Expert Patients and Researchers EURORDIS Summer School “ExPRESS Yourself!” A capacity building programme for patient representatives & researchers on information and access to orphan, paediatric, advanced therapies and health technology assessment. Nancy Hamilton

Overview of the programme Medical research & development.   Ethics in medical research & development Statistics in medical research Regulatory Procedures. European Medicines Agency. Pharmacovigilance and Benefit Risk. Market Access and Health Technology Assessment.

EVIDENCE-BASED MEDICINE Care of individual patients is based on evidence From medical research From medical expertise and experience Medical research “gold standard”: randomised, controlled trial (RCT) Methodological principles

Studies should be conducted ”double-blind” whenever possible SHORTCOMINGS? Randomisation does not guarantee that the study setting is free from bias, particularly if The participant, the investigator or both know what treatment the individual will receive (open-label study) Studies should be conducted ”double-blind” whenever possible Methodological principles

TO CONCLUDE Randomised, controlled, blinded studies provide best scientific evidence of benefit and risk Not always possible Alternative designs to be agreed with authorities in advance Methodological principles

Medical research involving human beings: an attempt at a definition ‘The primary purpose of medical research involving human subjects is to understand the causes, development and effects of diseases and improve preventive, diagnostic and therapeutic interventions (methods, procedures and treatments)…’ (Declaration of Helsinki, General Principles art. 6) Ethical Aspects of Medical Research Involving Human Beings

Which benefits for which risks? Safety? Efficacy? Quality? François Houÿez Eurordis Summer School 2017, Barcelona Which benefits for which risks?

A closer look: Autonomy Informed consent on the basis of full information The right to refuse to be included without repercussions on subject treatment The right to withdraw at any time (without giving an explanation) without repercussions on participant treatment Identity of the investigator and information on how to reach her/him Opportunity to ask questions and consult an independent physician The opportunity to consult family, acquaintances or one’s own General Practitioner Ethical Aspects of Medical Research Involving Human Beings

What is the European Medicines Agency (EMA) The EMA is the EU regulatory body responsible for the scientific evaluation and supervision of medicines developed by pharmaceutical companies for use in the European Union (Human and Veterinary)

What is the EMA doing? 27 February 2018 Facilitate development and access to medicines Evaluate marketing authorisation applications Protect human and animal health Provide information on medicines to healthcare professionals and patients Monitor the safety of medicines throughout their life cycle Presentation title (to edit, click Insert > Header & Footer)

Centralised Procedure Individual member state(s) 27 February 2018 The European System In Europe all medicines must have a marketing authorisation before they can be put on the market There are two ways of obtaining an authorisation: Centralised authorisation procedure National marketing authorisation procedures National procedures Decentralised Procedure Mutual Recognition Centralised Procedure EMA (All member states) Individual member state(s) 12 12

+ working parties and scientific advisory groups How is EMA organised? Management Board Executive Director EMA staff CHMP Committee for Human Medicines COMP Committee for Orphan Medicines HMPC Committee for Herbal Medicines PDCO Paediatric Committee CAT Committee for Advanced Therapies PRAC Pharmacovigilance Risk Assessment Committee + working parties and scientific advisory groups EU institutions ~4000 European experts National Agencies Healthcare professionals Patients Academia Learned societies

List of Outstanding Issues/ Oral explanation Evaluation overview - CHMP Joint Assessment Report Day 150 List of Outstanding Issues/ Oral explanation Day 180 Start Day 1 Assessment Report Day 80 List of Questions Day 120 Commission Decision Day 277 Opinion Day 210

How do we monitor the safety of medicines already on the market? 27 February 2018 How do we monitor the safety of medicines already on the market? Final decision from the EC Communication to the network Reports from patients and healthcare professionals CHMP Clinical studies CAPs + NAPs EMA/PRAC assessment Medical literature PRAC recommendation Regulatory bodies outside the EU NAPS only Final decision from CMDh Patient registries Various/potential data inputs received that might lead to safety concerns Presentation title (to edit, click Insert > Header & Footer)

Patient contribution Patient involvement in MoCA is essential to bring the patients’ voice to the table as legitimate experts on: The disease they are suffering from The disease’s impact on their daily lives The solutions offered by available medicines The unmet needs that new treatments should aim to fill The impact of the therapy in real-life Patient-relevant outcome measures How patients will be affected if the medicine is only accessible in some countries and not others

Three categories of patient participation: Patients representing the patient community Patients representing their organisation Patients as individual experts 1 2 3

1. Patients representing the patient community Members of : EMA Management Board (MB) Committee for Orphan medicines (COMP) Committee for paediatric medicines (PDCO) Committee for advanced therapies (CAT) Pharmacovigilance Risk Assessment Committee (PRAC)

Orphan drug legislation The main objective of the Orphan Regulation is to ensure that patients suffering from rare conditions have the same quality of treatment as any other patient in the EU Incentives: marketing exclusivity in the EU for 10 years after approval protocol assistance access to the Centralised Procedure for Marketing Authorisation