University joins Industry: Clinical Trials & Drug Safety Aula Magna-Facultad de Farmacia 11 Marzo 2015
Contents Background, key points and basic knowledge Department tasks and responsibilities Importance of the department within the Pharmaceutical Industry Career development Personal skills
Clinical Trials Human research CLINICAL TRIALS
Ethics and Clinical Trials Nuremberg Code (1947) Declaration of Helsinki (1964) Belmont report (1978) Core principles: Respect for persons Beneficence Justice Areas of application Informed consent Assessments of risks and benefits Selection of subjects
Regulation and Clinical Trials Good Clinical Practise (GCP) International Conference Harmonisation (ICH) Directive 2001/20/EC Regulation EU No 536/2014 Real Decreto 223/2004
Definition of Clinical Trials Clinical trials are studies that are intended to discover or verify the effects of one or more investigational medicines. The regulation of clinical trials aims to ensure that the rights, safety and well-being of trial subjects are protected and the results of clinical trials are credible. Arguments in favour of performing clinical trials are those pointing out that the alternative: uncertainty medical practice is always worst Evidence Based Medicine
Main objective of Clinical Trials DESCRIPTIVE : broaden knowledge ANALITYCAL : evaluate intervention (hypothesis testing)
CONFIDENCIAL ESTEVE, 2015 8
Phase I : healthy subjects (ocasionally patients) to evaluate pharmacokinetic, pharmacodynamics giving preliminary information about safety and efficacy of the drug. Non therapeutic benefit. CONFIDENCIAL ESTEVE, 2015 Dr. Enrique Jiménez 9
Fases de los E.C. CONFIDENCIAL ESTEVE, 2015 Dr. Enrique Jiménez 10
Phase II : patients to get the most effective dose of the drug for a specific disease. Preliminary information on efficacy and safety and first hints on therapeutic effect. Fases de los E.C. CONFIDENCIAL ESTEVE, 2015 Dr. Enrique Jiménez 11
Fases de los E.C. CONFIDENCIAL ESTEVE, 2015 Dr. Enrique Jiménez 12
Phase III : CT designed to know drug safety and efficacy compared to a drug of known efficacy in a sample of patients representative of the general population. Fases de los E.C. CONFIDENCIAL ESTEVE, 2015 Dr. Enrique Jiménez 13
Fases de los E.C. CONFIDENCIAL ESTEVE, 2015 Dr. Enrique Jiménez 14
Phase IV : CT with a marketed drug to evaluate the effectivenes and long term use of a drug (both efficacy and safety). Fases de los E.C. CONFIDENCIAL ESTEVE, 2015 Dr. Enrique Jiménez 15
Stakeholders in Clinical Trials Sponsor Monitor (Clinical Research Associate) Investigator Health Authorities: AEMPS, EMA, FDA. Ethics Committees PATIENTS/SUBJECTS!!!
Some figures in Clinical Trials In the EEA, approximately 4,000 clinical trials are authorised each year. This equals approximately 8,000 clinical-trial applications, with each trial involving two Member States on average. Approximately 61% of clinical trials are sponsored by the pharmaceutical industry and 39% by non-commercial sponsors, mainly academia.
Some figures in Clinical Trials
Some figures in Clinical Trials
Spain competitivity in Clinical Research
Department tasks and responsibilities SPONSOR PROTOCOL/INFORMED CONSENT/CASE REPORT FORM/INVESTIGATOR BROCHURE (IB) INVESTIGATOR/MONITOR selection ETHICS COMMITTEE AND HEALTH AUTHORITIES approval PROVIDE DRUG STUDY medication SUBMIT ANY SERIOUS ADVERSE EVENT occurred during study PROVIDE INSURANCE to patients participants COLLECTION and ANALYSIS of patient data ELABORATTE FINAL REPORT PUBLISH RESULTS following transparency policy
Clinical Trials within Pharmaceutical Industry Preclinical Phase I Phase II Phase III Submission LCM Commercialization Global Product Team Manufacturing Team Regulatory Team Clinical Team Commercial Team Emerging BU Task Force
Internal Interfaces CLINICAL TRIAL TEAM Data Management Drug Safety Medical Monitor Clinical QA Clinical Pharmacology Regulatory Affairs TRIAL MANAGEMENT TEAM Clinical Trial Director Clinical trial Manager Clinical trial monitor Vendors Management Trial supply group Medical Writing Statistics Finance Legal
External Interfaces CLINICAL TRIAL TEAM Manufacturing providers CROs Health Authorities Partner Due dilligence World Couriers TRIAL MANAGEMENT TEAM Clinical Trial Director Clinical trial Manager Clinical trial monitor Investigators Ethics Commi ttees Media Press Steering Committees Laboratory Data Patients
Career development EARLY CLINICAL DEVELOPMENT: Design of phase I/II studies for small and biotech companies (medical writing, monitoring, analysis and data entry, statistics and publication) LATEST CLINICAL DEVELOPMENT Operational aspects of clinical trials: monitor/cra Regulatory: regulatory and GCP compliance Medical writing and publication Data management and statistics
Personal Skills Clinical Research Associate Core Competencies: Leadership skills Team work Negotiation skills Conflict management Familiar with basic computer and database applications Good leadership, analytical, problem solving and time management skills Comunication skills
Drug Safety/Pharmacovigilance Public health activity with the main objective of identification, quantification, evaluation and decission taking in front of the presence of durg risks once are marketed. Legal framework Spain: - Real Decreto 1344/2007 - Reglamento 1235/2010 - Directiva 2010/84 - Buenas Prácticas de Farmacovigilancia ( 21 de Diciembre 2011) EU: - Regulation 1235/2010 - Commission Implementing regulation (EU) No 520/2012 - Directive 2010(84 - Good Pharmacovigilance Practices (GVP)
Background history 1937 Renal failure by dietilenglicol/sulfamide elixir 1938 FDA demands toxicological and preclinical controls for drug investigation 1950 Cloranfenicol, causal agent of aplastic anemia 1960 FDA initiates the collection of Adeverse Drug Reactions in the Johns Hopkins H & Boston Collaborative Drug Surveillance Program: intrahospitalary monitorization
Background history 1960-62 The Thalidomide DISASTER Cases of focomelia (congenital malformation). The first case was published in Lancet (WG McBridel) suggesting a relationship with the thalidomide ingestion. Thalidomide was withdrawn in 1962 after more than 4.000 cases were registered worldwide. 1962 WHO initiates an international program to collect and monitor adverse drug reactions.
Drug safety tasks and responsibilities Pharmacovigilance System Master File (PSMF) of the company Individual Case Safety Reports management Data entry in database Medical evaluation & reportability assessment to regulators and/or licensors; Interaction to obtain follow up. Weekly Scientific/Medical Literature Search Periodic Safety Update Reports (PSUR)s creation Preparation and scientific assessment of data in Periodic Safety Update Reports (PSUR), Annual Safety Report (ASR), etc. Responses to R-PSURs assessment reports Labeling Review of safety data of all SmPCs/PILs to be created/harmonised according to guideline on SmPCs (October 2005) and legibility test. Preparation and scientific assessment of data in Periodic Safety Update Reports (PSUR), Annual Safety Report (ASR), etc. Risk Management Plan (RMP) elaboration Benefit/risk evaluation SOP creation and update Safety Data Exchange Agreements (SDEA) Maintenance and update Training of sales network and Company employees Audits
External Interfaces Toxicology Services Medical Literature Hospitals Autonomous Community AEMPS Local Health Authorities Drug safety & Pharmacovigilance Department Licensors Safety Data Exchange Agreements EMA FDA Other ROW International Congresses Cooperative Groups Consumers/ Patients Health Professionals
Internal Interfaces Quality Assurance Databases CEO Legal Department Sales Network Regulatory Affairs Clinical Research Drug safety & Pharmacovigilance Department Licensors Medical Affairs Quality Control Marketing Technical Director
Career development Every single company needs to have a Drug Safety Responsible: EU QPPV (Qualified Person for Pharmacovigilance) and back-up Local Safety Officer (multinational company) Regulatory and Good Pharmacovigilance Practises (GVP) compliance: Drug Safety Officer (DSO): pharmacist, biologist, chemistry Medical Drug Safety Officer (MDSO): benefit/risk assessment of the drugs Compilating of pharmacovigilance documents: PSURs, RMPs, PASS DSO MDSO EU QPPV
Personal Skills Drug Safety Officer Core Competencies: Comprehensive knowledge of international drug safety and pharmacovigilance principles and regulations Extensive knowledge of drug safety and drug development process and procedures In-depth knowledge of coding principles, submission criteria, regulatory timeline requirements, technical requirements and guidelines Possess sound communication skills, both in verbal and written Familiar with basic computer and database applications Good leadership, analytical, problem solving and time management skills
Highly appreciated Values