CLINICAL TRIALS

AstraZenecas commitment to ensuring the highest standards of ethical practice when designing and conducting clinical trials
Sverker Ljunghall VP Science Relations

Clinical trials in AstraZeneca

> Critical to the development of new medicines. > A candidate medicine enters clinical development only after potential efficacy and safety confirmed in pre-clinical trials. > All clinical trial proposals are subject to stringent internal review and approval by an external independent ethics committee or institutional review board, and the appropriate regulatory agency. > All trials must comply with all relevant local laws and regulations and with our own standards which are in line with international codes such ICH and the Declaration of Helsinki. > One global clinical organisation; one set of policies and SOPs*.
* Standard Operating Procedures

Clinical trials

How it all fits together

Declaration of Helsinki ICH-GCP AstraZeneca SOP Quality Control Protocol/Planning Conduct Reporting Quality Assurance

Inspections
Clinical trials

Developing the strategy

Target Product Profile Target Product Claims Clinical Development Plan Clinical Study Protocols Publications Study Reports Marketing claims
Defines clinical strategy and activities
Formulations Doses Comparators Description of all proposed studies
(Study Design Concepts)

Overall project management plan Ethical considerations Risks & contingencies

Probability of success

Clinical trials

Worldwide
> Most of our studies are conducted across a broad geographic span:
> To ensure the diversity of targetted patient populations is fully represented > To help identify those patients for whom the treatment will be most beneficial

TOTAL NUMBER OF PATIENTS 60,000 West Europe East Europe US Asia Latin America Canada South Africa Japan Australia 20,000 15,000 10,000 3,500 3,000 2,500 2,000 1,000 1,000

> Our standards apply across all geographies and include:

> > > > Quality of the study / patient safety Informed consent procedures Right to withdraw Privacy of healthcare information

> Our Clinical Quality Assurance teams conduct a wide range of audits of our clinical research activities whether being done inhouse or by a CRO.

Clinical trials

> Approximately 25% of our clinical studies are conducted by third parties who are contractually required to operate to our standards.

Committed to transparency
> Committed to providing relevant information to support best treatment decisions. > Publish our hypothesis-testing clinical trials on clinicaltrials.gov:
> Make public all 20 data elements requested by ICMJE > 370 trials have been registered as of 31 August 2007

> Comprehensive AstraZeneca clinical trials website:

> Retrospective data since AZ created in April 1999 > Contains results from 361 AZ trials as of 31 August 2007 > Whether favourable or unfavourable to AstraZeneca

> Other proactive trial registry:

> Serious and life-threatening diseases via clinicaltrials.gov > Crestor safety information via rosuvastatininformation.com > Participation in the PhRMA Clinical Trials Database
Clinical trials

Quality assurance strategy

Key Objectives
> Fulfil regulatory requirements for independent QA > Add value to the Clinical Function/Business

Principles
> Single standard of GCP world-wide > Quality assurance programmes directed towards projects systems facilities > Audit group part of clinical team but independent Input to procedures and training - closing the loop Audits selected based on a calculated risk analysis using agreed risk assessment criteria

Clinical trials

Safety surveillance
1 Individual Case Review (ICR)
Electronic Daily Medical Review Global introspection GDSP review (loop) Weekly SUSAR Listing review

2 Routine Signal Detection

Routine regular review of safety data Quantitative & qualitative detection methods Analysis of trend and case series

cess ICR Pro

Ad An Hoc aly is s

R ou tine

SD

Surveillance Process

SERM Process

3 Ad Hoc Analyses
Analyses in Clintrace DB searches (case series, data-mining) Analysis of external safety databases (WebVDME on FDA-AERS)
* Safety and Evaluation Review Meeting

4 The SERM* Process

Pre-SERM and SERM

Clinical trials

Summary
AstraZeneca is committed to: > High quality clinical research of new medicines that meet patient needs. > Consistently high standards of clinical trial conduct worldwide. > Transparency of trial data to inform patients and doctors. > Ongoing safety surveillance.
Clinical trials