Study Protocol (Study Plan)

Several types of documents are required to direct the

conduct of the study. These aim to :
State general policies, decisions and principles
Inform the staff carrying out the study
Provide retrospective documentation of what was planned

The documents types include
Policy statements,
Standard operating procedures, and
The protocol or study plan.

The study Protocol contains the overall plan of the study,
describing the methods and materials to be used.
Protocol/Study Plan
The protocol is a pivotal document
For communication to study staff
To fix study objectives
For contractual reasons (e.g. between contracted lab and
sponsor)
To provide overall timelines (the Master plan)

Functions of the protocol
Specification for study activities (which activities, when?)
Defines responsibilities
Defines resource needs
A basis for contracts
Basis for regulatory discussions (QA, Audits)
Protocol/Study Plan
GLP Requirements
I: Study Identification
Must be unique to each study
Used to identify study data
Must identify study compound
May identify concerned department
Can be cross-referenced to other studies
Protocol/Study Plan
GLP Requirements
II. Title and statement of purpose
Why the study is being performed
Regulatory considerations
The title contains information on at least, the species,
duration, test article and route of administration

The study has to be planned in advance, the designer should
have a clear understanding of the purpose.
To ensure that the results cannot unknowingly be utilised
for a purpose for which they are unsuited
Protocol/Study Plan
GLP Requirements
III. Test and control item description
Chemical name
Batch identification
Specifications

IV. Test facility/sponsor information
Addresses
Location(s) of study
Use of consultants
Use of sub-contractors
Protocol/Study Plan
GLP requirements
V. Study Director and responsible personnel
Must identify
The Study Director
Principal Investigators for multi-site studies
May identify
Other Responsible Scientists
The Study Monitor

VI. Dates
Proposed start and finish dates
Protocol approved by Study Director
Date signed by management and by sponsor
Protocol/Study Plan
GLP requirements
VII. The test system
A description of
Species, strain, health status
Age, weight, source
Environmental conditions, husbandry
Diet, source and possible contaminants

Justification of choice
Guidelines, regulations
Background data
Protocol/Study Plan
GLP requirements
VIII. Experimental design (depends on study type)
Gives information about
a) Dosing details
Dose levels and frequency
Vehicles
Preparation
QC

b) Randomization
Pretest
During study/cages/racks
Protocol/Study Plan
GLP requirements
VIII. Experimental design (cont`d)
c) Parameters during the study
Body weights
Clinical pathology
Necropsies/pathology

d) Statistical methods
e) Archives post-study
f) Quality assurance
Protocol/Study Plan
Approval/Review
Approved and dated by Study Director BEFORE start
Allow time for protocol review by QA
Allow time for corrections
Allow time for distribution to study staff
Allow time for pre-study meeting


Protocol/Study Plan
Protocol Amendments
Planned study changes to react to results or other factors
Clear and complete reason for amendment
Has to be approved by Study Director and Sponsor
Must be circulated to all staff
Must go through the review process
New instructions must be clear

It is not acceptable to use amendments to legalize
omissions or errors during the study!
Standard Operating Procedures
SOPs are
Written detailed instructions
Cover all lab activities
Provide in-depth description of who does what, when,
where, how?

Use standards (i.e. SOPs) as the liberator that relegates the
problems that have already been solved to the field of
routine, and leaves the creative faculties free for the
problems that are still unsolved
Standard Operating Procedures
SOP Characteristics:
Cover all activities: administration, safety/hygiene, technical
Readable, clear precise, practical
Staff must fully understand and rigorously follow the SOP
There must be a responsible person for each SOP
There should be a formal control system for easy and rapid
update (SOP is a dynamic document, amendments are
evidence that the lab uses the SOPs)
Should be immediately available to the person doing the
work
There must be a centralized organization

Standard Operating Procedures
A centralized organization ensures:
A standard SOP format is set and imposed
A single point for ID/numbers issuance
management of changes (versions) for traceability
SOP distribution or withdrawal (destruction)
Cross-departmental coherence of SOPs
SOP review by QAU

Standard Operating Procedures
Benefits from a good SOP system
Standardized, consistent procedures reduce test-to-test
variability
Optimizes the way things are done
Recorded technical and administrative improvements
Approval by management formalizes their commitment to
quality
Ease of documenting complicated techniques
Continuity in case of personnel turn-over
A means of communication e.g during audits, visits,
technology transfers

Standard Operating Procedures
Sections in SOPs should be standardized e.g.
Title
Purpose
General: highlights principal features, gives background
information
Procedure: instructions in logical chronological order
References and help (who to contact in case of problems
Date: At first Lumbar puncture, completion of treatment,
scheduled follow-up visits and unplanned visits as the case may
necessitate
Place: Omugo Health centre
Responsible: Dr. Enock Matovu, Mr. Albino Louga

Purpose/Objectives
To describe the process for estimation of the CSF IgM concentration in patients
treated in the Clinical study comparing the nifurtimox eflornithine combination
with the standard eflornithine regimen for the treatment of Trypanosoma brucei
gambiense human African trypanosomiasis in the meningo-encephalitic phase.

Principle
The latex Igm is used to detect IgM in cerebraspinal fluid. When testing serial
dilutions of CSF, an end titre is obtained, which gives an estimation of the CSF
IgM concentration as well as the presence of intrathecal IgM synthesis. This
indicates inflammation of the Central Nervous system, that may result from
invasion of the compartment by trypanosomes. It therefore gives indirect evidence
that the CNS has been invaded by trypanosomes.
Example of an SOP:

SOP for determination of CSF IgM titres


Applicability:

Principal Investigators, Co-Investigator(s), Study Coordinator, Local Safety
Monitor, Statistician, Clinical Monitor and Data Manager, Nurse(s), Project
Manager

Version History:
Prepared by:
Dr. Enock Matovu Co-Investigator
Signature Date:
Approved By:
Dr Freddie Kansiime
Dr. Charles Wamboga
Dr. Lawrence Yamuah
Dr. Deborah Kioy
Principal
Investigator
Co-Investigator
Clinical Monitor
Project manager
Signature
Signature
Signature
Signature
Approval date:
Approval date:
Approval date:
Approval date:
Version Type of version Application Date
2.0 Creation of SOP September 19, 2005
Approval:
Procedures

Reconstitution of the lyophilised latex reagent
1. Resuspend the latex reagent with 1ml of buffer per vial.
2. Mix gently for 30 seconds.
3. Use the same day, or store any left over in the freezer for future use

Diluting the test CSF samples
1. For each sample, fill all the wells of a microtitre plate row with 50l of buffer
2. Pipette 50l of the CSF sample into the first well of the respective row. Mix well
by pipetting 5 times, then transfer 50l from the first into the next well.
3.Repeat the mixing and transferring until the last well in the row. In this way you
will have prepared a dilution series 1:2-1:4096 (you may mark the dilutions on the
upper border of the plate to avoid confusion)

Execution of the test
1. Adjust the speed of the rotator to 70 rotations per minute
2. Dispense 20l of latex reagent onto a test zone of test card
e.t.c