Evolving Requirements For Posting Clinical Trial ...1).pdf · Evolving Requirements For Posting...

Oladayo Oyelola, PhD, SC (ASCP)Director, Clinical Trial Information DisclosureDaiichi Sankyo Pharma DevelopmentEdison, NJ 08837

Evolving Requirements For Posting Clinical

Trial Information on the EudraCT and the EU

Portal: Potential Impact on Demand

CBI Clinical Data Disclosure and Transparency

Philadelphia, PA. 18 & 19 January 2017

2

Disclaimer

The opinions expressed in this presentation are my own,and not that of Daiichi Sankyo Inc.

The presentation is for informational purposes only.There are no representations or warranties expressed or

implied, with respect to the usefulness or sufficiencyof the presentation for the purposes of

clinical trial information disclosure.

Evolving EudraCT and EU Portal Requirements

3

Presentation Outline

Background and Timelines of Clinical Trial Information Disclosure

Overview of US and EU Clinical Trial Disclosure Regulations and Requirements

EMA Regulation (EU) No. 536/2014

New EU Portal and Database

EudraCT vs CT.gov (US) Data Elements


4

Clinical Trial Disclosure Background & Timelines


1988/1997

US HOPE Act

/ FDAMA

2000

Clinical

Trials.gov

Launched

in US

2004/2005

ICMJE trial

registration

requirement for

publication

consideration.

EFPIA/IFPMA/

JPMA/PhRMA

Joint Position

Statement.

Other regional

and national

disclosure laws

2008 - 2010

EU Directives on

trial disclosures

Japan: MHLWNotification #415

Joint Position

revised

Joint Position of

Clinical Trial

Results in

Scientific

Literature

Other national

disclosure laws

2007

FDAAA

2011

EU-CTR.

2012

US disclosure of

results

notification

process during

informed consent

(in effect 2012)

US TEST Act

introduced to

expand

requirements (not

enacted)

2013

WMA’s Declaration of

Helsinki Revised

article 26

Alltrials Campaign

Launched

PhRMA / EFPIA’s

principles for

responsible data

sharing

EU Ombudsman’s

petition for access to

research data

2014

NIH proposals to

enhance transparency

of clinical trial results

TransCelerate

recommendation on

non promotional Lay

Summaries

EMA New Clinical

Trial Regulation –

Policy 0070

2015

IOM issues report on

sharing clinical trial

data

EMA Policy 0070 in

effect

WHO position

Statement on ethics

of publication and

data sharing

Good Pharma

Scorecard initiative

2016

EMA Policy 0070

Final Guidance

TransCelerate MRCT

white paper on return

of results to clinical

trial participants

(input from EMA /

FDA)

ICMJE data sharing

proposal for

publication

Open Knowledge:

Online database of

clinical trials

US White House

Cancer Moonshot

Initiative

Modified from TransCelerate BIOPHARMA INC

2017?

5

US Public Law 110-85: FDAAA/Final Rule (2007/2016)

Scope: Registration of clinical trials for Drugs & Medical devices

• Applicable to all Phase II to IV trials (Phase I trials are optional)

• ClinicalTrials.gov registry site launched in 1999

• Sponsors or PI submit information on registration system managed by the NIH

• Registration within 21 days of subject enrollment

• Standard statement on registration required in informed Consent forms

Study results data interface activated in 2007

• Results submission within 12 months of primary / study completion date

• Delayed submission may be approved, if

• certify seeking initial approval (new product license) or new use or new indication

Protocol registration & study results posting on ClinicalTrials.gov

• Registration certification, Form 3674 for US IND submissions

• FDA Compliance Program Guidance Manual - "Registration of Studies on ClinicalTrials.gov"

(Section D of Chapter 48)

Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting – Oct 2016


6

EU Trial Disclosure/Registration

EU Article 57(2) of Regulation (EC) No 726/2004

• Applies to adult trials within EU and third countries, if part of Paediatric Investigation Plan (PIP)

• Applicable to Phase II to IV trials + Phase I, if part of a PIP

Article 41(2) of Regulation (EC) No 1901/2006

• Applies to paediatrics trials within EU and third countries, if part of PIP

• Applicable to Phase I to IV trials

New EMA Regulation (EU) No. 536/2014

• Scope the same Art 41 and 52 - interventional clinical trials of medicinal products

• A new single EU portal and database planned to support:

• One application dossier for each clinical trial and/or modifications

• Coordinated approach to clinical trial authorization and supervision

• Transparency of clinical trial authorization, conduct and results

Study Protocol information registration site launched in March 2011

• EMA extracts and registers protocol information in EudraCT

• As submitted in the Clinical Trial Application (CTA) form before enrolment

• Direct disclosure on EU-CTR at the time of clinical trial authorisation


7

EU Clinical Trial Disclosure Regulations

• Study Results data and information site launched in October 2013

• Scope covers all studies conducted in the EU or 3rd country, if part of PIP

• Studies in the EudraCT database from 2004 to date

• Compliance effective date is 21 July 2014

• Paediatric study results disclosure within 6 months of study completion – LSLV

• Adults study results disclosure within 12 months of study completion – LSLV

• Results of studies ending after date will be required as indicated above

• Results of studies that ended before July 2014, to be completed within 24 months

• Study data entry by Sponsor, Marketing Authorisation Holder, or

PIP addressee

• Applicable to all medicinal products - licensed/marketed and those

in development

Disclosure on EU-Clinical Trial Register - Clinicaltrialsregister.eu


8

Overview of EMA Policy - 0070

• The new policy will exist alongside the current access to documents policy

• The policy applies prospectively, it will not apply to legacy data submitted prior to the implementation of the policy

• Policy scope: clinical data submitted on/after the implementation date in relation to EU centralized procedure (CP) and article 58 applications (WHO).Does not apply to clinical data submitted for non-CP products.

• Clinical data: clinical reports and individual patient data (IPD)

• Clinical reports: CTD Modules 2.5 Clinical overview; 2.7 – synopses, ISS,

ISE and 5 CSR plus appendices 16.1.1 (Protocols), 16.1.2 (CRF) & 16.1.9 (SAP)

• The policy is effective 1 January 2015 – implementation in 2 phases

o Phase 1: Publication of clinical reports – in effect

o Phase 2: Review of “various aspects” in relation to IPD

• Policy 0070 implementation updates:

o Users survey – June 2015

o Public consultation on procedural guidance - October 2015


9

EMA Regulation (EU) No. 536/2014*

• Single EU portal and database to support:

One application dossier for each clinical trial or modifications

Coordinated approach to clinical trial authorisation and supervision

Transparency of clinical trial authorisation, conduct and results

• One clinical trial application form and supporting dossier to cover:

One or more Member States, and all regulatory and ethics assessment

Public registration of the trial and its subsequent updates, including the necessary elements of international registration at WHO ICTRP portal

Providing the trial design elements to support subsequent entry and publication of the summary of results


*Slides 9 -16: from Marcal A, EMA: ‘EU Portal : a Gate way to Simplified Clinical Research’ 17 Oct 2016.

10


• Simplified process for Sponsors with EU/EEA Member State requiring a single:

Uniform procedure in EU: whether single or multi- country clinical trials

Communication hub: Electronically by Portal

Clinical trial number

Contact per clinical trial part I: Reporting Member State

Set of documents per initial clinical trial and follow up

Common assessment (part I) by all concerned Member State together

Decision per Member State (Part I + II)

Fee per Member State

Safety reporting: SUSAR and Annual Safety Report to PV database


11


• EU Portal and Database:

Single EU entry point for clinical trial applications

Enables supervision at EU level, including inspections

Provides workspace collaboration tools, workflow and document management capabilities

Provides publicly available trial information

• Safety Reporting:

Delivers a module for the electronic reporting of suspected unexpected serious adverse reactions (SUSARs)

Delivers an electronic reporting system for annual safety reports (ASRs)

• EudraCT Legacy System:

Delivers transition between the current and new systems


12

EU Portal and Database


Submission Workspace for Sponsors Authority Workspace for Member States

• Clinical trial overview & search • Clinical trial overview & search

• Clinical trial application dossier • Clinical trial detail screen

• Requests for information & notices • Documents

• Documents • System interfaces

• System interfaces • Tasks

• Sponsor user management • Member state user management

• Inspection

Public Website for Public, EMA and Member State Concerned (MSC)

• Entry site

• Public Clinical Trial Data

• Public Search

• Content management for the EMA

13



14



15



16


• EMA’s activities in developing the system

Engaging stakeholders to support implementation of clinical trial regulation

Governance and working groups discussing the requirements for and development of the system

Ensuring data standardization for the WHO, NIH (US Registry) and CDISC

Embarking on Users Acceptance Tests of the system

• key Milestones & Transition Periods to the New System

Audit: Aug to Nov 2017; European Commission Notice: Mar 2018

System goes live with new regulations: Oct 2018

Period 0: CTA submitted still governed by the old Directive until 3 years after go live

Period 1: CTA may be submitted in EudraCT or the New EU portal

Period 2: All initial CTAs must be submitted using the new EU portal and be governed by the new Regulation

Period 3: All CTs are governed by the new Regulations, regardless of their date of submission.


17

Clinicaltrials.gov vs EudraCT: Data Mapping*


Number of Fields

Direct Mapping

Needs Change

Total Fields on the CTA Form 257

Can be Mapped from CTA or CT.gov Results 158

Mapped from CTA 34 30 4

Mapped from CT.gov Results 124 102 22

Created in Results form (No mapping required) 15

Calculated value 8

Default content 7

Additional CT.gov mapping possible 21

Mapping from CT.gov Protocol Registration 21

Cannot be mapped 63

Unique to EudraCT Results 55

Different categories 8

*Slides 17 – 19 From Wicks T, TrialScope: ‘ClinicalTrials.gov to EudraCT Data Mapping’

18

Sections Unique to EudraCT

55 of 257 fields (25%) are unique to the EudraCT

• Trial Identification

Paediatric regulatory details

Public contact point

Results analysis stage

General information about trial

• Population Of Trial Subjects

Subject number per country

Age range

• Subject Disposition

Pre-assignment period

Post-assignment period


19

Sections Unique to EudraCT

• Baseline Characteristics

Baseline characteristics – settings

Subject analysis sets

Age, gender, study specific characteristics both categorical and

continuous

• End Points Statistical analysis details

Chart attachments

• Adverse Events Information on fatalities

Dictionary specifications

• More Information Substantial protocol amendments

Interruptions


20

Summary and Conclusions

Globally, clinical trial disclosure requirements continue to evolve

The new EU regulations impact is mostly in the CTA submission and

evaluation processes

Data elements remain essentially the same with about 25% unique

to the EudraCT compared to CT.gov

The EMA Policy 0070 expands trial disclosure requirements with

full clinical documents and individual patient data

submission/public access

The US Final Rule also makes a number of previously optional data

elements on CT.gov mandatory for submission and disclosure

A data mapping post-Final rule implementation and EudraCT

system upgrade will be necessary

Potential impact of the updates and revisions on demand will be

obvious when all systems are in place soon.


Put Your Mouth Where Your Money Is!

Evolving EudraCT and EU Portal Requirements page 21

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References

1. Anabela Marcal, EMA: ‘EU Portal : a Gate way to Simplified Clinical Research’ 17 Oct 2016

2. Thomas Wicks, TrialScope: ClinicalTrials.gov to EudraCT data mapping

Thank you!

Arigato!


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