E6: CLINICAL TRIAL PROTOCOL AND PROTOCOL AMENDMENT(S)

Question 1

Clinical Trial Protocol and Protocol Amendment(s)

6

Answer 1

The 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.

Question 2

Clinical Trial Protocol and Protocol Amendment(s)

General Information

6.1.1

Answer 2

Protocol title, protocol identifying number, and date. Any amendment(s) should also bear the amendment number(s) and date(s).

Question 3

General Information

6.1.2

Answer 3

Name and address of the sponsor and monitor (if other than the sponsor).

Question 4

General Information

6.1.3

Answer 4

Name and title of the person(s) authorized to sign the protocol and the protocol amendment(s) for the sponsor.

Question 5

General Information

6.1.4

Answer 5

Name, title, address, and telephone number(s) of the sponsor’s medical expert (or dentist when appropriate) for the trial.

Question 6

General Information

6.1.5

Answer 6

Name and title of the investigator(s) who is (are) responsible for conducting the trial, and the address and telephone number(s) of the trial site(s).

Question 7

General Information

6.1.6

Answer 7

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).

Question 8

General Information

6.1.7

Answer 8

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.

Question 9

6.2 - Background Information

6.2.1

Answer 9

Name and description of the investigational product(s).

Question 10

Background Information

6.2.2

Answer 10

A summary of findings from nonclinical studies that potentially have clinical significance and from clinical trials that are relevant to the trial.

Question 11

Background Information

6.2.3

Answer 11

Summary of the known and potential risks and benefits, if any, to human subjects.

Question 12

Background Information

6.2.4

Answer 12

Description of and justification for the route of administration, dosage, dosage regimen, and treatment period(s).

Question 13

Background Information

6.2.5

Answer 13

A statement that the trial will be conducted in compliance with the protocol, GCP and the applicable regulatory requirement(s).

Question 14

Background Information

6.2.6

Answer 14

Description of the population to be studied.

Question 15

Background Information

6.2.7

Answer 15

References to literature and data that are relevant to the trial, and that provide background for the trial.

Question 16

6.3 - Trial Objectives and Purpose

Answer 16

A detailed description of the objectives and the purpose of the trial.

Question 17

6.4 - Trial Design

6.4.1

Answer 17

The 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.

Question 18

Trial Design

6.4.2

Answer 18

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.

Question 19

Trial Design

6.4.3

Answer 19

A description of the measures taken to minimize/avoid bias, including:

(a) Randomization.

(b) Blinding.

Question 20

Trial Design

6.4.4

Answer 20

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 product(s).

Question 21

Trial Design

6.4.5

Answer 21

The expected duration of subject participation, and a description of the sequence and duration of all trial periods, including follow-up, if any.

Question 22

Trial Design

6.4.6

Answer 22

A description of the “stopping rules” or “discontinuation criteria” for individual subjects, parts of trial and entire trial.

Question 23

Trial Design

6.4.7

Answer 23

Accountability procedures for the investigational product(s), including the placebo(s) and comparator(s), if any.

Question 24

Trial Design

6.4.8

Answer 24

Maintenance of trial treatment randomization codes and procedures for breaking codes.

Question 25

Trial Design

6.4.9

Answer 25

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.

Question 26

6.5

Selection and Withdrawal of Subjects

Answer 26

6.5.1 Subject inclusion criteria.

6.5.2 Subject exclusion criteria.

6.5.3 Subject withdrawal criteria (i.e., terminating investigational product treatment/trial treatment) and procedures specifying:

(a) When and how to withdraw subjects from the trial/ investigational product treatment.

(b) The type and timing of the data to be collected for withdrawn subjects.

(c) Whether and how subjects are to be replaced.

(d) The follow-up for subjects withdrawn from investigational product treatment/trial treatment.

Question 27

6.6 Treatment of Subjects

Answer 27

6.6.1 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.

6.6.2 Medication(s)/treatment(s) permitted (including rescue medication) and not permitted before and/or during the trial.

6.6.3 Procedures for monitoring subject compliance.

Question 28

6.7 Assessment of Efficacy

Answer 28

6.8.1 Specification of safety parameters.

6.8.2 The methods and timing for assessing, recording, and analysing safety parameters.

6.8.3 Procedures for eliciting reports of and for recording and reporting adverse event and intercurrent illnesses.

6.8.4 The type and duration of the follow-up of subjects after adverse events.

Question 29

6.9 Statistics

Answer 29

6.9.1 A description of the statistical methods to be employed, including timing of any planned interim analysis(ses).

6.9.2 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.

6.9.3 The level of significance to be used.

6.9.4 Criteria for the termination of the trial.

6.9.5 Procedure for accounting for missing, unused, and spurious data.

6.9.6 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 appropriate).

6.9.7 The selection of subjects to be included in the analyses (e.g., all randomized subjects, all dosed subjects, all eligible subjects, evaluable subjects).

Question 30

6.10

Direct Access to Source Data/Documents

Answer 30

The 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.