DR. RAJESH RAJAN MD, Ph.D, D.CARD, FESC, FACC, FAHA. Cardiologist, AMIRI HOSPITAL, MOH, Kuwait.
ESC Working Group Meeting „Cardiovascular Pharmacotherapy“ - How to run a trial efficiently, May...
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Transcript of ESC Working Group Meeting „Cardiovascular Pharmacotherapy“ - How to run a trial efficiently, May...
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