How was the Common Protocol Template Developed and What Does it Look Like? November 2018

How was the Common Protocol Template (CPT) First Developed How was the Common Protocol Template (CPT) First Developed? Structure and Content Structure – Level 1 and 2 Headings Main focus - Streamlined structure for logical flow Review of structure (Table of Contents) of anonymized 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 Legally approved Oct-2018 Content development was a logical, thoughtful approach, acknowledging that not one member company protocol was preferred over another, as all meet the GCP and ICH requirements.  The main focus was to streamline the content to allow for consistency across the pharma industry. The structure of the Level 1 and 2 headers are intended to be used/adopted for use without changes.  If a section does not apply, retaining the heading and inserting “NA” or “Not applicable” will allow a consistent protocol structure for multiple sponsors across industry.  The impact will be that the Investigators, study staff and IRBs will be able to locate the same information in the same place and meaning the same thing across multiple protocols. The Level 3 headers and lower level headers can be adjusted as needed . GCP and ICH guidance was reviewed as the initial step for creating common core content.  A comparison of the content in the member companies protocols was completed as part of the development of the common core content. With intended focus on sites (investigators/coordinators), the core includes content to (1) evaluate whether a site has the patients/facilities/time to conduct a protocol, and (2) the specific information needed to conduct the protocol. Other items have been placed in appendices (including governance-related text) where they are accessible but do not impact the flow of the core information. The core content guidance provided with the template also suggests that the reader refer to the primary sources of information (e.g. IB), where possible, rather than bulk repetition in the protocol. This organization in the document has the added advantage of streamlining the protocol overall. This streamlining is expected to allow more efficient use of the protocol. ​ 

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

How was the CPT Developed? Final Template Focus on sites (investigators/study staff) to have access to protocol information. 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. Specific information to evaluate the ability to conduct a protocol, e.g. does the site have the patient population. Refer to primary sources of information (e.g. Investigator Brochure) instead of duplicating information in the protocol. Model sections and text located in Appendices to be accessible, but will not impact the flow of the core protocol-specific information Legally approved Oct-2018 Content development was a logical, thoughtful approach, acknowledging that not one member company protocol was preferred over another, as all meet the GCP and ICH requirements.  The main focus was to streamline the content to allow for consistency across the pharma industry. The structure of the Level 1 and 2 headers are intended to be used/adopted for use without changes.  If a section does not apply, retaining the heading and inserting “NA” or “Not applicable” will allow a consistent protocol structure for multiple sponsors across industry.  The impact will be that the Investigators, study staff and IRBs will be able to locate the same information in the same place and meaning the same thing across multiple protocols. The Level 3 headers and lower level headers can be adjusted as needed . GCP and ICH guidance was reviewed as the initial step for creating common core content.  A comparison of the content in the member companies protocols was completed as part of the development of the common core content. With intended focus on sites (investigators/coordinators), the core includes content to (1) evaluate whether a site has the patients/facilities/time to conduct a protocol, and (2) the specific information needed to conduct the protocol. Other items have been placed in appendices (including governance-related text) where they are accessible but do not impact the flow of the core information. The core content guidance provided with the template also suggests that the reader refer to the primary sources of information (e.g. IB), where possible, rather than bulk repetition in the protocol. This organization in the document has the added advantage of streamlining the protocol overall. This streamlining is expected to allow more efficient use of the protocol. ​ 

What Does the CPT Look Like? Libraries group and store point and click content used to populate the template Core streamlined, focused on site needs Participant Libraries Core Protocol Backbone Common Level 1 & 2 Headings Common text Used across all phases Focus on sites (investigators/study staff) Healthy Volunteer Patient Common Text can be used “as is”- relevant across study types Pediatric Therapeutic Area Libraries (various) Endpoint Definitions modeled for TAs/indications Legally approved Oct-2018 Backbone contains the protocol information common to all phases, populations, and therapeutic areas. The core is streamlined and focused on the sites’ needs. Libraries group and store content to be inserted into the core backbone and contain specific information related to therapy, country, study population (e.g., patient, healthy volunteer) needs.   Appendices provide additional information that can be accessed when needed (e.g., abbreviations, company specific content). Appendices are omitted if not applicable. Highlight that the template is for all TAs. Additional content available for some specific therapeutic areas. Appendices to apply as applicable Appendices Non-study specific info, items triggered by event A sustainable Governance Model is in development Common Protocol Template and Guidance Governance Model Implementation Toolkit Materials

What Does the CPT Look Like? CPT Editions Basic Word Edition A document based template for use across phases and study types Use as-is or modify current format template to reflect CPT content Initial Public Release: December 2015 Technology Enabled Edition An MSWord-based template with add-ins Automation to leverage “point and click” protocol text Capture of protocol-level metadata to facilitate content reuse and extraction Initial Public Release: June 2016 For Microsoft Windows-based usage, not compatible with Apple iOS. Legally approved Oct-2018

What does the CPT Look Like? Basic Word Edition Word documents; No installation needed. Locate the Basic Word Edition files on the TransCelerate CPT Website Under” Common Protocol Template Tools and Resources,” click on the blue bar “Basic Word Edition Template and Guidelines” to reveal all of the available resources. To download the CPT BWE, click on “Basic Word Edition Core Template.” Participant and Therapeutic Area Libraries are also available. To download any of the files, click on the file and “Save As” to add the files to your desktop or local drive. Start authoring your protocol. Legally approved Oct-2018

What does the CPT Look Like? Basic Word Edition Instructional text provided as red hidden text available by toggling paragraph marks “Start” and “stop” of common text is indicated in green font Legally approved Oct-2018 “Start” and “stop” of common text is indicated in green font

What Does the CPT Look Like What Does the CPT Look Like? Tech-Enabled Edition It still looks like paper….but its not! The Technology Enabled Edition of the Common Protocol Template (CPT) avoids media breaks by capturing structured and unstructured information in variables available for export and reuse downstream. Libraries make model content available Common layout of content Export variables to XML or Excel for reuse in other processes Legally approved Oct-2018 Information is captured in variables

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