1. Implementation Toolkit Executive Summary
November 2018

2. A Not-for-Profit Entity Created to Foster Collaboration
TransCelerate:
A Not-for-Profit Entity Created to Foster Collaboration
Our Shared Vision:
To improve the health of people around the world by accelerating and simplifying the research and development of innovative new therapies.
Legally approved 4-Oct-2018

3. The Reach of our Global Membership is Expanding
Membership is available to biopharmaceutical research and development organizations that engage in innovative discovery, development and manufacturing of new medicines*.
There are
over
1,000
people
from Member Companies that design and develop TransCelerate solutions.
Legally approved 4-Oct-2018
* to be eligible for membership, companies must meet specified eligibility criteria.

4. Why a Common Protocol Template?
Patient Advocate
“Just because ‘subject’ is in the regs, doesn’t mean you have to use it. Patients think of ‘subject’ as a verb, and who wants to be subjected to something? Please use ‘trial participant’ instead.”
FDA
“If you have standards without traceability, then you aren't really CDISC compliant.”
Investigator
“Patient recruitment is challenged by the complexity of protocols. Sponsors do the same things too many different ways. Just make it the same!”
Legally approved 4-Oct-2018
Let’s start our discussion by looking at the drivers for a common protocol template – Why did we set out to create the CPT?
At many meetings, for some time, we had been hearing a variety of voices commenting on how Sponsors design and implement trials. This slide summarizes some specific input heard at a DIA meeting in 2015.
Investigators spoke of the increasing complexity of our protocols and the fact that every Sponsor seems to do things differently. This further complicates study execution for any site who is working with multiple sponsors.
<TRIGGER ANIMATION>
Sometimes a simple choice of words can also be of concern. We heard from patient advocacy groups that there was a sensitivity to the use of the word “subject” in many protocols. This reminded us that the trial participants themselves would also be a key stakeholder group to be considered.
A key Health Authority perspective was expressed by an FDA colleague, who reminded us that we would need to go beyond modeling common text. To achieve CDISC compliance, we would need to ensure end-to-end traceability of data from source to final datasets.
Heard at a June 2015 DIA meeting…

5. Background: Why a Common Protocol Template?
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 streamlined 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.
Legally approved Oct-2018
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.

6. The Common Protocol Template Potentially Benefits Many Stakeholders
Near Term Benefits to Sponsors
Reduction in redundant protocol content
Enabling of therapeutic area standards
Improved conduct of the study and quality of data collected
Near Term
Potential Future State
Potential Future Benefits to Sponsors
Automation of downstream processes and reuse of content
Enabling of therapeutic area standards in additional TAs
Enabling collaborative clinical trials
Potential Future Benefits to Regulators
Increased ease of data interpretation and ability to compare protocols (improves input on protocol design),
Increased use of data standards enabling end-to-end use of metadata and traceability
Sponsor
Sites
IRB
Patient
Regulator
Near Term Benefits to Sites
Protocols streamlined and organized with an investigator focus
Reduced burden on sites working on multiple studies
Near Term Benefits to Regulators
Protocols streamlined, increased consistency between sponsor protocols to ease review
Legally approved 4-Oct-2018
So, we set out to develop a Common Protocol Template that would offer benefit to a number of stakeholders, both in the near term, and also into the future.
<TRIGGER ANIMATION>
Starting with the Sponsor, a common template could reduce redundancy, and drive therapeutic standards, thereby enabling operational efficiency and improved data quality.
Over time, model content could be reused to automate downstream processes, and would also enable improved collaboration across Sponsors.
Sites would immediately recognize streamlined and better organized protocol content, and see a reduced burden when working across multiple studies.
In the future, a common protocol template could allow for harmonization of other site documents and processes that stem from the protocol.
Institutional Review Boards or Ethics Committees would enjoy the same benefits as the sites. Finding the same information in the same location in protocols written across multiple sponsors could facilitate their review of protocols.
Over time, harmonized structure and model content would also support easier automation of IRB submissions.
From the patient perspective, some of these immediate benefits to sites and IRBs would translate to increased efficiency in study start-up and improved quality in ongoing trials for participants.
In the future, the automation of downstream processes beyond the protocol could allow Sponsors to get medicines to patients faster.
Finally, Regulatory authorities will see near term benefits in terms of streamlined and more consistent protocols that are therefore easier to review.
Over time, more commonality and increased use of automation and data standards will enable easier interpretation and comparison of results, and could allow for more efficient reviews.
Potential Future Benefits to Sites
Opportunity to harmonize additional documentation
Enable consistency of some case report forms
Potential Future Benefits to Patients
Improved access to protocol information
Getting medicines faster, for participants & future patients
Near Term Benefits to IRBs
Increased consistency between sponsor protocols: easier review and faster approval
Near Term Benefits to Patients
Increased efficiency / quality in clinical development for participants & future patients
Potential Future Benefits to IRBs
Enabler for automation of IRBs submissions

7. Common Protocol Template is Intended to Prepare for the Future State
Foundation
Future
Human- Readable Protocol
Disclosure
SAP
CSR
IRB/IECs
Sites
Regulators
Machine- Readable Protocol
Content Reuse
Metadata driven processes
eCRF
Statistical Output
A common protocol template structure with harmonized language
Streamlined content enables identification of critical information for end users
Begin working towards model endpoint definitions to align with Clinical Data Interchange Standards Consortium (CDISC) Therapeutic Area (TA) data standards.
TA Libraries available
Reconnect processes (protocol, eCRF, development)
Transformation of the design process
Analytics-driven trial design, modelling, scenario planning
Role-based access to protocol information (Principal Investigator [PI], Ethics, Participants)
Connection to other systems
Legally approved 4-Oct-2018
Progress to date on the CPT includes the development of a human-readable template document. This will enable sites, reviewers, ethics committees and regulators to find the same information in the same place and have it mean the same thing.
<TRIGGER ANIMATION>
The template consists of a core of model content supported by a series of libraries appropriate for a given study type or disease area. Critical protocol level content has been aligned to the data standards project which is a collaboration between TransCelerate and Coalition for Accelerating Standards and Therapies (CFAST). The alignment of objectives, endpoints and procedures is a critical element of the document-based solution.
This template paves the way to evolving to a machine-readable protocol where content is reused, and metadata drives downstream processes, introducing the possibility of establishing the protocol as a digital platform with analytic trial design, role-based access to protocol information, etc.
In both the document based environment as well as the digital environment it will be critical to reconnect certain processes and develop critical study components in parallel rather than serially (e.g. eCRF, Statistical Analysis Plan –SAP)
At this time, the template core will support trials in any Therapeutic Area. As a first step toward enabling data standards, disease specific libraries have been created, with common endpoint definitions based on the CDISC Therapeutic Area User Guide (TAUG).

8. Current State/Future State: Establishing Our Direction
Today
Manual processes and interventions
Duplication of company efforts
Disconnected interfaces
Lot of customization
Long cycle times
Variable quality
High costs
Rework
Where we should be…
Digital, Cloud-based, computable, re-usable
Patient-centric clinical trial design
Automated/seamless interfaces / parallel processing
Quality by design
Shorter cycle times
Cost efficient
“Integration of Data Analytics”
Transformational
Where we are…
Electronic, document based
Legally approved Oct-2018
Incremental
Where we started…
Paper-based, manual processing

9. How was the CPT Developed? Initial Advisory Committee Engagement
FDA 18-Mar-2016: “Today we’re announcing a draft clinical trial protocol template developed by the Food and Drug Administration (FDA) and National Institutes of Health (NIH) that should help with that. …..We are aware of other efforts in this area, including one undertaken by TransCelerate Biopharma Inc. (TransCelerate), which has issued a common protocol template intended to be the basis for a forthcoming electronic protocol. Although our initial target audiences differ, we plan to collaborate with groups like TransCelerate to help ensure consistency for the medical product development community.”
“…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)”
eProtocol Advisory Committee
Legally approved Oct-2018
TransCelerate sponsored formation of the Electronic Protocol Advisory Committee to inform the initial 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. This Advisory Committee was designed to be similar to, but lighter version of, the Coalition for Accelerating Standards and Therapies (CFAST) structure. Input has been received from some eProtocol Advisory Committee members, and additional input is being requested. The intent is to promote “energy” around the idea of an eProtocol platform, and to drive alignment around end to end traceability, automation, and reuse. Through this Advisory Committee, TransCelerate workstreams will continue to get advice, and access to external “know-how.” The groups across the bottom of this slide are not directly involved in this Advisory Committee, but their outputs have been considered in developing the CPT, and their influence is considered via the other Advisory Committee channels. Tufts was consulted specifically regarding CPT project scope, priorities, and deliverables. The SPIRIT checklist was a key reference and influenced the creation of the text-based structure and content. A consultative meeting was held with the Budapest Working Group, with additional input pending. It is envisioned that additional advisors, such as HL7 and IHE, will be pursued as we move toward development of the machine-readable template
“EMA has not agreed to take up a position on the Advisory Committee…..Happy to provide comments on any draft templates…”
Other Advisors or Influencers

10. Alignment of CPT with NIH-FDA Template – May 2017
Rationale/Goal
Mutual desire to harmonize CPT and NIH-FDA templates
Acknowledged different audiences: NIH-FDA template targeted at single-center and investigator led studies; CPT targeted at multi-center studies.
Harmonizing templates will drive harmonization in resulting protocols regardless of template used
Both CPT and NIH-FDA templates to be maintained, modifications made to each to achieve greatest harmonization
Updates Included
Alignment on all Level 1 headings, and most Level 2 headings
Revised order/placement of several sections
Where different Level 2 headings are required, they are placed after the common Level 2 headings.
Combined several sections
Harmonized terminology where applicable
NIH-FDA Joint Protocol Team
NIH
Michelle Culp
Cynthia Boucher
Christine Cutillo
Daniel Falk
Shanda Finnigan
Adam Haim
Barbara Karp
Petra Kaufmann
Lynette Nieman
Sarah Read
Megan Ryan
Galia Siegel
Steven Sparenborg
Betty Tai
Aynur Unalp-Arida
James Witter
Anne Zajicek
FDA
Melissa Robb
David Cho
Owen Faris
Peter Kim *
Peter Marks
Eileen Navarro-Almario *
Vaishali Popat *
Rachel Sherman
Legally approved Oct-2018
* Also on FDA’s CPT Working Group

11. Value Proposition – Why Should Sponsors Adopt?
Quality
The expertise of 18+ sponsors has been tapped to develop the template with input from regulators, sites, CROs and an IRB – the work has been done for you.
The template includes TA –specific libraries based on sponsor best practices.
Stakeholders have the opportunity to suggest revisions; the template will be maintained and updated over time.
Broad adoption will help drive greater efficiency for investigators, sites, sponsors, and regulators.
Efficiency
Sponsors can spend less time on low-value customization, and reduce time managing template maintenance.
The template is easy for authors to use.
Sponsors can adopt in a phased approach, and can choose to use either the Word version or Tech-Enabled version. You don’t have to go “all in” at the outset.
Compliance
The template is supported by FDA, and Health Authority feedback to date has been unanimously positive.
Legally approved Oct-2018
Quality + Efficiency + Compliance = Value
Harmonization Value

12. Common Statistical Analysis Plan (SAP) Template - Benefits
Integration of templates
The Common SAP Template seamlessly integrates with the CPT and Common CSR simultaneously decreasing the overall complexity and variability between SAP template structures without limiting or dictating the type of analyses conducted resulting in increased ease of use and efficiency for sites and sponsors leading to downstream improvements in quality for patients.
Efficiency of authoring
The seamless content re-use and consistency in structure between CPT, Common SAP and Common CSR templates ensures that content can be efficiently authored with end uses clearly understood.
Legally approved Oct-2018

13. Common SAP Template – How was it developed?
Inputs:
Member Company SAP templates
Prior FDA feedback on CPT/Statistical Content and CPT version 2 (on which the FDA review was based)
Gamble C, Krishan A, Stocken D, et al. Guidelines for the Content of Statistical Analysis Plans in Clinical Trials. JAMA. 2017;318(23):2337–2343
ICH E9 (R1) draft ‘addendum on estimands and sensitivity analysis in clinical trials to the guideline on statistical principles for clinical trials’  2017
Process:
Author core content based upon review of Member Company templates and other documents
Developed a lean structure focusing on the needs of investigators and regulatory authorities
Incorporated estimands concept based upon draft ICH addendum
Review by extended TransCelerate member company representatives
Legally approved Oct-2018

14. Background: Why a Common Clinical Study Report (CSR)?
Problem Statement
Format and core content of study reports vary from sponsor to sponsor making review difficult for regulators
Study reports have become increasingly complex and lengthy driving up cost and time
Solutions
Develop a streamlined model clinical study report, including format and core content, to ease interpretation
Avoid redundancy
Enable downstream automation of many clinical processes like transparency and submission document authoring
Legally approved Oct-2018
Guiding Principles
Adherence with ICH E3 and CORE (Clarity and Openness in Reporting: E3-based)
“Common” in a CSR: 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 regulators are the first priority
A human readable template that paves the way for content reuse for transparency and submission document authoring

15. The Common CSR Potentially Benefits Many Stakeholders
Near Term
Potential Future State
Near Term Benefits to Sponsors
Reduction in redundant content
Improved way of working - writing lean CSRs with direct references to the protocol & SAP when applicable
Improved efficiency and reduced cycle time for the clinical study report and submission
Near Term Benefits to Regulators
Clinical Study Reports are lean (with direct references to the protocol & SAP when applicable, less duplication)
Aligned with ICH E3, CORE, EU CTR and PDUFA VI
Increased consistency between sponsors
Ease of review
Sponsor
Patient
Regulator
Potential Future Benefits to Sponsors
Availability of machine readable CSR with Content Reuse capability
Automation of downstream processes and reuse of content for transparency
Legally approved Oct-2018
The benefit of the Common Protocol Template (CPT) will be felt by the separate and inter-related groups, as illustrated here.  The first step is the CPT will be used to create protocols supplied by the sponsor to the Investigators.  The Investigator and the site staff will see the common protocol structure in use, ideally by multiple sponsors, with same information in the same section across multiple sponsors.  The use of the CPT is expected to enable the site staff to more quickly develop their required study documents and tools by saving time looking for specific sections in a protocol document. 
Protocols written using the CPT will be sent to the IRBs and Regulators.  The same effect is expected; the IRBs and Regulators will find the same information in the same location in protocols written using the CPT across multiple sponsors.  Use of this CPT, is expected to ease and facilitate the IRB review of protocols.
The use of the CPT is projected to potentially shorten the start-up at the sites and the review by the IRBs and Regulators who will be reviewing information in the same structure across multiple sponsors.
This may result in the study starting sooner, with a benefit to the patient who may be waiting to enter a clinical study.
Potential Future Benefits to Regulators
Increased ease of data interpretation
Increased use of data standards enabling end-to-end use of metadata and traceability
Potential Future Benefits to Patients
Faster access to study results through reuse of content for transparency

16. Thank you