Encl. 4 European Curricula for Global Expertise PharmaTrain Manual Curriculum Standards and Best Practices Postgraduate Training Programmes aligned with the Bologna principles: Diploma in Medicines Development / Pharmaceutical Medicine DiMD Master of Medicines Development / Pharmaceutical Medicine MMD Specialist in Pharmaceutical Medicine SPM MMR Master of Medicines Regulation Elective Modules on Continuing Professional Development, CPD, Platform Clinical Investigators Certificate CLIC for trainees and trainers on PharmaTrain e-Campus www.pharmatrain.eu This is Version 0.7 (4.4.2011) of our PharmaTrain Manual. There still are a number of issues for discussion as well as some additional new training programmes in need of more in depth preparation before inclusion in the Manual. The Manual is a living document in an advanced stage but finalisation is planned only with the termination of the PharmaTrain project. Next version updates follow after each (Annual) General Assembly meeting. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 1/79 PharmaTrain Executive Board Members and Co-Authors Public partners: Rolf Bass, Fritz R. Bühler, Jean-Marie Boeynaems, Susanne Daniel, Kirsteen Donaldson, Dominique Dubois, Brian Gennery, Jean-Marc Husson, Stuart Jones, Behrouz Kassai, Sandor Kerpel-Fronius, Heinrich Klech, Ingrid Klingmann, Hans Linden, Annette Mollet, Gerfried Nell, Sam Salek, Peter Stonier, Thomas D. Szucs; Mary Teeling Private partners: Anthony Chan, Matthias Gottwald, Mike Hardman, Ruth Hargreaves, Juan Lahuerta, Detlef Niese, Wolf R. See, Dominic Smethurst, Armel Stockis The PharmaTrain Collaborative Network 2009-2014* University/Base Diploma Course and Master Programmes Providers (Fig. 1) Training Centres Base Diploma Courses 30 ECTS (1) MMD, ECTS 60+ 1 Brussels, Pharmed www.ulb.ac.be/medecine/pharmed 2 Basel, ECPM www.ecpm.ch 3 Budapest Semmelweis http://gyogyszerfejlesztes.hu (2) 4 University of Barcelona www.uab.es 5 Lyon, Eudipharm www.eudipharm.net 6 Cardiff www.cardiff.ac.uk 7 Duisburg-Essen www.uni-due.de 8 Hibernia College www.hiberniacollege.net 9 King's College London www.kcl.ac.uk 10 Milano www.maserfarmaco.medicina.unimib.it 11 Rome www.rm.unicatt.it/master 12 Surrey www2.surrey.ac.uk 13 Trinity, Dublin www.pac.ie/tcd (3) (1) Base Diploma Modules, DIMD (2) Extension Master Programme (12 total), MMD (3) Integrated Master Programme (12 total), MMD Public Partners (Universities) University of Basel, European Center of Pharmaceutical Medicine , ECPM Pharmed, Université Libre de Bruxelles Semmelweis University, Budapest University Claude Bernard Lyon Cardiff University University of Surrey Newcastle University Hibernia College University of Dublin, Trinity College Vienna School of Clinical Research University of Vienna University of Belgrade University of Duisburg-Essen * It is planned that after termination of the funding period in 2014 PharmaTrain activities and infrastructure will be sustained by the European Federation of Course Providers in Pharmaceutical Medicine/Medicines Development, EFCPM, which is allied to the European Chapter of the International Federation of Associations of Pharmaceutical Physicians, IFAPP. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 2/79 University Hospital, Freiburg Fondation Health Sciences e-Training (HSet), University of Lausanne University of Copenhagen Université de Strasbourg Catholic University of Rome University of Barcelona Autonomous University of Barcelona Universitat Pompeu Fabra, Barcelona King’s College London Public Partners (Learned Societies) European Federation of Course Providers s in Pharmaceutical Medicine, EFCPM International Federation of Associations of Pharmaceutical Physicians, IFAPP Faculty of Pharmaceutical Medicine, Royal Colleges of Physicians of the United Kingdom Institute for Education in Pharmaceutical Medicine, PME Drug Information Association Europe, DIA European Federation of Pharmaceutical Sciences, EUFEPS Medicines and Healthcare products Regulatory Agency, MHRA Swissmedic European Organisation for Research and Treatment of Cancer, EORTC Dutch Top Institute Pharma European Forum for Good Clinical Practice, EFGCP Private Partners Amgen AstraZeneca AB Pfizer Ltd. Bayer Healthcare AG F. Hoffmann-La Roche AG GlaxoSmithKline Research and Development Ltd. Janssen Pharmaceutica NV (Johnson & Johnson) Almirall S.A. Laboratories del Dr. Esteve, S.A. Merck KGaA / Merck Serono Novartis Pharma AG Novo Nordisk A/S Orion Corporation, Orion Pharma Sanofi-Aventis R&D UCB Pharma SA Advisory Group in PharmaTrain American Course of Drug Development and Regulatory Sciences, ACDRS Council for Education in Pharmaceutical Medicine, CEPM, IFAPP Europa Bio European Medicines Agency, EMA PriceWaterHouseCoopers, PWC Affiliated Universities Charles University, Praque (CEDDC) Faculty of Pharmacy, Comenius University, Slovak Republic (CEDDC) Medical University of Warsaw (CEDDC) Medical University of Gdansk (CEDDC) Medical Academy, Lithuanian University of Health Sciences, Lithuania (CEDDC) University of Gazi, Medical School, Turkey (CEDDC) Medical University Sofia, Bulgaria (CEDDC) University of Ljubljana, Faculty of Pharmacy, Slovenia (CEDDC) University of Medicine and Pharmacy from Targu-Mures, Romania (CEDDC) University Milano Bicocca 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 3/79 Executive Office EFCPM c/o ECPM, University of Basel, Klingelbergstrasse 61, CH-4056 Basel T: +41 61 265 76 50, F: +41 61 265 76 55, [email protected], [email protected] www.pharmatrain.eu PharmaTrain Identifier: to be uploaded on individual partners’ web sites and printed on programmes or leaflets We are an official partner of the European IMI PharmaTrain project and adapt our training activity to the new shared standards of PharmaTrain. PharmaTrain is one of the IMI JU projects on Education and Training and addresses Pharmaceutical Medicine/Drug Development Sciences. IMI stands for Innovative Medicines Initiative, a Joint Undertaking of the European Commission and European Federation of Pharmaceutical Industries and Associations, EFPIA. Consult www.pharmatrain.eu and www.imi.europa.eu 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 4/79 Content 00. Glossary....................................................................................................................... 8 0. Executive Summary .................................................................................................... 9 1. PharmaTrain Training Initiative ................................................................................ 12 1.1 Introduction ........................................................................................................ 12 1.2 Programme aims and objectives ........................................................................ 12 1.3 Shared standards and common understanding in PharmaTrain ......................... 13 1.4 The PharmaTrain Continuing Professional Development, CPD Platform overview ............................................................................................................. 16 1.5 PharmaTrain Centres of Excellence as an internal Quality Standard and PharmaTrain Centres Recognition ..................................................................... 16 1.6 The Process of PharmaTrain Continuing Performance Improvement ................. 17 2. Syllabus, Modules and Learning Outcomes............................................................ 18 2.1 The PharmaTrain Syllabus and Curriculum ........................................................ 18 2.2 Learning Outcomes ............................................................................................ 18 2.3 e-Campus: e-learning, blended learning ............................................................. 18 2.4 The CPD Platform and Elective Modules............................................................ 19 3. Base Diploma Course and Master Programme Modules for Medicines Development / Pharmaceutical Medicine................................................................. 20 3.1 Base Diploma Course (Base Modules, n = 6, 30 ECTS) .................................... 20 3.2 Extension Modules (n = 4) and Elective Modules (n = 2) .................................... 38 3.3 Integrated Master Programme (Integrated Modules (n = 10) and Elective Modules (n = 2) + Master Thesis; 60+ ECTS) .................................................... 49 3.4 Elective Modules 1-10 ........................................................................................ 53 3.5 Additional PharmaTrain Programmes ................................................................. 57 3.5.1 Master of Medicines Regulation, MMR ................................................. 57 3.5.2 Clinical Investigator Certificate/Courses, CLIC and e-CLIC .................. 58 4. Qualifications, Examinations and Recognitions ..................................................... 59 4.1 Entry Requirements ........................................................................................... 59 4.1.1 Applicants who wish to register for a programme.................................. 59 4.1.2 Applicants who do not wish to register for a programme ....................... 59 4.1.3 Students undertaking Pharmaceutical Medicine Specialist Training / Specialist in Medicines Development, SMD .......................................... 59 4.2 Accreditation of prior learning ............................................................................. 59 4.3 Outcomes and qualifications .............................................................................. 60 4.3.1 PharmaTrain module ............................................................................ 60 4.3.2 1st tier: (Base) Diploma Course ............................................................. 60 4.3.3 2nd tier Master Programme.................................................................... 60 4.3.4 3rd tier of the Masters Programme ........................................................ 60 4.4 Assessments/Assignments................................................................................. 61 4.4.1 General principles of assessment ......................................................... 61 4.4.2 Types of assignment ............................................................................ 61 4.5 Integrated examination ....................................................................................... 62 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 5/79 4.6 4.7 4.8 Master dissertation/thesis ................................................................................... 63 Professional recognition/certification/accreditation ............................................. 64 4.7.1 Goal of recognition ............................................................................... 64 4.7.2 Physicians in countries recognising the specialty of Pharmaceutical Medicine ............................................................................................... 64 4.7.3 Non-physicians and physicians in other countries................................. 65 4.7.4 Examples on the national level ............................................................. 65 Continuing Professional Development ................................................................ 66 5. Programmes Quality Management Systems ........................................................... 68 5.1 European Quality Assurance Framework ........................................................... 68 5.2 Quality Management System ............................................................................. 68 5.2.1 Quality assurance ................................................................................. 69 5.2.2 The quality management and process translational part; the three step training-centre accreditation process .................................................... 69 5.2.3 Course quality control and university centre assessment...................... 70 5.2.4 Quality Control of the Integrated Examination ....................................... 72 5.3 Elements of quality control ................................................................................. 72 5.3.1 Student feedback.................................................................................. 72 5.3.2 Board of Studies ................................................................................... 72 5.3.3 Independent observers from national associations .............................. 72 5.3.4 Programme revalidation........................................................................ 72 5.3.5 Criteria and principles for accreditation of Training Modules/Course programmes ......................................................................................... 73 6. Structure of training programmes ........................................................................... 74 6.1 Academic structure ............................................................................................ 74 6.1.1 Education Board ................................................................................... 74 6.1.2 External examiners ............................................................................... 74 6.1.3 Programme contacts ............................................................................ 74 6.2 Duration of Programmes .................................................................................... 74 6.3 Examination process .......................................................................................... 75 6.4 The Cooperative European Drug Development Course (CEDDC) – a geographical extension concept ......................................................................... 76 6.4.1 Managing curriculum implementation ................................................... 77 6.4.2 Selection of course language................................................................ 77 6.4.3 Organisation ......................................................................................... 78 6.4.4 Preparation of the module programme ................................................. 78 6.4.5 Accreditation......................................................................................... 78 7. Appendices and Details of Additional Training Programmes ................................ 79 7.1 Training Programmes Regulations (template for local use!) ............................... 79 7.2 PharmaTrain Syllabus 2010 ............................................................................... 79 7.3 PharmaTrain e-Campus, including e-library and e-products ............................... 79 7.4 PharmaTrain CPD Platform ................................................................................ 79 7.5 PharmaTrain Quality Assurance Guide .............................................................. 79 7.6 Cooperative European Drug Development Course, CEDDC .............................. 79 7.7 Master in Medicines Regulations, MMR ............................................................. 79 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 6/79 The following programmes will be added later: 7.8 7.9 Diploma Course in Medical Device Regulation, DMDR Diploma Course for Clinical Trial Professionals, DCTP 7.10 Clinical Investigator Certificate Course , CLIC 7.11 NN ? (7.xx The PharmaTrain Manual Slide Show) 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 7/79 00. Glossary ACDRS: American Course on Drug Development and Regulatory Sciences ACRP: Association of Clinical Research Professionals APPI: Associations for Pharmaceutical Physicians and Investigators AZ. AstraZeneca CCDRS: Chinese Course of Drug Development and Regulatory Science CEDDC: Cooperative European Drug Development Course CLIC: Clinical Investigator Course CPD: Continuing Professional Development DCTP: Diploma for Clinical Trial Professionals DIA Europe: Drug Information Association Europe DIMD: Diploma in Medicines Development DMDR: Diploma in Medical Device Regulation EC: European Commission ECMDR: European Course of Medical Device Regulation ECPM: European Center of Pharmaceutical Medicine ECRIN: European Clinical Research Infrastructures Network ECTS: European Credit Transfer and Accumulation System EFCPM: European Federation of Course Providers in Pharmaceutical Medicine EFPIA: European Federation of Pharmaceutical Industries Associations EIM: Entry into Man EMA: European Medicines Agency EMTRAIN: European Medicines Research Training Network ENQA: European Association for Quality Assurance in Higher Education EORTC: European Organisation for Research and Treatment of Cancer EU: European Union EUDIPHARM: Training Course provided at Universite Claude Bernard Lyon 1 EUFEPS: European Federation for Pharmaceutical Sciences EU2P: European Programme on Pharmacovigilance and Pharmacoepidemiology FPM: Faculty of Pharmaceutical Medicine GCP: Good Clinical Practice GSK: GlaxoSmithKline HSET: Health Science eTraining Foundation IFAPP: International Federation of Associations of Pharmaceutical Physicians LO: Learning Outcomes MHRA: Medicines and Healthcare Products Regulatory Agency MMD: Master of Medicines Development MMR: Master of Medicines Regulation MS: Master of Science NDA: New Drug Application PharMED: Postgraduate Programme in Pharmacology and Pharmaceutical Medicine at the Free University of Brussels PM: Pharmaceutical Medicine POC: Proof of Concept QA: Quality Assurance QC: Quality Control QM: Quality Management SafeSciMET: European Modular Education and Training Programme in Safety Sciences for Medicines SE: Semmelweis University SMD: Specialist in Medicines Development SPM: Specialist in Pharmaceutical Medicine TA: Therapeutic Area UB-IL3: Instituto de Formación Continua at University of Barcelona, UCB: Pharmaceutical Company (headquarter in Brussels) VSCR: Vienna School of Clinical Research 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 Some examples, more to come! 8/79 0. Executive Summary The PharmaTrain Manual distils the principles of shared standards and best practices which have emerged from the PharmaTrain project collaboration into a document for pan-European implementation. This will be applied by all partner university training centres in PharmaTrain and newly affiliated universities. PharmaTrain is one of the Innovative Medicines Initiative (IMI) Joint Undertaking (JU) educational projects and addresses Pharmaceutical Medicine / Medicines Development. It is a Public Private Partnership (PPP) of 22 University partners, 14 Learned Societies/Associations and several partner training organisations, including Regulatory Authorities, and 15 EFPIA companies. Most universities are members of the European Federation of Course Providers in Pharmaceutical Medicine, EFCPM. They provide five ‘Base’ Diploma Courses, twelve master level programmes and a large number of elective and special training modules which will be offered as part of the PharmaTrain project on the PharmaTrain Continuing Professional Development CPD Platform. IMI JU is a jointly funded undertaking between the European Commission and the European Federation of Pharmaceutical Industries and Associations (EFPIA). The Aim of the Project is to provide courses which are designed to meet the needs of professionals working in medicines development. The main objective of the PharmaTrain project is to harmonize, build and implement modular Master level programmes in Pharmaceutical Medicine / Medicines Development. These programmes will enable graduates to lead the drug development process, aiming to give Europe a competitive advantage in developing innovative medicines. The programme enhances career opportunities for graduates by providing education aiming at understanding the industry’s integrative medicines development processes and requirements and allowing individuals to build a portfolio of recognised and transferable Credit Points in the European Credit, Transfer and Accumulation System (ECTS) in a modular fashion, with the highest achievement of a Master Degree. PharmaTrain will strive to maintain and to improve the standards and quality of courses through a quality management and improvement framework. The programme will encourage exchanges between the industry, regulators and academia. It will produce and promote e-learning programmes and so increase flexibility, transferability and mobility of participants. By providing a database of available education and training programmes at different levels across Europe, PharmaTrain will identify available courses, and map regions and subjects where gaps exist that should be addressed. Modular Structure of PharmaTrain Diploma (Base) Courses, Extension and Integrated Master Programmes (Master of Medicines Development, MMD) – the 3-tier Modular Structure Extension Master Programme: five universities provide a postgraduate diploma consisting of 6 Base Modules including an Introductory Module (30 ECTS, 1st tier). By completing an additional six Extension / Elective Modules and a Master thesis a successful student will achieve a Masters’ degree (60+ ECTS, 2nd tier). Integrated Master Programme: eight universities and colleges provide a master programme with a continuity of modules and a Master thesis (60+ ECTS, 2nd tier). The 3rd tier is required in some countries for specialist certification through workplace-centred competency-based training. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 Discuss Discuss 9/79 Modular Structure: all 13 institutions are constructing comparable modules aligned with the Bologna process with Learning Outcomes which are assessed to facilitate pan-European mobility. The PharmaTrain Syllabus for Pharmaceutical Medicine / Medicines Development provides the content for all education and training activities including Introductory, Base Diploma Course and Master Programme Modules. It covers the drug development process from discovery of a new chemical or biological entity through research and development to regulatory approval, pharmacovigilance, health economics, commercialisation and lifecycle management of a medicine (183 topics in 14 sections, see Appendix 7.2). An Introductory ‘Module One’ (two of the four days of module one) will contain the core subjects of the PharmaTrain Syllabus, covering in a standardised format the context for the more detailed modules to follow. It is adopted by all PharmaTrain programmes and is designed so that other IMI Education &Training programmes may use it as well. Modular assessments are expected to be implemented at the different course sites. An integrated examination concept is structured to be used for the theoretical testing of the Specialist Diploma (see section 4.5). The Specialist in Pharmaceutical Medicine is currently recognised and accredited by national professional associations in three European countries (Switzerland, UK, and Ireland). It is considered how to expand this medical specialty across Europe. A comprehensive Quality Management System supports and translates the principles and standards into training practice to ensure the quality of the 3-tier training curriculum as well as the operation of the entire PharmaTrain programme (see section 5). The PharmaTrain Centres of Excellence status can be achieved by each partner institution by striving for a high level of education and training quality according to the PharmaTrain standards over the coming years. A Centre of Excellence must deliver a full master training programme as well as an additional other training activity. Before obtaining the Centre of Excellence status, a given Training Centre can call on a Coaching Visit, then in a next step for an Audit for PharmaTrain Centre Recognition, and eventually for an Audit for a Centre of Excellence. The PharmaTrain e-Campus integrates state-of-the-art newly developed blended learning modules with those collected from continuing survey to create a directory of online courses, the PharmaTrain e-library, see www.pharmatrain.eu. This is open to all partners, allowing them to blend the content into their modular courses in the way best suited to their institution. The following e-modules are in the design phase: an Introductory Module and five Modules to supplement the Base Diploma Course subjects, a Clinical Investigator Course, and one Therapeutic Area Module. Other Therapeutic Area Modules will be made available for use within PharmaTrain. The repository will allow institutions to continue to develop more specialised extension modules, enhancing the learning experience by creating a holistic environment of teaching methodologies supporting the programme. In addition, this repository will evolve into a pan-European online e-campus, supporting faculty and students. Supporting material (e.g. book chapters, publications etc.) will be added and become part of the online repository. The PharmaTrain CPD-Platform for Continuing Professional Development (CPD) includes elective and extension modules and stand-alone modules pro- 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 10/79 vided by PharmaTrain to facilitate lifelong learning, and which also offer participants opportunities to complete their Master programmes with two Elective Modules. Of note: all modules within PharmaTrain whether within a master programme or stand-alone can be considered for CPD and can be used to build a portfolio of competencies for lifelong learning by an individual professional. For geographic extension of PharmaTrain in Europe, there is a new Cooperative European Drug Development Course (CEDDC) using the PharmaTrain standards. Semmelweis University, Budapest, has started a new ‘Base Diploma Course’ programme which will be integrated into this international organisation of newly affiliated universities. In a collaborative effort, the universities of Basel and Copenhagen and King’s College London, along with our EFPIA partners and regulatory agencies have developed the content and structure of a new Master of Medicines Regulation. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 11/79 1. PharmaTrain Training Initiative 1.1 Introduction The discovery and development, regulation and market introduction of medicines have become increasingly complex. The annual number of approved New Drug Applications, NDAs, over the last 30 years has remained about the same (around 20 per year) despite enormous efforts by the pharmaceutical and biotechnology industries, including a tenfold increase in costs and continuing change programmes to control and accelerate the process. There is a need for a larger number of professionals to understand the integrated process of medicines development in order to manage the interfaces between discovery, development, regulation, market introduction and lifecycle management of medicines more efficiently. People were ‘learning by doing’, but there was insufficient high-quality teaching, and teaching did not include many aspects of the rapidly progressing scientific knowledge and the ensuing more stringent legislation. The present PharmaTrain project was launched in 2009 to address these training gaps by systematic and holistic training of all professionals involved in the integrated drug development process in Europe with the expectation that this new high-quality education and training will improve the global process of medicines development, regulation and use by physicians and patients. 1.2 Programme aims and objectives Objectives The programmes aim at augmenting proficiency across the fields of Pharmaceutical Medicine and Medicines Development and enhancing understanding of the underlying scientific disciplines and the applicable legal and ethical framework. Teaching and training across the Modular Training Programmes aim to provide multi-disciplinary training in pharmaceutical medicine/medicines development by bringing together expert lecturers from academia, industry and regulatory authorities; provide a comprehensive understanding of the entire medicines development process from molecule to marketplace, including discovery, non-clinical and clinical development, drug formulation, safety and regulatory requirements, pharmacoeconomics, marketing and promotion of medicines ; enable students to analyse, evaluate and synthesise information and to place it in a practical decision-making context enable application of innovative methods, tools and strategies that best utilise recent scientific advances and technologies for medicinal product design, development and regulatory review; address real world challenges encountered during the development, manufacture, review and commercialisation of a medicinal product; cover the entire medicinal product lifecycle; enable students to understand future directions in global pharmaceutical and health economics and business environments, and their impact on product development and evaluation obtain a broad outlook on the global pharmaceutical industry provide university, regulatory and industry professionals with a platform and network for the discussion of central issues concerning medicines development and new therapies; foster collective teaching and learning of academic and industrial professionals. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 12/79 enhance a student’s career opportunities by increasing his/her professional expertise Examination, Quality Control, Mobility, Transfer of ECTS ensure the standard of assessment is maintained at a high level using appropriate quality control and quality management procedures that are consistent with the requirements of the partner university regulations. facilitate the accumulation of credits by individuals towards building a personalised portfolio of recognised competencies and/or the awards of a Master in Medicines Development (MMD), Postgraduate Diploma or Postgraduate Certificate. These elements are detailed in section 4 and 6. 1.3 Shared standards and common understanding in PharmaTrain Bologna principles PharmaTrain is fully based on the Bologna process, which is well established in Europe. PharmaTrain relies on the European Credit Transfer and Accumulation System, ECTS: 1 ECTS = 25-30 student investment hours. 3-tier and 2-track modular structure The principal structure of the training programmes is illustrated in Fig. 2. Specialist track Diploma Exam Concept • Syllabus-based • Learning outcomes • Base Diploma Course / Master Modules • Modularity • ECTS/modul (1+2+2) • Mobility • “Good Bologna Practice, GBP” (Base) Diploma Courses Extension Modules MMD Work-Project • Thesis (10 ECTS) • Electives • (Research) Project Master track Learning Paths • mono-centric, 20% e-blended • multi-centric, 50% e-blended • distant, 80% e-blended CPD Platform(s) Workload 60 ECTS à 30 hrs = 1800 hrs = 1 academic year 30 ECTS Knowledge 60+ ECTS Expertise Fig. 2: Postgraduate 3-tier (30 ECTS Diploma (Base) Course, 60+ ECTS Master programme, and 3rd-tier workplace-centred competency-based CPD platform (university). Two track Modular Curricula: the Master-track (blue) and the Specialist (Professional) track (red) The three tiers are shown, with the six modules of the first tier in the solid circle, the additional extension and elective modules of the second tier in the solid ellipse, and a variety of elective modules (from other PharmaTrain products and partnering IMI projects) in the outer stippled ellipse, the CPD platform. First tier (30 ECTS): the core of PharmaTrain is a Base Diploma Course comprising 6 modules covering the PharmaTrain syllabus with assignments in each module, as shown in the solid circle. Assessments will be conducted at the end of each module. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 13/79 Second tier (30 ECTS leading to 60+ ECTS): additional extension and elective modules, shown in the solid ellipse. With a Master thesis (60+), this leads to a Masters Degree. .Assessments will be conducted at the end of each module. To obtain the Masters degree, in addition the Masters thesis must be defended. Third tier: workplace-centred competency-based training – incl. the use of the CPD platform – to achieve specialist status. An alternative approach used by some universities is the integrated programme, in which the first and the second tiers are merged into a single programme covering the same 60+ ECTS. B6 Healthcare Marketplace and Economics of Healthcare E10 Special Populations: Clinical Trial Practice and Regulation E11 B2 Non-clinical Testing to Proof of Concept in Humans B1 Introductory Module One E9 Biologicals and Advanced Therapies B5 Regulatory Affairs, Safety and Pharmacovigilance Master-Thesis E8 Drug Safety, Pharmacoepidemiology Surveillance, Riskmanagement B3 Exploratory and confirmatory Clinical Development B4 Clinical Trials: Methodology and Biostatistics E12 E7 Healtheconomics / Markets Fig. 3a: This ‘ellipsogram’ depicts the 6 Base Diploma Course Modules and the additional 6 ‘Extension’ Modules of which two are electives (from the CPD platform) for the MMD B6 Healthcare Marketplace and Economics of Healthcare E10 Special Populations: Clinical Trial Practice and Regulation E11 B2 Non-clinical Testing to Proof of Concept in Humans B1 Introductory Module One E9 Biologicals and Advanced Therapies B5 Regulatory Affairs, Safety and Pharmacovigilance Master-Thesis E8 Drug Safety, Pharmacoepidemiology Surveillance, Riskmanagement B3 Exploratory and confirmatory Clinical Development B4 Clinical Trials: Methodology and Biostatistics E12 E7 Healtheconomics / Markets Fig. 3b: The alternative Integrated 12 Module Concept for the MMD 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 14/79 The two tracks comprise the academic (university-master) track and the vocational (professional-specialist track). The University-Master track (including Certificate and Diploma) The horizontal dimension defines a series of six modules for the Base Diploma Course and four extension modules + two electives or an Integrated Programme both of which, together with a Master Thesis, lead to a university degree of Master in Medicines Development (MMD). Assessments are conducted per module. A certificate is issued per module and serves to accrue ECTSs towards a portfolio of recognised competencies for the individual. A diploma is issued after completing all Base Diploma Course modules and serves the same purpose. To obtain the Masters degree, in addition to the completion of all required modules (Base Diploma Course and extension / elective modules or Integrated Programme) the Masters thesis must be defended. The Specialist (Professional) track (Specialist title for physicians) With the same series of modules (Base Diploma Course and Extension or Integrated Programme), and having passed the integrated final examination and a workplace-centred competency-based programme, physicians can apply through their national medical associations for the Specialist Title in Pharmaceutical Medicine (at present in three European countries). The Modular Structure A PharmaTrain Module (5 ECTS) is characterised as follows: Usual duration 4 days face-to-face course at a university centre (2 ECTS) Pre-Course work and (e-)preparation (1 ECTS) Post-Course work: research, reading, assignments (2 ECTS) Modules usually have assessments at the end of the Module. The PharmaTrain Modules for the Base Diploma Course (n = 6) and Master programmes (Base Diploma Course modules n = 6 + extension modules n = 6) are designed as follows: Base Diploma Course Module 1: Introductory Module, Principles of Discovery of Medicine and Development Planning Base Diploma Course Module 2: Non-Clinical Testing, Pharmaceutical and Early Clinical Development Base Diploma Course Module 3: Exploratory and Confirmatory Clinical Development Base Diploma Course Module 4: Clinical Trials Base Diploma Course Module 5: Regulatory Affairs; Drug Safety & Pharmacovigilance Base Diploma Course Module 6: Healthcare Marketplace; Economics of Healthcare Extension Module 1: Health Economics Extension Module 2: Drug Safety : Pharmacoepidemiology, Pharmacovigilance, Risk Management Extension Module 3: Biologicals and Advanced Therapies Extension Module 4: Special Populations: Clinical Trial Practice & Regulation Electives Modules: select 2 from a list of more than 50 The PharmaTrain Modules for the Integrated Programme may vary in number (depending on the university) but will cover the same syllabus and curriculum. Please note that course providers are free to vary the titles of the above mentioned modules but have to guarantee that the PharmaTrain Syllabus 2010 (V1.0) is covered. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 15/79 1.4 The PharmaTrain Continuing Professional Development, CPD Platform overview Each Training Centre offers all its modules on the Continuing Professional Development, CPD, Platform, in order to furnish Master programmes with Elective modules as well as providing an additional à la carte module directory from which to select modules of interest to enable personalised/individual training. All modules can be taken independently for the purpose of building an individual portfolio of competencies. In addition to the face-to-face Elective Modules a number of e-learning products are available on our e-Campus, e-products developed by PharmaTrain (on the PharmaTrain e-library) as well as recommended products (see also sections 2.3, 2.4 and 3.2). e-Library n = 9 (-30!) B6 Healthcare Marketplace and Economics of Healthcare B2 Non-clinical Testing to Proof of Concept in Humans E11 n=6 B5 Regulatory Affairs, Safety and Pharmacovigilance B1* Introductory Module One Electives n = 70 E7 Biologicals E8 Special Populations Trial Practice n = 3-4 E9 Pharmacoepidemiology Drug Safety Surveillance B3 Exploratory and confirmatory Clinical Development B4 Clinical Trials: Methodology and Biostatistics Non-IMI E12 Eu2P E10 Pharmacoeconomics / Markets SafeScMET EMTRAIN * B1 first 2 days = generic introduction, second 2 days = discovery research Fig. 4: PharmaTrain CPD Core Platform (n > 100 Elective Modules) 1.5 PharmaTrain Centres of Excellence as an internal Quality Standard and PharmaTrain Centres Recognition The PharmaTrain shared standards enable partner universities to develop into a PharmaTrain Centre of Excellence over the coming years. This is a self-selective and inter-centre competitive process for quality and overall training leadership in the field of Medicines Development. Criteria are: an established quality controlled programme for a Master in Medicines Development, MMD, and an additional training activity chosen from the menu summarised below. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 16/79 Before obtaining the PharmaTrain Centre of Excellence status, a given Training Centre can call on a Coaching Visit, then in a next step for an Audit for PharmaTrain Centre Recognition, and eventually for an Audit for a Centre of Excellence. To achieve a PharmaTrain Centre Recognition course providers have to show that the Syllabus, Curriculum and associated Learning Outcomes are in place. The status of a PharmaTrain Centre Recognition will be the prerequisite for EFPIA companies to designate course fees as in-kind contribution (see also section 5.2.2). 1.6 The Process of PharmaTrain Continuing Performance Improvement The components of the training processes are depicted in a logical sequence of events in a circular fashion. Each component of this value chain can be improved and contributes to overall training programme performance improvement. Performance Improvement Syllabus / Content Learning Outcomes Accreditation e-learning / e-preparation Quality Assurance Modules / Curricula CPD Core Platform Specialist-track integrated examination Master-track modular assessments / assignments Fig. 5: The PharmaTrain Continuing Performance Improvement Cycle On this basis a user-friendly three step Quality Assurance System is in plan (see also section 5). 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 17/79 2. Syllabus, Modules and Learning Outcomes 2.1 The PharmaTrain Syllabus and Curriculum Syllabus: a list of topics comprising a subject, discipline or specialty field. Based on the IFAPP Syllabus for Pharmaceutical Medicine PharmaTrain has extended and adapted the syllabus to form the PharmaTrain Syllabus, V1.0, 2010. This Syllabus has been transferred into the Base Diploma Course and Extension Modules (section 3) and the modules for the Integrated Master programme. The Curriculum is the guideline to transfer the content of the Syllabus into the modular structure and is a statement of the aims and objectives, content, experiences, outcomes and processes of a programme, including a description of the structure and expected methods of learning, teaching, feedback and supervision. The curriculum sets out what knowledge, skills, attitudes and behaviours the trainee will achieve (see Learning Outcomes, below). 2.2 Learning Outcomes Learning Outcomes are statements of what a student is expected to know, understand and/or be able to demonstrate after completion of a process of learning. These are the guiding principles for the development of the curriculum and each module, enabling mutual recognition between different institutions across Europe. Learning Outcomes are integral parts of the Curriculum. Discuss 2.3 e-Campus: e-learning, blended learning e-learning materials on pharmaceutical medicine and related disciplines available within PharmaTrain or available on the world-wide-web have been collected in a directory on the PharmaTrain website platform. The material ranges from an entire distant learning programme (Hibernia College, Dublin) to a single video on clinical pharmacology. The entire collection can be accessed via the PharmaTrain e-Library (the e-campus on www.pharmatrain.eu). It is up to an individual course provider to decide whether to use any part of the collection as part of the combined learning process (blended learning). E-learning can provide an important contribution to the Continuing Professional Development (CPD) of pharmaceutical industry professionals. This CPD-Platform is also part of the ‘on course’ database (www.emtrain.eu) – of all four IMI E&T projects – and can be used both for complementary electives for the PharmaTrain programmes and for maintaining training after accreditation There are several sections of e-learning that are being developed by the PharmaTrain group. Identified areas where distance e-learning appears to be most costeffective and valuable are as follows: Group 1: Modules associated with the various Base Diploma Course Modules e1. An introductory module (two of the four days of Module One) provides prelearning before the first face-to-face module of the Base Diploma Course. This introductory module will be particularly useful for participants who have no experience of drug development and the pharmaceutical industry. e2. Translational medicine, from target to proof of concept/dose finding (Lead CCPM Hibernia as a co-production with ECPM and in collaboration with Novartis) 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 18/79 e3. Biologic/monoclonal antibody: entry into man and full development; currently in development by UB-IL3. e4. Safety module (in collaboration with SafeSciMET): plan to be developed e5. Medicines regulation (in collaboration with EMPRA): plan to be developed e6. Health economics and market introduction (Lead: Annette Mollet, ECPM); plan to be fully developed Group 2: Modules on therapeutics. Modules on therapeutics to provide an introduction to pathologies and therapeutics to people who have no previous medical background. e7. Module on therapeutic area 1, Parkinson’s disease. The basic material has been provided by UCB Pharma. Additional sections have been added covering new targets, advanced therapies, and guidelines for clinical development. Available for internal use within PharmaTrain. http://mphar.hiberniacollege.net/mphar/2010/mphar_ther/park/mphar_ther_park.htm e8. Module on therapeutic area 2. will be redefined! Group 3 e9. An online Clinical Investigators Course (e-CLIC) that will help improve understanding of clinical research for clinical research scientists and staff. It is consistent with the objectives of Innovative Medicines Initiative that can be accomplished both by face-to-face courses and e-learning, depending on individual preferences. http://clic.bio-med.ch/dataCLIC/Content/Homepage/index.asp e10. A “train the trainers” initiative will also be developed to improve the faculty of the various courses to understand and assimilate the possibilities offered by elearning further and pedagogy of e-teaching. 2.4 The CPD Platform and Elective Modules (see also p. 54) The CPD platform includes elective and extension modules and stand-alone modules provided by PharmaTrain to facilitate lifelong learning, and which also offer participants opportunities to complete their Master programmes with two Elective Modules. Of note: all modules within PharmaTrain whether within a master programme or stand-alone can be considered for CPD and can be used to build a portfolio of competencies by an individual professional. More than 50 modules / courses have been provided by partners in PharmaTrain. Course Quality criteria have to be implemented. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 19/79 3. Base Diploma Course and Master Programme Modules for Medicines Development / Pharmaceutical Medicine Individual module content is linked to the PharmaTrain Syllabus 2010 (Appendix II) and bundled in Learning Outcomes as shown in the mapping process (right columns in the panels). 3.1 Base Diploma Course (Base Modules, n = 6, 30 ECTS) PHARMATRAIN BASE DIPLOMA COURSE MODULE M1a (INT): INTRODUCTORY PROGRAMME LEARNING OUTCOMES At the end of this module the student should be able to demonstrate an understanding of the: 1. Process of drug development and identity of critical factors and decision points. 2. Importance of the patient in drug development. 3. Background to the development of the regulation of medicines and the role of the competent authorities. 4. Monitoring of drug safety. 5. Principles and practice of medical marketing. PHARMATRAIN BASE DIPLOMA COURSE MODULE M1b (M1): PRINCIPLES OF DISCOVERY OF MEDICINE AND DEVELOPMENT PLANNING LEARNING OUTCOMES At the end of this module the student should be able to demonstrate an understanding of the: 6. Role of pathophysiology and molecular biology-based pharmacology in drug devel- 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 20/79 opment. 7. Principal steps in discovering, modifying, assessing and patenting new chemical and biological compounds (including advanced therapies) according to their therapeutic indication. 8. Resource planning (in terms of project management, budgeting and cost-control) involved in the management of a drug development programme. 9. Principles of translational research and its role in drug development. 10. Functions and elements (including business aspects) involved in the integrated development of a new drug. MODULE M1a (INT): INTRODUCTORY PROGRAMME INT CURRICULUM CONTENT LEARNING OUTCOMES MAPPING SYLLABUS MAPPING INT1 Setting the scene: medicines market overview and the Industry we are in. 1, 2, 3, 5 13.6, 13.8 INT2 Meeting the challenges of developing new, more effective, safer medicines. 1, 2, 3 INT3 The highly regulated and ethical environment of medicines development. 1, 3 INT4 The patient’s view. 2 INT5 The discovery process & non-clinical development. 1 INT6 The target product profile (TPP) as the blueprint; satisfying the patients, doctors, regulators and payers. 1, 2, 3, 5 INT7 A helicopter view of integrated drug development including: attrition, orientation of the phases (0, 1, 2a, 2b, 3 & 4); modern approaches (learn, confirm), and conditional approvals. 1 INT8 Exploratory Development: translational medicine; predictive science and personalised health care. 1, 2 INT9 Confirmatory Development. 1, 2 INT10 Principles of drug regulation and approval. 3 INT11 Patient safety, pharmacovigilance and pharmacoepidemiology. 4 INT12 The payers, market support activities and health economics. 5 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 2.2, 8.1 21/79 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 22/79 MODULE M1b (M1): PRINCIPLES OF DISCOVERY OF MEDICINES AND DEVELOPMENT PLANNING M1 CURRICULUM CONTENT LEARNING OUTCOMES MAPPING SYLLABUS MAPPING M1.1 Strategy and organisation of research including collaborative approaches e.g. with academia. 10 1.1 M1.2 Disease models; target identification, validation and selection. 7 1.2, 1.4 6 1.3, 3.1 Principal steps in discovering, modifying, assessing and patenting new chemical and biological compounds. M1.3 Pathophysiology and molecular biology-based pharmacology. Molecular-based approaches: agonists, antagonists, enzyme inhibitors; genomics, proteomics, epigenetics. M1.4 Chemical and biological medicinal agents, natural medicines, medicine-coupled devices and advanced therapies. 6, 7 1.5 M1.5 Lead optimisation and development candidate selection; testing for biological activity. 7 1.6, 1.7 M1.6 Principles of translational medicine: relationship between animal and human pharmacology, molecular biological and physiological approach e.g. biomarkers, functional imaging, modelling and simulation. 9 1.8, 1.9 M1.7 Global integrated development of new medicines, including quality management. 10 2.1, 2.5 M1.8 Project management techniques: central role of development plan, project teams, tools and decision-making from target product profile (TPP) and target product claims (TPC) to registration dossier submission. 8 2.3, 2.7 2.2, Resource planning, budgeting and cost control, in- and outsourcing. M1.9 Development programme planning for small and / or special populations. 7 2.4 M1.10 R&D portfolio planning; in- and out-licensing of medicines. 10 2.6 M1.11 Therapeutic Topic 1 14.1 14.10 – M1.12 Therapeutic Topic 2 14.1 14.10 – 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 23/79 PHARMATRAIN BASE DIPLOMA COURSE MODULE 2: NON-CLINICAL TESTING, PHARMACEUTICAL AND EARLY CLINICAL DEVELOPMENT LEARNING OUTCOMES At the end of this module the student should be able to demonstrate an understanding of the: 1. Choice and predictive value of the non-clinical testing programme as part of the overall drug development plan for chemical and biological compounds. 2. Integration of non-clinical tests into the overall drug development plan (including scheduling of toxicology tests with respect to clinical trials). 3. Steps in the pharmaceutical development of a drug substance and final drug product (including chemical and biological compounds). 4. Planning of clinical trial supplies for test substance(s) and comparators (active and placebo). 5. Overview of non-clinical study requirements prior to First-in-Man studies. 6. Molecular and cellular basis of toxic reactions. 7. Principles and practical application of pharmacokinetics and toxicokinetics. 8. Early exploratory development in man. 9. Principles of clinical pharmacology and their application to clinical development. 10. Influence of genetic factors in drug development and drug response. MODULE M2: NON-CLINICAL TESTING, PHARMACEUTICAL AND EARLY CLINICAL DEVELOPMENT M2 CURRICULUM CONTENT LEARNING OUTCOMES MAPPING SYLLABUS MAPPING M2.1 Principles of non-clinical testing: differences and similarities between small molecule and biological macromolecule active agents and between the pharmacology and toxicology of compounds and their metabolites in animals and man, and their qualitative and quantitative assessment. 1 3. 2, 3.3 M2.2 Descriptive and quantitative in vitro and in vivo testing of new compounds; the choice and predictive value of these tests for acute, chronic, reproductive, genetic and immune toxicology, and carcinogenicity. 1 1.7, 3.5 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 3.4, 24/79 M2 CURRICULUM CONTENT LEARNING OUTCOMES MAPPING SYLLABUS MAPPING M2.3 Common mechanisms of damage to organs: their detection and elucidation. Molecular and cellular basis of toxic reactions. 6 3.6 M2.4 The scheduling of toxicology tests linked to development 2 plans, regulatory needs, human and animal pharmacology, and to intended clinical uses and route(s) of administration. The size, cost and administration of the toxicology programme, its data management, quality assurance and report writing. 3.7, 3.8 M2.5 The continuous review of toxicology, its inclusion into clinical trial protocols, and investigator brochures, and the planning and correlation with the clinical evaluation of potential and observed toxicity in patients. 2 3.9 M2.6 Safety pharmacology; hypersensitivity 5, 6 3.10 M2.7 In vitro & in vivo study of metabolism; Absorption, Distribution, Metabolism, Elimination (ADME); toxicokinetics. 7 3.11 M2.8 Pharmaceutical development of drug substance (small chemical molecules or biological macromolecules) and upscaling: manufacture and supply of materials; stability and storage; purity; compatibility; disposal. 3 4.1 M2.9 Pharmaceutical development of drug product and upscaling: formulation(s); manufacture and supply of materials; labelling and presentation; stability and storage; purity; compatibility; disposal. 3 4.1, 4.2 M2.10 Choice of formulations and delivery systems depending on characteristics of compound and intended uses; testing formulations leading to a final specification, including bioequivalence. 3 4.3, 4.4 M2.11 Safety specification; pharmacopoeias. 3 10.20, 10.22 M2.12 The concept of blinding: preparing matching placebo and comparator products. Planning clinical trials supply requirements; packaging and labelling of clinical trial supplies (including stability and storage requirements); distributing supplies and disposing of remaining stocks. 4 4.5, 7.14 M2.13 Assessment of non-clinical data and risk as prerequisites before administration to man: description of intended therapeutic indications, biomarkers, surrogate endpoints and criteria for ‘go’ ‘no-go’ decisions. 5, 7 5.1, 5.2 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 4.6, 25/79 M2 CURRICULUM CONTENT LEARNING OUTCOMES MAPPING SYLLABUS MAPPING M2.14 The early clinical development plan: objectives, design, conduct and analysis; tolerability, metabolism, pharmacokinetics, pharmacodynamics and safety in man; risk mitigation strategies; first-into-man studies, including exploratory strategies (Phase 0). 8 5.3, 5.4 M2.15 Clinical pharmacodynamics and pharmacokinetics: ADME; determinants of PK parameters; bioavailability and bioequivalence; extrinsic and intrinsic factors affecting drug metabolism (e.g. drug-drug, drug-food, drug-disease interactions). 9 5.5, 5.6, 5.7, 5.8 M2.16 Pharmacogenetics, pharmacogenomics, population pharmacokinetics, genetic factors influencing PK, PD and response to therapy. Personalised medicine. 3, 10 5.9, 5.10 M2.17 Applicability of pharmacokinetics to dosage regimen and study design. Pharmacokinetic / pharmacodynamic modelling and simulation. 9 5.11 M2.18 Therapeutic Topic 3 14.1 14.10 – M2.19 Therapeutic Topic 4 14.1 14.10 – 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 26/79 PHARMATRAIN BASE DIPLOMA COURSE MODULE M3: EXPLORATORY AND CONFIRMATORY CLINICAL DEVELOPMENT LEARNING OUTCOMES At the end of this module the student should be able to demonstrate an understanding of: 1. Early studies in patients: dose-finding / proof of concept studies and their impact on drug development plan. 2. Clinical trial design (including legal, regulatory, ethical and practical aspects and GCP). 3. Principles and application of statistics in clinical trials. 4. Procedures for clinical trial data collection (paper and electronic) and data management (including validation processes) to ensure optimal quality data. 5. Key strategic and operational issues in the clinical trial process, in terms of legislative requirements and Good Clinical Practice (GCP). 6. The role of the investigator drug brochure (IDB). 7. Principles and practical relevance of ethical issues in biomedical research. 8. Legal and ethical provisions for protection of clinical trial subjects. MODULE M3: EXPLORATORY AND CONFIRMATORY CLINICAL DEVELOPMENT M3 CURRICULUM CONTENT LEARNING OUTCOMES MAPPING SYLLABUS MAPPING M3.1 First administration to patients; principles of proof of concept and dose-finding studies. 1 5.12 M3.2 Concept of blinding. 2 4.5 M3.3 Trial design: pre-trial decisions and specifications; literature review; incidence and prevalence of the disease; risk factors; confounding variables; dealing with confounding factors and bias; review of literature. 2 9.8, 9.25, 9.11, 9.20, 9.24 M3.4 Clinical trials regulations; EU Directives and Guidance and their diversity in national implementation; CTA including IMPD, substantial amendments. Clinical trial regulations in other regions e.g. the US IND process. 2, 5 10.10 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 27/79 M3 CURRICULUM CONTENT LEARNING OUTCOMES MAPPING SYLLABUS MAPPING M3.5 Protocol writing: detailing choice of location(s), trial design, blinding, placebo or other comparators, end-points, patient population, informed consent, sample size, randomisation, statistical methods, interim analysis. 2, 3 7.6 M3.6 Analysis of efficacy endpoints & of safety; intention to treat 3 principles, handling of missing data etc.; interim analysis; statistical tests (sensitivity and specificity of tests; paired and non-paired tests, parametric and non-parametric tests, confidence limits). M3.7 Options for data collection (manual and electronic) and standardisation; creation, maintenance and security of databases, software validation and archiving. 4 9.1, 9.3 M3.8 Case report form (CRF) design and review. 4 9.2 M3.9 The purpose and fundamentals of statistics. The role and responsibilities of the statistician. Statistical considerations of study design: hypothesis testing (the Null hypothesis, type I and type II error, significance, power), randomisation, sample size. The Statistical Analysis Plan (SAP), including interim analysis. 3 9.5, 9.6, 9.7, 9.9, 9.10, 9.11, 9.15 M3.10 Principles of Good Clinical Practice and procedures applied in all stages of the clinical trial process to ensure subject protection, scientific validity and safety. Clinical trial registries. 5 7.4, 7.11 M3.11 Investigator Brochure: content, review and maintenance. 6 7.5 M3.12 Ethics: principles, history including Declaration of Helsinki, EU Directive 2001/20/EC, ethical review process, informed consent, safety and human dignity of research subjects. Ethical issues in biomedical research and pharmaceutical medicine. 7 8.1, 8.2 M3.13 Protection of research subjects. Risks, benefits and burden of study participation. Minimising risk including site qualification assessment; ethical aspects of subject contact and recruitment, and of reimbursement, compensation and inducement; indemnity and insurance for participants, investigators, institutions; complaint procedures. 7, 8 8.3, 8.6, 8.7, 8.8, 8.11 M3.14 Ethical aspects of research questions and study designs for first-in-human to post-marketing and epidemiological studies, including post-study follow-up procedures, placebo and comparator choice. 7, 8 8.4, 8.12 M3.15 Conflict of interest and equipoise. 8 8.5 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 9.14, 9.15, 9.16, 9.18, 9.19 28/79 M3 CURRICULUM CONTENT LEARNING OUTCOMES MAPPING SYLLABUS MAPPING M3.16 The informed consent process. Privacy, confidentiality and data protection. 7, 8 8.9, 8.10 M3.17 Ethical aspects of taking trial samples for genomic and related analyses. 8 8.13 M3.18 Ethical aspects of clinical trials in vulnerable populations. 8 8.14 M3.19 Ethical aspects of advanced therapy medicinal products. 8 8.15 M3.20 Ethical aspects of international clinical trials, considering socio-cultural differences. 7, 8 8.16 M3.21 Therapeutic Topic 5 14.1-14.10 M3.22 Therapeutic Topic 6 14.1-14.10 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 29/79 PHARMATRAIN BASE DIPLOMA COURSE MODULE M4: CLINICAL TRIALS LEARNING OUTCOMES At the end of this module the student should be able to demonstrate an understanding of the: 1. Various types of clinical studies and the methods used to choose the appropriate design. 2. Main statistical methods used in clinical research. 3. Key issues involved in the conduct of a clinical study including investigator and site recruitment, investigative site management and conflict resolution. 4. Collection, evaluation and reporting of adverse event data in clinical trials. 5. Various quality management issues in clinical trials. 6. Impact of emerging results on the drug development plan. 7. Key operational and strategic issues in the clinical development plan. 8. Evaluation of the outcome of drug development: final therapeutic profile / usage of a medicine. 9. Role of the Target Product Profile (TPP) and Target Product Claims (TPC). 10. Role of the Drug Safety Monitoring Board (DSMB) and other relevant study committees. 11. Statistical issues in statistical report writing. 12. Evaluation and interpretation of clinical trial results. 13. Principles and practical application of critical appraisal. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 30/79 MODULE M4: CLINICAL TRIALS M4 CURRICULUM CONTENT LEARNING OUTCOMES MAPPING SYLLABUS MAPPING M4.1 Choice of interventional clinical trial design, of placebo and other comparators, of patient populations, of locations. New trial designs e.g. adaptive design. Non-interventional / observational study design. 1 7.1, 7.2, 7.3 M4.2 Types of data and standardisation of measurement e.g. handling of rating scales, including visual analogue scales and laboratory values. Statistical analysis of efficacy end-points and of safety. Patient-reported outcomes e.g. diaries; quality-of-life measures 2 9.12, 9.13, 9.14, 9.17 M4.3 Feasibility testing and investigator recruitment; pre-study visits and investigator meetings; investigator training; contractual arrangements with investigators and contract research organisations, including matters such as publication rights and conflicts of interest. 3 7.7, 7.8, 7.10 M4.4 Project management: EUDRACT, CTA and ethics opinion, resources and budget, timelines, conflict resolution (e.g. investigator discontinuation). 3 7.9 M4.5 Clinical trial conduct / investigative site management: Trial Master File (TMF), monitoring and source document verification, study medication handling and drug accountability. 3 7.12, 7.13, 7.14, 7.15, 7.16, 7.17 Within-trial decisions (e.g. code-breaking, premature termination); emergency coverage. M4.6 Quality management: quality assurance and quality control; SOPs; audits; inspections. 5 7.18 M4.7 Fraud and misconduct in biomedical research and clinical development. 3, 5 8.17 M4.8 Assessment and classification of adverse events (AEs), adverse drug reactions (ADRs), serious adverse events (SAEs) and suspected unexpected serious adverse reactions (SUSARs); evidence for association and causality. 3, 4 11.2 M4.9 Collection of adverse events in clinical trials; role of sponsors and investigators in reporting; regulatory requirements. 3, 4 11.4, 11.5 M4.10 Impact of results on the drug development plan (DDP) and possible need for further toxicology / pharmaceutical development data; regulatory review of existing and emerging research results. 6 5.13, 6.6 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 31/79 M4 CURRICULUM CONTENT LEARNING OUTCOMES MAPPING SYLLABUS MAPPING M4.11 Final definition of therapeutic indications. Categories of patients, delivery system(s), dosage forms and dosage regimens. 8 6.1 M4.12 Planning and global coordination / harmonisation of preand post-licensing clinical trial programmes; use of nonclinical and existing clinical trial data. 7 6.2 M4.13 Decision points, schedules & resources required for confirmatory clinical development plan (CDP). Calculation of clinical trial supplies and costs up to registration. 7 6.3, 6.4 M4.14 Review and maintenance of Target Product Profile (TPP) and Target Product Claims (TPC). 9 2.3 M4.15 The role of the independent Drug Safety Monitoring Board (DSMB) and other relevant study committees. 10 7.13 M4.16 Measurement and types of data; monitoring of clinical trials; source document verification, CRF review and correction, data entry, query generation and resolution, coding of adverse events, database lock. 2, 4 7.16, 9.4 M4.17 Preparing the statistical report: interpretation of analyses; assessment of violations, withdrawals, errors, bias; data manipulation, transformation and merging. 11 9.21, 9.22 M4.18 Clinical interpretation of study analyses and results. 12 7.19, 9.23 13 9.25 The clinical trial report. M4.19 Critical review of publications. M4.20 Therapeutic Topic 7 14.1-14.10 M4.21 Therapeutic Topic 8 14.1-14.10 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 32/79 PHARMATRAIN BASE DIPLOMA COURSE MODULE M5: REGULATORY AFFAIRS; DRUG SAFETY & PHARMACOVIGILANCE LEARNING OUTCOMES At the end of this module the student should be able to demonstrate an understanding of: 1. General principles of medicines regulation (both pre- and post-approval) at EU and global level. 2. Impact of medicines legislative requirements on regulatory activities within a pharmaceutical company. 3. Role of national agencies and international bodies in medicines regulation. 4. National provisions for management of (1) off-label / unlicensed use of medicines; (2) controlled drugs. 5. Place of International Conference on Harmonisation (ICH) in medicines regulation (including Common Technical Document [CTD]). 6. Regulatory processes in the EU / EEA areas. 7. Regulation and legal considerations of Product Information. 8. Principles and practical application of medical devices regulation. 9. Roles of the various stakeholders (including pharmaceutical and other healthcare professionals, investigators, regulatory authorities) in drug safety and pharmacovigilance. 10. Classification of adverse events / adverse drug reactions. 11. Safety reporting requirements (according to the type of adverse event / reaction) preand post-approval. 12. Ongoing management of drug safety issues pre- and post-approval (including Risk Management Plans [RMPs], Periodic Safety Update Reports [PSURs]); ongoing benefit / risk assessment throughout the life-cycle of a medicine. 13. Role of pharmacoepidemiology in the life-cycle management of a medicine. 14. Factors influencing medication safety from the perspective of each stakeholder. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 33/79 MODULE M5: REGULATORY AFFAIRS; DRUG SAFETY & PHARMACOVIGILANCE M5 CURRICULUM CONTENT LEARNING OUTCOMES MAPPING SYLLABUS MAPPING M5.1 General principles of medicines regulation; philosophy of regulatory oversight; input of international bodies; evolution of control mechanisms; general differences between agencies; International Conference on Harmonisation (ICH). 1, 5 10.1, 10.2, 10.3, 10.4 M5.2 Overview of relevant regulatory Directives; overview of Good Practices (e.g. GCP, GMP, GLP) including inspections. 1, 5 10.5 M5.3 Integration of regulatory affairs in pre- and post-marketing company activities; planning and reviewing product strategy. Prescription-Only-Medicines (POM) and Over-TheCounter (OTC) medicines; OTC switching strategies. Generics and biosimilars. Parallel imports. 2 10.6, 10.16, 13.10 M5.4 Common Technical Document (CTD & eCTD). Overviews; aggregate clinical trial report reviews, including annual reports and CTD summaries. 5 10.11, 10.12 M5.5 Regulatory systems in Europe, US, Rest of the World (ROW), and local special regulatory requirements. The preparation and submissions of marketing authorisation applications in major countries. 1, 2, 3 10.9, 10.13 M5.6 Approval, appeals and referral processes in Europe (Centralised Procedure, Mutual Recognition Procedure, Decentralised procedure, national procedures); updating and maintaining Marketing Authorisations (variations regulation); aspects of confidentiality and transparency. 6 10.7 M5.7 Regulation of Product Information: Summary of Product Characteristics (SmPC), labelling, US Prescribing Information, EU Package Leaflet; EU readability testing. 7 10.14 M5.8 National differences in regulations / procedures for using locally unlicensed medicines (e.g. compassionate use). Off-label use and misuse. 4 10.17, 10.26 M5.9 Controlled drugs regulation. 4 10.25 M5.10 Medical device regulation. 8 10.19 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 34/79 M5 CURRICULUM CONTENT LEARNING OUTCOMES MAPPING SYLLABUS MAPPING M5.11 Risk management; EU Detailed Description of Pharmacovigilance System (DDPS); EU Risk Management Plan (RMP); Risk Evaluation and Mitigation Strategies (REMS) in the USA. 12 10.21 M5.12 The role of the pharmaceutical professional in drug safety and pharmacovigilance. 9 11.1 M5.13 The concept of benefit / risk assessment. Assessment and classification of adverse events (AEs), adverse drug reactions (ADRs), serious adverse events (SAEs) and suspected unexpected serious adverse reactions (SUSARs); evidence for association and causality. 10, 12 11.2, 11.3 M5.14 Risk factors for adverse events. 14 11.6 M5.15 Spontaneous reporting of suspected adverse drug reactions in the post-licensing phase. 11 11.7 M5.16 Dosage, drug accumulation, medication errors and interac- 14 tions. 11.8 M5.17 Drug adherence / compliance. 14 11.9 M5.18 Periodic Safety Update Reports (PSURs). 11, 12 11.10 M5.19 Pharmacoepidemiology; main sources of epidemiological pharmacovigilance information. 13 11.11, 11.12 M5.20 Signal detection, interpretation and management. 12 11.13 M5.21 Post-Authorisation Safety Studies (PASS). 12, 13 11.14 M5.22 Post-authorisation risk management including issue and crisis management, risk communication with all the stakeholders; Direct Healthcare Professional Communication (DHPC). 12 11.15. 11.16 M5.23 Product withdrawal procedures; product defects and recall. 12 10.18, 10.24 M5.24 Therapeutic Topic 9 14.1-14.10 M5.25 Therapeutic Topic 10 14.1-14.10 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 35/79 PHARMATRAIN BASE DIPLOMA COURSE MODULE M6: HEALTHCARE MARKETPLACE; ECONOMICS OF HEALTHCARE LEARNING OUTCOMES At the end of this Module the student should be able to demonstrate an understanding of: 1. Life-cycle management (clinical, regulatory and marketing). 2. Processes of production and review of product information to ensure adherence to ethical and legal principles pertaining to marketing activities (Good Promotional Practice). 3. Role of patient organisations. 4. Principles and practical application of health economics and patient-reported outcomes within the pharmaceutical industry. 5. Principles of health technology assessment (HTA) and its role in the supply of medicines to the marketplace. 6. Principles and practice of marketing within the pharmaceutical industry. 7. Drug budget control; pricing mechanisms. MODULE M6: HEALTHCARE MARKETPLACE; ECONOMICS OF HEALTHCARE M6 CURRICULUM CONTENT LEARNING OUTCOMES MAPPING SYLLABUS MAPPING M6.1 Life-cycle management planning: extension of therapeutic claims, new formulations, new dosage schedules by perimarketing trials, post-marketing (surveillance) studies, OTC studies and quality of life measures. 1 6.5, 13.4, 13.10 M6.2 Information, promotion and education; information to patients, prescribing and patient compliance. Direct Healthcare Professional Communication (DHPC). 2 10.23, 12.1 M6.3 Advertising and promotion regulations; advertising claims: ethics, control and approval; promotional materials; Codes of Practice; promotional policy & procedures; Good Promotional Practice; promotional material and product support on the basis of the Marketing Authorisation. 2 10.5, 12.2, 12.3, 12.4, 12.5 M6.4 Role of patient organisations. 3 12.1 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 36/79 M6 CURRICULUM CONTENT LEARNING OUTCOMES MAPPING SYLLABUS MAPPING M6.5 Overview of healthcare economics, health economic evaluation studies. Principles of pharmacoeconomics and evidence based medicine. Measurement of healthcare efficiency. Governmental policy and third party reimbursement. 4 13.1, 13.2, 13.3, 13.7, 13.11 M6.6 Evidence-based Medicine (EBM), Health Technology Assessment (HTA), Treatment Guidelines. 5 13.11 M6.7 Quality of Life, concept and measurement instruments. 4, 5 13.4 M6.8 Principles and practice of marketing; market structure and competition; market analysis; medical marketing and market access. Economics of industry: competition, licensing, comarketing. 6 13.5, 13.6, 13.8 M6.9 Publication strategy; educational meetings; sponsored meetings and publications. 2, 6 12.6, 12.8 M6.10 Sales representative training; material and aids. 2, 6 12.7 M6.11 Drug budget control; pricing mechanisms; methods of reimbursement. 7 13.1, 13.5 M6.12 Therapeutic Topic 11 14.1-14.10 M6.13 Therapeutic Topic 12 14.1-14.10 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 37/79 3.2 Extension Modules (n = 4) and Elective Modules (n = 2) EXTENSION MODULE 1 HEALTH ECONOMICS LEARNING OUTCOMES At the end of this module the student should be able to: 1. Explain the multidisciplinary nature of pharmacoeconomics and ethical boundaries, and the need for integration of knowledge from a range of health science disciplines in the management of sustainable health service challenges in the 21st century. 2. Use in an appropriate manner the fundamental scientific theories underlying the application of health economic techniques to a range of healthcare interventions. 3. Recognise and be capable of utilising basic relationships and techniques of healthcare management to maximise benefits from a given resource. 4. Explain and present information associated with economic appraisal and assessment of new medicines carried out by NICE or similar agencies. 5. Explain the role of the agencies which police the economic viability of existing and new medical technologies. 6. Compare and contrast the different challenges of healthcare expenditure presented in different economies. 7. Outline the structure of the global drug development and regulatory framework with emphasis on risk management in the context of benefit/risk assessment and the role of pharmacoeconomics and quality-of-life, and be capable of explaining its evolution, strengths and weaknesses. 8. Explain methods utilised in clinical trials for examining cost-effectiveness of new pharmaceutical products. EXTM 1 EXTM 1.1 EXTENSION MODULE 1 HEALTH ECONOMICS CURRICULUM CONTENT LEARNING OUTCOME MAPPING SYLLABUS TOPIC MAPPING Economics of industry and corporate finance: - pharmaceutical development strategic planning and the role of pharmacoeconomics; - product life-cycle management / re-positioning and the role of pharmacoeconomics. 1, 2, 7, 13.8 13.9 13.10 Drug budget control methods. Pharmaceutical pricing mechanisms. Financial management and the accounting framework: - organisation of the finance department; - internal control, forward planning. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 38/79 CURRICULUM CONTENT LEARNING OUTCOME MAPPING SYLLABUS TOPIC MAPPING 2, 3, 6 13.1 2, 4, 7, 8 13.7 13.11 2, 7, 8 13.2 13.3 13.7 Cost of management of clinical trials. Budgeting and cost behaviour. EXTM 1.2 Principles of health economics: - overview of economic theories; - global understanding and approach to ‘Macro’ & ‘Micro’ economics; - supply and demand concept; - economic margin of benefits; - sustainable economic environment; - money, cost, resource, input and output, tradeoff; - scarcity, opportunity cost; - utility judgement; - role of ‘Need’ as an alternative distribution mechanism to ‘Demand’. Priority setting in healthcare and the reasons for it: - economic objectives of healthcare; - allocative vs. technical efficiency. Constraints on clinical freedom: - principles of common good; - social ethics and utilitarianism, and potential conflicts between medical ethics & economics. EXTM 1.3 Economic evaluation in healthcare: review of the four (4) main techniques of economic evaluation in healthcare (cost minimisation, cost-benefit, cost-effectiveness and cost-utility analyses). Reasons why each economic evaluation is used in their appropriate situations and types of studies (clinical trials; naturalistic) suitable for economic evaluations. Review of alternative criteria for choice; margin and efficiency as a social goal. Current methodological controversies and consideration of practical difficulties encountered in the actual conduct of economic evaluation studies. EXTM 1.4 Pharmacoeconomic theory: - approaches to the evaluation of pharmacoeconomics; - hierarchy of evidence; - measuring outcomes for drug interventions. Outcome research (effectiveness and efficiency) vs. clinical research and controversies surrounding outcomes research. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 39/79 CURRICULUM CONTENT LEARNING OUTCOME MAPPING SYLLABUS TOPIC MAPPING 2, 4, 5 13.2 13.4 13.7 13.8 13.11 Utility theory and methods of measuring utility including multi-attribute utility theory; - when is utility measurement appropriate? Quality Adjusted Life Year (QALY) and Healthy Year Equivalent (HYE). EXTM 1.5 Application of pharmacoeconomic theory: - pharmacoeconomic methodological issues and external vs. internal validity; - application of results to different settings; - use of models and their appropriateness; - decision analysis in modelling and sensitivity analysis. Different approaches to reimbursement for medicines in EU and the role of Health Technology Assessments (HTAs). Similarities and differences between Regulatory and HTA agencies. Drug development prioritisation decisions. Indirect costs and outcomes. Willingness to pay. Use of statistics in pharmacoeconomic evaluation including systematic review and meta-analysis. Design of pharmacoeconomic studies: - general principles and types of studies - purpose and application of pharmacoepidemiology in economic studies of drugs. Health-related quality of life (HRQoL) studies: - how is HRQoL measured? - methodological consideration in HRQoL measurement; - non-utility HRQoL studies, practical considerations, interpretation of score changes, examples of generic and disease-specific instruments, choice of HRQoL instruments in naturalistic and controlled studies. Policy implications of pharmaceutical resource allocation league tables in healthcare. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 40/79 CURRICULUM CONTENT EXTM 1.6 Medical marketing and market access: - market forces, market dynamics, production and distribution of outputs. LEARNING OUTCOME MAPPING SYLLABUS TOPIC MAPPING 1, 3, 5, 6 13.6 13.8 Reason for market failure (uncertainty, monopoly power, problems of competition and externalities). The nature of the commodity ‘Healthcare’: - how & to what extent ‘Healthcare’ differs from other market goods; - challenges to consumer sovereignty; - role of the concept of agency in healthcare; doctor as a perfect agent; public good and merit argument; healthcare in the marketplace. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 41/79 EXTENSION MODULE 2 DRUG SAFETY: PHARMACOEPIDEMIOLOGY, PHARMACOVIGILANCE AND RISK MANAGEMENT LEARNING OUTCOMES At the end of this module the student should be able to: 1. Explain the role of pharmacovigilance in monitoring of drugs in non-clinical and clinical research and in the marketplace. 2. Appraise common nomenclature associated with pharmacovigilance (incl. AE & ADR, listedness, expectedness, causality etc). 3. Demonstrate the sources of safety data: methods for collection, analysis, interpretation and reporting drug safety data, including electronic safety data reporting. 4. Evaluate the assessment of causality. 5. Analyse the application of signal generation and handling of drug safety data in premarketing (clinical trial) and post-marketing (pharmacovigilance) contexts, including automated methods. 6. Explain the principles of pharmacoepidemiology and examine the different types of pharmacoepidemiological studies used in evaluating drug safety including the choice of the most appropriate study design. 7. Describe pharmacovigilance aspects of medicines regulation throughout the life-cycle of a medicine. 8. Critically appraise the principles of risk-benefit analysis and management using qualitative and quantitative approaches. 9. Evaluate the background and purposes of Risk Management Plans (RMPs) and Risk Evaluation and Mitigation Strategies (REMS). 10. Describe the role of the EU Qualified Person in PharmacoVigilance (QPPV). 11. Describe major routes for reporting and communication of pharmacovigilance data. 12. Evaluate the aetiology, mechanisms and pathology of major classes of adverse drug reactions and interactions. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 42/79 EXTM2 EXTM 2.1 EXTENSION MODULE 2 DRUG SAFETY: PHARMACOEPIDEMIOLOGY, PHARMACOVIGILANCE & RISK MANAGEMENT CURRICULUM CONTENT LEARNING OUTCOME MAPPING SYLLABUS TOPIC MAPPING Background to and general principles of medicines regulation (with reference to PV responsibilities of all stakeholders). 1, 7, 10 10.1 10.5 Regulatory requirements and legal aspects of pharmacovigilance. Good Pharmacovigilance Practice (GPvP). The evolution of drug surveillance methods and pharmacovigilance regulations worldwide, their harmonisation, and company systems for assembling and reporting adverse events. EXTM 2.2 Practical input of international bodies e.g. WHO, WMA, CIOMS, CHMP, ICH and national agencies in the regulatory oversight of pharmacovigilance. 1 10.2 EXTM 2.3 The role of the pharmaceutical professional in drug safety and pharmacovigilance: 10 11.1 2, 3, 4 11.2 10.4 - the responsibilities and liabilities of investigators, clinicians, study monitors and manufacturers in the pre- and post-marketing phases to detect, assess and report adverse events associated with medicines; - the roles and responsibilities of the EEA Qualified Person for Pharmacovigilance (QPPV). EXTM 2.4 Assessment and classification of adverse events (AEs), adverse drug reactions (ADRs), Serious Adverse Events (SAEs) and Suspected Unexpected Serious Adverse Reactions (SUSARs). The principles of causality assessment: - evidence for association and causality; - causality algorithms to classify events as to their likely causal attribution to a particular medicine. Case narrative writing for reporting adverse events. EXTM 2.5 The concept of benefit / risk assessment, determination of causal relationship between the medicinal product and the adverse event. 4, 8 11.3 EXTM 2.6 Pre-clinical safety and mechanisms of ADRs. 1, 8, 12 14.6 The mechanisms of drug interactions. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 43/79 CURRICULUM CONTENT LEARNING OUTCOME MAPPING SYLLABUS TOPIC MAPPING EXTM 2.7 Collection of adverse events in clinical trials: 1, 5, 7 7.15 EXTM 2.8 Role of sponsors and investigators in reporting adverse events and suspected adverse drug reactions: - the characteristics that make an AE/ADR reportable according to international guidelines. 1, 5, 7 11.5 EXTM 2.9 Drug safety in the marketplace: 1, 3, 5, 10 11.7 EXTM 2.10 Periodic Safety Update Reports (PSURs). 3, 7 11.10 EXTM 2.11 Risk factors for adverse events. 1, 4, 5, 12 11.6 EXTM 2.12 Dosage, accumulation, medication errors and interactions. 1, 3, 5 11.8 EXTM 2.13 Drug adherence / compliance. 1 11.9 EXTM 2.14 Advanced Pharmacoepidemiology: - main sources of epidemiological pharmacovigilance information; - non-interventional / observational study design in pharmacoepidemiology; - dealing with confounding factors and bias. 6 11.11 Record Linkage & pharmacovigilance databases: 3, 5, 7 11.11 5, 8 11.13 EXTM 2.15 11.4 - adverse event assessment and reporting in clinical trials; - the structure, roles and responsibilities of the data safety monitoring board (DSMB) in clinical trials. - spontaneous reporting post-marketing; - Prescription Event Monitoring (PEM). 11.12 7.3 9.24 - the characteristics of commonly used databases; - General Practice Research Database (GPRD) and others. The major methods of post-marketing surveillance: - the requirements for Post-Authorisation Safety Studies (PASS). EXTM 2.16 The methods and applications of all signal generation methods in pharmacovigilance and the processes required for prioritisation and evaluation of detected signals. Benefit-Risk review. The European procedures for reassessment of benefitrisk. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 44/79 CURRICULUM CONTENT LEARNING OUTCOME MAPPING SYLLABUS TOPIC MAPPING EXTM 2.17 Regulatory actions in drug safety including: 1, 7, 11 11.15 EXTM 2.18 Post-authorisation risk management including issue and crisis management. 9, 11 11.15 EXTM 2.19 Risk management: - Risk Management Plans (RMPs) in the EU; - Risk Evaluation and Mitigation Strategies (REMS) in the USA. 9 10.21 EXTM 2.20 Risk communication: - the requirements for informing prescribers, investigators, ethics committees, and regulatory agencies of important safety concerns; - Direct Healthcare Professional Communication (DHPC) related to drug safety issues; - the external factors affecting response to drug safety issues (e.g. public freedom, political agendas, patient organisations). 7, 11 11.16 EXTM 2.21 Product defects and recall. 7, 11 10.18 EXTM 2.22 Principles and process for development of Safety Specifications documents. 1, 7 10.22 EXTM 2.23 Impact of emerging safety issues on Product Information. 11 12.2 EXTM 2.24 Defining the key markers of progress – examination of evidence that the output from safety surveillance systems has improved and safeguarded (public) health. 1 11.1 - Marketing Authorisation (MA) Variations, Urgent Safety Restrictions, MA suspension and withdrawal; - Risk minimisation strategies. 10.23 Communications to doctors and patients. The CYP450 isoenzymes and their role in safety aspects of medicines development and surveillance. Safety aspects of gene therapy and other new technologies. The potential for pharmacogenomics / pharmacogenetics to enhance the safety of medicines. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 45/79 EXTENSION MODULE 3 BIOLOGICALS AND ADVANCED THERAPIES LEARNING OUTCOMES At the end of this module the student should be able to: 1. Demonstrate an understanding of the regulatory, ethical and legal issues that are peculiar to biological and advanced therapies. 2. Demonstrate an understanding of the challenges presented in constructing a package of non-clinical data to support the clinical development and marketing of biological and advanced therapies. 3. Recommend a clinical trial plan that is appropriate for the different types of products and technologies represented by biological and advanced therapies. 4. Demonstrate an understanding of the technical and manufacturing issues that are peculiar to biological and advanced therapies. 5. Critically review general articles on new or prospective biological or advanced therapies, and published papers describing the clinical trials of biological and advanced therapies. 6. Describe the new technologies now available and those in development; describe the therapeutic opportunities that might arise from the technology. 7. Critically analyse the differences between natural and modified proteins. 8. Describe the global need for new and improved vaccines and the barriers to their development. 9. Describe what a therapeutic vaccine is and how it could influence therapy in a common disease area. 10. Discuss the history and future prospects for gene therapy, and the technical difficulties developing a gene therapy product. 11. Describe the concept of stem cell therapy, what opportunities it might present, and the ethical issues that are unique to this technology. 12. Describe the particular ethical and regulatory issues of advanced therapies and how The Advanced Therapy Directive is addressing these. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 46/79 EXTM 3 EXTM 3.1 EXTENSION MODULE 3 BIOLOGICALS AND ADVANCED THERAPIES CURRICULUM CONTENT LEARNING OUTCOME MAPPING SYLLABUS TOPIC MAPPING Overview of new and developing technologies and therapies. 1, 2, 3, 4, 5, 6 1.1, 1.2, 1.3, 1.4, 1.5, 1.7, 1.8, 14.2, 14.3 2, 6, 7 3.2, 4.1, 4.2, 4.3, 7.1, 8.1, 10.5, 10.8 6 1.3, 3.2, 4.1, 5.10, 7.1, 8.15, 10.8, 11.14, 13.6 8 1.1, 1.5, 2.4, 2.5, 6.2, 8.14, 8.15, 8.16, 14.3 Brief description of the regulatory challenges, how approaches to preclinical testing and clinical development differ from small molecules. General description of macromolecules, including therapeutic peptides, proteins and polysaccharides; manufacture, formulation, analysis and assessment in vivo. EXTM 3.2 Recombinant DNA technology. Isolation and construction of the gene, plus any modifications. Selection of the host cell, bacteria, yeast or mammalian. Production and quality issues, including structure of the final protein. Pre clinical and clinical trial issues, including identifying potential risks. Modified proteins, insulin analogues etc. EXTM 3.3 Monoclonal antibodies. Identification of the target. Methods of constructing and producing an antibody. Pre clinical testing. Issues of phase 1 studies with Mabs. Potential long-term safety issues of Mabs. Pricing issues, assessing and accessing the patient population. TGN 1412 case study EXTM 3.4 Prophylactic Vaccines. Vaccines against infectious disease. History of vaccination and the on-going need. Construction of a vaccine, production methods. Pre-clinical testing and batch testing. Clinical trials, how to measure outcomes. New challenges, HIV and malaria. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 47/79 CURRICULUM CONTENT LEARNING OUTCOME MAPPING SYLLABUS TOPIC MAPPING EXTM 3.5 Therapeutic Vaccines. 9 1.1, 1.2, 1.4, 1.8, 3.2, 4.1, 7.1, 10.8, 10.19 EXTM 3.6 Polysaccharides. 6 1.3, 1.4, 3.1, 3.2, 4.1, 4.3, 10.8, 14.3 EXTM 3.7 Definition of advanced therapies. 6 1.1, 1.5, 2.1, 5.1, 7.1, 8.15, 10.8, 11.14, 13.6, 14.2, 14.3 EXTM 3.8 Gene therapy. 10 1.1, 1.4, 1.5, 1.8, 2.1, 2.2, 2.4, 4.1, 5.12, 8.15, 10.8, 11.14, 13.6, 14.3 EXTM 3.9 Stem cell therapy. 11 1.1, 1.2, 1.5, 2.2, 3.1, 4.1, 5.3, 6.1, 7.3, 8.15, 10.8, 11.14, 13.3, 14.3 The concept of developing a therapeutic vaccine, identifying the target and developing the molecule. Pre-clinical testing issues and clinical trial design. Regulatory and quality control issues of ‘personalised’ vaccines. Examples in cancer / non-cancer areas, including therapeutic vaccines against infection. Production and quality issues, including structure of the final product. Pre-clinical and clinical trial issues, including identifying potential risks. The breadth of advanced therapies that are available and in development. Development plans; clinical and regulatory challenges. Current market analysis and future trends. The concept of gene therapy. How to identify the candidate gene. Isolating and validating the gene. Selecting the vector. Pre-clinical testing. Quality control and manufacturing procedures. Clinical trial design. Why has gene therapy failed so far? The Gelsinger case What is a stem cell? Differentiate between somatic cells and germ line cells. Definition of embryonic stem cells and adult stem cells. Potential uses of stem cells. Retro engineering cells to become stem cells. Ethical and technical controversies. Pre-clinical and clinical testing. Long term safety monitoring, the use of ‘traceability’. Rogue stem cell centres. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 48/79 EXTM 3.10 CURRICULUM CONTENT LEARNING OUTCOME MAPPING SYLLABUS TOPIC MAPPING Short interfering RNA. 6 1.1, 1.2, 1.3, 1.6, 3.2, 4.1, 5.1, 5.12, 8.15, 10.8, 11.14, 13.6, 14.2, 14.3 6 1.1, 1.2, 1.3, 1.4, 1.5, 3.2, 5.12, 8.15, 10.8, 11.14, 14.2, 14.3 6 1.1, 1.4, 1.8, 2.2, 4.1, 5.3, 8.15, 10.8, 11.14, 13.6, 14.2, 14.3 12 8.13, 8.14, 8.15, 8.16, 10.5, 10.8, 10.17, 11.15 What is SiRNA. Use of short interfering RNA. How to define a target and construct the molecule. What areas are currently being researched? Off target interference and how to avoid it. EXTM 3.11 Epigenetics. What is epigenetics? How to identify a target. What areas of therapy might be helped? Evidence that epigenetic changes can alter phenotype. Evidence that epigenetic changes can be inherited. How to modify an epigenetic change; chemical approaches. Pre-clinical and clinical testing. EXTM 3.12 Tissue engineering and regenerative medicine. Models of tissue engineering, individual reconstruction and generic platforms. Selection of a scaffold. Pre-clinical testing. Regulatory and ethical issues. Long term safety monitoring, the use of ‘traceability’. EXTM 3.13 Overview of ethical, legal and regulatory issues. The use of embryonic stem cells. The Advanced Therapy Directive. 3.3 Integrated Master Programme (Integrated Modules (n = 10) and Elective Modules (n = 2) + Master Thesis; 60+ ECTS) The above 6 Base Diploma Course Modules and 4 Extension/2 Elective Master Modules are similarly translated into 10/12 Modules in the 12 Integrated Master Programme. Since the both the Base and Extension Modules are held at a Master-level, this Integrated Master Module will provide a similar outcome based on the Syllabus, Learning Outcomes and modular assessments. Mapping of Syllabus items and Learning Outcomes in the 10 mandatory modules are being defined. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 49/79 EXTENSION MODULE 4 SPECIAL POPULATIONS: CLINICAL TRIAL PRACTICE AND REGULATION LEARNING OUTCOMES At the end of this module the student should be able to: 1. Relate life-time changes in body composition and function to drug effects in different age groups. 2. Create a drug development programme tailored to medical needs, age-specific physiological differences, ethical issues, legal and regulatory requirements. 3. Assess the influence of the changed body composition on the pharmacokinetic behaviour of drugs and the effects of drugs on the developing new organism. 4. Plan the non-clinical and clinical drug development programme considering the specific conditions of pregnant and lactating women and of the breast-fed baby. 5. Compare pharmacokinetic behaviour and pharmacodynamic effects of drugs in the elderly and those observed in the normal adult population. 6. Consider the need to develop drugs with elderly specific strength, combinations and drug containers, making a drug application easier in old patients. 7. Assess and balance the therapeutic needs of elderly patients with the specific legal and ethical issues relating to trials involving this specific population. 8. Evaluate the scientific, socio-ethical, pricing and reimbursement problems related to developing and marketing orphan drugs. 9. Design a clinical drug trial protocol considering scientific goal(s), target patient population, suitable methods and feasibility. 10. Create an ethics committee review considering the scientific goal(s), target patient population, suitable methods and feasibility. 11. Appraise the suitability of traditional trial designs or develop possible new approaches for emerging technologies. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 50/79 EXTM 4 EXTENSION MODULE 4 – SPECIAL POPULATIONS; CLINICAL TRIAL PRACTICE AND REGULATION CURRICULUM CONTENT LEARNING OUTCOME MAPPING SYLLABUS TOPIC MAPPING EXTM 4.1 Introduction Life-time changes in body composition, physiology, pharmacokinetic processing and pharmacodynamic effects of drugs from the neonate to the very old individual. 1 5.5, 5.6, 5.7, 5.8, 5.9, 5.11, 6.1, 14.5 EXTM 4.2 Drug development for the paediatric population Pre-clinical requirements for drug development in the neonates and children. 2 2, 4, 3.5, 3.7, 4.3, 7.1, 7.11, 8.2, 8.3, 8.6, 8.8, 8.9, 8.14, 10.8, 11.15, 11.16 3 5.5, 5.6, 5.8, 5.9, 8.4, 11.6, 11.8, 11.15, 11.16 Clinical trial programme designed for the paediatric population. Regulatory, legal and ethical requirements (Paediatric Regulation, PIP, Ethical Guidelines). Drug evaluation and development of specific pharmaceutical formulations for the different paediatric age groups. EXTM 4.3 Drug development for pregnant and lactating women Pharmacokinetic behaviour and pharmacodynamic effects of drugs during pregnancy and lactation. Transfer of drugs into the milk. Drug groups forbidden in pregnant and lactating women. EXTM 4.4 The non-clinical study and the clinical evaluation of drugs to be used in pregnant and lactating women and their impact on the breast-fed baby. 4 2.4, 3.5, 3.6, 3.7, 3.9, 5.11, 5.13, 7.1, 7.11, 8.3, 8.8, 8.9, 8.11, 8.12, 10.14, 10.17 EXTM 4.5 The elderly population Relate altered pharmacodynamic effects, more frequent occurrence of side effects and drug interactions in the elderly to old age-dependent involution of physiological functions and impaired homeostatic mechanisms. 5, 6 3.7, 5.5, 5.6, 5.7, 5.8, 6.5, 7.1, 7.2, 7.3, 10.14, 10.17, 11.6, 11.8, 11.9, 11.15, 11.16 The different therapeutic needs of elderly and very old populations. Non-clinical and clinical development of drug formulations and treatment strategies optimised for the aged population. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 51/79 EXTM 4.6 Specific regulatory, legal, organisational and ethical issues related to clinical trials in elderly patients (inc. Informed consent, therapeutic nihilism in the elderly, limited enrolment in clinical trials). 7 2.4, 4.3, 6.1, 6.2, 6.5, 7.1,, 7.15, 8.2, 8.3, 8.8, 8.9, 8.12, 8.14 EXTM 4.7 Orphan drug development Definition of rare diseases and the need for specific medicinal products. 8 4.6, 5.2, 5.4, 5.5, 5.7, 5.10, 5.11, 5.12, 5.13, 6.1, 6.2, 6.3, 6.4, 7.1, 7.2, 7.7, 7.9, 7.11, 7.14, 7.15, 8.3, 8.6, 8.8, 8.9, 8.14, 8.16, 10.8, 13.8, 13.9 Diagnostic difficulties of rare diseases. The role of biomarkers in developing orphan drugs. Regulatory requirements for obtaining orphan status. Specific scientific, financial and administrative support needed for running clinical trials and obtaining marketing authorisation. Collaboration with patient organisations. Potential business models. EXTM 4.8 Advanced exercises Protocol writing: prepare a clinical trial protocol dealing with a drug designed for a defined patient population including special patient populations. 9 7.6, 7.7, 7.11, 8.12, 8.14, 8.16 EXTM 4.9 Ethics Committee decision: write an ethics committee application of a clinical trial protocol considering the goals, selection of patient population, methods applied, risks involved, informed consent, etc. 10 8.6, 8.8., 8.9, 8.15 EXTM 4.10 Design a protocol: develop a protocol dealing with new emerging drug types, targeted therapy, advanced therapy or a medicinal device. 11 8.4, 8.13, 8.15 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 52/79 3.4 Elective Modules 1-10 The following first set of Elective Modules 1-10 have been defined and need further specification. First set of Elective Modules Using the format of other modules in the PharmaTrain programme (5 ECTS – with one ECTS preparation, two ECTS face-to-face interaction and another two ECTS assignments) PharmaTrain has identified topics to be recommended as Electives. The organisation of these Elective Modules will follow eligibility criteria which have to be defined by their educational objectives/learning outcomes respect ethical preclinical and clinical research ensure transparency of speakers’ origin and address any conflicts of interests. ELECTIVE MODULE 1 – GENERIC AND BIOSIMILAR MEDICINAL PRODUCTS LEARNING OUTCOMES At the end of this module the student should be able to: 1. Compare the scientific and regulatory basis for the definitions of the various types of follow-on drugs: generic, biosimilar and analogue medicinal products, define their significance in the life-cycle management of medicines. 2. Choose the right timing of pharmacokinetic studies during generic drug development. 3. Select the appropriate “in vivo” methods to establish equivalent bioavailability of generic drugs. Assess the significance of food and alcohol interactions in bioequivalence studies. 4. Assess the scientific basis and methods used for the “in vitro” equivalence estimation of generic drugs. 5. Analyse the diversity caused by the development of independent formulations for the same active ingredients by the follow-on producer. 6. Understand and critically review the international regulatory differences in the evaluation of marketing authorisation applications for generic products. 7. Comprehend and appreciate the causes leading to the diversity of the biosimilar medicinal products manufactured by different producers. 8. Evaluate the complex non-clinical and clinical comparative study requirements needed to evaluate the biological and immunogenic properties of biosimilar drugs. 9. Appreciate the specific production problems of complex biosimilar monoclonal antibodies needed for targeted therapy. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 53/79 10. Analyse, comprehend and assess the complexity and international diversity of regulatory requirements for evaluating the efficacy and immunological safety of follow-on biological products. 11. Appraise the various clinical pharmacological issues related to the clinical interchangeability of generic and biosimilar drugs. ELM 1 ELM 1.1 ELECTIVE MODULE 1 GENERIC AND BIOSIMILAR MEDICINAL PRODUCTS CURRICULUM CONTENT LEARNING OUTCOME MAPPING SYLLABUS TOPIC MAPPING The various meanings of follow-on drugs used in drug development. The definition of generic, similar biological (follow-on; biosimilar) medicinal products and analogue drugs. Their classification in the ATC system. 1 1.4, 6.5, 6.6, The role of follow-on drugs in the pharmaceutical development strategy and life cycle management of drugs. ELM 1.2 Necessity and timing of pharmacokinetic investigations during the discovery and development phases of generic medicinal products. 2 5.4, 5.5, 5.7, 5.8, 5.12 ELM Bioequivalence studies of generic medicinal products. The importance of food-drug and food-alcohol interactions in the development of generic medicinal products. 3 5.4, 5.5, 5.7, 5.8, 5.12 Biopharmaceutics Classification System (BCS) based “in vitro” drug equivalence testing. 4 The biopharmaceutical formulation of generic medicinal products, conventional formulations, reverse engineering. 5 4.1, 4.2, 4.3, 4.4, 6 10.1, 10,3, 10.5, 10.7, 10.9, 10.11, 10.13 1.3 ELM 1.4 4.1, 4.2, 4.3, 4.4, The optimisation of the pharmacological effects by the application of innovative formulations, modified-release drug products, super-generics and nanoformulations. ELM 1.5 International regulatory trends in the marketing authorisation of generic medicinal products. The criteria for accepting Biopharmaceutics Classification System (BCS) concept-based bio-waiver applications by the different competent authorities. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 54/79 CURRICULUM CONTENT LEARNING OUTCOME MAPPING SYLLABUS TOPIC MAPPING ELM 1.6 The differences between the biological systems used for the production of similar biological products. The need for the combined application of physicochemical and biological methods for controlling the production and the quality of the final product. 7 1,7, 2.2 ELM 1.7 The need for comparative evaluation of the pharmacological properties and immunogenicity of the original and the similar biological products. 8 Sections 3 to 7 ELM 1.8 The structural complexity of monoclonal antibodies. The added difficulties associated with the production of biosimilar monoclonal antibodies. 9 Sections 3 to 7 10 Section 10 11 Sections 13 and 14 Follow-on monoclonal antibody constructs. ELM 1.9 The international differences of the regulatory and legal evaluation of follow-on similar biological medicinal products. The biosimilar concept of the EMA. Social relevance of production costs, the issue of public safety. ELM 1.10 Differences in the clinical interchangeability of generic and similar biological medicinal agents. The unresolved issue of exchanging biological drugs in the same patients. The specific problems of the therapeutic exchange of analogue drugs, therapeutic reference pricing. Additional plans for Elective Modules 2-10: 2 Rare and orphan diseases Draft programmes have been created to include specific issues of rare disease therapies, trial needs, the role of patients (groups), relevant designs, controlling interventions, multi-centre trials in rare diseases, specifics of biomarkers and surrogate endpoints. 3 Drug evaluation in geriatric patients Special issues in drug development in elderly individuals include social and political aspects of the elderly in Europe, regulatory aspects (E7 new text, specific request for biologicals), daily care, genetic aspects, ethical issues (information, consent, ethics committees etc.), simulation and modulation in extreme age groups. 4 Pregnancy and the newborn This programme will include best prescription during pregnancy, preclinical studies (teratoxicity, placental drug transfer etc.), clinical studies (fetotoxicity and requests during second and third trimester of pregnancy, pre-natal screening, trials during pregnancy, ethical issues, maternal need for adequate therapy), clinical studies and expert working groups, institutional activities including medication 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 55/79 during pregnancy (the Pregmed network), antiretroviral therapies during pregnancy, the case of isotretinoin. 5 Drug evaluation in children (two modules) The evaluation of medicinal products in children deserves special attention, in particular since these issues often fall short in other training programmes. There is one day each on specific aspects of paediatric pharmacology, specific issues related to clinical trials and drug use in children, methodological aspects related to clinical trials and drug use in children as well as time for the state of the art evaluation of medicines in specific therapeutic areas in children (including vaccination). 6 Biologicals This module will be harmonised with similar modules of other programmes and the topics include the biological medical product market; regulatory request, the European Commission and the role of EMA; life cycle management; genetic engineering of biological products; drug development plans; safety issues specific to biological products; manufacturing; new diagnostic tools; etc. The module will address different types of biological products including vaccines, blood derivatives, GMOs etc.) 7 Simulation and modelling Models are often used in the development and innovation of new drugs. This module seeks to present different aspects of drug development using modelling and other statistical tools. 8 Ethics throughout medicines development 9 Meta-analysis Meta-analysis is a technique used in medicines development for elaboration of therapeutic strategies and to make recommendations for treatment. The module will address meta-analysis to evaluate a rare, adverse effect or to demonstrate efficacy. 10 Biomarkers Biomarkers and surrogate endpoints are useful when conducting clinical trials. This module is designed to explore their methodology and statistical validation. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 56/79 3.5 Additional PharmaTrain Programmes (see Appendices 7.5-7.10, www.pharmatrain.eu) 3.5.1 Master of Medicines Regulation, MMR The development process of medicines is as important for medicines regulators as for medicines developers. This Master programme, developed by regulatory experts from regulatory authorities and industry, uses the same standards as all PharmaTrain programmes. This programme is open to other interested regulatory agencies and other European Universities. R7 Pharmacovigilance R6 Principles of Clinical R+D R2 EU Regulatory Legislation R1 Intro R11 R8 Marketing Authorisation R5 Non-clinical Development Master-Thesis R9 Life Cycle Mangement R3 EU Regulatory Procedures R4 Pharma Quality / CMC R12 R10 Quality Management / Inspections Non-IMI Eu2P SafeScMET EMTRAIN Fig. 6: Master of Medicines Regulation, MMR The MMR-Brochure in App. 7.4 contains details of this PharmaTrain programme. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 57/79 3.5.2 Clinical Investigator Certificate/Courses, CLIC and e-CLIC The new electronic investigator training course established by PharmaTrain to reach investigators all over Europe. The course comprises an Introductory element and a basic training element. The Introductory element gives an overview over the medicines development process and the elements of GCP. The basic element provides a solid and clear overview and opportunities to practice all managerial, regulatory and ethical aspects of planning, performing and reporting a clinical trial from the investigator’s point of view. The face-to-face CLIC project is based on the curriculum of the European Science Foundation and has been started at different university centres of PharmaTrain. Discussion on optimal interaction with the current PharmaTrain activities is in progress. These additional PharmaTrain programmes described briefly above are detailed in the individual training brochures in App. 7.7 and 7.8. At the same time, all modules are part of the PharmaTrain CPD Core Platform, www.pharmatrain.eu and incorporated in the ‘on course’ database of EMTRAIN. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 58/79 4. Qualifications, Examinations and Recognitions 4.1 Entry Requirements Students on these courses are normally science or medical graduates working in the pharmaceutical industry. Competence in both written and spoken English is a requirement; a qualification in English language may be requested. 4.1.1 Applicants who wish to register for a programme Acceptance onto a programme is based upon the applicant having sufficient academic and/or professional qualifications and experience to satisfy the programme directors of his/her fitness for the course of study. Before entering the course, students must have sufficient factual knowledge and work experience to analyse, synthesise, evaluate and apply information in practice. Typical entry requirements are a medical, pharmaceutical or natural science education which led to a university degree or equivalent professional qualification and/or a minimum of two years in a post that provides practical experience and training in pharmaceutical medicine / medicines development. One or two referees who can provide a written report of the applicant’s suitability and motivation to undertake a postgraduate academic programme of study of this nature might be nominated; an interview may also be required before the offer of a place can be made. 4.1.2 Applicants who do not wish to register for a programme Applicants can register for individual modules as an occasional student. There are no formal entrance requirements, although a scientific background to at least bachelor degree level and ability to analyse, synthesise, evaluate and apply information in practice is recommended. 4.1.3 Students undertaking Pharmaceutical Medicine Specialist Training / Specialist in Medicines Development, SMD Medically-qualified individuals who wish to attend modules approved by the relevant medical registration authority as part of their training plan for the purpose of specialty training in pharmaceutical medicine should agree this in advance with the Course Director and their Educational Supervisor and should state at the time of registration that they wish to attend the module(s) for this purpose. 4.2 Accreditation of prior learning Exemption from part of a course can be sought on the basis of relevant prior academic and professional qualifications or experience demonstrated by performance appraisals, record of professional achievements, publications, etc. Information on the process should be readily available to applicants, including any restriction on the maximum number of ECTS that may be credited for prior learning. Requests for exemption should be submitted in accordance with local guidelines and will be considered by a panel that includes an external member from the pharmaceutical industry or nominated by the board of the national association for Pharmaceutical Medicine. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 59/79 4.3 Outcomes and qualifications Students participating in this programme can select the level of learning that is appropriate to their needs. Some choose simply to study just one or two modules for the purpose of Continuing Professional Development (see Fig. 3 and Section 4.8) or to address a new need that has arisen in their work. Others will participate in a course of study leading to an award at one of three levels. Course providers will provide transcripts documenting the student’s achievements that may be transferred between courses following the Bologna rules. 4.3.1 PharmaTrain module Each PharmaTrain module consists of a curriculum that is mapped to the PharmaTrain syllabus with defined learning outcomes. Students’ participation in the module comprises: personal preparation and participation by attendance, e-learning, or blended learning and formal assessment to confirm that the student has achieved the module learning outcomes; this will normally be conducted using a variety of assessment methods as described in Section 4.4 Successful completion of the module including all assessments merits 5 ECTS that may be transferred. 4.3.2 1st tier: (Base) Diploma Course The Base Diploma Course comprises: satisfactory completion of Module 1, the Introductory Module followed by 5 further modules as described in Section 3.1 and additional assessments as required by the course provider Successful completion of the Base Diploma Course including all 6 modules and all assessments will merit 30 ECTS (1st Tier). 4.3.3 2nd tier Master Programme The 2nd tier of the PharmaTrain programme requires satisfactory completion of 12 modules. This can be achieved in one of two ways: Base Diploma Course plus six (4 extension and 2 elective) additional modules described in Section 3.2 corresponds to the Extension Master Programme or Integrated Master Programme, described in Section 3.3, in which the same material is taught without dividing the course into base and extension parts and additional assessments as required by the course provider Requirements for a master’s degree vary somewhat between different universities and local rules should be referred to. Assessments that are required by the university typically include a dissertation or thesis focusing on any relevant syllabus topic (Section 4.6) Successful completion of the 1st & 2nd tiers including all 12 modules and all assessments, including the dissertation merits 60+ ECTS. 4.3.4 3rd tier of the Masters Programme Discuss an integrated examination (Section 4.5) workplace-centred competency-based assessment. Successful completion of the 3rd tier including all 12 modules of 1st & 2nd tiers and all assessments, including the integrated examination merits 60+ ECTS. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 60/79 4.4 Assessments/Assignments Assessing what students have gained in terms of knowledge, understanding and application is the final part of any learning process. There are a number of ways that this can be achieved. The first is by formal examination. This is dealt with in Section 4.5. The other tool is post-course/module assignments. Again, there are a variety of approaches that will test various aspects of the learning experience. 4.4.1 General principles of assessment Discuss There are a number of basic principles that need to be followed if the maximum benefit is to be gained from thus type of assessment. The assignments must test the learning outcomes of the module. This is fundamental and all learning outcomes should be tested in some way. The assignments should be based on the teaching that has been delivered. This may be the formal classroom teaching, any web-based learning or the directed pre- or post-course reading. The number of assignments should be reasonable, ideally three as this allows the students to demonstrate a wide variety of skills and knowledge without overloading them. The assignments should test the students beyond just repeating what they have learned in the face-to-face classroom teaching and should require some form of original literature or web-based research. Each assignment should have a word limit set against it, somewhere between 800 and 1200 words, not including references or tables etc. This tests the ability of the student to think clearly as to what they are trying to say and express it in a concise way. Students should be asked to list all relevant references used to complete each assignment and may be asked to provide copies during assessment. The person setting the assignment should set out a model answer at the time of setting the assignment, attributing marks to key points anticipated in the answers. The assignments should be marked by two people who are both familiar with the teaching given and the academic standards required and are blind, that is unaware of the identity of the student or of the mark awarded by the other assessor. The pass mark – mean value of the two assessors’ marks – should be set in line with the general examination and assignment policies of the university providing the course. Students must be made aware of the university’s policy on plagiarism and make a declaration that the work is theirs and they have only sought general advice from colleagues. 4.4.2 Types of assignment There are a variety of approaches that test different aspects of the learning experience. The following paragraphs described some of these different approaches. The course provider will select one or more approach that is appropriate to each module. Critical review Students are asked to undertake a critical review of a published paper, which covers a topic from the module. For example, if dealing with a clinical trial, the critical appraisal should include study objectives, design, and description of primary endpoint, power calculation, subject disposition, analysis, discussion and conclu4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 61/79 sion and the relevance of the paper for clinical practice at local / national level. Commentary pieces on drug development or regulation or drug safety issues may also be included here and the student asked to comment on the validity of the argument and the relevance for pharmaceutical medicine etc. Research and discussion Students are asked to present an analysis of a topic covered in the module and to discuss the impact of this on the process / practice of pharmaceutical medicine / industry/regulation etc. They will be expected to undertake a literature search on the topic and to provide arguments, backed up by relevant references, for their opinions. Examples of this type of assignment include an evaluation of a therapeutic area (e.g. a specific orphan disease) or an analysis of new R & D tools (e.g. genotyping). Discussion on general pharmaceutical industry issues Students are asked to review and comment on a recent activity relating to one or more pharmaceutical companies/pharmaceutical industry in general. Examples would include review of research pipelines based on published data (comparison between companies), the future of R & D in general, impact of recent regulatory changes / voluntary codes of practice on the industry at local and international level, etc. Data Analysis Students should be expected to be able to analyse datasets, particularly relating to studies from each section of the R & D programme and from drug safety issues. In this type of assignment, students will be presented with a set of data and asked to describe what the data are telling them and how it will inform the future development / continued usage of the product and e.g. how it will contribute to / change the content of the target product profile. General public health issues It is reasonable to expect students to have a general understanding of public health issues as they might affect the pharmaceutical industry, especially if they might impact on health technology assessments. Questions involving such concerns are a good way of testing the broad understanding of students about the overall environment within which the pharmaceutical industry operates. 4.5 Integrated examination An examination covering all parts of the syllabus forms a summative assessment of the knowledge-base required for certification as a specialist in pharmaceutical medicine/Medicines Development. In addition, for those not eligible for registration as a specialist, success in this examination provides a stand-alone demonstration of the level of knowledge achieved. It is emphasised that this is a postgraduate examination that is unlikely to be appropriate to any who do not have a relevant degree and minimum of two years of experience in the pharmaceutical industry/CRO/regulatory authority. Any candidate without a relevant degree is advised to have at least five years such experience at the time of sitting the examination. Candidates should have attended one of the Europewide education and training programmes on integrated drug development / pharmaceutical medicine compliant with the PharmaTrain curriculum and / or attained an equivalent level of knowledge through workplace-based training and experience, private study, and other courses. The examination will comprise three methods of assessment including a multiple choice question paper and at least one other format of written assessment e.g., short 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 62/79 answer questions and/or essay. For students who have completed one of the PharmaTrain programmes, satisfactory completion of the assignments at the end of each module could constitute the second written assessment. The examination may include an oral component. The integrated examination will adhere to the principles summarised in Section 6.3. 4.6 Master dissertation/thesis The term dissertation or thesis refers to the same endeavour, which is to present evidence that demonstrates that the student has grasped the essential elements of planning, researching, writing-up, and presenting the results and conclusions of a project that they have undertaken. This would normally be the end product of an MMD/MSc course and in most institutions a degree would not be awarded without this. It is important to recognise that this is not a PhD research project and the much more extensive PhD thesis; it is essential to help the students understand what is expected of them. Essential elements are: Planning. The student should be able to demonstrate that they have thought through what they are planning to do. This is often achieved by writing an abstract and presenting this to their supervisor for the project. It should define the research question that they are asking and how they are going to approach obtaining the data and analysing them. Research. This will vary widely in nature and could consist of a study that the student is doing as part of their normal work. In this case it will be necessary for them to demonstrate what their role was in the project such that they had influence over the way the study was conceived and executed. They will need agreement from their employer to use the research study for the purpose of dissertation. An alternative could be a literature-based project. In this case it is of particular importance to ensure that the research question is carefully framed and is not simply an extended essay. Writing-up. This is the end-product of the project and will be the basis on which the examiners will determine if the student merits a pass. It will also be the document that is filed in the institution’s archives. Writing-up will include a statement about the research question, the way the research was undertaken, how the data were analysed and what the results and conclusions were. Where appropriate, write one or two papers based on the research that can be published in peer-reviewed journals. Management of the project Management of the project should rest entirely with the institution at which the student is registered. This will include the appointment of supervisors, the resources made available to the student and the style and presentation of the project. Some institutions will insist on an oral discussion/examination of the project and others will only ask for this under defined circumstances. Learning outcomes At the end of the project the student should be able to: 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 63/79 Define a simple research question Create a plan to answer the question Carry out the necessary investigations / research Analyse the data that have been generated Write up the project in a logical and readable way. Assessment of the dissertation As with all assessments, the dissertation should be marked independently by two examiners who will focus on the ability of the student to analyse, synthesise and evaluate the topic. An oral defence may be required. An external expert in the field may be approached for comment and an external examiner will moderate the marks. The examiners will make one of the following recommendations, as appropriate: that the thesis/dissertation is of pass standard that the thesis/dissertation is of pass standard, subject to specified minor corrections that the thesis/dissertation be failed but that the student be permitted to submit a revised dissertation by a specified date that the dissertation be failed Specified corrections should be completed within a defined time frame and verified by one of the examiners. 4.7 Professional recognition/certification/accreditation 4.7.1 Goal of recognition Training of specialists in pharmaceutical medicine is one of the primary objectives of PharmaTrain. Clear paths to professional acknowledgement combined with CPD should be defined for both physicians and non-physicians. 4.7.2 Physicians in countries recognising the specialty of Pharmaceutical Medicine For physicians, the framework is laid down in Council Directive 93/16/EEC, which was issued to “facilitate the free movement of doctors and the mutual recognition of their diplomas, certificates and other evidence of formal qualifications.” It aims for harmonisation of the medical degrees in the European Union and covers the qualifications needed, especially in Articles 23 and 24. The main features of a specialist training programme should include: Free movement of doctors between member states, mutual recognition of formal qualifications, grant of certificate of completion of training (CCT); Recognised, structured training programmes that are supervised, monitored, accessible, flexible, deliverable; Defined competitive entry criteria, minimum period of specialist training, defined exit criteria; Accreditation of the competency of specialists, capable of independent unsupervised practice. Details of the specialist training are regulated by a national competent body. Currently, pharmaceutical medicine is recognised as a specialty in only a few countries in 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 64/79 Europe. To be recognised as a specialist in these countries, trainees must demonstrate a sufficient level of theoretical knowledge and of practical workplace-based competency. The theoretical part of the specialist’s education should be demonstrated by satisfactory performance in an integrated examination and covering all parts of the syllabus (Section 4.5). Working in an accredited training site with an educational supervisor, and within a framework of assessment, appraisal and annual review of achievement and progress is required for specialist certification and accreditation in Pharmaceutical Medicine. The national competent body accredits training sites. 4.7.3 Non-physicians and physicians in other countries For other students, the theoretical (academic) requirements are also covered by academic courses in Pharmaceutical Medicine providing a minimum of 30 ECTS (Base Diploma Course). Students might, in addition, take specialist elective module(s) and/or submit a dissertation/thesis, leading to a Masters of Medicines Development / Pharmaceutical Medicine. The possibility of a certificate based on theoretical education plus practical training e.g., in project work in clinical development, drug safety, medical-scientific information and regulatory submissions should be available. This could be done by the national association for Pharmaceutical Medicine (see Swiss example below). Otherwise, those who successfully complete the 3rd tier Master/Specialist level programme comprising a dissertation/thesis and/or specialist elective modules and/or workplace–based training with competency-based assessments leading to a Masters in Pharmaceutical Medicine/Medicines Development (MMD) /Specialist in Pharmaceutical Medicine may be considered specialists. 4.7.4 Examples on the national level UK The Faculty of Pharmaceutical Medicine of the Royal Colleges of Physicians of the UK (FPM) is the professional standards body for pharmaceutical physicians in the UK. A minimum of four years in a position that gives broad experience of patient care and prescribing or equivalent are required after graduation as a physician before issue of a national training number (NTN) and entry into the Pharmaceutical Medicine Specialty Training (PMST) programme. Once in the programme, a further four years supervised learning and review are required for progression. The UK Diploma in Pharmaceutical Medicine, which allows successful students to apply for Membership of the Faculty and demonstrates acquisition of the knowledge element of Pharmaceutical Medicine Specialty Training in (PMST) uses the PharmaTrain Syllabus, 2010, and the PharmaTrain modular training programme provides an appropriate route to achieving the required knowledge. Details of the regulations and procedures can be obtained from the FPM office or website. Switzerland To apply for the specialist title in Switzerland, a trainee has to show evidence of theoretical (an academic course in Pharmaceutical Medicine comprising 30 ECTS) and practical training. The practical training has to include two years patientrelated training and three years discipline–specific training in Pharmaceutical Medicine at a postgraduate training centre accredited by the Swiss Medical Association. Evidence of responsible project work in at least 2 core topics of the syllabus such as the fields of drug safety, medical scientific information and registration over these three years must be provided. The acknowledgement is based on 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 65/79 examination covering the content of the Base Diploma Course in Pharmaceutical Medicine. For non-physicians, the SwAPP (Swiss Association of Pharmaceutical Professionals, http://www.swapp.ch/about-us/) offers a diploma in Pharmaceutical Medicine based on a 30 ECTS academic course in pharmaceutical medicine and 5 years of practical experience in the pharmaceutical industry. Belgium In Belgium, certificates of Physician Specialists in Pharmaceutical Medicine are awarded by the Belgian College of Pharmaceutical Medicine (BCPM). The College is recognised by the two Belgian Royal Academies of Medicine so all specialists whose names appear on the Register are recognised as Physician Specialists in Pharmaceutical Medicine. To be considered for membership, candidates are required: To hold a recognised medical qualification To have graduated in pharmaceutical medicine To have practiced for at least four years full time (or equivalent part time) in pharmaceutical medicine (including the time spent to obtain the graduation in pharmaceutical medicine). Candidates who have not yet graduated in pharmaceutical medicine or had a practice of at least four years full time or the equivalent can apply for a Candidate Fellowship of the College. In addition to awarding fellowship titles, the College maintains the Register of Physician Specialists in Pharmaceutical Medicine, promotes Continued Medical Education (CME) and Continued Professional Development (CPD), and verifies the CME and CPD activities of its members to ensure their continued competence. Fellows of the BCPM must participate in the continuous professional development (CPD) / medical education program (CME). 4.8 Continuing Professional Development (see also Fig. 3) . Continuing Professional Development, CPD is a continuing learning process that helps professionals keep up to date with scientific advances and develop new skills, enabling them to maintain and improve their professional practice to the highest possible standard. PharmaTrain recommendations for CPD are based on the CEPM Guidance Notes for the establishment of Structured National CME/CPD Programmes for pharmaceutical physicians, Council for Education in Pharmaceutical Medicine, 16 February 2006. There have been some attempts at European harmonisation by private associations e.g. European CME/CPD Academy (http://www.cme-cpd.eu/specific/home.aspx). CME/CPD programmes are based on the following principles, which apply to all specialists, physicians and non-physicians. Certification as a specialist should be limited in time; To renew certification in a specialty, specialists should provide proof that they have participated in and completed CPD activities of appropriate quantity and 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 Discuss 66/79 quality to justify re-certification; this must be auditable; A national committee of CPD should set the standards and have a team of reviewers in charge of verifying at appropriate intervals the quantity and quality of CPD programmes followed by the specialists; Initiation of a CPD programme should start promptly after completion of training and being awarded the title of specialist in this specialty; CPD should cover a spectrum of topics encompassing general professional development, pharmaceutical medicine / drug development, and personal development; Similarly, CPD should cover a spectrum of activities such as attendance at professional meetings, congresses, seminars, conferences, round-table discussions, workshops, in-house training courses or educational activities, structured selflearning programmes, presentation(s) / posters / abstracts / publications, teaching, private study, and sitting on Committees of Experts and/or Advisory Boards. Where possible, national guidance on the amount and nature of CPD should be followed; if this is not available, the CEPM Guidance Notes should be referred to. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 67/79 This section 5 needs additional conceptualisation 5.1 European Quality Assurance Framework and text adThe quality criteria recommended in this document align with pan-European initia- aptations tives to harmonise course quality criteria, both in higher education (the European Standards and Guidelines for Quality Assurance in the European Higher Education Area) and in vocational education and training (European Quality Assurance Reference Framework to promote and monitor continuous improvement of national systems of vocational education and training). We have also mapped the IMI Education and Training quality criteria to those used by professional bodies of relevance to medicines research and development. 5. Programmes Quality Management Systems Our ultimate goal is to move towards a more unified system for recognising individuals with the necessary knowledge, skills and competences to excel in medicines research and development, and thereby to enhance European competitiveness in this area, in line with IMI’s goals. These goals align strongly with the European Commission’s Strategic Framework for European Cooperation in Education and Training (ET2020). 5.2 Quality Management System PharmaTrain implemented a quality management system by a team of industry and academia partners that will establish and control new quality standards. These are applied to all programmes in PharmaTrain at all levels: participating students, faculty members, courses, training sites, university sites and overall conduct of training programmes with annual assessments and reports. This is summarised in the PharmaTrain Continuous Performance Improvement Cycle in Fig. 5. The quality process expands into the appropriate certification and re-certification of pharmaceutical medicine professionals, setting standards and proposing appropriate processes. Items for quality improvement will be fed back to individual training programme providers for implementation, controlled through the quality management cycle. Throughout the PharmaTrain programme, there is a built-in three-level dynamic quality improvement process which targets training content, examinations, university sites and Centres of Excellence as well as Bologna-based unified accreditations. The three levels, Quality Assurance, Quality Management, and Quality Control, are shown in the quality management pyramid, Fig 7. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 68/79 Fig. 7: Roles, outputs and ownership of the 3 PharmaTrain Quality Management Pyramid elements 5.2.1 Quality assurance The top of the pyramid puts standards, processes and policies in place designed to provide low failure rates at or before the quality control output gate. 5.2.2 The quality management and process translational part; the three step training-centre accreditation process Accreditation of training centres will be performed in a structured way according to pre-set criteria. The Training Centre’s accreditation process comprises three steps. The first level is a Coaching Process, which helps the participating centre to set up the system in conformity with the PharmaTrain Manual Curriculum Standards and Best Practices. This first helping hand does not have any elements of evaluation, rating or auditing. The second level, the PharmaTrain Centre Recognition (audit 1), contains formal checks of compliance with the PharmaTrain Syllabus, modularity, Learning Outcomes as well as assessments. Satisfactory centres are awarded the PharmaTrain centre recognition and, most importantly, are eligible for additional in-kind contribution via student’s sponsorship. A third quality level is the PharmaTrain Centre of Excellence (audit 2), defined as in Section 1.5. These coaching and auditing steps can be requested and timed ad lib by an individual centre once they feel that they are ready/eligible for a given step, initiating the centre-driven, user-friendly process. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 69/79 Operations of the quality management teams With the bottom-up centre feedback report and the top-down quality assurance, together with an office-based analysis and evaluation, site visits to targeted centres might be triggered to discuss shortcomings and ways to improve. Student feedback is obtained via individual Student Feedback Forms (see example on section 5.3.8) summarised in a Training Centre Feedback Report established by the Centre. An important quality control element is the examination of the system of the individual participants as well as the examination of the performance of a centre which leads to the accreditation of the individual performance i.e. certification, diploma, master title and/or a specialist in pharmaceutical medicine/drug development sciences. Feedback of information/results accumulating at the quality assurance office with a thorough analysis of the Centre Feedback Report and an overall examination report against the background of the centre accreditation by the Quality Assurance Office is held to provide feedback to the individual Centre relative to the meta-analysis of all feedback reports. This feedback goes to the different Centres as well as to the translational quality process management teams (2nd level). There is a Centre Quality Officer who owns and is responsible for the local quality process including the Student’s Feedback Form, the Centre Feedback Report and Quality Control Guidelines (SOP). For these three documents, a PharmaTrain template is appended in this Manual, which can be adapted locally to fulfil local rules. A Coaching / Auditing Team has been defined for each involved centre, which will accompany the centre through the three-step implementation process. Teams are composed of a member of the PharmaTrain Executive Board, a member of the PharmaTrain Quality Assurance team and a representative of a national member association of IFAPP (nMA Quality Specialist). These teams are composed of individuals with longstanding experience in developing PharmaTrain, a quality management specialist and a member of the national organisation, which in later years will be part of the sustainability process; in this case it is a European IFAPP member which is part of PharmaTrain and will be part of the successor organisation, namely the EFCPM. Members of these teams (trios) will be replaced as necessary. 5.2.3 Course quality control and university centre assessment Quality control tests the output to ensure appropriate standards are met at each PharmaTrain Centre and assesses basically three elements. These elements translate the process systems standards into the executing quality control system. Operations of the quality management teams With the bottom-up centre feedback report and the top-down quality assurance office comparative analysis the auditing teams are held to induce site visits to discuss short-comings and ways to improve assigned centres. These teams (trios) are regenerative i.e. they replace members leaving the team. Student feedback by virtue of individual Student Feedback Forms (see section 5.3.8), summarised in a Training Centre Feedback Report established by the Centre. An important quality control element is the examination of the system of the individual participants as well as the examination of the performance of a centre which then lead as a result to the accreditation of the individual perfor- 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 70/79 mance i.e. certification, diploma, master title and/or a specialist in pharmaceutical medicine/drug development sciences. Feedback of information/results accumulating at the quality assurance of with a thorough analysis of the Centre Feedback Report and an overall examination report against the background of the centre accreditation the Quality Assurance Office is held to provide a feedback to the individual Centre relative to the metaanalysis of all feedback reports. This feedback goes to the different Centres as well as to the translational quality process management teams (2nd level!). A Training Centre Accreditation will be performed in a structured way and according to pre-set criteria to become an accredited Centre of the IMI PharmaTrain organisation (and at the same time of the IFAPP organisation!). The Training Centre’s accreditation process is set up in three steps and the Centre requests and initiates the process (Centre driven, user friendly): The first level is defined as a Coaching Process which helps the participating Centre to set up the system in conformity with the PharmaTrain Manual Curriculum Standards and Best Practices. This first helping hand does not have any elements of evaluation or rating (or auditing). The second level is called PharmaTrain Centre Recognition (audit 1) and this contains audited checks of compliance with the PharmaTrain Syllabus, modularity, Learning Outcomes as well as modular and integrated examination leading to a Diploma in Medicines Development (after 30-60 ECTS), DMD. After 60 ECTS and a defended Master Thesis to a Master of Medicines Development, MMD. In this system individual modules are composed of a preparational e (introductory) product (1 ECTS) four days F2F interactive learning with including presentations, break-out case studies, state of the art lectures etc. and this is followed by an assessment at the end of each F2F part as well as an assignment which is an indebts study resulting in an essay, mini-thesis, blended learning reading or possibly additional e-learning (see assignments section 4.4). Centres which comply with these criteria are awarded the PharmaTrain centre recognition and – most importantly – are now eligible for additional in-kind contribution via student’s sponsorship. A third quality level is defined as the PharmaTrain Centre of Excellence (audit 2) and this is defined by fully complying with the curriculum of an MMD as combined with one of the following training activities: an additional Master Programme e.g. EMPRA (all 60+ ECTS) Diploma for Clinical Trial Professionals, or a Diploma of Medical Device Regulation, DMDR (all 30 ECTS) a Clinical Investigator Certificate (CLIC) two Elective Modules which are part of the PharmaTrain CPD Platform and thereby adhere to the Course Quality criteria These coaching and two auditing steps can be requested and timed ad lib by an individual Centre once they feel that they are ready/eligible for a given step is a selfadministrated Centre-driven, user friendly ‘call’ mechanism. There is a Centre Quality Officer who owns and is responsible the local quality process including the Student’s Feedback Form, the Centre Feedback Report as Quality Control Guidelines (SOP). For these three documents, a PharmaTrain template is appended in this Manual, which can be adapted locally. To execute coaching and auditing, for each involved centre a Coaching / Auditing Team has already been defined, which accompanies a given Centre through the three-step implementation process. Teams are composed of a member of the PharmaTrain Executive Board, a member of the PharmaTrain Quality Assur4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 71/79 ance team as well as a member of the national Member Association, nMA, i.e. a representative of a national member of the IFAPP (nMA Quality Specialist). In essence, these teams are composed of individuals with longstanding experience in developing PharmaTrain, a quality management specialist and a member of the national organisation which in later years will be part of the sustainability process; in this case it is a European IFAPP member which is part of PharmaTrain and will be part of the successor organisation, namely the EFCPM. 5.2.4 Quality Control of the Integrated Examination All examinations and assessments will be assessed for compliance with the PharmaTrain standards as described in Section 4 of this manual. 5.3 Elements of quality control The content and format of each module is reviewed each time it is run primarily by the following mechanisms. 5.3.1 Student feedback Students attending each module are asked to complete a feedback-form anonymously on each day of attendance. This information is used as a basis for curriculum improvement and monitoring the quality of each module. The results of all student module assessment forms are collated and made available as feedback to presenters on the course. Presentations which score poorly are reviewed in detail to identify areas for improvement. All students are encouraged to comment on any aspect of the course via feedback forms or directly to programme staff. 5.3.2 Board of Studies The Programme Directors liaise with external lecturers, specialist module leaders and programme advisors to ensure currency and validity of modules. Any changes are reported to the Programme Boards of Studies. When major revisions to modules are required, these are first discussed informally between academic programme staff with relevant input from external advisers and then at the Boards of Studies for formal approval. 5.3.3 Independent observers from national associations Modules which are approved for specialist training are approved and validated regularly by independent observers from national associations to ensure it meets the curriculum requirements and to provide feedback on both module content and delivery. 5.3.4 Programme revalidation University regulations require regular programme review through a formal revalidation process carried out every five years. This process reviews all aspects of the programmes to ensure they meet and University standards, making recommendations for changes to improve programme delivery. At this time all modules will be from CPTF upgraded to the shared PharmaTrain standards. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 72/79 5.3.5 Criteria and principles for accreditation of Training Modules/Course programmes The set of quality criteria is based on the following principles: Trainees are supported to acquire the necessary knowledge and skills Course structures encourage exchange and multidisciplinarity Facilities, infrastructure, leadership and competencies adequate to deliver the approved curriculum Equality principles Teaching methods appropriate to the goals of the course Transparency regarding potential conflicts of interest To be documented criteria for individual modules, courses or course programmes that include the following: Defined and transparent admission criteria. A predefined set of teaching objectives, leading to defined learning outcomes. The facilities, infrastructure, leadership and competences available for the support of student learning should be adequate, appropriate and up to date for the training offered. Assessment of the students' achievement in accordance with the agreed learning outcomes of the training offered. A system for collecting, assessing and addressing feedback from learners, teachers, technical/administrative staff and programme/course/module managers. For details on implementation of QA incl. templates for Student Feedback Form, Centre Feedback Report and Training Centre Guidelines (SOP) see Appendix 7.5). 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 73/79 6. Structure of training programmes Discuss 6.1 Academic structure 6.1.1 Education Board Each programme has an Education Board comprised of the Programme Director, the Module Leaders, Head of administration, two external programme advisors and two student representatives. The Education Board meets regularly and operates in accordance with local University regulations. Its responsibilities include: Academic policy of the programme, programme entry requirements, methods of assessment, academic content General conduct of the programme including assessments Monitoring student progress and reviewing requests for temporary withdrawal or other actions or recommendations Reviewing applications for exemption from part(s) of the programme Reviewing dissertation proposals Reviewing external examiners' reports and recommendations for action Formulating and maintaining Programme Regulations Implementing any recommendations for programme revisions 6.1.2 External examiners Responsible for: Review and approval of marks allocated for all assignments/assessments in the programmes for which the Education Board is responsible Review of marks allocated for a candidate’s work in written assignments and the masters dissertation to ensure that they are fair and adequate Approving recommendations for student progress and awards by the Programme Director Providing confidential Annual Programme Reviews to the University on aspects of the teaching, structure and content of the programmes as they affect the assessment of students 6.1.3 Programme contacts Individual personal tutors are not allocated by the University for each student due to the modular nature of the programmes. The first point of contact is normally Programme Administration, who will evaluate any issues and pass them on to the appropriate party. Alternatively, students can contact the Programme Director directly. If no resolution is agreed, the issue should be dealt with by the Education Board or, ultimately, the authorities of the university responsible for the course. Students on the training programmes can also raise any issues of concern through student representatives on the Education Board. Student representatives are elected by the body of registered students for a period of up to 3 years. Each representative may be re-elected providing they have not completed their programme before the specified term of office expires. 6.2 Duration of Programmes Unless specified by the course provider, the number of modules taken in each year is up to the individual. It is strongly recommended that modules are not taken any 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 74/79 more frequently than one every 3-4 months. The minimum time allowed for completion of all programmes is 24 months. The maximum time allowed for completion of all programmes is 3 years (36 months) for the 1st tier; 4 years (48 months) for the 2nd tier and 6 years (72 months) for the 3rd tier. A Student Progress and Assessment Board, on the recommendation of the Programme Director / Dean of Faculty, may extend the maximum period of registration for a given award for an individual student by not more than one year at one time. Applications for extensions to the registration period together with reasons for any delay in completing the programme should be submitted in writing to the Programme Director and will be reviewed by an academic panel. 6.3 Examination process Discuss Assessments may be conducted at different stages in the PharmaTrain programme, after participating in a course module or as an integrated examination covering the whole syllabus (see Section 4.5). Any examination will comply with specified principles as follows. Candidates Defined eligibility criteria Examiners must have evidence of postgraduate training and experience in an appropriate specialty with a relevant professional qualification have evidence that professional knowledge and skills are being kept up-to-date e.g., participation in a CPD scheme as an examiner, undergo introductory training/guidance, participate in an ongoing training programme and undergo monitoring of the reliability of their marking/grading with re-training or de-selection effected as appropriate Examiners must have 2 years of experience working as a professional in drug development / pharmaceutical medicine with evidence of postgraduate training and/or experience, demonstrating expertise in all of the following: understanding and operating within the legislative framework of medicines regulation thorough knowledge of the principles and practical application of the pharmacological basis for medicinal interventions ability to develop and utilise concepts in therapeutics intervention understanding of statistical concepts, ability to generate and analyse clinical data thorough knowledge of processes in development of new medicines knowledge and application of safety systems in pharmaceutical medicine knowledge of and ability to operate effectively in the healthcare marketplace Discuss Ethics and regulations There must be clear regulations covering impersonation of a candidate use of mobile telephone or any other electronic device in examination room helping or receiving help from another candidate copying from/communicating with another candidate non-permitted items at desk permitted items with excess annotation consulting materials outside examination room while examination in progress attempting to influence an examiner/script marker/other official 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 75/79 writing notes on the examination script behaviour considered inappropriate in the examination room or which might bring the institution into disrepute Marking assessments There should be: examiner briefing with model answers and marking scheme all answers to the same question marked for all candidates independently by the same examiners (a system of overlapping pairs of examiners may be used if the number of scripts is excessive) with a defined method of independent adjudication a moderator should mark a proportion of scripts Examination standards and reliability There should be a formal assessment of the reliability of the examination, using a statistical approach if the number of candidates permits. Marker questions should be used for test equating year-on-year and between examination providers Exchange of examiners between different examinations is encouraged 6.4 The Cooperative European Drug Development Course (CEDDC) – a geographical extension concept The overall goal of the geographical extension programme is to support the establishment of PharmaTrain courses in regions not hitherto covered by training programmes. The establishment of a Cooperative European Drug Development Course (CEDDC) is the primary objective. Semmelweis University in Budapest, Hungary through its partnership in PharmaTrain, forms the initial starting point and hub of the expansion initiative. The Hungarian Faculty ran a successful pilot programme with the emerging PharmaTrain syllabus. With some minor alterations, to adopt the modular system and Learning Objectives, will become the basis for designing the joint CEDDC curriculum. The CEDDC differs from national courses by its cooperative university network structure. It will offer the harmonised PharmaTrain education programme to a group of students coming primarily from the participating countries. The training is provided by a joint educational staff selected from the best experts of the region. . It will guarantee better international acceptance of the degree than those provided by local courses. A number of universities are interested in cooperating to initiate a pharmaceutical medicine/medicines development course or merge their existing programmes into the planned CEDDC (figure below). 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 76/79 • • • • • • • • • • • • • • • • Bulgaria Croatia Czech Republic Estonia Greece Israel Hungary Lithuania Poland Romania Serbia Slovakia Slovenia Turkey Austria (VSCR) Ireland (Hibernia Coll.) Fig. 8: Universities interested in participating in CEDDC negotiations 6.4.1 Managing curriculum implementation Although PharmaTrain has developed a harmonised syllabus and curriculum, the implementation of the joint principles differs according to local university and national regulations. Implementation is more complex when dealing with a group of universities in a network structure, with a number of different university regulations and national legal and accreditation requirements for delivering the course and providing a joint degree. The administrative tasks will be handled according to the regulations of the coordinating university. Many of the education-related tasks are detailed in the other sections of the manual, in this part only some additional points will be considered. 6.4.2 Selection of course language For multinational courses and international cooperation an official language must be selected both for teaching and communication; and only students who speak this language can be enrolled. Guidelines of drug discovery and development are published in a number of languages to support the activities of pharmaceutical companies and regulators. Nonetheless, most scientific literature dealing with these subjects is written in English, which is consequently the primary language for communication in globalised pharmaceutical research and development. Therefore English as the official language is chosen. This will also help students to become better integrated into international pharmaceutical business and additionally fosters the international recognition of the course. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 77/79 6.4.3 Organisation Advisory Board The Executive Board of PharmaTrain acts as an Advisory Board for the organisation. Module leaders Module Leaders are appointed by the Education Board, preferring experts with both academic and industrial experience. Teaching experience will be considered is a an asset for planning and presenting the programme. Candidates with broad international experience are preferred. Lecturers Lectures are selected by the Module Leaders to prepare and deliver the modular programme. In appointing the lecturers it will be considered that pharmaceutical medicine/medicine development deals both with theoretical knowledge and its practical application. Therefore, the educational staff will be recruited both from the academic-scientific and industrial environments. Although internationally well-known experts are recommended for presenting specific issues, the aim is to involve as many local experts as possible. They will be able to relate the course content more efficiently to the possibilities and needs of the local industry. 6.4.4 Preparation of the module programme Discuss The Module Leaders prepare a detailed module timetable in agreement with the Education Board. Although the harmonised curriculum should be adhered to, modules might vary due to the different cultural environment, experience and interest of the lecturers. This is acceptable provided the syllabus is adequately covered and the teachers are able to achieve the main learning outcomes. In the detailed programme, the titles of the lectures, assignments and cases to be discussed must be fixed. 6.4.5 Accreditation The complex quality assurance programme of this university network is being developed jointly with PharmaTrain cooperation. Since there is no internationally harmonised accreditation process for masters degrees, CEDDC participants have to obtain separate national accreditations. In addition, the course will be submitted for international professional accreditation by IFAPP. Since achieving formal national and international accreditation processes by the new affiliated University training providers of CEDDC is a lengthy process, an interim solution is planned with immediate implementation. Using the format of mutual recognition, , the PharmaTrain organisation will mentor a similar process for all CEDDC network universities which at present have no accreditation process in place. Another example is the mutual recognition process for the examination for physicians, the specialist in Pharmaceutical medicine among the FPM, Royal College of Physicians UK, the University of Basel and the University of Brussels. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 78/79 7. Appendices and Details of Additional Training Programmes (see also 3.5and www.pharmatrain.eu) 7.1 Training Programmes Regulations (template for local use!) 7.2 PharmaTrain Syllabus 2010 7.3 PharmaTrain e-Campus, including e-library and e-products 7.4 PharmaTrain CPD Platform 7.5 PharmaTrain Quality Assurance Guide 7.6 Cooperative European Drug Development Course, CEDDC 7.7 Master in Medicines Regulations, MMR The following programmes will be added later: 7.8 Diploma Course in Medical Device Regulation, DMDR 7.9 Diploma Course for Clinical Trial Professionals, DCTP 7.10 Clinical Investigator Certificate Course , CLIC 7.11 (7.xx NN ? The PharmaTrain Manual Slide Show) This is a nutshell summary (slide show based on Figures) of the PharmaTrain Manual core content for the fast reader and teacher/presenter; it is more Manual focused than the PharmaTrain Slide Deck. 4.4.2011, Version 0.7 for discussion at GA, Berlin 12./13.4.2011 79/79
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