Post on 20-Jan-2017
WRITING A PHASE I PROTOCOL:
A MULTIDISCIPLINARY TEAM APPROACH
Ellen Van Bavel, PhD
Senior Medical Writer, SGS Life Science Services
SAFETY & EFFICACY CLINICAL TRIAL SOLUTIONS SGS Life Science Services Biopharm Day Seminar – Antwerp, October 29, 2015
2 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015
MISCONCEPTIONS OF CLINICAL TRIAL
PROTOCOL DEVELOPMENT
1 day to
develop
protocol
synopsis
1 week to
develop
protocol
Why do we
need input
from Stat?
Half page
synopsis is
sufficient to
develop protocol
3 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015
DEFINITION OF CLINICAL TRIAL PROTOCOL
ICH E6 definition
A document that describes the objective(s), design,
methodology, statistical considerations, and organization
of a trial.
Detailed information in ICH E3 guideline for Clinical Study
Report writing => designing CTP corresponding to
methods of ICH E3:
Ensures CTP contains text required for CSR
Simplifies CSR writing
4 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015
DEVELOPMENT OF CLINICAL TRIAL PROTOCOL
STUDY CONCEPT
PROTOCOL SYNOPSIS
CLINICAL TRIAL PROTOCOL
5 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015
PROTOCOL SYNOPSIS: BASIC ELEMENTS
Sponsor’s name CLINICAL STUDY PROTOCOL - Study number xx-mmm-yyyy (draft x)
PROTOCOL SYNOPSIS
Study Title
Product Clinical Phase
Protocol Number Indication
Eudract Number
IND Number
Sponsor Sponsor’s name
Sponsor Representative Sponsor Representative, MD
Clinical Center(s)
Objectives:
The primary objective of this study is to ...
Secondary objectives are to …
Overview of Study Design:
Open-label / double-blind
Parallel / crossover
Number of treatments (dose regimen, formulation, duration etc)
Method of assignment to treatment
Single / multi center
Control: placebo, no treatment, active drug, historical?
…
Study Population:
e.g. healthy male volunteers
In total x subjects are planned to be enrolled.
Eligibility Criteria:
Inclusion Criteria:
Exclusion Criteria:
Test Product, Dose, Mode of Administration:
Reference Product, Dose, Mode of Administration:
Study/Treatment Duration:
e.g., The study consists of a screening phase (within x days before the first administration of study drugs),
…. The total study length is approximately x days; which includes the screening phase.
Criteria for Evaluation:
Pharmacokinetic
6 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015
FULL CTP - ADDITIONAL ELEMENTS
Introduction
Rationale of design (ICH E3)
Prior and concomitant medication
Stopping rules (subject/study, criteria)
Replacement of subjects
More elaborate description of assessments
Statistics: Data analysis
7 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015
Medical
Expert
Sponsor
Stat
PM
PK
CRC
CTP WRITING - CORE TEAM
Medical
Writer
8 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015
Medical
Expert
Sponsor
Stat
PM
PK
CRC
Involved in:
Synopsis
Design
Objectives/Endpoints
Selection criteria
Assessments
Flow chart
Full CTP
Introduction
Prior and concomitant
medication
Stopping rules
CTP WRITING - CORE TEAM
Medical
Writer
9 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015
Medical Expert not
involved:
e.g. SAD study
period between
subsequent dosing too
short to evaluate sufficient
(safety) data Medical
Expert
Sponsor
Stat
PM
PK
CRC
CTP WRITING - CORE TEAM
Medical
Writer
10 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015
Medical
Expert
Sponsor
Stat
PM
PK
CRC
Involved in:
Synopsis
Sample size
Objectives
Endpoints
Full CTP
Statistical methods
CTP WRITING - CORE TEAM
Medical
Writer
11 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015
Medical
Expert
Sponsor
Stat
PM
PK
CRC
Statistician not involved
Sample size too low:
clinically meaningful
difference between
treatment groups
undetected
CTP WRITING - CORE TEAM
Medical
Writer
12 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015
Medical
Expert
Sponsor
Stat
PM
PK
CRC
Involved in:
Synopsis
Sample size
Objectives/Endpoints
Start dose, SAD, MAD
Timing PK samples
PK parameters
Concomitant medication
Full CTP
Statistical methods
CTP WRITING - CORE TEAM
Medical
Writer
13 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015
Medical
Expert
Sponsor
Stat
PM
PK
CRC
PK expert not involved:
e.g. MAD:
wrong frequency to
administer
investigational drug
CTP WRITING - CORE TEAM
Medical
Writer
14 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015
Medical
Expert
Sponsor
Stat
PM
PK
CRC
Involved in:
Synopsis
Flow chart: Practical
feasibility assessments
Full CTP
Calculation total blood
volume
Lab safety
Study drug preparation
Availability of registered
product to site
Sample logistics
CTP WRITING - CORE TEAM
Medical
Writer
15 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015
Medical
Expert
Sponsor
Stat
PM
PK
CRC
CRC not involved:
More assessments
planned than can be
performed in practice
protocol deviations,
depending on time
window defined
CTP WRITING - CORE TEAM
Medical
Writer
16 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015
Medical
Expert
Sponsor
Stat
PM
PK
CRC
Involved in:
Map out expectations of
Sponsor
Develop detailed timelines
for protocol development
Requirements for study
set-up
Data Management section
CTP WRITING - CORE TEAM
Medical
Writer
17 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015
SDO RA
MA specialist
Lab
Compliance with regulatory
guidance
Liaises with HA
Submission IMP Dossier
Sample handling
Randomization section
Adverse Event section
CTP WRITING - OTHER STAKEHOLDERS
Medical
Writer
18 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015
STABLE PROTOCOL
SYNOPSIS
Assumptions synopsis
Study design is fixed and is endorsed by upper
management/important stakeholders of the client
Elements of protocol synopsis are defined and clear
Flowchart in place
MW department to:
Take ownership of protocol writing activities
Develop full final protocol starting from synopsis
Review sponsor and sites
Timelines protocol finalization
Min. 6 weeks for simple early phase study (FIH + 2 weeks)
Includes 2 drafts and 1 final version
19 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015
NO STABLE PROTOCOL
SYNOPSIS
Assumptions synopsis
Usually no counterpart, or counterpart is not experienced
Study design to be fully developed
Example for simple Phase 1 PK study
Project Manager: 20 hours
Medical Director: 40 hours
PK expert: 16 hours
Statistician: 8 hours
Medical Writer: 16 hours
CRC/PI if CPU involved
Medical expert in therapeutic area (specialist)
Timelines
Additional 4 weeks for development stable synopsis
Other timelines of case study for development full final protocol with
stable synopsis stay applicable
20 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015
KEY MESSAGES
Invest sufficient time in development of protocol synopsis
Contribution of each team member is important
Protocol writing is a team effort!
21 SGS LIFE SCIENCE SERVICES BIOPHARMA DAY – OCTOBER, 29 2015
Life Science Services Van Bavel Ellen
Senior Medical Writer
SGS Belgium NV Phone: +32 (0)15 29 93 13
Generaal De Wittelaan 19A b5 Fax: +32 (0)15 27 32 50
2800 Mechelen, Belgium
E-mail : ellen.vanbavel@sgs.com
Web : www.sgs.com/lifescience
THANK YOU FOR YOUR ATTENTION
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+ 1 866 SGS 5003
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