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The Disclosure of Clinical Trial
Results and the Redaction of
Clinical Study Reports (CSRs)
Petra Evenäs, PhD
Senior Clinical Trial Disclosure Manager, LEO Pharma
Publication and Clinical Trial Disclosure; CBI
Brussels, 24 June 2015
Disclaimer
This presentation represents the views of
Petra Evenäs
and not necessarily that of LEO Pharma A/S
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Content
p. 03
• Redaction of
CSRs
• Disclosure-friendly
documents
The Story of LEO Pharma
p. 04
- begins more than 100 years ago
•
Founded in 1908 – first pharmaceutical
company in Denmark
•
Global organisation (~5000 employees in >60 countries)
Headquarter in Ballerup, DK
•
Decades of diversified business:
1912
1923
1940
1945
Dermatology
1958
1962
1973
1991
“We help people achieve healthy skin”
Disclosure as CSR
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Part of authorisation dossier
EFPIA + PhRMA: Principles for
responsible clinical trial data sharing
• Minimum synopsis of CSR
(US + EU; following approval)
EMA Policy 0070 (Proactive publication
of clinical trial data)
(Irrespectively of outcome
(approval/refused/withdrawal))
Regulation (EU) No 536/2014
(Irrespectively of outcome
(approval/refused/withdrawal))
• CSR: Body of report + Appendices:
o 16.1.1 (protocol and protocol
amendment)
o 16.1.2 (sample case report form)
o 16.1.9 (documentation of statistical
methods)
• CSR: Body of report + all Appendices,
except these with data listings (16.2)
Common Aspects
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EMA Policy 0070 & Regulation (EU) No 536/2014
Interest of public
health
Protection of
research investments
Safeguarding personal data!
• “Clinical reports” (CSRs, other CTD documents etc.) do not, in general,
contain commercial confidential information (CCI) – but they may…
• Justification for redaction of CCI required – EMA final word
• No definition in the EU law - high level definition adopted by EMA:
“Any information which is not in the public domain or publicly available
and where disclosure may undermine the economic interest or
competitive position of the owner of the information”
*
The Clinical Study Report (CSR)
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• Regulatory requirement (at least an abbreviated format)
• One of many regulatory documents required
in an application – Module 5 of the CTD
• Modular approach:
o Synopsis
o Core report
o Appendices
• Several guidance documents
o ICH E3. Structure and Content of Clinical Study Reports. Nov 1995
o M4E (R1). The Common Technical Document for the Registration of
Pharmaceuticals for Human Use Efficacy. Sep 2002
o Guidance for Industry, Submission of Abbreviated Reports and Synopses
in Support of Marketing Applications, 1999
o …
Scope of LEO Pharma Commitments
Position paper – Public access to
clinical trials information (24 Oct 2013)
• Trial registration (protocol information)
• Result reporting on external registries
(ClinicalTrials.gov, EudraCT,
(ClinicalTrials.gov,
EudraCT)national)
• Result
Result posting
postingon
onLEO-Pharma.com
LEO-Pharma.com
• Data sharing
(anonymised individual patient-level data)
• Publication in scientific
peer-reviewed
journals
scientific
of all
Phase-IIIoftrials
journals
all phase-III trials
Available on the LEO corporate web site
p. 08
Result Posting on LEO-Pharma.com
p. 09
CSRs excluding the appendices & CSR summaries
Criteria for posting of results as:
Year of trial
protocol
1990-2013
Summary
CSR
Approved product,
indication*
Approved product,
indication*
Interventional trial
Interventional trial
Irrespectively of
approval status
Approved product,
indication*
2014-
Abandoned project
Interventional trial
Interventional trial
and NIS**
Time aspect for posting
Completed by
31 December 2016
Summaries: Within 1 year
after study completion (LSLV)
CSR:
After publication in scientific
literature; if no publication
planned, within 1 year after
study completion (LSLV)
*
Indicates trials in approved products in approved indications, including supportive trials,
e.g. phase I (PK, PD, safety).
**
Non-interventional studies.
Protection of
Confidential Information
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Responsible Function
•
Personal data
Medical Department
(relating to an identified or identifiable person)
•
Patent sensitive information
Patents
•
Commercial confidential
information (CCI)
Scientific Affairs
*.
Redaction of Personal Data
Internal guidance document for pre-redaction & review
References:
• EU Data Protection Regulation No. 45/2001 and Data
Protection Directive 95/46/EC
• HIPAA Privacy Rule
• HMA/EMA Working Group on Transparency – Guidance
document. March 9, 2012.
• Hrynaszkiewicz, I., M. L. Norton, et al. (2010). “Preparing raw
clinical data for publication: guidance for journal editors,
authors, and peer reviewers.”BMJ 340: c181
• PhRMA, EFPIA “Principles of Responsible Clinical Trial Data
Sharing”. July 18, 2013
• TransCelerate “Clinical Study Reports Approach to Protection
of Personal Data”. August 28, 2014
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Redacted – or Removed or Replaced
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Internal guidance document
• Names - incl. Principle Investigator & the legal representatives of the Sponsor
• Academic/organisational title
• Addresses to all except the Sponsor
• Authors of internal Sponsor reports
• Subject identifiers (incl. medical record no, initials, case numbers, etc.)
• Dates relating to individual subjects (incl dates of visit/treatment, birthdates, etc)
• Age deviation + elderly (>90 years)
• Individual outcome/demographic characteristics (incl country, sex, ethnicity, etc)
• Extraordinary data range limits (case-by-case assessment)
• Verbatim text (case-by-case assessment) – e.g. replaced by MedDRA terms
• Subject narratives & listings
Retained
Internal guidance document
• Study roles
• Academic qualifications
• Country in addresses
• Published citations & references
• Dates not related to study participants
• Study ID + public register ID numbers (EudraCT, NCT no, etc.)
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Non-Privacy Aspects
Internal guidance document
Redacted
• Chemical structure/formula
• Excipients/propellants/etc. (for non-approved products)
Retained
• Batch number/Lot no.
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Disclaimers
Information on scope, purpose & why redacted
CSRs + CSR summaries
CSRs
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Redaction Process
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Pre-redaction
Review; further redaction
Update; QC
Secure
Viewable, searchable & downloadable
Posting on LEO-Pharma.com
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Andreas Snitkjær, layout
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Why Disclosure-Friendly Documents?
• Additional audience (regulatory bodies plus
public) – confidentiality aspects
• Save time & resources
o Redaction
o Review
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Disclosure-Friendly Documents
General considerations
• Update templates & processes
o Consider EMA’s instructions on where CCI may appear
o Learn from peers
o Ensure consistent redaction; incl. assigned reviewers
• Cross-functional engagement
o CCI perspective
o Additional documents
• Should not be treated in isolation
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Considerations for the CSR
ICH E3 format (Heading 1 level)
2. Synopsis
References to other public platforms:
EudraCT no, NCT no...
…+ peer-reviewed scientific journals
3. Table of Contents
Conclusion needed in Synopsis?
1. Title Page
4. List of Abbreviations …
5. Ethics
6. Investigators and Study Adm..
Limit & move to relevant appendices
7. Introduction
Restriction to what’s necessary
8. Study Objectives
9. Investigational Plan
10. Study Patients
Reduce info copied from CSP
Consistency in usage of
subject ID, subject no….
11. Efficacy Evaluation
12. Safety Evaluation
13. Discussion and Overall Conclusions
14. Tables, Figure and Graphs…
Restriction to what’s necessary
Careful wording of conclusion
15. Reference List
16. Appendices
Standardise CV for investigators
Update of Appendix 16.1.9 - subject ID
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?