1. What should be the optimal Design for TAVI Procedure.
CRT 2010
Washington DC, January 21, 2010
What should be the optimal Design for TAVI Procedure.
Eberhard Grube, MD, FACC, FSCAI
St.Elisabeth Hospital, Heart Center Rhein-Ruhr, Essen, Germany
Instituto Cardiologico Dante Pazzanese, São Paulo, Brazil

2. Eberhard Grube, MD DISCLOSURES Consulting Fees Honoraria
Abbott Vascular, Boston Scientific Corporation, Cordis, a Johnson & Johnson Company, Medtronic CardioVascular, Inc.
Honoraria
Biosensors International , Boston Scientific Corporation, Medtronic CardioVascular, Inc
Ownership Interest (Stocks, Stock Options or Other Ownership Interest)
Biosensors International , Medtronic CardioVascular, Inc.
I intend to reference unlabeled/ unapproved uses of drugs or devices in my presentation.
I intend to reference off-label use of stents and valve prosthesis.

3. Evidence is key in Establishing TAVI as a new standard
Evidence is critical is gaining
Regulatory approvals
New Indications and Applications
Coverage and reimbursement
Adoption by implanters
Adoption by referrers

4. To make TAVI the Gold Standard, what data to collect? – Everything !
The key aspects need to be collected:
Safety
Effectiveness
Clinical Outcomes
Cost Effectiveness
Durability
Need to cover all timeframes:
Procedural / Accute
Short Term
Long Term
We need to progressively cover all population groups:
Inoperable
High Risk
Medium Risk
Lower Risk patients
All Applications:
Transfemoral, Transapical, Direct Aortic
Re-Dos, Valve-in-Valve

5. Issues with current data accumulated
Comparisons of outcomes between TAVI and Surgical are neither fair nor favorable
Key issues are disparities:
Different population groups being compared
Different maturities of the technologies
Other issues:
Little long term data accumulated so far
Initial studies were started with little understanding of the landscape, patients groups, and potential outcomes

6. Differences of perspective by specialty/therapy are key
Higher Risk Patients
Lower Risk Patients
TAVI Candidates
Surgical Candidates
Surgeons’ view
Surgical Candidates
TAVI Candidates
Interventionalists’ view
Clearly TAVI area
Clearly Surgical
TAVI/Surgical zone of contention

7. And they feed the debate on comparative outcomes
Higher Risk Patients
Lower Risk Patients
Surgeons’ view
TAVI Candidates
Surgical Candidates
Interventionalists’ view
TAVI Candidates
Surgical Candidates

8. Randomized Trials have strong appeal but they have their drawbacks
RCTs are trusted by all agencies
They offer really good controls over the population groups being studied
They are very effective in pre-market conditions
They are extremely expensive, require huge infrastructure
They only offer a narrow, specific slice of the population
Risk of selective enrolling once commercial options are available, on or off-label

9. Observational studies have another set of drawbacks
Observational Studies are cheaper and faster to enroll
They offer a broad slice of real-world population
They are effective in post-market conditions
The results are sometimes second-guessed
The results tend to be blurred by the mix of different patients subgroups
They are hard to use to get new indications or approvals

10. There are specific issues with these trials in the context of TAVI
The comparison with the established Surgical outcomes looks unfavorable:
Because of adverse patient selection
Because of early user experience in TAVI vs experienced users in Surgical
There is no clarity on what the patients’ risks profiles are:
Some surgeons will operate on anybody, others will be more conservative
Differences between what people would say and what they would do with these patients
Risk profiles STS or EuroScores are outdated with the current technologies
Hence the difficulty for TAVI to establish itself:
No clarity for which exact patient group TAVI is indicated
No clarity of what the true comparative advantages and disadvantages of TAVI are over surgery in groups where both are indicated

11. A potential third way? TAVI Observational Arm
If Surgeons agree they are not surgical candidates
Review by Surgeons and Interventionalists
Surgical Observational Arm
If Interventionalists agree they are surgical candidates
Patients
Randomized group between TAVI and Surgical
If there is a doubt

12. The three-arms design has advantages in terms of control of the population
TAVI Observational Arm
If Surgeons agree they are not surgical candidates
Confirms that there are truly inoperable patients
Lack of viable alternative legitimates observational approach
Outcomes in this cohort would be isolated and not compared to straight surgical results
Surgical Observational Arm
If Interventionalists agree they are surgical candidates
Would keep the truly surgical candidates in surgery
Would keep the outcomes as specific to that population
Randomized group between TAVI and Surgical
If there is a doubt or conflict
Would allow randomization without adverse selection bias
Would allow somewhat more homogeneous population selection (reverse consensus)

13. TAVI Observational Arm advantages
Would prevent adverse selection bias in RCT group by isolating the highest risk TAVI patients
Could provide meaningful data on outcomes and long term benefits for high risk / inoperable
Would quantify concretely the magnitude of the inoperable / high risk population
Could be used for coverage and/or indications expansion in that category

14. Surgical Observational Arm Advantages
Would prevent adverse selection bias in RCT group by isolating the lowest risk Surgical patients
Would establish a clear benchmark for TAVI to meet in order to expand into lower risk patients

15. Randomized TAVI/Surgical Arms
Randomized group between TAVI and Surgical
Obvious TAVI or surgical candidates would be sent to their specific arms
RCT Arm would be made up of more homogeneous risk profile
Outcomes’ comparisons would be more valid between TAVI and Surgical randomized groups

16. In summary
A hybrid approach could be advantageous, leveraging the observational arms to maximize the effectiveness of randomization over a naturally well-selected group