Collaborazione Sponsor - CRO

Come si organizza una multinazionale italiana

Cristina Ghezzi Recordati S.p.A.

Geographical presence

Subsidiaries

Branches and other forms of territorial presence

Countries where Recordati products are sold (under license or exported)

The collaboration with a CRO is a MUST!!!

• Only monocenter Italian studies are usually performed with internal personnel

• For all other studies (Phase I-IV) a collaboration with a CRO is necessary

Sponsor CRO

Our CRO selection strategy

Stage I: Strategic partnership with a trusted vendor

Stage II: No preferential vendors

Stage III: ?

….. (hopefully) towards a short lists of qualified vendors

CRO selection

Small or big?

Phase I

POC

Adaptive design

Rare disease

PIPPASS

Phase II-III

Phase IV

Italian

EU

EU/US

Russia

Initial Technical Assessment

Initial assessment by the Clinical Project Leader :

ü CRO organization and facilitiesü Study type (Phase, study population, design)ü Experience in therapeutic area ü Previous positive experience

Selection of 3-4 candidates

Request for proposal (RFP)

Ø Confidentiality Agreement

Ø RFP* including:

• Background information on IMP• Study objective• Draft study synopsis and flow-chart• Study assumptions • Tasks and responsibilities (CRO/Sponsor) • Grid for cost estimate• Clinical Service Agreement template

* Copy to Purchase and Legal Department

Study assumptions

• Timelines• Sample size• No. Countries • IWRS• e-CRF• e-PRO• Central Lab• Centralized analyses/readings • PK analysis• Investigator’s meetings• ……..

Definition of tasks and responsibilities

Definition of tasks and responsibilities

Definition of tasks and responsibilities

Definition of costs: professional fees

Other costs

• Pass- trough costs(Travel, subcontractors, couriers, EC fees, etc)

• Investigators’ grants

Comparative analysis of costs

CRO 1Professional fees €)

CRO 2Professional Fees (€)

Task Unit cost

No. of units

Type of unit

Total cost

Unit cost

No. of units

Type of unit

Total cost

Monitoring Visits 2.103,79 450 Visit 946.705 1.817,25 450 Visit 817.762

Close-out Visits 2.026,00 50 Visit 101.300 1.735,76 50 Visit 86.788

Project manager 25.409,65 42 Month 1.067.205 31.750,38 42 Month 1.333.515

Analysis of proposals

• Clinical Project Leader

• Purchase Department

• Legal Department CRO selection

From selection to activation

Legal Department

• Discussion on contract

Quality assurance

§ System audit (mandatory for new CROs)

Clinical Service agreement- Exibit A: Protocol synopsis- Exibit B: Assumptions- Exibit C: Tasks and responsibilities- Exibit D: Cost proposal - Exibit E: Appointment of data processor

Purchase Department

• Discussion on costs

Clinical Project Leader

Clinical Team

• CRA• Data-manager• Statistician• Coordinator

IMP supply

CRO oversight plan1

1 INTRODUCTION 2 SPONSOR RESPONSIBLE PERSONNEL 3 ABBREVIATIONS 4 SELECTION OF CRO 5 MANAGEMENT OF CRO 5.1 CRO RESPONSIBLE PERSONNEL 5.2 PROJECT PLAN 5.4 SELECTION OF CENTRES 5.5 APPROVALS BY EC/CA 5.6 THIRD PARTIES 5.7 DATA MANAGEMENT 5.8 RANDOM LIST 5.9 DRUG PREPARATION AND MANAGEMENT 5.10 INITIATION VISITS 5.11 UPDATES ON STUDY PROGRESSION 5.12 MONITORING 5.13 GCP AUDIT 5.14 MEDICAL MONITORING 5.15 PHARMACOVIGILANCE 5.16 STATISTICAL ANALYSIS 5.17 TRIAL MASTER FILE 5.18 CLOSE-OUT ACTIVITIES 5.19 BUDGET ADMINISTRATION 5.20 CLINICAL STUDY REPORT 5.21 STUDY DATABASE TRANSFER 5.22 FINAL EVALUATION OF CRO

For each activity:

- Sponsor responsible personnel- Action - Deadline

From activation to study start

Kick-off meeting

• Training on IMP and study • Definition of study team• Applicable SOPs• Feasibility Questionnaire• Study timelines

Feasibility study

§ Phone/visits§ Analysis of results

Project Plan (Trial Management Plan)

§ Overall strategy for timelines, management and conduct of the trial

§ Reference to specific plans:- Drug Management Plan- Safety Management Plan- Monitoring Plan - Audit Plan- Data Management Plan- Statistical Analysis Plan- Filing Plan- etc, etc

Feasibility studies

A joint CRO/Sponsor effort

• Ask questions… How is the CRO planning to perform it?• Are they asking the correct questions?

• Phone interviews?• Personal contact?

• Consider different sources of information

Start –up activities

Sponsor CRO

Protocol x Revision

ICF (template) x RevisionLocal ICFs

e-CRF Revision/UAT x

IB x

IMPD x

CTA Revision x

Center selection Approval x

The same document is read by:

• Principal investigator

• Co-Investigators

• Ethics Committees

• Competent Authorities

• Monitors

• Data manager

• Statisticians

• Central Laboratory

• ….

The protocol

Sponsor

• Presentation of study drug• Presentation of protocol

CRO

• Organization• Procedures• Timelines

The Investigators’ meeting

CRO oversight when the study is ongoing

Document revision

• Monitoring reports• Plans

Co-monitoring visits

• At selected sites

Audits

• TMF• Sites

Study updates

• TCs• Meetings• Newsletters

Investigators’ newsletter prepared by CRO and Sponsor

• To maintain high the interest in the study • To give updates (sites / enrolment / milestones)• To stimulate competition• To focus on critical aspects/procedures • To avoid errors • To provide clarifications

Enrollment….

Expected enrolment from feasibility study

Actual enrollment

…. and timelines

Sponsor - CRO relationship

X

The Sponsor’s opinion…• Poor quality of documents • Wrong selection of centers• No proactive attitude• Etc. etc.

Study start Study ongoing

Team effort

• Realistic approach• Analysis of causes• Proposed solutions• Action !

Study conclusion

Sponsor CROBlind review meeting x xCSR Revision and approval xTMF Check and archiving xSAS datasets Check and archiving xPosting results x

Completion of the CRO evaluation form!

Don’t forget!