DocumentationGlossary Term
ICH E6(R3) 1.44
A document that describes the objectives, design, methodology, statistical considerations, and organization of a clinical trial.
The protocol serves as the scientific and operational foundation of every clinical trial, functioning as the authoritative document that defines precisely how the study will be conducted from initiation through completion. This comprehensive document describes the background and rationale for the trial, specifies the objectives and endpoints, details the study design and methodology, establishes the statistical approach, and outlines the organizational structure and responsibilities. Every aspect of trial conduct flows from the protocol, making it the essential reference document for all personnel involved in the study.
A well-constructed protocol provides sufficient detail to ensure consistent implementation across all participating sites while maintaining scientific rigor. Key elements include clear statements of primary and secondary objectives, precise definitions of the study population through inclusion and exclusion criteria, detailed descriptions of study procedures and assessments with specific timing requirements, specifications for the investigational product including dosing regimens and administration requirements, and comprehensive guidance on safety monitoring and adverse event reporting. The protocol must also address statistical considerations including sample size justification, analysis populations, and the planned analytical approach for primary and secondary endpoints.
The protocol must receive approval from relevant Institutional Review Boards, Independent Ethics Committees, and regulatory authorities before trial initiation, and any subsequent changes must be implemented through formal protocol amendments. Deviation from the approved protocol is generally prohibited, as such departures may compromise participant safety, data integrity, or the scientific validity of the trial. However, the protocol itself must acknowledge that immediate deviations to protect participant safety are always permissible and indeed required when necessary. Investigators and study staff must be thoroughly familiar with protocol requirements before initiating any study activities.
Protocol development represents a collaborative effort involving clinical scientists, regulatory specialists, biostatisticians, and operational experts. The document must balance scientific rigor with practical feasibility, recognizing that overly complex protocols may lead to implementation challenges and higher deviation rates. Modern protocols increasingly incorporate adaptive design elements that allow pre-specified modifications based on accumulating data, though such modifications must be carefully planned and controlled to maintain trial integrity.
Study initiation
"Before enrolling the first participant, the investigator conducted a site initiation meeting ensuring all staff had reviewed the protocol thoroughly and understood the visit schedules, assessment requirements, and safety reporting procedures."
Eligibility determination
"The clinical research coordinator consulted the protocol's inclusion and exclusion criteria to confirm that the prospective participant's medical history and current medications did not preclude enrollment in the study."
Protocol amendment
"When preliminary safety data revealed an unexpected finding, the sponsor developed a protocol amendment adding more frequent monitoring assessments and submitted it for IRB approval before implementing the change at any site."
A printed, optical, or electronic document designed to record all protocol-required information on each trial subject.
Documents that individually and collectively permit evaluation of the conduct of a study and the quality of the data produced.
A compilation of the clinical and nonclinical data on the investigational product that are relevant to the study of the product in human subjects.
A written description of a change or formal clarification to a protocol that must be approved by the sponsor, IRB/IEC, and regulatory authorities before implementation.
Original documents, data, and records from which a subject's clinical trial data are obtained, including hospital records, clinical and office charts, laboratory notes, memoranda, pharmacy records, and patient diaries.
ICH E6(R3) 1.44
A document that describes the objectives, design, methodology, statistical considerations, and organization of a clinical trial.
The protocol serves as the scientific and operational foundation of every clinical trial, functioning as the authoritative document that defines precisely how the study will be conducted from initiation through completion. This comprehensive document describes the background and rationale for the trial, specifies the objectives and endpoints, details the study design and methodology, establishes the statistical approach, and outlines the organizational structure and responsibilities. Every aspect of trial conduct flows from the protocol, making it the essential reference document for all personnel involved in the study.
A well-constructed protocol provides sufficient detail to ensure consistent implementation across all participating sites while maintaining scientific rigor. Key elements include clear statements of primary and secondary objectives, precise definitions of the study population through inclusion and exclusion criteria, detailed descriptions of study procedures and assessments with specific timing requirements, specifications for the investigational product including dosing regimens and administration requirements, and comprehensive guidance on safety monitoring and adverse event reporting. The protocol must also address statistical considerations including sample size justification, analysis populations, and the planned analytical approach for primary and secondary endpoints.
The protocol must receive approval from relevant Institutional Review Boards, Independent Ethics Committees, and regulatory authorities before trial initiation, and any subsequent changes must be implemented through formal protocol amendments. Deviation from the approved protocol is generally prohibited, as such departures may compromise participant safety, data integrity, or the scientific validity of the trial. However, the protocol itself must acknowledge that immediate deviations to protect participant safety are always permissible and indeed required when necessary. Investigators and study staff must be thoroughly familiar with protocol requirements before initiating any study activities.
Protocol development represents a collaborative effort involving clinical scientists, regulatory specialists, biostatisticians, and operational experts. The document must balance scientific rigor with practical feasibility, recognizing that overly complex protocols may lead to implementation challenges and higher deviation rates. Modern protocols increasingly incorporate adaptive design elements that allow pre-specified modifications based on accumulating data, though such modifications must be carefully planned and controlled to maintain trial integrity.
Study initiation
"Before enrolling the first participant, the investigator conducted a site initiation meeting ensuring all staff had reviewed the protocol thoroughly and understood the visit schedules, assessment requirements, and safety reporting procedures."
Eligibility determination
"The clinical research coordinator consulted the protocol's inclusion and exclusion criteria to confirm that the prospective participant's medical history and current medications did not preclude enrollment in the study."
Protocol amendment
"When preliminary safety data revealed an unexpected finding, the sponsor developed a protocol amendment adding more frequent monitoring assessments and submitted it for IRB approval before implementing the change at any site."
A printed, optical, or electronic document designed to record all protocol-required information on each trial subject.
Documents that individually and collectively permit evaluation of the conduct of a study and the quality of the data produced.
A compilation of the clinical and nonclinical data on the investigational product that are relevant to the study of the product in human subjects.
A written description of a change or formal clarification to a protocol that must be approved by the sponsor, IRB/IEC, and regulatory authorities before implementation.
Original documents, data, and records from which a subject's clinical trial data are obtained, including hospital records, clinical and office charts, laboratory notes, memoranda, pharmacy records, and patient diaries.