CLINICAL TRIAL PROTOCOL AND PROTOCOL AMENDMENT(S)
contents of a trial protocol should generally include the following
topics. However, site specific information may be provided on separate
protocol page(s), or addressed in a separate agreement, and some of
the information listed below may be contained in other protocol referenced
documents, such as an Investigator's Brochure.
Protocol title, protocol identifying number, and date. Any amendment(s)
should also bear the amendment number(s) and date(s).
Name and address of the sponsor and monitor (if other than the sponsor).
Name and title of the person(s) authorized to sign the protocol and
the protocol amendment(s) for the sponsor.
Name, title, address, and telephone number(s) of the sponsor's medical
expert (or dentist when appropriate) for the trial.
Name and title of the investigator(s) who is (are) responsible for
conducting the trial, and the address and telephone number(s) of the
Name, title, address, and telephone number(s) of the qualified physician
(or dentist, if applicable), who is responsible for all trial-site
related medical (or dental) decisions (if other than investigator).
Name(s) and address(es) of the clinical laboratory(ies) and other
medical and/or technical department(s) and/or institutions involved
in the trial.
Name and description of the investigational product(s).
A summary of findings from nonclinical studies that potentially have
clinical significance and from clinical trials that are relevant to
Summary of the known and potential risks and benefits, if any, to
Description of and justification for the route of administration,
dosage, dosage regimen, and treatment period(s).
A statement that the trial will be conducted in compliance with the
protocol, GCP and the applicable regulatory requirement(s).
Description of the population to be studied.
References to literature and data that are relevant to the trial,
and that provide background for the trial.
Trial Objectives and Purpose
detailed description of the objectives and the purpose of the trial.
scientific integrity of the trial and the credibility of the data from
the trial depend substantially on the trial design. A description of
the trial design, should include:
A specific statement of the primary endpoints and the secondary endpoints,
if any, to be measured during the trial.
A description of the type/design of trial to be conducted (e.g., double-blind,
placebo-controlled, parallel design) and a schematic diagram of trial
design, procedures and stages.
A description of the measures taken to minimize/avoid bias, including:
A description of the trial treatment(s) and the dosage and dosage
regimen of the investigational product(s). Also include a description
of the dosage form, packaging, and labelling of the investigational
The expected duration of subject participation, and a description
of the sequence and duration of all trial periods, including follow-up,
A description of the "stopping rules" or "discontinuation
criteria" for individual subjects, parts of trial and entire
Accountability procedures for the investigational product(s), including
the placebo(s) and comparator(s), if any.
Maintenance of trial treatment randomization codes and procedures
for breaking codes.
The identification of any data to be recorded directly on the CRFs
(i.e., no prior written or electronic record of data), and to be considered
to be source data.
Selection and Withdrawal of Subjects
Subject inclusion criteria.
Subject exclusion criteria.
Subject withdrawal criteria (i.e., terminating investigational product
treatment/trial treatment) and procedures specifying:
When and how to withdraw subjects from the trial/ investigational
The type and timing of the data to be collected for withdrawn subjects.
Whether and how subjects are to be replaced.
The follow-up for subjects withdrawn from investigational product
Treatment of Subjects
The treatment(s) to be administered, including the name(s) of all
the product(s), the dose(s), the dosing schedule(s), the route/mode(s)
of administration, and the treatment period(s), including the follow-up
period(s) for subjects for each investigational product treatment/trial
treatment group/arm of the trial.
Medication(s)/treatment(s) permitted (including rescue medication)
and not permitted before and/or during the trial.
Procedures for monitoring subject compliance.
Assessment of Efficacy
Specification of the efficacy parameters.
Methods and timing for assessing, recording, and analysing of efficacy
Assessment of Safety
Specification of safety parameters.
The methods and timing for assessing, recording, and analysing safety
Procedures for eliciting reports of and for recording and reporting
adverse event and intercurrent illnesses.
The type and duration of the follow-up of subjects after adverse events.
A description of the statistical methods to be employed, including
timing of any planned interim analysis(ses).
The number of subjects planned to be enrolled. In multicentre trials,
the numbers of enrolled subjects projected for each trial site should
be specified. Reason for choice of sample size, including reflections
on (or calculations of) the power of the trial and clinical justification.
The level of significance to be used.
Criteria for the termination of the trial.
Procedure for accounting for missing, unused, and spurious data.
Procedures for reporting any deviation(s) from the original statistical
plan (any deviation(s) from the original statistical plan should be
described and justified in protocol and/or in the final report, as
The selection of subjects to be included in the analyses (e.g., all
randomized subjects, all dosed subjects, all eligible subjects, evaluable
Direct Access to Source Data/Documents
sponsor should ensure that it is specified in the protocol or other
written agreement that the investigator(s)/institution(s) will permit
trial-related monitoring, audits, IRB/IEC review, and regulatory inspection(s),
providing direct access to source data/documents.
Quality Control and Quality Assurance Procedures
of ethical considerations relating to the trial.
Data Handling and Record Keeping
Financing and Insurance
and insurance if not addressed in a separate agreement.
policy, if not addressed in a separate agreement.
(NOTE: Since the protocol and the clinical trial/study report are closely
related, further relevant information can be found in the ICH Guideline
for Structure and Content of Clinical Study Reports.)