clinical trial transparency: status quo and important trends · 3 live better. feel better. look...

Live better. Feel better. Look better.

Clinical Trial Transparency: Status Quo and Important Trends17-May-2019: SanaClis – XIV. Interdisziplinäres Expertengespräch

Dr. Matthias Zerm

Lead Expert Clinical Trial Disclosure and R&D ProcessesGlobal Clinical DevelopmentMerz Pharmaceuticals GmbH, Frankfurt am Main, Germany

2

Disclaimer

The following presentation represents solely the view of the author.

It does not necessarily reflect positions or policies of Merz.

Financial Disclosure Statement

I am an employee of Merz Pharmaceuticals GmbH

3 Live better. Feel better. Look better.

• Focus: • Interventional studies with drugs and medical devices

• Emphasis on regulations at EU level and in the USA

• Not covered at all

• Plethora of mostly local disclosure requirements for non-interventional studies

Clinical Trial Transparency (CTT): Status Quo and Important Trends

8/9/20174 Live better. Feel better. Look better.

A short look back…

How did we get here?


Public Disclosure: Snapshot Sep 2010-> Protocol registration and tabular results


Status quo

The brave new world of clinical trial transparency (CTT)


Public disclosure (protocol registration, results summaries): growing field

…countries

have some

disclosure

requirements

…new

registries

between 2006

and 2016

…countries

were studies

are

conducted

Key trial

registries:

Global

disclosure

standards

0

~30

>12>90

200


Public disclosure: scale and volumeCourtesy of Thomas Wicks, TrialScope , Inc


CTT – Main Players (excl. public audience)

Scientific

Publications on CTT

WHO

“Good Pharma

Score Card”

Regulators

Patient

Advocacy

Groups

Academic Research

(Groups)

HTA

Bodies

Media (e.g. Stat News)

NIH NHS

HCPs/

Physicians

Academia

Legislators

Governments

Industry

ICMJE

Data Generators

“Watch Dog Activities”

Secondary Data Users

IOM

AllTrials: - Transparency Index

- FDAAA Trials Tracker

- EU Trials Tracker

Industry

Rule Makers

IRBs / Ethics

Committees

Research

Funders

ISO

Industry

Trade

Associations

Declaration

of Helsinki

DIA CTD

CommunityFacilitators

TransCelerate

Data Sharing

Platforms

CTT

Vendors?Investors

Research

FundersIndustry Trade

Associations

PhUSE

Industry via

Company

Policies


Levels of Clinical Trial Transparency(excl. scientific publications and assessment/review reports)

EudraCT (phase 2-4 trials)

Germany §42b

Upcoming: EU CTReg (phase 1-4 trials)

Protocol

registration

Upcoming: EU MDR likely

Post-MA only

Declaration of Helsinki (any research in humans) *

efpia/PhRMA Commitment: “Responsible Data Sharing” (18Jul2013)

* Results in registries and/or publications; ** DoH mandates that research subjects be informed about study results

**

Tabular results

(approved

products)

CSR

Synopsis

Tabular results

(unapproved

products)

Full protocol

and SAPFull CSR

Lay language

results

summaries

Full IB, ICF,

IMPD (excl.

quality)

Patient level data

N

e

x

t

?

likely: IB, ICF

ClinicalTrials.gov

EMA Policy 070p

phase 1

Upcoming: EMA

Policy 070 phase 2

Health Canada

Upcoming: Ukraine,

?Switzerland, ?UK,

?USA

Access to documents

regulations (e.g. EMA

policy 043)

Drugs Medical Devices Both


EMA Policy 070 (drugs, proactive publication)

Source: EMA Presentation by Anne-Sophie Eude, DIA CTD Conference, London, 06Dec2017

-> Health Canada follows similar approach as from Mar 2019, but: - Also for medical devices- Also retrospectively upon

request!


EMA Policy 070 (drugs, proactive publication)Amount of Commercially Confidential Information (CCI) included in published reports

Source: EMA Presentation by Anne-Sophie Henry-Eude, DIA CTD Conference, London, 06Dec2017


From redacting clinical reports towards anonymization (e.g. EMA Policy 070, Health Canada)

• Aim: maintain data utility while keeping the risk of re-identification of trial subjects below a certain threshold (usually 0.09)

• Growing number of vendors offering redaction and/or anonymization services/tools

• Cave: wording in ICF?-> Anonymized data ≠ personal data

Source: Presentation by Janice Branson (Novartis), DIA CTD Conference, London, 06Dec17


Lay language results summaries

• Health literacy framework, e.g. less numbers, more graphs/visuals

• EU guidance document: >30 pages for implementationunder CTReg

• Many other sources/tools available (e.g. from MRCT)

• Growing number of vendors offering lay language services

• Need also lay language translations!

• May be used to inform study participants about study results(-> industry self-commitment!)

Source: https://www.novonordisk-trials.com/advanced-search

Source: https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-

10/2017_01_26_summaries_of_ct_results_for_laypersons.pdf

https://www.novonordisk-trials.com/advanced-search

https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-10/2017_01_26_summaries_of_ct_results_for_laypersons.pdf


Patient level data sharing

• Main driver: efpia/PhRMA “Principles for Responsible Clinical Trial Data Sharing“ July 2013

• Single- or multi-sponsor systems, industry and/or academic

• Typical workflow – key elements: 1. Interested researcher sends research proposal and request for data from clinical study/ies

2. Sponsor checks whether study/ies are in scope of own policy/commitment

3. Independent review panel checks if research proposal is legitimate and scientifically sound

4. Data sharing agreement between sponsor and researchers (incl. terms of use)

5. Anonymized data sets and pertinent supporting information is made accessible to researcher on secure platform that allows performance of analyses (but no data download)

6. Publication of results


The future of CTT

Where are we heading?


Situation only very recently:

not public

public

Full protocol

SynopsisIB

Clinical reports in dossiers

Publications, peer-

reviewed journals

Other publications

Full report

Patient Level Data

Results in public registries

(may include summary

documents)

Protocol information in

public registries (may

include lay summaries)

ICF

Press releases

Abstracts/ Posters/

Presentations

Labels

Lay results summaries

IMPD

SAP

Promotional materials

EPARs, Review Reports

Recruitment

ads

Synopsis


Future: Holistically aligning the different ways of disseminating CT information to the public

not public

public

Processes:

• Public disclosure

• Lay language summaries

• Reviewing/redacting external reports

• Redacting clinical documents

• Anonymizing clinical documents and data sets

• Access to unpublished data

• Sharing of patient level data

• Press releases

• Publications

Full protocol

SynopsisIB

Clinical reports in dossiers

Publications, peer-

reviewed journals

Other publications

Full report

Patient Level Data

Results in public registries

(may include summary

documents)

Protocol information in

public registries (may

include lay summaries)

ICF

Press releases

Abstracts/ Posters/

Presentations

Labels

Lay results summaries

IMPD

SAP

Promotional materials

EPARs, Review Reports

Recruitment

ads

Synopsis


• Building expertise for anonymization of documents/datasets

• Building expertise for lay language results summaries

• CTT may include nonclinical study reports (policy EMA 043, upcoming: Ukraine MoH)

• CTT is new in the EU medical device industry (Medical Device Regulation (EU 2017/745) comes with extensive transparency provisions)

• CTT vs. GDPR (=> legal basis for secondary re-use of data: consent vs. other legal grounds)

• New developments in clinical research <-> data models in public registries

• Adaptive designs, “basket trials”, “cluster trials”

• Concept of “estimands” in upcoming ICH E9 (R1) Addendum

• Real world data, “big data”

• Role of public disclosure groups at industry sponsors? • All content/documents to be published

or

• Feeding registries, redactions (and anonymizations), involvement in template development for other documents

Current and future challenges


• CTT complexity is still increasing

• CTT harmonization remains utopia - hope dies last!

• Sponsors need: • Dedicated experts and CTT aspects/procedures built into routine business processes (=> CTT is not an add-on!)

• Shift in mindset is key to achieve efficiency and compliance

• Top management: commitment to CTT –> top-down implementation of standards and procedures

• Overall: Actively embracing the CTT reality => pre-condition for: • Getting the job done (shift in mindset, compliance, efficiency)

• Making use of potential benefits, e.g. retaining/gaining positive reputation, (competitive) intelligence, learnings from other studies, potentials for collaborations

Concluding Observations


[email protected]

Key source for anyone working in the CTT field:

Drug Information Association (DIA) - Clinical Trial Disclosure Communityhttps://communities.diaglobal.org/search?s=tags%3a%22Clinical+Trial+Disclosure%22&executesearch=true

Questions?

mailto:[email protected]

https://communities.diaglobal.org/search?s=tags:%22Clinical+Trial+Disclosure%22&executesearch=true

clinical trial transparency: status quo and important trends · 3 live better. feel better. look...

Documents