Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 1 The Implementation Toolkit...

Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 1

The Implementation Toolkit is: – High level roadmap of activities recommended to

support implementation of the Common Protocol Template (CPT) across project management, people, process & technology

– Templates and materials to communicate the initiative to various audiences

– Available to any Company or Sponsor who chooses to implement

.. but is not:– A detailed step-by-step workplan

– Activities that must be followed exactly, including Company or Sponsor-specific documentation

Objectives and Guiding Principles for the Implementation Leader

Guiding Principles– Each TransCelerate member company or non-member Sponsor is free to decide and must

decide for itself whether and in what manner to adopt any or all of the CPT components.

– This toolkit is intended to help those Companies or Sponsors who decide to adopt any CPT component to do so in the most efficient way possible.

– Implementation components are generic and may need to be tailored to a sponsor prior to use

– While TransCelerate member companies or non-member Sponsors have absolute discretion to implement TransCelerate solutions as they see fit, changing certain CPT tools will likely reduce some of the benefits associated with the tools.

– It is up to each TransCelerate member company or non-member Sponsor to define further the detailed steps for each implementation component within their respective organization.

The toolkit can be used in a highly flexible manner, as reflected in the guiding principles below.

i

<Audience and Date><Insert description of member company or sponsor audience for this presentation – e.g. senior leadership, group of stakeholders for doing impact assessment, participants authoring “pilot” trials, team members who will review and approve the protocol for “pilot” trials, broad audiences>

Common Protocol Template (CPT) Implementation Toolkit


TABLE OF CONTENTS

Introduction to TransCelerate

Common Protocol Template (CPT) Background

Model for the CPT

CPT Implementation Plan: Stakeholders, Advisors, and Company Plans

CPT Tools and Training for implementation

Other Tools to Support Implementation


What is TransCelerate?

Our visionTo improve the health of people around theworld by accelerating and simplifying the research and development of innovative new therapies.

Our missionTo collaborate across the global research and development community to identify, prioritize, design and facilitate implementation of solutions designed to drive the efficient, effective and high-quality delivery of new medicines.

TransCelerate is a not-for-profit entity created to drive collaboration across the pharmaceutical industry as a means to developing solutions for overcoming inefficiencies

Our core values Quality

Transparency & Openness to new ideas

Trust & Integrity

Collaboration

Courage


Engagement With the Wider Clinical Ecosystem Globally

Research

and

C

RO

Co

mm

un

ityIn

vestigative sites

Strategically focusing engagement efforts with selected key stakeholder groups – the intent is not to recreate, but partner whenever feasible

Reg

ula

tory

Bo

die

sIn

du

stry

Init

iati

ves

http://www.jcroa.gr.jp/eng/index.html

http://sitesolutionssummit.com/wp-content/uploads/2012/01/SCRS-Logo_web600px_medium.png

http://www.aaci-cancer.org/index.asp

http://www.transceleratebiopharmainc.com/

http://www.pmda.go.jp/english/index.html

http://www.pmda.go.jp/english/index.html


How Does TransCelerate Work?

Member Companies

WORKSTREAM

Define problem scopeShare best practicesDiscuss challengesCo-create solutions

Support & Resources (subject matter experts, time,

overhead)

Industry Solutions


14 TransCelerate Initiatives Chartered -

All initiatives are voluntary

Common Protocol Template6e-Consent1

4

Pediatric Trial Efficiencies 8Clinical Trial Diversification9Clinical Data Transparency1

0 Quality Management System11

*Original initiative which began in 2012

Model Approach for High-Quality, Risk-Based Monitoring*1Shared Site Qualification and Training*2Shared Investigator Platform*3Clinical Data Standards* (as a collaborator in CFAST)4Comparator Drugs for Clinical Trials*5 Placebo / Standard of Care1

2 e-Labels13Investigator Registry7


TransCelerate and CPT Workstream Membership

8

20 membercompanies in TransCelerat

e

17 member

companies

participate

in theCommonProtocol Templateworkstrea

m


Why a Common Protocol Template?

Heard at a recent DIA meeting…

“Patientrecruitmentischallengedbythe

complexityofprotocols.Sponsorsdothesame

thingstoo many different ways. Just make it the same!”

“Ifyouhavestandardswithouttraceability,thenyouaren'treally

CDISCcompliant.”

Investigator

FDA

“Justbecause‘subject’isintheregs,doesn’tmeanyou

havetouseit.Patientsthinkof‘subject’asaverb,andwho

wantstobesubjectedtosomething?Please use ‘trial

participant’ instead.”

PatientAdvocate


Problem Statement – Format and core content of study

protocols vary from sponsor to sponsor making interpretation difficult for study sites, IRBs, and regulators.

– Study protocols have become increasingly complex and lengthy driving up cost and time.

– Manual set-up of clinical systems based on non-standard “manual” protocols is time consuming, costly, and prone to error.

Solutions– Develop a model clinical trial

protocol, including format and core content, to ease interpretation and enable down-stream automation of many clinical processes.

– Develop model protocol endpoint definitions, incorporate into piloting of the template.

Background: Why a Common Protocol Template?

Guiding Principles– “Common” in a CPT: information always in the same place, means the same thing.

– Is it better? Move beyond incremental improvements and current limitations.

– It has to be better for everyone, but Investigators/Sites are the first priority.

– A human readable template that paves the way for an automated solution and facilitates the use of data standards.


End-User Stakeholders and Key “Must Haves” Define Scope and Solutions

PhysiciansClinical Scientists

Operations

RegulatorsData Scientists

Stats & Programming

Objectives Endpoints Methods Time & Events Supplies

Protocol Representation Models (CDISC)Data FlowsData StandardsProtocol ElementsConcepts

Investigators / SitesIRBs

Metadata

Traceability

Reuse

Automation


The Common Protocol Template Potentially Benefits Many Stakeholders

Sponsor

Sites

IRBPatient

Regulator

Operational efficiencies in creation of protocols

Reduction in redundancy in protocol content Enabling of therapeutic area standards Improved conduct of the study and quality

of data collected

Near Termand Potential Future State

Improved access to information with protocols streamlined and organized with an investigator focus

Increased consistency between sponsor protocols makes it easier when conducting multiple studies

Reduced need for additional documentation (e.g., study manuals)

Improved access to information with protocols streamlined

Increased consistency between sponsor protocols - easier review and faster approval

Improved communication from sites due to Increased consistency between protocols

Improved access to protocol information

Increased efficiency in clinical development, for participants & future patients

Reduction in complexity of regulatory reviews – easier reviews due to common structure and content

Increased ease of data interpretation Improved ability to compare protocols,

which improves quality of regulatory input on protocol design

Automation of downstream processes and reuse of content

Enabling of therapeutic area standards in additional TAs

Enabling collaborative clinical trials

• Opportunity for harmonization of additional documentation (e.g., study manuals)

• Enabling increased consistency of some case report forms

• Enabler for automation of IRBs submissions

Getting medicines faster, for participants & future patients

• Increased use of data standards, enabling end-to-end use of metadata and traceability


• A single, common protocol template structure with harmonized language

• Streamlined content enables identification of critical information for end users

• Begin working towards common endpoint definitions to align with Clinical Data Interchange Standards Consortium (CDISC) Therapeutic Area (TA) data standards. Asthma and Diabetes available in the first release.

• Reconnect processes (protocol, eCRF, development)

• Transformation of the design processo Analytics-driven trial design,

modelling, scenario planning

• Role-based access to protocol information (Principal Investigator [PI], Ethics, Participants)

• Connection to other systems

Common Protocol Template is Intended to Prepare for the Future State

Human- Readable Protocol

Human- Readable Protocol

IRB/IECsSites

Regulators

Foundation

Machine- Readable Protocol Metadata driven

processes

Content ReuseDisclosure

SAPCSR

eCRFStatistical Output

Future


The Model for the Common Protocol Template

LibrariesCore Protocol

Backbone

Common Level 1 & 2 Headings

Common text

Used across all phases

Focus on investigators

Healthy Volunteer

Patient

Asthma

Diabetes

AppendicesNon-study specific info, items

triggered by event

Implementation materialsinToolkit

Coreisstreamlined andfocusedonsite needs

ProposedAppendices toapplyasapplicable

Librariesgroupandstorecontentwhichisusedtopopulatethetemplate

Endpoint Definitionsdevelopedforasthmaanddiabetes

AsustainableGovernance Modeliscurrentlyindevelopment

Common Protocol Template and GuidanceGovernance Model


Template Development:Structure and Content

Structure – Level 1 and 2 Headings• Main focus -

Streamlined structure for logical flow

• Review of structure (Table of Contents) of member company templates

• Input from SCRS (Society for Clinical Research Sites) Site Advocacy Group

Section Content• Identification of common

wording in Core Backbone

• Review of GCP, ICH, and EU requirements

• Review of content from member company templates

Final CPT Structure and ContentFocus on sites (investigators and study staff) to have access to protocol information1. CPT Structure and Content will provide value to

Investigators, site staff, IRBs, regulators The same information is located in the same

place and means the same thing across Sponsors

Locked text (Level 1 and 2 Headings) is not to be modified or removed. “Not Applicable” is inserted if a section is not applicable.

2. Specific information to evaluate the ability to conduct a protocol, e.g. does the site have the patient population.

3. Refer to primary sources of information (e.g. Investigator Brochure) instead of duplicating information in the protocol

4. Model sections and text located in Appendices to be accessible, but will not impact the flow of the core protocol-specific information


Advisory Committee

eProtocol Advisory

Committee

Budapest Working Group (E3 & E6)

STAKEHOLDERFEEDBACK

“…to inform the development of a common human readable and electronic protocol template and

provide a forum for key stakeholders to inform future

direction and provide know-how

(Committee Charter)”

“EMA has not agreed to take up a position on the Advisory

Committee…..Happy to provide comments on any draft templates…”

OtherAdvisorsorInfluencers

http://www.ctti-clinicaltrials.org/


Case Study: Member Company Pilot of TOC

The DRAFT CPT TOC (Level 1 and 2 headers) was used by a member company to author 3 protocols. There were no comments on the protocol TOC from the IRBs or the FDA or other Health Authorities for Trial 1 or 2 or 3. Several ex-US HA approvals are pending.

Trial

Type of Study

Phase

Indication

# of IRBs/EC Approved

FDA Review Approval

Ex-US Health Authority Review Submitted

ProtApproved to date by Ex-US HA

1 Oncology II Gastric 38 yes UK, Belgium, Canada, Czech Republic, Germany, Greece, Italy, Spain, Sweden, Turkey, Ukraine

All approved except Ukraine pending

2 Oncology II Gastric 43 yes Argentina, Australia France, Hungry, Poland, Romania, Russia, Slovakia, UK

All approved expect Argentina pending

3 Auto-immune

III Psoriasis 124 yes Argentina, Australia, Brazil, Canada, Czech Republic, Germany, Hungry, Japan, Mexico, Poland, Romania

All approved except Brazil pending


Ongoing CPT Maintenance/Governance: Business Continuity Plans

OngoingMaintenance&Governanceof

Template*

Collectandreportmetricsandfeedback

Updatestothetemplatesand

libraries

Governance Model being refined

Posted Template & Implementation Toolkit Member companies Public

• Metrics to monitor extent of adoption, regulator feedback

• Metrics to assess efficiencies gained

• Feedback collected via the TransCelerate website

• Update of the template and libraries as needed based on stakeholder feedback, regulatory guidance etc.

• Additional TA libraries


How will we go about adopting the CPT?

Options for Adoption of Common Protocol Template

TransCelerate Sponsor

Mapping Table Exercise forassessing the impact of CPT

Plan for Implementation at

_Sponsor_

Each Sponsor to tailor this slide.!


Options for Adoption of the Common Protocol Template

CPT Components

Companiesselectwhichtouse

TOC/Headingstructure

Commonlanguage

(core/appendices)

HealthyVolunteerLibrary

PatientLibrary

AsthmaLibrary

DiabetesLibrary

Companies and Sponsors choose their own path to adoption

• By phases• By use of libraries• By use of organization/structure and

content only (i.e., existing sponsor technology used, but headings/content adapted to mirror CPT)

Companies and Sponsors set their roll-out timeline

• Slowly introduce through pilots• Hard cut over date• Somewhere in between


Mapping Table Exercise to Assess Impact of CPT

Completing the Mapping Table Exercise will highlight the impacts and risks of adopting the CPT. Consider:

- Impact to sites/regulators- Sponsor responsibility for regulatory

compliance- Impact to internal sponsor processes and

documents downstream from protocol

Identify content used in a company sponsor template that is not included in the CPT

- Consider: Is this information found elsewhere (e.g., CTA, Monitoring Guidelines, Standard Operating Procedures, policy documents)?

Identify content in the CPT that is not currently in a company or sponsor template.

- Consider: Impact to adding this content?

Identify differences in wording of same topics in company or sponsor template vs CPT.

- Consider: Can company decide to accept CPT wording?

EXAMPLE


Mapping Tool:Results of Initial Impact Assessment

*Insert Company or Sponsor Specific Details*

Share results of Mapping Tool Exercise

Propose mitigation for content removed from template

Downstream impacts of content changes – distinguish between what needs to be mitigated for initial implementation vs longer term updates to SOPs

• Documents (SOPs, monitoring plans, agreements, etc.)

• Processes

Each Company or Sponsor to tailor this slide.

!


Proposed Implementation at____Sponsor ___

*Insert Company or Sponsor Specific Details*

Pilot with X trials

• Trials X, Y, Z

• Use template on desktop, not installed in authoring tool for initial implementation• Training/Orientation to template details

• Timing

• Assessment of results

Each Company or Sponsor to tailor this slide.

!


How to Use the Common Protocol Template

CPT Version 1.0 – Basic Word CPT Core Backbone and Libraries in

MSWord (.docx) Instructional text provided as red

hidden text available by toggling paragraph marks

Word doc, no installation needed (Open file and “Save As”)

Open on a workstation to author a protocolorUse for mapping exercise to compare sponsor template to CPT


What will be provided to support Implementation?

Tools What is it?

Introductory Video Short video providing an introduction to the template and the CPT Project

CPT Implementation Toolkit – Slide deck

This deck. Used for communication to various company or sponsor audiences – e.g. senior leadership, group of stakeholders for doing impact assessment, participants authoring “pilot” trials, team members who will review and approve the protocol for “pilot” trials, broad audiences for awareness.

Frequently Asked Questions (FAQs)

A summary of questions, and responses from the team, that various stakeholders may have about how the CPT was developed, how it will be implemented, and how it will be maintained.

Mapping Table Exercise; Mapping Table Instructions

A tool to compare the CPT to a company or sponsor protocol template. Allows identification, section by section, of differences in headings and content, and prompts team members to assess impact of implementation and possible mitigations needed.

Stakeholder Map A tool to assess the impact that implementing the CPT will have on each stakeholder group. Allows the Implementation Lead to plan for appropriate training and mitigation of concerns.

Text Color Guide Color coding used within the Common Protocol Template to distinguish common, suggested, example and instructional text. Paragraph marks must be visible in order for the instructional text to be displayed.

CPT Feedback Feedback can be submitted via the TransCelerate website http://www.transceleratebiopharmainc.com/

http://www.transceleratebiopharmainc.com/

THANK YOU

Copyright ©2015 TransCelerate BioPharma Inc., All rights reserved. 1 The Implementation Toolkit...

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