ESC Working Group Meeting „Cardiovascular Pharmacotherapy“ - How to run a trial efficiently, May 29, 2015

Heinz Drexel, MD, FESC, FAHADepartment of Medicine and Cardiology &

VIVIT Institute at the Academic Teaching Hospital Feldkirch, APrivate University of the Principality of Liechtenstein, Triesen, FL

Drexel University College of Medicine, Philadelphia, PA, USA

The Role of the PI: Keys to Success, Perils and Tribulations

Personal Interest and Experience H. Drexel

National PI - Dyslipidemia International Study

(DYSIS, MSD) - ODYSSEY Outcome Study

(Alirocumab, Sanofi-Aventis)

-PI of ~ 15 parallel trials

-Long-term observational studies

Prerequisites for becoming trained in trials:the institution

• Earlier publications

• Sound scientific programme

• Ongoing trials

• Time offered by the team members

• High quality of mentor

• Recruitable patients

• Cooperation with the clinical unit

1997

Participation in Multicenter Trials

20152005

Molecular Biology Lab

Cooperation with Other Centers

Acquisition of Competitive Grants

Stages of development at our institution

Investigator Driven Studies, Recruitment of Large Cohorts

OUTLINEWhat do I want so share with you?

1. Definition of the PI2. Personal experience3. Your needs

OUTLINEWhat do I want so share with you?

1. Definition of the PI2. Personal experience3. Your needs

Definition of the Principal Investigator (PI)

A principal investigator (PI) is the lead scientist for a particular well-defined research project, such as a laboratory study or clinical trial. It is often used as a synonym for "head of the laboratory" or "research group leader", not just for a particular study.

Role of the Principal Investigator (PI)

= Contractor of the grant sponsors= Dual responsibility

Rights & obligations of the PI for the trial

– Preparation

– Conduct

– Administration

Role of the PI BEFORE the trial

First decision: accept or decline the trial!

Prerequisites for the selection of sites:– Personal network– Experience with the centers– Team of the particular site

(Investigator & research nurse)

Most important at the start

– inclusion criteria– exclusion criteria

OUTLINEWhat do I want so share with you?

1. Definition of the PI2. Personal experience3. Your needs

Rights & obligations of the PI for the trial

– Preparation

– Conduct

– Administration

Essential infrastructure of a site

• MD (with trial experience)• Study nurse• Study coordinator• Administration Support• Space and time for outpatient clinic

VIVIT TEAM

Main role of the PI DURING the trialSolution of problems with recruitment

• Proposal for revision of inclusion criteria• Exchange with PIs from other regions• Regular telephone conferences• Personal meetings• Share tips and tricks with subinvestigators (SI)• Motivation of sites • Tribulate…

Duties of the local PI DURING the trialSolution of problems with recruitment

• Trouble shooting within the center – weekly meetings

• Motivation of reluctant GPs• Improve cooperation between divisions

Rights & obligations of the PI for the trial

– Preparation

– Conduct

– Administration

Duties of the local PI DURING the trialPrevent GCP violations

Duties of the local PI DURING the trialPrevent GCP violations

• Check/sign informed consent sheets• Check/sign CRFs (case report forms)• Report SAEs and endpoints within 24

hours• Read/sign safety report forms• Take ample time for monitor visits• Be prepared for audits (sponsor,

gouvernment)

Rights & obligations of the PI for the trial:SUMMARY

– Preparation

– Conduct

– Administration

OUTLINEWhat do I want so share with you?

1. Definition of the PI2. Personal experience3. Your needs

• Enthusiasm• Good time management• GCP knowledge• Long-term commitment• Patience• Straightforwardness

Prerequisites for the young trialist

Range of priorities for the young researcher:A good example

1. Time for research

2. Clinical resident work

3. Outpatient clinic

4. Emergency medicine

5. Leisure time

1. Emergency medicine

2. Outpatient clinic

3. Clinical resident work

4. Leisure time

5. Time for research

Range of priorities for the young researcher:A bad example

Advantages and Disadvantages of Randomized Clinical Trials (RCT‘s)

PRO•Precise judgement of an intervention•In a precisely defined population•Prospective design•Minimizes (but not eliminates) bias•Allows for meta-analysis

CONTRA•Expensive•Time consuming•Depends critically on patient inclusion

From Dream to Nightmare: What makes a Trial Useless?

•Very similar trial already done and conclusive•Necessity for extreme patient numbers•Randomization unethical•Main question cannot be answered by a RCT

An Example

0400

62

ODYSSEY Phase 3 Programm

37

Fourteen global Phase 3 trials including >23 500 patients across >2000 study centres

HeFH population HC in high CV-risk population Additional populations

Add-on to max tolerated statin (± other LLT)

Add-on to max tolerated statin (± other LLT)

†For ODYSSEY COMBO II other LLT not allowed at entry.

Our Experiences: ODYSSEY-Trial

Odyssey Study: Study Update

AUSTRIA GLOBAL

Screened: 70 Screened: 19.034

Randomized: 26 Randomized: 9.393

Sites: 7 Sites: 1.235

Odyssey Study: 1 Year Experience

High drop outs after screening: •Adequately controlled lipid levels•Patient:

• Unwilling to subcutaneous injections • Right after the acute event (ACS)• Tired of hospital visits

•Local MD (GP) refused: Objectives of study unknown

After Randomization•Low drop outs (0 at our site)•Screened 34, Randomized 7, Drop outs 0

ESC Working Group Meeting „Cardiovascular Pharmacotherapy“ - How to run a trial efficiently, May 29, 2015

Heinz Drexel, MD, FESC, FAHADepartment of Medicine and Cardiology &

VIVIT Institute at the Academic Teaching Hospital Feldkirch, APrivate University of the Principality of Liechtenstein, Triesen, FL

Drexel University College of Medicine, Philadelphia, PA, USA

The Role of the PI: Keys to Success, Perils and Tribulations