University joins Industry: Clinical Trials & Drug Safety

University joins

Industry:

Clinical Trials & Drug Safety

Aula Magna-Facultad de Farmacia 11 Marzo 2015

•  Background, key points and basic knowledge

•  Department tasks and responsibilities •  Importance of the department within the

Pharmaceutical Industry •  Career development •  Personal skills

Contents

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)

•  Real Decreto 223/2004

• Directive 2001/20/EC •  Regulation EU No 536/2014

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

CONFIDENCIAL © ESTEVE, 2015 23.05.2006 Dr. Enrique Jiménez 9

Phase I : healthy subjects (ocasionally patients) to evaluate pharmacokinetic, pharmacodynamics giving preliminary information about safety and efficacy of the drug. Non therapeutic benefit.


Fases de los E.C.


Fases de los E.C.

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.


Fases de los E.C.

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.


Fases de los E.C.

Phase IV : CT with a marketed drug to evaluate the effectivenes and long term use of a drug (both efficacy and safety).

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.



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

Commercial Team

Manufacturing Team

Regulatory Team

Clinical Team

Emerging BU Task Force

Internal Interfaces

Data Management

Medical Monitor

Statistics

Clinical QA

Drug Safety

Trial supply group

Medical Writing

Regulatory Affairs

Finance Legal

Vendors Management

Clinical Pharmacology

TRIAL MANAGEMENT

TEAM

Clinical Trial Director

Clinical trial Manager

Clinical trial monitor

CLINICAL TRIAL TEAM

External Interfaces

Manufacturing providers

Health Authorities

Steering Committees

Partner Due

dilligence

CROs

Ethics Committees

Media Press

World Couriers

Laboratory Data

Patients

Investigators

TRIAL MANAGEMENT

TEAM

Clinical Trial Director

Clinical trial Manager

Clinical trial monitor

CLINICAL TRIAL TEAM

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.

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)

Legal framework

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

Drug safety & Pharmacovigilance Department

Toxicology Services

Medical Literature

International Congresses

Cooperative Groups

Licensors Safety Data Exchange Agreements

Health Professionals

Consumers/ Patients

EMA FDA Other ROW

Hospitals Autonomous Community

AEMPS Local Health Authorities

Internal Interfaces

Databases

Sales Network

Regulatory Affairs

Clinical Research

Legal Department

Medical Affairs

Licensors

Marketing Technical Director

CEO

Quality Control

Quality Assurance

Drug safety & Pharmacovigilance Department

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

Documents

University joins Industry: Clinical Trials & Drug Safety