sponsor/cro responsibilities-gcp workshop 27 feb 2017

GCP Workshop: Sponsor/CRO Responsibilities

Hanaa Abdel-Maguid

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GCP Definition

Sponsor/CRO Responsibilities

Regulatory Affairs

Project Management

Clinical Operations

Biometrics

Medical Writing

Pharmacovigilance

Quality Assurance

Contents

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GCP Definition


Definition

A person or an organization (commercial, academic, or other)

contracted by the sponsor to perform one or more of a sponsor's trial-

related duties and functions. ICH-GCP E6 (R2) § 1.2

CRO Responsibilities:

Implement systems and procedures for conduct of and assessment

of safety in clinical trials

Conduct CTs in accordance with the applicable regulations and

guidelines

Abide by contract signed with the sponsor

Communicate concerns to the sponsor in a timely manner

Maintain accurate records

Contract Research Organization (CRO)

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Pharmacovigilance& Safety Reporting

Medical & Biometrics Services

RegulatoryAffairs

CRO Responsibilities

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Project Management & ClinOps


Regulatory Affairs


Clinical trials should be conducted in accordance with the ethical

principles that have their origin in the Declaration of Helsinki, and that

are consistent with GCP and the applicable regulatory requirement(s).

(ICH GCP E6(R2) § 2.1

The role of RA department is to ensure compliance (in relation to

trials) Adherence to all the trial-related requirements, Good Clinical

Practice requirements, and the applicable regulatory requirements.

(ICH GCP E6(R2) § 1.15

This compliance is maintained by performing several activities in

Consequential manner.

Regulatory Authority


Regulatory Affairs Activities

1- Receipt of all Study Documents

2- Study Documents Country Adaptations

3- Translation & Verification (for any document handed to patients)

4- EC Submission & EC approval.

5- RA Submission & RA approval.

6- Concerned authorities submission and approval (in case of biological samples exportation).

7- Investigator Budget negotiation/ Contracts Execution

8- Import License submission & approval.

9- MOH Clearance Authorization submission & approval.

10-IMP delivery to sites & Site initiation.


Project Management

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Vendor Management and Qualification

Translation

Laboratories

Radiology

Drug Depot

Contracting (Sponsor, investigator, Vendor)

A written, dated, and signed agreement between two or more involved parties

that sets out any arrangements on delegation and distribution of tasks and

obligations and, if appropriate, on financial matters. The protocol may serve as

the basis of a contract. ICH-GCP E6 (R2) § 1.17

Clinical Project Management

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Project Oversight:

Ensure the interim and final project deliverables meet the sponsor’s

time, quality, and cost expectations;

Provide leadership, co-ordination and management of the project

team through start up, conduct, tracking, quality and regulatory

compliance and close-out activities;

Complete and monitor actual hours and expenses versus budget

Review and approve costs and ensure timely invoicing.

Clinical Project Management

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Monitoring Plan

Communication Plan

Risk Management Plan

Safety Plan

CRF completion guidelines

Data Management Plan

Clinical Project Plans

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ClinicalOperations Management

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Clinical Ops. Activities

• Site Selection (FQ)

• Pre-Study Visit (PSVs)

Start Up

• Study Site Initiation

• Clinical Monitoring• Monitoring

Report

Study Conduct

• Close Out Visits

Study Closure

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Clinical Monitoring

Monitor's Responsibilities

The monitor(s) in accordance with the sponsor’s requirements should

ensure that the trial is conducted and documented properly by carrying

out the necessary activities when relevant and necessary to the trial

and the trial site: ICH-GCP E6 (R2) § 5.18.4

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IRB/IECAPPROVAL

OPINION

SUBJECTENROLLMENT

MONITORING VISITS

During the monitoring visits, the Monitor will verify:

COMPLIANCEwith GCP andPROTOCOL

IP DISPENSING&

ACCOUNTABILITY

ADVERSEEVENT

REPORTING

CRFCOMPLETION

vs SOURCEDOCUMENTS

S FT IU LD EY

STUDYINITIATION

that the Investigator maintains the essential documents (ICH/GCP § 5.18.4)

S FT IU LD EY

Clinical Monitoring

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CRFCRF

CRF DRF

code breaking material

OTHER

MATERIALS INVESTIGATOR’s

FILE ARCHIVE

to ensure that :

all SAEs have been reported to the

Sponsor

all CRFs have been verified against

source documents

all queries have been resolved by the

Investigator

all unused drugshave been returned to

the Sopnsor for destruction, and all decoding envelopeshave been retrieved

all unusedmaterials

have been retrievedfrom the study site

all essential documents have been maintained by

the Investigator

all arrangements for archiving have been made

by the Investigator

CLOSURE VISIT TASKS

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Biometrics & Medical Writing

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Biometrics & Medical Writing Process

Protocol writing

CRF Design

Informed Consent

Development

Statistical Analysis Plan

Edit Checks Development

Database Design

Data Management

Plan

Data Validation Process

Query Management

Data Cleaning

Database Lock

Medical Coding

Statistical Analysis Report

Clinical Study Report

Manuscript

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Biometrics & Medical Writing

Informed Consent

A Process by which a subject voluntarily confirms his or her willingness

to participate in a particular trial, after having been informed of all

aspects of the trial that are relevant to the subject’s decision to

participate. Informed consent is documented by means of a written,

signed and dated informed consent form. ICH GCP E6(R2) § 1.28

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Medical Writing

Protocol

A clinical trial protocol is a document that describes the objective(s),

design, methodology, statistical considerations, and organization of a

trial. Detail on the background of and rationale for the trial is usually

included in the protocol, although this information could be provided in

other protocol referenced documents., use the term protocol to refer to

the protocol and protocol amendment(s). ICH GCP E6 (R2) §1.44

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Medical Writing

Clinical Study Reports (CSR)

A written description of a trial/study of any therapeutic, prophylactic, or

diagnostic agent conducted in human subjects, in which the clinical and

statistical description, presentations, and analyses are fully integrated

into a single report. ICH GCP E6 (R2) § 1.13

Manuscripts

A final document in the clinical trial that is written according to specific

guidelines for publication purpose.

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Biostatistics

Statistical Analysis Plan (SAP):

A document that contains a more technical and detailed elaboration of

the principal features of the analysis described in the protocol, and

includes detailed procedures for executing the statistical analysis of the

primary and secondary variables and other data.

Statistical Analysis Report (SAR)

A report that contains the statistical analysis of the primary and

secondary variables and other data according to the study protocol.

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Data Management

Case Report Form Design (CRF)

A printed, optical, or electronic document designed to record all of the

protocol required information to be reported to the sponsor on each trial

subject. ICH GCP E6 (R2) §1.11

Database Design

An electronic form designed according to the approved CRF for storing

data from a clinical trial in an organized format.

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Data Management

Data Management Plan Development

A document to facilitate forward planning of all data management activities,

provide technical information and act as a reference document for auditors

or retrospective retrieval of data.

Data Validation Process

A process to ensures that the data are complete, valid and consistent.

Query Management

A process of raising queries for incomplete, invalid of inconsistent data for

investigators resolutions and update the database accordingly.

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Data Management

Medical Coding

A process coding the Adverse events and concomitant medications

according to Medical dictionaries (MedDRA, WHO Drug)

Data Cleaning

A process that grants that all the data have been entered, queries have

been raised by the Data management and resolved by the investigator in

order to proceed with database lock and start the Statistical Analysis

process.

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Pharmacovigilance &Safety Monitoring

Safety Monitor is responsible for immediate and follow-up reporting of

any SAEs to sponsor/ RA according to the safety reporting timelines

The immediate reports should be followed promptly by details, written

reports.

The immediate and follow-up reports should identify subjects by unique

code numbers assigned to the trial subjects rather than by the subjects’

name, personal identification numbers, and/or addresses. ICH GCP E6

(R2) § 4.11

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Pharmacovigilance &Safety Monitoring

Adverse events and/or laboratory abnormalities identified in the protocol

as critical to safety evaluations should be reported to the sponsor

according to the reporting requirements and within the time periods

specified by the sponsor in the protocol.

For reported deaths, the investigator should supply the sponsor and the

IRB/EC with any additional requested information.

The investigator should also comply with the applicable regulatory

requirements related to the reporting of unexpected serious adverse

drug reactions to the regulatory authority(ies) and the IRB/EC

ICH GCP E6 (R2) § 4.11

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Quality Assurance

• Staff Training

• Systems, procedures and working practices

• Compliance ICH GCP, SA GCP, FDA …etc.

• Internal project-specific and system audits

Internal Functions

• Contracted trial site, laboratory & other vendors

• QA/training services (e.g. site training, GCP training)

External Functions

sponsor/cro responsibilities-gcp workshop 27 feb 2017

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