Protocol and Case Record Form

Definition : Protocol
A document that describes objective (s), design, methodology, statistical considerations, and organization of a trial

ICH-GCP Guideline, 1996

What is protocol?
The design and performance of each experimental procedure in humans should be clearly formulated in an experimental protocol A trial sets out to answer one or more questions or objectives that are presented as hypotheses amenable to statistical evaluation. The protocol states the objectives of the trial, provides a rationale for answering the proposed question, and describes the procedures that will be used to answer the study question. It should be detailed enough to allow the trial to be conducted by any appropriately qualified investigators. The protocol will be subject to regulatory and ethical review and should conform to relevant local regulatory standards and other guidelines.

Propose : Protocol
Is to answer the three main questions
Why ? What ? How ?

Anatomy of typical protocol

1. Introduction and Rationale
2. Study Objectives 3. Study Design 4. Study Population 5. Study Procedures 6. Data Analysis and Statistics 7. Ethical Considerations
How ?

Why ?
What ?

Why?
Drug/ Disease background Problem and its significant Rationale - for study/ study design - for dose selection (if applicable)

What?
Objectives
Primary Objective Secondary Objective

How?
Conceptual framework

Study design Study population

Statistician, Sponsor, Scientist, Investigator

Analysis plan
Study procedure

Study design
Open label

Single blind

Placebo control, Active product (s) control or no treatment

Double blind

Double blind, Double dummy

Study population
Type of subjects Inclusion/ Exclusion criteria Total number of patients (N = ???) Hypothesis Statistical testing Study Endpoint (variable)

Study procedure
Study visit (week) ICF Med. history Physical exam Lab tests Drug administration Concomitant Medication Adverse events screening X X X X X X X X X baseline Week 4 Week 8 Week 12

Throughout the study Record throughout the study Record throughout the study

Analysis plan
Efficacy Analysis
Primary endpoints Secondary endpoints

Safety Analysis

Adverse Event

Others
Withdrawal Direct access to source data/document Quality control Ethics committee Data Handing and Record keeping Financing and insurance Publication policy Supplement

Study Procedure and Administrative Manual (SPAM)

Support document of protocol, including detail of study procedures e.g. tissue preparation, preparation of serum samples for central laboratory Including administrative issues, e.g. list of study t e a m , a d dr e s s o f c en t r a l l a b or a t or y

Protocol Amendment
Concern of the deficiencies of protocol - Resulting the removal or addition of selection criteria Concern safety - Newly found (Serious) Adverse Event Interim analysis shows the study drug has outstanding efficacy, then protocol amendment should be made. Otherwise, the patients lose benefit if they still receive placebo.

Protocol deviation/ Violation

Minor Violation Noncompliance with the protocol but the incident does not significantly effect on the study participants right, safety, welfare or on the integrity of the resultant data e.g. having protocol-required laboratory test 1 day out of time window of protocol

Protocol Deviation/ Violation

Major Violation Noncompliance with the protocol but the incident significantly effects on the study participants right, safety, welfare or on the integrity of the resultant data (the data cannot be used to support of the study drug), e.g. recruitment of patient that did not meet eligibility requirement

Reporting of protocol Violation/Deviation to FDA

If the protocol violations result in; The termination of the study Falsification of data

Note: If the protocol deviations present a serious risk to study subjects, those incidents should be reported to ethics committee

Whats the different from general practice

More strictness on every details; Medical Record Physical Examination Lab Tests Drug Administration Concomitant medication Adverse event

Concomitant disease/ medication/ procedure?

To purify the efficacy and safety Usually protocol also requests to record previous diseases together with procedures and treatments that used with those diseases. To prevent drug interaction

Case Record Form (CRF)

document designed to record all of protocol required on each clinical subject

A printed, optical, or electronic

How are clinical data collected for the analysis?

Protocol is written perfectly. Eligible patients are enrolled into study. The investigator has a professional team. All components can not produce the good result of the study if all clinical data can not be properly collected and transferred for analysis. But how?

How are clinical data collected for the analysis?

All relevant information have to be recorded on CRF. So much missing information, the result of the study can be distorted.

Anatomy of typical CRF

Easy to read and follow Easy to fill in Self-explanation Questions are organized in repeated sequence across visits, if possible Construct on a visit-by-visit basis Designed to match with required data
LOCK & KEY

Protocol Name

Example of Printed CRF

1. Age < 45 2. Nave case

1. Hypersensitivity to study drug 2. Woman with child bearing potential

Complete The inclusion/ exclusion criteria

Protocol name

Thank you