use of computer development process proceeds from Good Clinical Practice (GCP)? systems employed to generate, the specifications to documentation, manipulate, store or transmit data programming and Code Review, no 4 • february 2015 no 4 • february in clinical trials. In general, the including configuration and testing. Compliance with Good Clinical validation process follows a V-model A system validation plan describes Practice (GCP) is a prerequisite for (Fig. 1). The V-model is a Software the IQ/OQ/PQ protocols (Installation many clinical trials and it is increasingly Development Life Cycle process Qualification, Operational Qualifi- recommended for all types of trials. that shows how three qualification cation, Performance Qualification), For computerised systems used in activities (installation, operation and test scripts, test SOPs. Finally, clinical trials GCP requires that all performance) are linked to design and a validation report summarises clinical trial information be recorded, functional specifications. the results and declares a system handled, and stored in a way that installation to be validated. The most allows its accurate capture, reporting, The left side of the V represents the important parts of the V-model are: interpretation and verification. The specifications (user requirements, confidentiality of information that functional specifications, hardware • User Requirement Specifications could identify participants of trials and software design specifications with definitions of what the user should be ensured, respecting the and module specifications); the right wants the system to do privacy of patient data in accordance side represents the verification part • Functional Specifications with with applicable regulations. The (tests against the corresponding definitions of what the system is sponsor (trial chairman) of a trial specifications). User requirements supposed to do should ensure and document that the describe the system as it is intended • Design Qualification: electronic data processing systems to function in its area of use (e.g. in documented evidence that the are conform to the established a clinical trial centre, study centre). system has been clearly defined requirements for completeness, The system specification is typically • Installation Qualification: accuracy, reliability, and consistent written by the system user. Because docu-mented evidence which intended performance. This means the system will be used in clinical guarantees that the system has that the computer system needs to trials, GCP requirements become been installed correctly be validated before it can be used for part of the user requirements. The • Operation Qualification: a trial. This includes the provision of Standard Operating Procedures (SOP) and manuals for using and training these systems. A security system prevents any unauthorised access to the trial data, maintaining backups of the data and safeguarding the blinding. A data audit trail must be provided, the automatic logging of data entry that allows a reconstruction of the course of events.

Computer system validation (CSV)

The purpose of CSV is to provide an organized and consistent plan to ensure the integrity and quality of the computerized system throughout its entire life cycle. It is a method to maintain procedures that allow all computer systems that are used in a regulated environment to be maintained in a validated state. For Fig. 1: The V-model for CSV. Performance verification and system validation may be this purpose, policies have to be conducted in a single step.

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documented evidence which guarantees that the installed system works as specified • Performance Qualification: 2015 no 4 • february documented evidence which guarantees that the system performs as expected under all operating conditions and according to user requirements. In our approach performance qualification and system validation are conducted in a single step (Fig. 1).

Fig. 2: Necessary step for employment of software for GCP trials Developer assessment – a (CSV=Computer System validation) necessary evil

No software developer wants to in the validation. The assistance of that a product meets specified be subject of a quality evaluation. the developer comprises support requirements. This testing must be But according to GAMP1 , software during specification, configuration, documented and later provided for and computer systems should be verification and the operation of the validation as documented proof that validated and qualified during the systems. Custom specific applications a quality system was in place during entire duration of the software life also require support during system development. Especially processes cycle, beginning already during the operation that has to be ensured on or components with a high GCP risk software design phase. GAMP, but a contractual basis (e.g. maintenance, should not show low test coverage. also the OECD consensus paper 52 , bug fixes). All this testing, verification and states that it is the responsibility of documentation is necessary to move the end user (e.g. trial chairman, trial the software as a research project sponsor) to ensure that the software Quality assurance in software forward to the software as a product is validated. In addition, Annex 113 development to be used in the regulated area of requires that the user shall ensure clinical trials (Fig. 2). The success that the software has been produced of this process is dependent on in accordance with a system of quality All p-medicine developers are using the developers and other project assurance. However, the quality of agile development methods for members working together and the software cannot be assured by their software tools. But often the providing the necessary additional testing at the clinical trial site. Quality documented quality management features and documentation. In must be incorporated during design that accompanies the development summary, CSV should not only be and development, which can only be process shows gaps. During the regarded as additional burden, but as done by the developers themselves. development of products and a business enabler for the developed Therefore, GAMP requires that the services, quality assurance is the software product. software provider should participate systematic process of testing

1 GAMP® 5: A Risk-Based Approach to Compliant GXP Computerized Contact Systems. ISPE, Tampa, US 2008 If you have any questions concerning the system validation process, please 2 OECD CP No 5: Compliance of contact the CRI group at UDUS. Laboratory Suppliers with GLP Principles (revised 1999) http://www.uniklinik-duesseldorf.de/en/startseite/institute/clinical- 3 EudraLex: Volume 4. Good research-informatics/ Manufacturing Practice. Annex 11: Computerised Systems (2011)

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predicting drug side effects: opportunities and challenges Dr. Andreas Persidis, Biovista Inc.

Adverse Events and Side Effects is a legal concept that captures significant step in the direction of (AESEs) are the risk element of the this predicament and provides presenting a technological capability benefit/risk profile of every drug. pharmaceutical companies with that, as mentioned above, is capable no 4 • february 2015 no 4 • february They are an inevitable corollary of the a basis to refuse additional tests of predicting AESEs with sufficient complexity of biological systems and (suggested or demanded for example confidence for these predictions to of our state of biological knowledge. by the regulatory authorities) after be “actionable” by the regulatory They reflect the fact that we do not a certain number has been carried authorities and the pharmaceutical know exactly how biological systems out (or to carry them out in the first companies. It is by no means the work and interact, we do not know place) if the prediction itself is not end of this very hard road but it is a exactly how each disease modifies “sufficiently justified”. So this brings first step in the right direction, that the “healthy state” of organisms, nor us full circle back to the necessity puts AESEs in a different light and are we 100% sure of how the drugs for a technical ability that predicts helps remove some of the scepticism we develop work within our bodies. AESEs with sufficient confidence to with which they are treated by the justify the undertaking of additional industry. AESEs are a given evil in our efforts to expensive development work cure patients or increase their quality proactively. It is also important because AESEs of life. They are also “bad news can be exploited by pharmaceutical for business” since in the extreme The p-medicine consortium is at companies and other stakeholders case they can cause death, impact the forefront of this effort through in a positive way. Rather than shying the reputation of pharmaceutical the work of partner Biovista and away from them, developers can use companies and decrease the potential Saarland University. Biovista’s COSS insights on AESEs to help optimize market of any given drug. As a result it platform has been developed within clinical trials and identify factors should come as no surprise that AESEs the project and used to predict side that can be used to meaningfully are being treated by pharmaceutical effects that have subsequently been differentiate one drug from its companies with significant concern. confirmed in patient claims records competitors. In the emerging belonging to Clalit, the biggest health healthcare environment where It is not that the industry does not insurance provider in Israel. This the need to bring down costs and wish to find a solution or be able to work and the resulting publication, provide true value for money become predict AESEs and take appropriate which is currently under review, is a paramount, we expect to see the action proactively. It has to do with the state of our knowledge but also the fact that one is attempting to predict a negative event; in other words an event which is not “acknowledged” until it actually occurs. Simply put, if a predicted AESE does not happen within a certain timeframe, this does not mean that it may not happen in some subsequent time period.

And as if the above is not tough enough, acting on AESEs proactively can be a very expensive proposition since it may cause a pharmaceutical company to spend large amounts of additional development funds to allay regulatory fears of a predicted SE that may never materialize. Pharmaceutical companies are therefore right to be skeptical.

Undue burden (loosely defined as “anything creating significant difficulty and/or expense to meet all aspects of some obligation”)

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demand for action in this respect us achieve and so for p-medicine to of clinical trials will further help the increase significantly. succeed one of the things we need vision of putting the prediction of to ensure is that the tools that are AESEs to good use leading to better, There is an additional reason why such accessible through it are useful and cheaper and more differentiated 2015 no 4 • february work is important for p-medicine accepted by their target users. (personalized) treatments. itself. At its heart, p-medicine aims to create an infrastructure that doctors, The AESE-prediction work addresses drug developers and scientists will this goal and is expected to help use to design and manage clinical with the promotion and subsequent Contact trials, carry out research, discover exploitation of the p-medicine new therapies, exchange information infrastructure. At the ‘technical level’ Andreas Persidis and collaborate. Infrastructures are integrating this capability more tightly Email only as good as the tasks they help with the design and management Website browse-directed search: a tool for generating hypotheses Biovista Inc.

We all know keyword-based search. Google, PubMed and other search tools are great at it. You know what you are looking for, you describe it with a few keywords and then you get links to the most relevant documents or other resources in the case of Google. In some cases you can even get the actual answer to a specific question like for example “what is the capital of Germany”.

However in a discovery context, we may not always know exactly what we are looking for. We may have a very good idea of what we would like to know, and also we may certainly have a good appreciation of the general problem space in which we are seeking to make some discovery, but often in this situation the hardest part is to ask the right question(s); in other words, to be aware of what we do not know but might be relevant to the p-medicine platform, is one such The taxonomy currently consists the problem we are seeking to solve. tool. Using the scientific literature of over 30 UMLS classes including, Not knowing what we do not know as its primary data resource and a amongst others, the more obvious is why it is hard to ask these right taxonomy of biologically relevant genes, pathways, diseases and drugs, questions and so any tool that helps concepts as its organizing framework but also others less frequently used us to “know” what we do not know for search, it helps scientists identify such as cell lines, PTMs and Fluids promises to be a useful resource for non-obvious correlations amongst and secretions. Within COSS search systematic discovery and innovation. biologically relevant entities that may is best described as a “graph-based, be useful in their problem context directed, step-wise browsing through Biovista’s literature-based discovery and that they might not have been a network of connected entities”, an platform (COSS), made available via aware of. entity being a specific gene such as

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HIF-1, a pathway such as apoptosis or regulates PTEN, leaving the user to COSS (named Correlation Viewer a disease such as Wilms tumor. discover this for themselves. While within p-medicine) is being used this setup results in more “potential systematically to help find new uses no 4 • february 2015 no 4 • february Each search query (or step) consists relationships” being recorded by COSS for existing drugs, to identify drug of selecting one or more entities and and also increases the number of Adverse Events (AEs), to elucidate then selecting a class (such as genes, false positives, it represents a design mechanisms of action of drugs and diseases, PTMs and pathways) with decision which recognizes: identify potential targets related to members of which COSS will seek to diseases of interest. In p-medicine identify connections of the selected a) That in a discovery context it is COSS is made available to clinicians entities. So for example a typical preferable to increase the chances and other users with the goal of “query” in COSS is of the type “show that “no stone is left unturned” even helping them identify new therapies, me drugs that are related (somehow) at the expense of some additional identify potential AEs of drugs or to Wilms tumor”. In such a query, the filtering work by the user rather drug-drug interactions and based on selected entity is “Wilms tumor” the than the opposite that could lead to this information identify populations selected class of interest is “Drugs” missed discovery opportunities. at-risk and optimize the design of and the output will be a set of specific b) That a relationship such as up- clinical trials. drugs that are related with Wilms regulates may be true in some tumor. context but not in another. The Correlation Viewer is Given the complexity and rich accessible via the following link: Within COSS, two entities are interconnectedness of biological https://srv-eu.biovista.com/p- “related” if they co-occur within systems and processes and the fact medicine-client/? a specific scientific publication. that our current state-of-the-art No attempt is made by COSS to solutions do not capture biological For more information please send an characterize the nature of the context in a satisfactory way, it is email to: [email protected] relationship and so COSS does not best to leave this for the user to indicate that, for example, HIF-1 up- discover and judge.

p-medicine comic competition 2014 We are pleased to announce the winner of our p-medicine comic competition: Mr Alberto Anguita from the Technical University of Madrid (UPM).

p-medicine newsletter 11 partners in depth: Biovista

made these capabilities accessible via browser interfaces and build on social media resources to support open Contact collaboration models for therapy development and other knowledge 2015 no 4 • february intensive applications. Biovista Biovista Inc. is a Greek-American 34 Rodopoleos Street SME focusing on drug repositioning Biovista is a recognized leader Athens 16777, Greece services and the application in the space of systematic drug of literature and data mining repositioning with its staff members www.biovista.com technologies to systematic having contributed many articles, innovation in the healthcare and life book chapters and recently its sciences industries. The company’s President being appointed Editor in COSS (Clinical Outcomes Search Chief of the 1st journal dedicated to Space) platform technology combines drug repositioning (Drug Repurposing, proprietary information extraction, Rescue and Repositioning ISSN: 2332- literature-based discovery, database 0257). It is also working actively retrieval and visualization algorithms to help define a future healthcare to support human-driven exploration, ecosystem that will better address hypothesis generation and discovery. the challenges faced by society and the industry in the coming years. Recent developments of COSS have

Short CV: Dr Eftychia Lekka

Eftychia Lekka is a senior investigator in Drug Discovery at Biovista. She holds a PhD in Cancer Immunology and Immunotherapy and a Master degree in Human Molecular Genetics (ICL). Prior to joining Biovista, Eftychia worked in the Cancer Immunology and Immunotherapy Center (CIIC) in Saint Savvas Cancer Hospital, Athens, mainly focusing on the development of peptide vaccine therapeutics for breast and prostate cancer. Furthermore, she has conducted research work in the field of genomic imprinting of fetal growth and development while at the Institute of Reproductive and Developmental Biology (IRDB) in Hammersmith Hospital, London. Alongside her research activities, she has prior expertise in prenatal genetics, particularly in the karyotypic detection of chromosomal abnormalities.

Eftychia is responsible for Biovista’s therapy development work in p-medicine.

Short CV: Dr Vassilis Virvilis

Vassilis Virvilis received a Diploma degree in Physics from the University of Crete, Herculanum, as well as a Ph.D. degree in Neural Networks from the University of Athens. During his doctoral work he developed billnet, a highly modular and efficient neural network simulator that has already been used to several real world problems along with research projects. He is an award winner of the software carpentry project for the design of a software configuration tool. His research interests include novel neural networks algorithms’ complexity and their appliance in intelligent image and search.

Vassilis is leading Biovista’s IT team working in p-medicine.

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ecrin (european clinical research infrastructures network) and p-medicine

An infrastructure for European providing services for any category of clinical research clinical research.

no 4 • february 2015 no 4 • february ECRIN is coordinated by Programme Clinical research plays a key Coordinator Jacques Demotes (Fig. role both in the development of 2). He has pointed out that creating innovative health products and in the a single area for clinical research in optimisation of medical strategies, Europe will ensure easier patient leading finally to evidence-based recruitment and allow industry practices. The European Clinical and academic projects to directly Research Infrastructures Network access multiple research sites. It will Fig. 2: Jacques demotes at CRI Solutions (ECRIN) is a sustainable, not-for- strengthen the attractiveness of Day 2014 in Düsseldorf. profit infrastructure supporting Europe for clinical trials through the multinational clinical research creation and maintenance of national projects in Europe. ECRIN is based infrastructures sharing common on the connection of coordinating tools, standards and procedures1. centres (EC) for national networks ECRIN has been officially awarded of clinical research centres (CRC) the legal framework for a European and clinical trials units (Fig. 1) that Research Infrastructure Consortium provide support and services to (ERIC) (Fig. 3). One focus of ECRIN is multinational clinical research (www. the certification of data centres to ecrin.org). Furthermore, ECRIN is ensure a high degree of quality in data developing, upgrading and expanding management, as well as compliance its infrastructure by means of an with GCP and the ability to support Integrating Activity Program (ECRIN- international clinical trials2. IA) and thereby building support Fig. 3: ECRIN partners (2014) and their for the three medical areas of rare In p-medicine, ECRIN is represented status in the network diseases, medical devices, and by the Coordination Centre for nutritional research. ECRIN offers Clinical Trials (KKS) of the Heinrich- supports multi-centre clinical trials integrated support to multinational Heine University Düsseldorf (UDUS). considering Good Clinical Practice clinical research projects through The KKS is a central part of the (GCP) standards, as well as legal and information, consultancy, and by Faculty of Medicine of UDUS and scientific criteria. In collaboration with KKS, the area of IT and computer support is covered by the Clinical Research Informatics (CRI) Group that provides an interface between clinical research, routine patient care and information technology (IT). The CRI Group has developed the Clinical Study Registry for the Medical Faculty and is collaborating with the different p-medicine groups to enable the integration of p-medicine into the ECRIN clinical research infrastructure.

In addition to their involvement in p-medicine, KKS and CRI participate in several other EU projects, most notably TRANSFoRm, and EHR4CR. Here the focus is likewise on legal/ethical aspects, semantic interoperability, knowledge sharing solutions, and the provision of Fig. 1: ECRIN infrastructure (EC: EU Correspondent, DM: data management centre, NNC: requirements engineering, software national network coordination). evaluation and system validation. The

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international ethical and scientific ECRIN to provide adapted knowledge quality standard for designing, exchange and support in local conducting, recording and reporting languages. For this approach a joint trials. service strategy including all support 2015 no 4 • february activities must be developed and The evaluation showed that system validation has to be extended integration of p-medicine tools and to the area of service provision. services into the ECRIN infrastructure must be done on three levels: business, process, and technical level Fig. 4: CRI Solutions Day 2014: (Fig. 5). This has to be a step-wise presentation of ObTiMA approach, depending on tool/service maturity, available documentation 1 Creating a single European area CRI Group has recently organised the and the extent of validation. The for clinical research, published ECRIN Clinical Research Informatics expertise of ECRIN has enabled the by Horizon2010 newsroom editor Solution Days 2014 (May 26-27, consideration not only of technical (31/03/2014). Available online: http:// 2014) covering software solutions and legal aspects, but also of business ec.europa.eu/programmes/ for advanced IT-support from and sustainability issues. horizon2020/en/news/creating- EU-projects for the challenges of single-european-area-clinical- clinical research, including several To further the employment of research p-medicine tools (Fig. 4). p-medicine tools in ECRIN, the 2 Requirements for Certification of concept of “reciprocal integration” of ECRIN Data Centres with Explanation services was developed. On the one and Elaboration of Standards, Version Collaboration between p-me- side, ECRIN can provide experience 2.2, July 2012. Available online: dicine and ECRIN in conducting international clinical http://www.trialsjournal.com/ trials, requirements (processes, content/supplementary/1745- validation), training, and usability; 6215-14-97-s3.pdf Within p-medicine, UDUS and ECRIN on the other side, p-medicine 3 ICH Topic E 6 (R1) Guideline for Good have determined user requirements provides personalised medicine tools Clinical Practice. EMA, London. CPMP/ and specifications for the integration and services and a data protection ICH/135/95 (2002). Available online: of p-medicine tools into the framework. Based on the ECRIN http://ichgcp.net/pdf/ich-gcp- ECRIN infrastructure and their data structure of national hubs (EU en.pdf management systems. The effective Correspondents), it is possible for integration of p-medicine tools into clinical trials infrastructures was prepared by means of a gap analysis, evaluation of tool development and system validation. For Deliverable 6.2 developers of p-medicine tools were surveyed to evaluate the software maturity and usability of p-medicine tools for ECRIN using requirements for GCP compliance, quality management, sustainability/business planning and process conformity. The results of the gap analysis are going to be used for the system validation of p-medicine tools. To be employed in a clinical research infrastructure p-medicine tools have to meet legal requirements and the GCP standards. Thus, before being able to be employed in ECRIN, p-medicine tools and services must be validated for their GCP compliance. GCP3 is an Fig. 5: Three levels of integration between p-medicine and ECRIN

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alga-bc: a web-based interactive empowerment tool for breast cancer patients

Considerable improvement of modulate the language, vocabulary, immediately stored and recoded in a communication between physicians and content of subsequent patient’s profile that is used by the and patients will progressively need discussions with the patient, thus physician to adjust content, level, and no 4 • february 2015 no 4 • february to occur as personalised medicine enabling easier understanding by modalities of verbal information to becomes the norm. An accurate the patient. This, in turn, helps the the patient’s needs. On the clinician’s profile of the patient’s cognitive and patient formulate questions and side, the ground-breaking element psychological status should help participate on an equal footing in the provided here is the possibility to the physician shape his language decision-making processes. Finally, have access to the data that is not and his messages to maximise the a preview is given on the techniques just medical, but rather centred on patient’s understanding of her under consideration for exploiting the values and needs of the specific management options. To this aim the constructed patient profile patient, through the profile originated a computerized tool (ALGA Breast by a personal health record (PHR). from an ALGA-BC. The combined Cancer questionnaire) has been Predefined rules will use a patient‘s clinical and psycho-cognitive created and validated. ALGA-BC is a profile to personalise the contents information becomes patient’s and multilingual, multidevice instrument, of the information presented and doctor’s common knowledge, around and its validation was carried out in to customise ways in which users which they can build together long healthy people and breast cancer complete their tasks in a PHR system. term efficient decision-making plans. patients. This optimises information delivery to patients and makes it easier for the However, ALGA-BC is not a The questionnaire is developed to be patient to decide what is of interest questionnaire thought to remain compatible with a variety of mobile to him/her at the moment. isolated for the health system, but devices and browsers. It is optimised part of a larger platform, the so- for the following mobile devices: The exploratory factor analysis called interactive empowerment iPhone, iPad, Nexus 7, Nexus 4, and revealed eight factors: global self- service (IEmS) platform. This platform for the following web browsers: rated health, perceived physical is developed within the European Chrome, Safari, Firefox, Opera, and health, anxiety, self efficacy, cognitive Union p-medicine project. Internet Explorer. closure, memory, body image, and sexual life. The internal consistency The ALGA-C questionnaire with In addition to the aforementioned and test–retest reliability were good. 29 items has been revealed a valid questionnaire, a patient profiling instrument to obtain a patient’s mechanism has also been developed. More specifically, while waiting for the profile that can help physicians who The ALGA-BC Profiler enables medical visit, the patient will fill in the encounter the patient for the first physicians to rapidly inspect each ALGA questionnaire on an electronic time to achieve a real personalized patient‘s individual psycho-cognitive device connected with the patient’s care that overcomes the limitations profile and see at a glance the areas of personal health record (PHR). The imposed by a pure biological and concern. With this tool, doctors can outcome of the questionnaire is genetic approach.

Data obtained by the questionnaire will be used to create the patient’s personal profile using the IT competences and to provide it to physicians, thereby facilitating the patient-physician interaction and to improve the patient’s involvement in the clinical decision process, finally leading to patient empowerment.

More information:

Video on the ALGA-C Questionnaire

e-learning module on ALGA-C An example of the answer-based question flow Quiestionnaire

p-medicine newsletter 15 myhealthavatar: a demonstration of 4d digital avatar infra- structure for access of complete patient information

MyHealthAvatar has been designed We strongly believe that providing a as your life-long companion for pleasant user experience is the key health. It is the place where you can to success in terms of engaging the hold consistent healthcare records targeted end-users. Hence we have 2015 no 4 • february right from your birth, offering great cast our focus on user experience, assistance to your healthcare. It will aiming at a range of functionalities help your doctors know more about that facilitate the users in uploading your health histories if you move to and managing their data in the a new place, or under an emergency MyHealthAvatar platform. opportunities for new business. New medical situation where the patient tasks are to be explored for increasing can not provide details of their There has been a great leap in the sustainability of the project personal health profiles. technology in recent years. For the outcomes through engaging with stakeholders of the MyHealthAvatar the industry. Also, these activities MyHealthAvatar will help you look system, this brings more have triggered new complexity in after your own health. This will opportunities. For example, sensor privacy protection and in the legal contribute to the new shift in future technologies and wearable computers framework. MyHealthAvatar supports healthcare systems where patients have opened a new door for us to entire data ownership of citizens and will be given more power and will also monitor ourselves for health-related the data sharing decisions will be be asked to make more commitment behaviors; Big Data management solely made by individuals who own to their own healthcare. By doing so, and cloud computing technology the data. To this end, new studies self-awareness and positive attitudes have increased our capability in are needed to allow citizens to easily towards healthy lifestyles and handling more and larger datasets. control their privacy under complex behaviors will be encouraged. From However, these new developments application scenarios. a more general perspective, citizen also imply more challenges ahead empowerment has recently attracted for the technologists since greater The initial version of the a lot of attentions for collective technology depth and width are MyHealthAvatar platform is ready at awareness and sustainability along required to be explored. myhealthavatar.org/mha/login. We the dimension of social innovation. are welcoming more participants to MyHealthAvatar contributes to new The new trend of citizen and use the platform and telling us your research in these directions. patient empowerment brings huge experience. vph-share makes impact at vph2014 in trondheim

VPH-Share sent a sizeable delegation intellectual standards, as a means who I had previously only known by to VPH2014, the conference which of realising the Virtual Physiological e-mail.” is the preeminent gathering of Human. the Virtual Physiological Human Also presenting from VPH-Share community. With keynote presentations were Piotr Nowakowski, who spoke including Professor Denis Noble, on the Development, execution and Led by Professor Rod Hose, who the conference is one of the most sharing of VPH applications in the presented VPH-Share: A Scalable important dates for those working in cloud with the Atmosphere Platform. Architecture for Scientific Cloud the field ofin silico medicine, offering Piotr said: “VPH2014 enabled us to Computing, the team gave a series an opportunity to identify the major showcase the VPH-Share platform of presentations, conducted live research and clinical challenges and explain its advantages to the demonstrations of its system and facing the field today. From VPH- broad VPH community. My personal staged a dedicated hands-on session, Share, Ernesto Coto, presented The highlights of the conference were the which taught users how to use the VPH-Share plugin for workflow keynote lectures by Denis Noble and VPH-Share infrastructure. composition and execution. Ernesto Mark Sagar.” said: “It was a useful opportunity to The conference, which took present at VPH2014, because the VPH-Share is in the process of place in Trondheim, Norway from focus of the conference is very close pursuing links made at VPH2014, as September 9-12, 2104 was focussed to the focus of our project. It was also it continues to expand its cohort on integrating the VPH community, very useful to finally see face-to-face of use-cases, in preparation for its by sharing common goals and several people involved in the project, completion in April 2014.

p-medicine newsletter 16

building policy recognition for vph research

remarks that the deployment of personalised medicine will be eHealth technologies such as VPH adequately represented in the next is an “economic imperative” which Horizon 2020 Work Programme for no 4 • february 2015 no 4 • february could help stem the tide of chronic Health, Demographic Change and diseases and control spiraling Wellbeing?” The VPH Institute is an international healthcare costs. non-profit organisation incorporated This question was tabled in advance in Belgium, whose mission is to In the coming months the European of a key meeting with some 10-12 ensure that the Virtual Physiological Parliament stood their ground on the Commission officials to address this Human (VPH) is fully realised, budget for Horizon 2020, called for very issue. Just days after presenting universally adopted, and effectively the budget to be increased to 100 to the European Commission on how used both in research and clinic. Since billion euro and would not accept the VPH could be supported, on August its incorporation back in spring 2011, Council’s proposal of a budget of 56 29, 2014, an official response from the VPH Institute has been constantly billion. In January 2014, the European the Commission was submitted active in building recognition of the Parliament, in an overwhelming where the Commission confirmed: value of the VPH research at political majority, voted in favor of a policy “…For the Work Programme 2016- level. that specifically endorsed VPH as 2017 the Commission intends to an example of a successful eHealth further support development of ‘in In early 2012, a workgroup on Policy solution. Through the adoption of silico’ models and methods. At this Affairs (PAWG) was created to text suggested by the PAWG, in the stage the input to be proposed to specifically concentrate on these European Parliament’s Motion for the Work Programme with respect activities. The group is chaired by Resolution on the eHealth Action to personalized medicine will be the Prof Liesbet Geris – University of Plan 2012-2020, the Parliament subject of further consultations and Liege, and it sees the participation of unambiguously called for the agreements.” a number of the VPH members. The continued funding of VPH research PAWG’s primary focus is to engage activities in the Horizon 2020 work This move opened a new important with the European Parliament and programme, urging the Commission scenario for in silico medicine, the European Commission, stressing and the Member States to continue establishing direct connections the importance of in silico medicine working through pilot projects, such between the VPH Institute and and the need for support for VPH in as the Virtual Physiological Human representatives of different EC units. European Policy. initiative, in order to develop pan- Ongoing discussions are still taking European interoperability, and to place, but the EC is considering The first important goal was achieved continue to support innovative different approaches to further in June last year, when the VPH solutions for person-centred care, sustain VPH research in the upcoming Institute organized a workshop including advanced modelling and H2020 calls that could go from further at the European Parliament in simulations, needed to achieve the implementations of the current Brussels that was co-hosted by two aims of predictive and personalised technologies to clinical validation. influential Members of the European medicine. Parliament: Seán Kelly and Vittorio In addition to these activities, the VPH Prodi. The event entitled “Towards With this important achievement Institute is also very active in scanning personalised and in silico medicine: in our hands, in July 2014, three the EU policy scenario and producing eHealth Action Plan and VPH” had Members of the European Parliament position statements on different the aim to introduce the concept representing the three largest hot research topics, highlighting of in silico medicine, reaffirming political groups in the Parliament the value of VPH research in solving the importance of research funding (Seán Kelly (PPE), James Nicholson some major economical and societal at a time when the entire Horizon (ECR), Claudiu Ciprian Tanasescu problems. Just to name some: 2020 budget was being called into (S&D)), backed up the VPH Institute question and presenting VPH as an and tabled a joint written question • Big data for personalised example of a successful eHealth to the European Commission on healthcare: the VPH Institute solution. The speakers’ presentations how they would respond to this endorsed that big data clearly showed that VPH can be used political demand, specifically asking: technologies have great potential to facilitate personalised medicine in “…What steps they would take to in the domain of computational Europe, reduce public health costs and ensure that Parliament’s request for biomedicine. While there is improve diagnosis and prediction. Mr. a greater focus on in silico methods clearly an important research Seán Kelly stressed in his concluding in the creation of predictive and space examining the fundamental

p-medicine newsletter 17

methods and technologies comprehensive solutions that involve Both these documents will be used for big data analytics, it is advanced modelling and simulation by the EC as a vehicle to further vital to acknowledge that tools, data acquisition and data implement research funding stream it is also necessary to fund management and advanced user on these specific topics. domain-targeted research that interfaces. All this will enable the 2015 no 4 • february allows specialised solutions clinical and industrial translation of Further information on: to be developed for specific the Digital Patient. applications, such as healthcare http://www.vph-institute.org/news/ in general, and computational In silico clinical trial roadmap: this european-parliament-hosts-event- biomedicine in particular. document is getting developed on-vph-and-ehealth-action-plan. • Petition requesting ban on all through the work of an ongoing html animal experiments in Europe: support action, Avicenna (FP7/2013- the VPH Institute endorsed the 2015), that focuses on designing a http://www.vph-institute.org/ three “R” approach, presenting the pathway towards the successful news/vph-meets-with-european- combination of VPH technologies modernisation of the clinical trials commission.html and computer simulations as the process, thanks to the application way forward to Reduce, Refine of modelling and simulation http://www.vph-institute.org/news/ and partially Replace animal technologies, that could contribute european-commission-ensures- experiments. to make clinical trials leaner, quicker, new-funds-for-in-silico-medicine- • Position Paper on Data Protection more efficient and less expensive. in-horizon-2020.html Regulation: the VPH Institute Via this project, the VPH Institute endorsed the LIBE Committee is working on the establishment a http://www.vph-institute.org/news/ report, emphasizing that access partnership between biomedical parliamentary-question-on-the- to health data is key to predicting, industries and European research protection-of-health-data-on-the- diagnosing and treating disease organisations, with the purpose of internet.html as well as for the development developing the technology, methods, of new therapies to tackle old protocols and standards required http://www.vph-institute.org/news/ health problems. In an age of to overcome the precompetitive european-parliament-endorses- increasing health challenges, the roadblocks in the use of computer vph.html Data Protection Regulation must simulations as components within ensure that responsible access to the clinical trials process. health data is maintained.

Final but not least, the VPH Institute also contributed to steer the community in the production of two import policy documents, covering both the clinical and industrial prospective of VPH research:

The Digital Patient research roadmap: final output of the DISCIPULUS support action (FP7/2007-2013), this document defines a concrete strategy for the realisation and wide scale adoption of results emerging from the VPH Initiative. Its vision is to identify key steps towards realising the Digital Patient, which is a new paradigm in personalised medicine, across the whole healthcare system by focusing on the needs of clinical practitioners and healthcare professionals, biomedical and clinical researchers. This vision will be achieved through www.vph-institute.org

p-medicine newsletter 18

announcement of upcoming events

IST-Africa 2015 Conference

May 5-8, 2015 no 4 • february 2015 no 4 • february Lilongwe, Malawi

Hosted by the Government of Malawi through the National Commission for Science and Technology, Supported by eHealth Week (Registration is now open! ) the European Commission and African Union Commission, IST-Africa 2015 will take place in Lilongwe from May 5-8, May 11-13, 2015 2015. Riga, Latvia

As part of the IST-Africa Initiative, which is supported by Taking place during the Latvian Presidency of the Council the 7th EC Framework Programme, IST-Africa 2015 is the of the European Union on May 11-13, 2015, eHealth Week 10th conference in a series of Annual Conferences which 2015 comprises of two main events: the High Level eHealth brings together senior representatives from leading Conference organised by the Latvian Ministry of Health commercial, government & research organisations across and the Latvian Presidency of the Council of the European Africa and from Europe, to bridge the Digital Divide by Union and WoHIT (World of Health IT Conference & sharing knowledge, experience, lessons learnt and good Exhibition) organised by HIMSS Europe. Attracting over practice and discussing policy related issues. 2000 international delegates and 75 exhibitors, the event will welcome global decision makers from public More information and private healthcare sectors, clinicians, hospital and IT managers and VIP guests.

All eHealth Week participants can attend a range of sessions and activities including mHealth Summit Europe, EU SME eHealth Competition, an onsite Matchmaking Event, the Continua Summer Summit and a state of the Workshop on Personalized Medicine art exhibition including country pavilions from all over the world. May 12-13, 2015 Cambridge, UK, More information

Within the scope of the Camebridge Workshop Series, SELECTBIO will host a workshop on Personalised Medicine on May 12-13, 2015 at Buckingham House, Murray Edwards European Cancer Congress 2015 College in Cambridge, UK. September 25-29, 2015 With the onset of the genomic era and increase in Vienna, Austria clinical molecular analysis, more and more, clinicians and researchers are clearly defining multiple disease subtypes The renowned biennial series of multidisciplinary for diseases that were once thought to be singular in European Cancer Congresses is back! They are recognised cause. This is opening the door to the discovery and as the premier cancer meetings in Europe. development of highly effective and targeted diagnostics and therapies that result in better patient outcomes The 18th ECCO – 40th ESMO European Cancer Congress, and the reduction in use of generalised treatments with which will take place in Vienna, Austria on September severe side effects. Despite these benefits the regulatory 25-29, 2015, will combine the united efforts of all partner and financial systems are not yet in place to enable this organisations to continue positioning multidisciplinarity revolution in healthcare to flourish and there are many as the way forward for improving the prevention, hurdles to overcome before personalized medicine can diagnosis, treatment and care of cancer patients - placing become commonplace. the patient at the heart of all our efforts and discussions.

Registration is now open! Early bird registration: April 7, 2015 Poster submission deadline: April 17, 2015 Abstract submission deadline: April 28, 2015

More information More information

p-medicine newsletter 19

editorial board

newsletter team

Norbert Graf Saarland University (USAAR), 2015 no 4 • february Coordinator of p-medicine

Corinna Hahn European Research and Project Office GmbH (Eurice)

Janine Jost European Research and Project Office GmbH (Eurice)

Holger Jung subscription European Research and Project Office GmbH (Eurice) The p-medicine newsletter is published once a year by the p-medicine consortium and is distributed free of charge. Nina Weiler European Research and Project All issues of the newsletter are available on our website. Office GmbH (Eurice)

For subscription to the newsletter please go to www.p-medicine.eu/news/newsletter consortium members

Töresin Karakoyun, Wolfgang Kuchinke Heinrich-Heine-University rss feed Düsseldorf (UDUS)

An RSS feed is available on the p-medicine website. For more information Gordon McVie please go to www.p-medicine.eu/news/rss-feed ecancer

Elisabetta Munzone, Alessandra Gorini, Gabriella Pravettoni Istituto Europeo di Oncologia s.r.l disclaimer (IEO)

The p-medicine project (Project Identifier: 270089) is funded by the Andreas Persidis, Eftychia Lekka, European Commission under the Seventh Framework Programme. Vassilis Virvilis BIOVISTA The content of this newsletter cannot be considered as the European commission’s official position and neither the European Commission nor any person acting on behalf of the European Commission is responsible guest authors for the use which might be made of it; its content is the sole responsibility of the p-medicine project partners. Martina Contin VPH Institute Although the p-medicine consortium endeavours to deliver high quality, no guarantee can be given regarding the correctness and completeness Feng Dong of the content of this newsletter due to its general informational University of Bedfordshire character. Project Manager of MyHealthAvatar

The p-medicine consortium is not responsible and may not be held Hannah Whitelam accountable for any loss suffered as a result of reliance upon the content The University of Sheffield of this newsletter. VPH-Share

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