What are the Sponsor responsibilities in GCP?

Nelle StocquartStrengthening Workshop, 13Jun2019

Nelle Stocquart

Compliance with this standard provides public assurance that

1. the rights, well-being and confidentiality of trial subjects are protected, and

2. that the clinical trial data are credible

ICH Good Clinical PracticeDefinition

Are GCP guidelines legal documents?

ICH GCP is a guideline, per see it is not a legislative document on itself

Due to regulatory requirements (EU Directive 2001/20/EC and Belgian Law), adherence to GCP is a legally binding requirement.

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ICH-GCP Content: Chapter 1: Definitions

Chapter 2: The Principles of ICH GCP

Chapter 3: The IRB/IEC

Chapter 4: The Investigator 13 responsibilities

Chapter 5: The Sponsor (Monitoring) 23 responsibilities

Chapter 6: The Clinical Trial Protocol & Amendments

Chapter 7: The Investigator’s Brochure

Chapter 8: The Essential Documents

If you apply for a KCE study as Coordinating Investigator you will have to fulfil Investigator and Sponsor responsibilities.Your Institution/Hospital will be accountablefor the study as Sponsor in accordance

with Belgian Law.

DEFINITIONS

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ICH-GCP Definition 1.34

Investigator: A person responsible for the conduct of the clinical trial at a trial site. If a trial is conducted by a team of individuals at a trial site, the investigator is the responsible leader of the team and may be called the principal investigator.

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ICH-GCP Definition 1.53

Sponsor: An individual, company, institution, or organization which takes responsibility for the initiation, management, and/or financing of a clinical trial

In Belgium an investigator cannot be a Sponsor, the law requests that this responsibility is taken over an Institution/Hospital. Ensure your organisation agreed to endorse this responsibility (support letter of the submission file)

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SPONSOR RESPONSIBILITIES

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ICH-GCP 5.0 Implement a risk-base quality management system*

ICH-GCP 5.1 Ensure quality assurance and quality control

ICH-GCP 5.2 Supervise delegation of tasks to Contract Research Organization*

ICH-GCP 5.3 Provide medical expertise

ICH-GCP 5.4 Design trial

ICH-GCP 5.5 Manage trial, handle data, keep records, validated computerized system

ICH-GCP 5.6 Select investigators

ICH-GCP 5.7 Allocate trial responsibilities

Refreshing ICH-GCP E6 (R2) Requirements Responsibilities of the Sponsor

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ICH-GCP 5.8 Have a trial insurance (& compensation) in place

ICH-GCP 5.9 Financial contract with the investigator/institution

ICH-GCP 5.10 Notify/Submit to regulatory authorities

ICH-GCP 5.11 Obtain confirmation of review/approval by IRB/IEC

ICH-GCP 5.12 Provide & update information on investigational products

ICH-GCP 5.13 Manufacturing, packaging, labelling, and coding investigational products

ICH-GCP 5.14 Supply & handling & inventory of investigational products

ICH-GCP 5.15 Ensure direct record access, verify informed consent

Refreshing ICH-GCP E6 (R2) Requirements Responsibilities of the Sponsor

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ICH-GCP 5.16 Evaluate & provide safety information

ICH-GCP 5.17 Report expedite serious adverse drug reactions

ICH-GCP 5.18 Monitor the trial (risk-based approach) *

ICH-GCP 5.19 Perform audits

ICH-GCP 5.20 Act on non-compliance (CAPA)*

ICH-GCP 5.21 Inform on premature termination/suspension of a clinical trial

ICH-GCP 5.22 Make the clinical study report

ICH-GCP 5.23 Coordinate multicentre trials

Refreshing ICH-GCP E6 (R2) Requirements Responsibilities of the Sponsor

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Sponsor responsibilities – How to fulfil them?The need for structural support

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CTU

CI

KCE - Sponsor- Project

management - Protocol writing- Data Mgt- Monitoring- Safety- Legal advice- Insurance- RA & EC- Finance- Logistics- QA & QC- …

- Funding- CTU capacity building

- Scientific ideas- Protocol writing- Scientific Follow up

Sponsor responsibilities – How to fulfil them?

In order to be GCP compliant, an investigator is not able to manage a multicentre trial with a limited team

Hospital Clinical Trial Centre/Unit collaboration and support is essential

CTU have the whole Quality management System in place

Data management will request a database and an eCRF

Monitoring must be done by experienced CRAs

Etc.

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The need for structural support

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HOSPITAL SPONSOR CAPACITY REVIEWED U U U U U U U NU NU NU NU

SPONSOR ORGANISATION AND MANAGEMENT

1. Organisation

2. Management Oversight

3. Quality Management System

4. Document Management Process

5. Staff and training

6. Regulatory knowledge

7. Quality Assurance and auditing processes

8. Non compliance and CAPA management

INFRASTRUCTURE FOR CLINICAL RESEARCH

1. Multicenter Clinical Trials

2. Protocol development

3. Sponsor Insurance

4. Site selection and oversight

5. Vendor Management

6. Recruitment Strategy, tracker, status reports and oversight

7. Trial Master File process, documentation and archiving

8. Data management processes

9 Pharmacovigilance processes

10. Biostatistics and reporting processes

11. Regulatory submission processes

12. Clinical Supplies processes

13. Central laboratory processes

INFRASTRUCTURE AND IT SUPPORT

1. Information Systems

ICH-GCP 5.6 Select investigators

5.6.1 The sponsor is responsible for selecting the investigator(s)/institution(s). Each investigator should be qualified by training and experience and should have adequate resources (see 4.1, 4.2) to properly conduct the trial for which the investigator is selected. If organization of a coordinating committee and/or selection of coordinating investigator(s) are to be utilized in multicentre trials, their organization and/or selection are the sponsor's responsibility.

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ICH-GCP 5.6 Select investigators

Having a study ready to start recruitment (SIV done) is time consuming and not easy

KCE Timelines:

From Funding (TB letter) confirmation to FPI ~ 60 weeks

From contract signed to FPI ~ 23 weeks

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Tufts Center for the Study of Drug Development June 2017

KCE recommendations

All identified sites should have a feasibility either F2F (+/- 50%) or by phone

KCE is strongly recommending to have the feasibility done with an external partner

KCE has contracted a CRO to support you with this

It allows independent assessment also on well known PI colleagues and then a better budget and timelines assessment

PI and/or PM and CTU representative should assist to the feasibility visit

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Lessons learned at KCE

A good feasibility is essential to define study timelines and final budget

Multicentre trials requests contact with « unknown » PIs –feasibility exercise is focusing on this ones

Going to sites is time consuming but useful to have a better feasibility assessment, to identify study challenges, potential recruitment issues and opportunities as protocol changes

Sponsor-Investigators and CTUs have few or no experience in such exercise

Advance available for feasibility (after recommendation for funding by TB)

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Take home messageClinical Trials must follow ICH-GCP in order to ensure subject

safety, data integrity and quality

There are 23 ICH-GCP sponsor responsibilities on the top of the 13 Investigator responsibilities

It requests a multi-disciplinary team

CTU involvement is key for success

Feasibility is crucial for recruitment and budget planning.

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