Do DCB Pre- Market Clinical
Studies in the US Capture Enough
Clinically Relevant Information?
D. Chris Metzger, MD
Wellmont CVA Heart & Vascular Institute
Kingsort, TN, USA
Disclosures (D. Chris Metzger, MD)
• Symposium Honoraria and Course Proctor
– Abbott, TriVascular/ Endologix
• Symposium Honoraria
– Bard, Cardiovascular Research Foundation, Boston
Scientific, CSI, Medtronic
• National PI
– CANOPY, SAPPHIRE WW, PREVEIL, CONFIRM,
CONFIDENCE
• Stock, Research Grants, etc- NONE
• VIVA Board Member
Brief Introduction of Chris…
• Intervent. cardiologist, ~85% PV, 600-1000 c/y
• Director Clinical Research, Director Cath & PV
Labs for private practice group of 50 docs (0$)
• Faculty, Live case operator many conferences
• High volume research, lead enrollers of 28
major trials (Levant 2-#1 US, 2 global; InPact#2, Levant Access Registry- #2; in others)
• 6 FDA audits- 
We Are ALL on the Same Team
(and want many of the same answers)
So, Do Our DCB Trials Give
Us Enough Clinical Data??
•Yes, No, and Maybe??
DCB RCT’s: Definitely Some Good Data
• Provide rigorous, adjudicated, impartial data
• Indicate whether DCB is clinically better than
available product (PTA) for specific lesions
• Give same safety comparisons to PTA
• Have opportunities for other measures of
importance including cost, quality of life,
walking distances, unexpected findings
• Provide 1 year “answer” AND longer follow up
What Do DCB RCT’s Not Give Us?
• They don’t indicate for sure if the DCB is superior
or safe for “real world” lesions not included in
the trial, & “real world” patients
• May not measure true “effectiveness to patient”
• They do not compare DCB results directly against
other DCB’s or non- PTA therapies
• Do not give robust enough data to evaluate true
outcomes in patient subsets
DCB RCT’s : Sponsor’s Perspective
• These are EXPENSIVE trials, usually after other
investments (bench, animal, R & D, FIM, etc.)
• Companies have investors and overhead, with
many large reimbursement cuts affecting them
• They must obtain FDA approval, AND
reimbursement
• They may need other trials, registries, etc.
• They have a lot of competition
Problems with US Research
• US enrollment in clinical trials is SLOW
• Academic centers often contribute few
patients and have IRB/ bureaucracy issues
• By the time the study is developed, approved,
and enrolled, the product is outdated
• There are a few sites enrolling most of the
patients
• Enrollment often shifted to OUS sites
So, How Does Sponsor Approach RCT’s?
• They will pick a “beatable control” – PTA
• They will cut and paste previous approved
protocols (perpetuating flaws)
• They will include easier lesions and patients
• They may not include all of their device sizes if
not in prior protocol inclusion criteria
• They may pick the same PI’s as other trials
“We Do Not Practice in an RCT World”
• There are a large % of patients that we treat
who were NOT specifically studied in the RCT
• There are MANY clinical issues which can
NEVER be studied in an RCT (CM use of RCTs)
• Usually < 10% of patients treated at a given
site are enrolled in the RCT Trial
• We are then asked to approve products, make
reimbursement decisions, and make clinical
decisions on patients not specifically studied
Issues from RCT- Driven Decisions
• We may exclude device sizes not studied- BAD?
– Example: Supera 7-9 stents DC’d in US after SUPERB
• We may require RCT’s that are almost unethical
– Ranger DCB vs PTA RCT (is this OK?)
– SFA ISR Trials DCB vs. PTA (I can not do)
• We may make incorrect extrapolations
– E.g. Nitinol stent low fracture rate in trials , BUT may
be worse for long lesions w/ overlapping stents
FDA/ Clinician Questions re: RCT’s
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What to do about real world lesions after RCT?
What to with (same!) device sizes not in RCT?
What to do with patient subset “signals” (rem:$)
Can we improve/ standardize Kaplan-Meiers?
What to do with device improvements?
How much OUS data is OK? (and do we need to
send all FIM studies outside US??)
Some Potential Solutions/ Ideas
• Study DCB ≥#4 (or DCB in ISR cases) against
pooled PTA arms of prior DCB RCT’s
• OR, study DCB≥#4 vs approved DCB (noninf.)
• Come up with standardized & collaborative
endpoints for Real World Registry studies that
can be utilized GLOBALLY to pool data
• Minimize request for additional “~100 patient
trials” for minor signals seen ($$)
• Do not exclude sizes not in RCTs (Registry FU)
US, Japan, & European Collaboration
• It would be great to have collaboration
between regulatory agencies globally
• Establish acceptable standards which allow
appropriate combining of data sets
• Such cooperation would reduce the same
issues all of us face: cost of trials, time to
complete enrollment, etc. and allows for
larger patient cohorts. (avoids duplication)
Conclusions
• DCB RCT’s provide important excellent data –
they should be improved but continued
• We must all accept that RCT’s are expensive,
AND that many patients we treat were not
included in the RCT’s: clinical judgment req’d
• Additional data can be obtained in
standardized global registries
• International collaboration will be helpful
Thank You for Your (Kaola- ty) Attention!