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HD InsightsLife Cycle of the Clinical Trial

Understanding the conceptual, planning and implementation phases of HD studies

Overall Planning and Implementation

“The key to understanding the overall planning and implementation of a study is to know how to plan a birthday party,” said Ira Shoulson, M.D., founder of the Huntington Study Group. Many activities require attention to detail, a good understanding of standard operating procedures and regulations, and numerous checklists.

What follows describes and provides guidance on the development and implementation of studies conducted by the Huntington Study Group (HSG). This includes activities performed during the conceptual, planning, implementation and closeout phases of a study, otherwise known as the life cycle of a clinical trial.

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Conceptual Phase

The conceptual phase is the initial step in the study development process. During this phase, a study concept and design are developed, and a protocol synopsis is produced. HSG leadership and other key contributors may be responsible for advising and assisting a sponsor in the development of the study concept via a protocol synopsis and protocol, as required. During this phase, a scope of work (SOW) between the HSG and sponsor is developed for the conceptual phase and later expanded to include the planning, implementation and closeout phases.

In HSG studies, during the conceptual phase, the Study Principal Investigator (SPI) and Co-study Principal Investigators are identified and they appoint a Study Steering Committee (SSC). The SSC oversees the conduct and analysis of the trial, and is composed of independent investigators and coordinators or individuals with a particular expertise in the investigational product (IP)/device or the disease/disorder being studied. In general, it is preferred that committee members not serve as enrolling site investigators.

Several planning meetings are held as needed with the sponsor, HSG leadership and other key contributors, as applicable. The purpose of these meetings is to discuss the development of a specific study protocol, protocol synopsis and global aspects of the study, and to determine the expectations of the sponsor and HSG regarding study activities.

Planning

The planning phase encompasses activities required to initiate the study, up to and including the investigator/coordinator orientation meeting. During this phase, the sponsor and HSG leadership. sign off on the study protocol. A member of the project team, usually the Project Manager (PM), will develop a model-informed consent form (ICF) based on HSG’s or the sponsor’s standard operating procedures (SOPs). The participant data collection tools/electronic case report form(s) (eCRFs) will be developed, based on the protocol, by the project team members, in conjunction with the sponsor and data management group, as applicable.

Concurrent with this process, HSG-credentialed sites (sites identified from the current HSG credentialed site list) are sent a site interest letter notifying them of a new study. They are asked to sign a confidentiality disclosure agreement (CDA) to receive the protocol synopsis. If the sites are interested, they complete a feasibility survey that asks questions about the site’s capabilities to perform the study.

Once sites indicate their interest and complete the feasibility survey, a SSC meeting is convened. The SSC is responsible for the selection of study sites, and designates the primary site, SI and primary Site Coordinator (SC), based on the feasibility data and metrics the HSG tracks on each of the sites, such as timeliness to IRB approval and first patient enrolled.

HSG Credentialed site map

Study Start-Up Activities

The identified sites are sent a site selection letter. This starts the study start-up activities and transition to collection of regulatory documents from the sites, as well as the building of the HSG trial master file (TMF) and the investigator site file (ISF) at the site level. In parallel, the HSG finance team will initiate subcontracts with the site.

During this time period, the protocol, ICF and other patient-facing materials will be sent to the central IRB and/or local site IRBs for review and approval. Once all regulatory documents are collected, IRB approval is obtained, training certifications are completed, and there is a fully executed contract, the site may be given the “green light” to begin.

Prior to enrolling the first patient, the site trial leaders must attend the investigator/coordinator meeting. In addition, the sites are asked to complete a dry run with a study participant facsimile to ensure all processes run smoothly.

Implementation

The implementation phase signifies the start of participant enrollment. This phase typically begins following the in-person investigator/coordinator meeting or webinar or one-on-one meetings with a site. Once implementation begins, the PM and Medical Monitor are responsible for maintaining regular communication, as applicable, with the study team and the study sites about screening potential participants, enrollment, study progress and problems, monitoring any safety issue such as serious adverse events (SAEs), compliance issues, protocol deviations, protocol waivers, investigational product disclosures, premature withdrawals, and dosage adjustments.

Study Closeout

The study closeout process has multiple components, including site closure, database closure, finalization of the TMF, analysis and publication.