Protocol Safety and Efficacy Assessment Template

Clinical Trial Application

PSEAT-CTA v2.0: Effective Date 2008-04-01

FOREWORD

The Protocol Safety and Efficacy Assessment Template-Clinical Trial Application (PSEAT-
CTA) should be used by sponsors to summarize the safety and efficacy information in clinical trial protocols that are filed with Health Canada pursuant to Part C, Division 5 of the Food and Drug Regulations.

When completing the PSEAT-CTA the sponsor should complete those sections and fields that apply. In addition, it is understood that certain sections and fields may not apply and should be indicated as such by reporting "Not applicable" in the appropriate area with an accompanying explanatory note. The use of tables to summarize the information is encouraged, where possible.

The PSEAT-CTA is replacing the Preclinical and Clinical Evaluation Report Template (PCERT) listed in Appendix 4 of the Guidance for Clinical Trial Sponsors – Clinical Trial Applications posted in June 2003. Therefore, for additional guidance on preparing the PSEAT-CTA, sponsors should consult the Appendix that accompanies the PSEAT-CTA.

When submitting the PSEAT-CTA to Health Canada, this Foreword note and the Appendix should be deleted.

1. INTRODUCTION

A. SUMMARY OF PRODUCT INFORMATION
Proprietary Name of Drug Product
Non-proprietary or Common
Name of Drug Substance
Sponsor
Dosage Form(s)
Strength(s)
Route of Administration
Proposed Indication(s)
B. INVESTIGATOR'S BROCHURE (if applicable)
Date and Version/Edition Number
Cut-off date for data included in this version/edition of the Investigator's Brochure
C. CONTACT INFORMATION
Contact Person/Name
Telephone and Fax Number, including area code
Email Address

2. PROTOCOL SUMMARY

Trial Title and Protocol Number/Code

Background and Rationale

Trial Objectives

Study Design and Duration

Total Number of Sites and Number of Canadian Sites

List of Investigators

Sample Size

Patient Population

Inclusion Criteria

Exclusion Criteria

Drug Formulation

Dosage Regimen

Washout Period

Pre-study Screening and Baseline Evaluation

Treatment / Assessment Visits

Concomitant Medication

Rescue Medication & Risk Management

Premature Withdrawal / Discontinuation Criteria

Efficacy Variables and Analysis

Safety Variables and Analysis

Statistical Analysis

APPENDIX: GUIDANCE NOTES FOR PROTOCOL SUMMARY

(The following information should be included in the Protocol Summary section of the PSEAT-CTA)

Trial Title and Protocol Number/Code

Provide the title and protocol number/code of the trial. The version number of the protocol should also be provided.

Background and Rationale

A brief, concise introduction into the clinical problem and previous treatments and developments, i.e., pertinent data from previous preclinical/clinical pharmacology studies and therapeutic exploratory studies taking into account relevant scientific literature (citations by consecutive numbering, with list at end of this section; important or not readily available references may be included with the paper submission, if appropriate). This section should also contain information on the new drug.

Rationale: Reasoning and justification for the proposed new approach/ therapy.

Trial Objectives

Statement of the precise goal(s) of the trial (may be subdivided into primary and secondary objectives) which may including testing of the null hypothesis (Ho), i.e., testing a new drug population/ indication etc., as applicable.

Study Design and Duration

1.	The statement of study design should include the method of randomization, blinding and the comparative agent, if applicable.

2.	A "Brief outline of the study conduct" should be included, if applicable.

3.	The design of the study should be able to support any claims related to the proposed study.

4.	Total study duration (anticipated starting/ finishing dates).

5.	Duration for each subject including post treatment period etc.

Total Number of Sites and Number of Canadian Sites

Total number of trial sites with list of countries/geographical areas and number of sites in Canada.

List of Investigators

Qualified Investigator at each Canadian site.

Rationale and calculation for sample size requirement, anticipated drop-out rate etc. The sample determination may include Ho testing and desired power of the study.

Description of specific characteristics of the trial participants (e.g. disease/ stage/ indication/ conditions/ treatment etc.) as applicable and of diagnostic criteria and assessment.

Enumeration of conditions determining participation in the proposed clinical trial.

Enumeration of conditions determining participation in the proposed clinical trial.

Brief description of the study drug(s) and formulation to be used in the clinical trial. The relationship to the formulations used in the preclinical and/or other clinical trials should be delineated, as applicable. This may also include disclosure of the formulation intended to be marketed and/or any bridging studies which may be necessary, planned, initiated and/or already performed if different formulations have been used during clinical development.

Instructions for safe handling.

Rationale for dose selection.
Description of the schedule(s) for using the study drug(s) including escalations/ maintenance / reductions / discontinuation, as applicable.
Description of other supportive measures and dose modifications for specific adverse events (anticipated toxicities), as applicable.

Description for pre-, during- and post-trial, as applicable.

Description of the process of clinical validation for participation in the clinical trial, including methodology / schedule of events.

Schedule of all events / visits / procedures during the clinical trial.

Enumeration and description of all dis-/allowed drug/ medications, in addition to the study drugs.

Description of available supportive measures/ antidotes/ medications/ dosages / procedures (including follow-up) used to help reverse untoward effects or lack of efficacy resulting from any applications of drug(s)/ procedures in connection with the clinical trial.

This section should include any risks, for example, dose dumping from slow release formulations or immunogenicity.

Enumeration of all conditions / criteria and management for drug/ patient's withdrawal or (premature) discontinuation, including voluntary withdrawal by subject without prejudice to future treatment by the physician.
Early stopping rules for the trial.

Description and validation of primary endpoint(s), ie. responses/changes from baseline over time in relation to clinical trial events. Description and validation of related secondary changes (secondary endpoints) following from clinical trial events.

Monitoring/ assessing adverse drug reactions/ adverse events/ toxicities/ clinical laboratory parameters etc. in relation to clinical trial events.

(The following points are presented for consideration while completing this section)

1.	Analysis of trial parameters (primary/ secondary endpoints), population, demographics, as applicable.

2.	Efficacy analysis methods and results of efficacy end-point analysis.

3.	Safety analysis methods and results of safety end-point analysis.

4.	Exploratory end-point analysis: evaluation effect(s) (or lack of effects) of relevant biochemical/ pharmacological etc parameters, as applicable.

5.	Pharmacokinetic endpoint analysis, as applicable.

6.	Interim analysis and role of Data Safety Monitoring Board, as applicable.