esc working group meeting „cardiovascular pharmacotherapy“ - how to run a trial efficiently, may...
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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
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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
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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
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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
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OUTLINEWhat do I want so share with you?
1. Definition of the PI2. Personal experience3. Your needs
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OUTLINEWhat do I want so share with you?
1. Definition of the PI2. Personal experience3. Your needs
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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.
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Role of the Principal Investigator (PI)
= Contractor of the grant sponsors= Dual responsibility
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Rights & obligations of the PI for the trial
– Preparation
– Conduct
– Administration
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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)
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Most important at the start
– inclusion criteria– exclusion criteria
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OUTLINEWhat do I want so share with you?
1. Definition of the PI2. Personal experience3. Your needs
![Page 13: ESC Working Group Meeting „Cardiovascular Pharmacotherapy“ - How to run a trial efficiently, May 29, 2015 Heinz Drexel, MD, FESC, FAHA Department of Medicine](https://reader037.vdocument.in/reader037/viewer/2022110210/56649e755503460f94b772ba/html5/thumbnails/13.jpg)
Rights & obligations of the PI for the trial
– Preparation
– Conduct
– Administration
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Essential infrastructure of a site
• MD (with trial experience)• Study nurse• Study coordinator• Administration Support• Space and time for outpatient clinic
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VIVIT TEAM
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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…
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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
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Rights & obligations of the PI for the trial
– Preparation
– Conduct
– Administration
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Duties of the local PI DURING the trialPrevent GCP violations
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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)
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Rights & obligations of the PI for the trial:SUMMARY
– Preparation
– Conduct
– Administration
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OUTLINEWhat do I want so share with you?
1. Definition of the PI2. Personal experience3. Your needs
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• Enthusiasm• Good time management• GCP knowledge• Long-term commitment• Patience• Straightforwardness
Prerequisites for the young trialist
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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
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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
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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
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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
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An Example
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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.
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Our Experiences: ODYSSEY-Trial
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Odyssey Study: Study Update
AUSTRIA GLOBAL
Screened: 70 Screened: 19.034
Randomized: 26 Randomized: 9.393
Sites: 7 Sites: 1.235
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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
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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
![Page 34: ESC Working Group Meeting „Cardiovascular Pharmacotherapy“ - How to run a trial efficiently, May 29, 2015 Heinz Drexel, MD, FESC, FAHA Department of Medicine](https://reader037.vdocument.in/reader037/viewer/2022110210/56649e755503460f94b772ba/html5/thumbnails/34.jpg)