CLINICAL TRIALS

Sverker Ljunghall VP Science Relations

AstraZeneca’s commitment to ensuring the highest standards of ethical practice when designing and conducting clinical trials

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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

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Protocol/PlanningConduct

Reporting

Declaration of Helsinki

ICH-GCP

AstraZeneca SOP

Quality Control

Quality Assurance

Inspections

How it all fits together

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Developing the strategy

Target Product Profile

Target Product Claims

Clinical Development Plan

Clinical Study Protocols

Publications Study Reports

Marketing claims

Doses

Formulations

Ethical considerations

Description ofall proposed

studies(Study Design

Concepts)

Comparators

Overall project

management plan

Probability of success

Risks & contingencies

Defines clinical strategy and activities

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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

> Our standards apply across all geographies and include:> Quality of the study / patient safety> Informed consent procedures> Right to withdraw> Privacy of healthcare information

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

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

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

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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

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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

Quality assurance strategy

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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

3 Ad Hoc Analyses• Analyses in Clintrace• DB searches (case series, data-mining)• Analysis of external safety databases (WebVDME on FDA-AERS)

Safety surveillance

SERMProcess

ICR Process Routine SD

Ad HocAnalysis

4 The SERM* Process • Pre-SERM and SERM

Surveillance Process

1 Individual Case Review (ICR)• Electronic Daily Medical Review• Global introspection• GDSP review (‘loop’)• Weekly SUSAR Listing review

* Safety and Evaluation Review Meeting

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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.