Highlights from ExL Pharma’s 5th Clinical Data Disclosure Summit

January 12-13, 2010

Washington, D.C.

Data Disclosure and TransparencyEuropean Requirements

Growing Public Interest in Transparency

Mandatory Israel Italy France Czech Republic Argentina South Africa China Taiwan Brazil India Netherlands Spain EU (Not yet implemented)

Proposed Croatia Switzerland Canada

Recommended Australia/NZ Germany Japan UK ISRCTN China Latin America Sri Lanka

Source: Adopted from June 2008 DIA meeting Pamela Rose presentation. Subject to changing legislation

For Regulators Eyes OnlyEudraCT: The European Clinical Trial Database

Created based on article 11 of Directive 2001/20 (“Clinical Trial Directive”)

Allows sharing of information by European health authorities (European Medicines Agency, Commission) on clinical trials

Provides for a unique trial identification number Access to regulators and EU Commission only Currently no direct data access by sponsors or

investigators EudraCT is currently a document management

system

How to Enter Information into EudraCT

Sponsor / investigator completes Trial Application Form and submits to participating NCA´s

Sponsor / Investigator requests EudraCT Nr.,

EudraCT

NCA´s, Commission*

*NCA: National Regulatory Authority** Drug Safety, Investigational Products, Approved Products

NCA´s*

Other Dbs**

EudraCT is ChangingNew features coming up

From version 8 EudraCT will be changed from a document storage to a true relational database

XML schema publicly accessible Will provide for multi-language fields Version 8 to go public Q2 2010

Public access to protocol information for ongoing and completed clinical trials (adult and paediatric)

Will be linked to EudraPharm for marketed products Version 9 release not yet defined (end 2010?)

Public access to clinical trial results (adult and pediatric, approved and investigational)

Making EudraCT Fit For for the PublicA Challenging Undertaking

Public Access Which information: Data fields, protection of confidential data,

languages When to release: Before / after trial start, Ethics Committee

vote How to access: Search engine, link to other registers and

portals Results

Which information and how: format, data fields Data Quality: Consistency with other result information (eg

FDAAA) Third Country Trials

EudraCT number for non-EU trials Link to EudraVigilance and Investigational Products database

Some Specific ChallengesTrial Registration

Registration in EudraCT is part of the trial application process which is a national process

Protocols for the same trial may differ between different countries (“local amendments”)

Some EU countries require all or part of the application in local language

For Trial Portals (e.g. IFPMA, WHO) and quality assurance: Which protocol version is the reference version?

Some Specific ChallengesRelease of Information to the Public

Release to information from EudraCT to the public will be triggered automatically once the trial is approved Trial may not start for significant time or not at all Reasons for Ethic Committee rejection will be made public Protocol may undergo numerous amendments before final

start Quality and consistency of information between

different EU countries and with non-EU registers for global trials For trial designs For result information

Creation of a search engine capable of handling multiple languages

Some Specific ChallengesThird Country Trials

Trials exclusively running outside of the EU do not normally require a EU trial application and no EudraCT number but have to be included in EudraCT when part of a paediatric investigation plan (PIP) Specific process for EudraCT number application Cannot be handled by National authorities Direct access necessary to EudraCT by international

sponsors / investigators Adverse drug experience from non-EU trials to be

entered into European Pharmacovigilance database Investigational Product database to capture non-EU

approved comparators

Developing Data Standards

The European Medicines Agency joined the CDSC and HL7 consortia

Objective is to harmonize electronic data definition standards for health related data on an internationally Study protocols Electronic health data Public health databases Etc

Common data definition standards should ease data exchange and maintain data quality

Transparency in Clinical TrialsWhat is Different in Europe Compared to US?

EU Pediatric Regulation

EU Regulation 726/2004

FDAAA

Scope All interventional studies Phases 2-4 Phase 2-4

Process Submission of information as part of the trial application process

Data entered by authorities

As paediatrics Submission of information independent of trial applicationData entered by applicant

Release Data automatically released after trial approval or rejection

As paediatrics Data release triggered by applicant

Language All official EU languages As paediatrics English

Versions One per participating country As paediatrics Single version

Scope All information currently in EudraCT wil be made publicly accessible

Only information defined by chapter 8

The Clinical Trials Registry- India (CTRI)

New Mandatory Registration: Overcoming the Hurdles and Best Practices for Compliant Registration with India’s Clinical Trials Registry

Increasing clinical trial flow to India is a result of several fundamental strengths

0 5 10

Cancer

Diabetes

HIV

Epilepsy

Hypertension

Schizophrenia

Asthma

Alzheimer's

Cardiac Deaths

• Large patient populations with

diseases of both developed &

developing world

• Competent medical

professionals

• Site infrastructure

• Potential for cost & time

savings

• Likely high growth market in

future

India has a large patient pool in diabetes, cardiovascular disease

HIV and Oncology.

Source: National Commission on Macroeconomics and Health , Ministry of Health &

Family Welfare, Government of India, New Delhi, September 2005

Mio Patients

40

34

150

India - the highest # of protocols and sites in AsiaBut still relatively limited number…

India- 2009 Clinical Study Start Up times

Time ( weeks)

TOTAL* 18-22 weeks

* Review time includes Export License approval

• No import duty on clinical trial supplies2003

Exemption from registration requirements for CTS 2003 Amendments to Schedule Y 2005

Export of biological specimens 2005

Exemption from Service Tax on new drug testing 2007

Need for export license (blood products) waived 2009

Mandatory registration of interventional Clinical Trials 2009

Key Regulatory milestones

Clinical Trials Registry - India

Set up by ICMR’s NIMS To encourage all registration of clinical trials prior to patient

enrolment Full disclosure of all WHO mandated items To improve transparency and accountability Improve internal validity Conform to accepted ethical standards Lead to reporting of all relevant results of all CTs in India and

the region

Registration of all clinical trials prospectively

Voluntary disclosure of all items in the register

To improve transparency

To improve internal validity of trials

Conform to accepted ethical standards

CTRI Vision

Encourage all clinical trials to be prospectively registered before enrolment of first patient

To comply with ICMJE and WHO-ICTRP requirements

CTRI Mission

Who is responsible for registering a trial?

Principle Investigator (PI) or the Primary Sponsor

For Multi-Centric and Multi-Sponsor Trials, it is the lead PI or lead Sponsor should take responsibility for registration.

In case of Multi-Country Trials, the Indian PI should also get the trial registered in CTRI quoting any other Registration number as its Secondary ID.

Internet

NIMS Campus

1. The NIMS Pilot CT Registry Portal will be hosted on the Internet 2. Responsible Registrants can register the details of the clinical trials directly on the portal3. Interested parties/general public can directly search for information on the registry.

Responsible Registrants

Leased Line to Internet(to be provided by NIMS)

Public/Interested parties

Pilot Implementation Server(to be provided by NIMS)

Firewall(to be provided by NIMS)

Layout of the Registry

Still have any questions? For additional information on ExL Pharma’s Clinical Data Disclosure Summits, please visit www.exlpharma.com