Writing A Phase I Protocol: A Multidisciplinary Team Approach

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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

Transcript of Writing A Phase I Protocol: A Multidisciplinary Team Approach

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

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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

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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

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DEVELOPMENT OF CLINICAL TRIAL PROTOCOL

STUDY CONCEPT

PROTOCOL SYNOPSIS

CLINICAL TRIAL PROTOCOL

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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

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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

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Medical

Expert

Sponsor

Stat

PM

PK

CRC

CTP WRITING - CORE TEAM

Medical

Writer

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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

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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

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Medical

Expert

Sponsor

Stat

PM

PK

CRC

Involved in:

Synopsis

Sample size

Objectives

Endpoints

Full CTP

Statistical methods

CTP WRITING - CORE TEAM

Medical

Writer

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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

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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

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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

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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

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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

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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

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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

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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

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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

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KEY MESSAGES

Invest sufficient time in development of protocol synopsis

Contribution of each team member is important

Protocol writing is a team effort!

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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 : [email protected]

Web : www.sgs.com/lifescience

THANK YOU FOR YOUR ATTENTION

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+ 1 866 SGS 5003

+ 65 637 90 111

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+ 1 877 677 2667

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QUESTIONS ?

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