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Chairpersons: Chris O'Connor (Inova, USA), Mona Fiuzat (FDA/Duke, USA)
8.00 am – 1.00 pm
 So-called “neutral” or “negative” trials contribute to the body of evidence with a
drug, device, or procedure. Such trials often provide relevant knowledge to the
field and often inform planning of subsequent randomized trials.
 When a trial fails to show statistically significant evidence of benefit of an
experimental intervention, the cardiovascular community should ask whether the
intervention worked, but the trial was flawed in some way, or the trial was valid
but the intervention was ineffective.
 The appropriate next steps after completion of an inconclusive trial are influenced
by 1) whether a strong mechanistic or biologic rationale supports use of the
treatment and 2) the overall assessment of potential reasons why the trial did not
meet its primary objective.
 It is crucial, but often difficult, to determine if a clinical outcomes trial did not show
a treatment effect because of errors in trial design or execution or if the treatment
was truly ineffective.
“Autopsy is performed by anatomists with the principal aim of an autopsy is
to determine the cause of death, the state of health of the person before he
or she died, and whether any medical diagnosis and treatment before
death was appropriate.”
 The objective of this session is to have trial specialists examine failed trials with
the aim of determining causes of failure, the robustness of the trials before they
failed, and whether any appropriate early examination or corrective action could
have prevented negative/neutral results.
 The aim is ultimately to draw lessons that may inform the design and the conduct
of future trials. Future trials may be designed addressing lessons learned from
informative but inconclusive trials, applying different patient populations, alternate
treatment regimens, or different outcomes. Alternatively, trials should be viewed
in the broader context of how the results can inform the field.
Chris O'Connor

One main reason I believe my trial didn’t meet its primary endpoint:
· RELAX-AHF-2: John Teerlink (San Francisco, USA)
· TRUE AHF: Milton Packer (Dallas, USA)
· TOPCAT: Bertram Pitt (Ann Arbor, USA)
· GUIDE IT: Michael Felker (Durham, USA)
· BLAST: Peter Pang (Chicago, USA)
· Vericiguat in HFpef : Javed Butler (New York, USA)
· HF ACTION: Dave Whellan (Durham, USA)
· BEST: Mike Bristow (Aurora and Boulder, USA)
· SERVE-HF: Faiez Zannad (Nancy, FRA)
Statistical viewpoint
Nancy Geller (NHLBI, USA)
Cyrus Mehta (Boston, USA)
Investigator viewpoint:
Karl Swedberg (Goteborg, SWE)
Industry viewpoint: Jim Carr (Stealth Peptide, USA), Claudio Gimpelewicz (Novartis,
CHE), Johannes Holzmeister (Cardiorentis, CHE); Lothar Roessig (Bayer, GER), James
Strait (Merck, USA)
NHLBI viewpoint:
George Sopko (NHLBI, USA)
CRO viewpoint
Monica Shah (Quintiles, USA)
Patient viewpoint : Natascha Van der Post (Nijmegen Area, NED)
The Forum. Moderated discussion with the audience
What lessons have we learned? How did is success secured in ongoing trials?
Chairpersons: Chris O'Connor (Inova, USA), Mona Fiuzat (FDA/Duke, USA)
Panelists: Mike Bristow (Aurora and Boulder, USA), Javed Butler (New York, USA), Jim
Carr (Stealth Peptide, USA), Michael Felker (Durham, USA), Mona Fiuzat (FDA/Duke,
USA), Nancy Geller (NHLBI, USA), Claudio Gimpelewicz (Novartis, CHE), Johannes
Holzmeister (Cardiorentis, CHE), Allen Kindman (Quintiles, USA), Cyrus Mehta (Boston,
USA), Chris O'Connor (Inova, USA), Milton Packer (Dallas, USA), Peter Pang (Chicago,
USA), Bertram Pitt (Ann Arbor, USA), Lothar Roessig (Bayer, GER), Monica Shah
(Quintiles, USA), James Strait (Merck, USA), George Sopko (NHLBI, USA), Karl
Swedberg (Goteborg, SWE), John Teerlink (San Francisco, USA), Natascha Van der
Post (Nijmegen Area, NED), Dave Whellan (Durham, USA), Faiez Zannad (Nancy, FRA)