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

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


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


DEVELOPMENT OF CLINICAL TRIAL PROTOCOL

STUDY CONCEPT

PROTOCOL SYNOPSIS

CLINICAL TRIAL PROTOCOL


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


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


Medical

Expert

Sponsor

Stat

PM

PK

CRC

CTP WRITING - CORE TEAM

Medical

Writer


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


Medical

Writer


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


Medical

Writer


Medical

Expert

Sponsor

Stat

PM

PK

CRC

Involved in:

Synopsis

Sample size

Objectives

Endpoints

Full CTP

Statistical methods


Medical

Writer


Medical

Expert

Sponsor

Stat

PM

PK

CRC

Statistician not involved

Sample size too low:

clinically meaningful

difference between

treatment groups

undetected


Medical

Writer


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


Medical

Writer


Medical

Expert

Sponsor

Stat

PM

PK

CRC

PK expert not involved:

e.g. MAD:

wrong frequency to

administer

investigational drug


Medical

Writer


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


Medical

Writer


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


Medical

Writer


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


Medical

Writer


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


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


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


KEY MESSAGES

Invest sufficient time in development of protocol synopsis

Contribution of each team member is important

Protocol writing is a team effort!


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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Writing A Phase I Protocol: A Multidisciplinary Team Approach

Health & Medicine

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