Forward Looking Clinical Trials
The Great Wall International Conference on Cardiology October 16 2014
Thach Nguyen, M.D FACC FSCAT
St Mary Medical Center
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1 Problems with traditional RCTs
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JUPITER |
Trial Design <<z22—-
JUPITER
Multi-National Randomized Double Blind Placebo Controlled Trial of
Rosuvastfatin in the Prevention of Cardiovascular Events
Among Individuals With Low LDL and Elevated hsCRP Rosuvastatin 20 mg (N=8901) — , No Prior CVD or DM troke
Men >50, Women >60 Hong
TSE 8 | 4week™, Placebo (N=8901) aria
hsCRP >2 mg/L "ịnC CABG/PTCA
Argentina, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Costa Rica,
Denmark, El Salvador, Estonia, Germany, Israel, Mexico, Netherlands, Norway, Panama, Poland, Romania, Russia, South Africa, Switzerland,
United Kingdom, Uruguay, United States, Venezuela
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= RCI is the best available technique for
eliminating confounding factors in the
assessment of a treatment effect
= With continued improvement in medical care,
most treatment effects of interest in
cardiovascular disease have only modest effects (RR reductions ~15-20%)
ms Only RCI can provide sufficient precision
Trang 7= RCI’s are best suited to evaluation of
“mature” therapies
m Clinical trials are a poor way to evaluate rapidly changing technologies, particularly
medical devices
m [rials are particularly vulnerable when
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In a registry, all of the interventions
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2 Which Data Can
Change the Way we
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Trang 15How to Be Successful
Trang 16How to Be Successful
= Politics (who is the winner?)
re" ` Giving You the Edge —
The Science of
Winning Elections
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1 Electronic health records serve as a
repository for information on millions of
people, will allow analysis of symptoms
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Artificial intelligence algorithms
1 will rapidly crunch massive amounts of data — including patient information, doctors’
notes, and results from genomics research and
clinical trials — by supercomputers and cloud-based
programs
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= [his trend toward relying on big data is
Trang 23Goals of Healthcare
Trang 25Goals of Healthcare
= Decision-making based on “comparative
effectiveness,” or what has been shown to
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= Medicine has always leaned on art and
intuition as well as on science But
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1 Use mobile and web-based applications 2 Record symptoms and treatments
3 Collect data on results
Trang 28Application la
= A patient uses a personal blood pressure monitor developed by device-maker
Ireaith
a Ihe monitor feeds BP wirelessly into an
Trang 29Application 1b
= In this case, the MD was informed that BP
was actually dangerously low The heart
rate was checked and was too low so
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= | Replace the general guidelines often used in deciding how to treat unstable
Trang 31= New risk models—powered by = Genomics, = Results of prior tests, ø B1lling records, = Demographics
Trang 32Application 2B = New risk models—powered by = Genomics, = Results of prior tests, m Billinø records, = Demographics
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= 500 patients with HF in NYHA FC Ill or IV = Follow-up from 2002 to 2004
= Ihe package survival available in the R
software was used to obtain the results for
model (1) Results for models (2) and (3)
were obtained in this same software using
the packages timereg and Coxvc, as well
Trang 36Table 2 Logrank test performed for each
CO Yall tally
Logrank test
Covariates Statistic p-value
Age (=60 and >60 yrs) 13.00 <0.001 Gender (male and female) 2.64 0.104 Race (white and others) 0.56 0.453 Diabetes mellitus (yes and no) 1.04 0.307
Hypertension (yes and no) 1.54 0.215
Current smoking (yes and no) 1.96 0.165 BMI (<25 and >25 kg/m2) 6.16 0.013 LV ejection fraction (<0.35 and =0.35) 10.70 0.001 LV mass (=243 and >243 g) 0.11 0.742 Serum sodium (=137 and >137 mEq/L) 27.9 <0.001 Hemoglobin (Hb) (=13 and >13 g/dL) 15.6 <0.001 Creatinine (<1.2 and >1.2 mg/dL) 23.4 <0.001 Etiology (Chagas and others) 13.13 <0.001 doi:10.137 1/journal.pone.0037392.t002
Trang 37Table 4 Tests associated with the additive
hazards model
Test for non-significant effect Test for time-invariant effects
Covariates Statistics Statistics p-value Intercept =9) 0001 Age 285 Serum sodium Hemoglobin 327 Creatinine LV ejection fraction 3.88
*Time-invariant effects suggested for age and serum sodium (p> 0.05)
All covariates were centered in their respective mean values do&10.1371/journal pone.0037392.t004
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Figure 3 Cumulative coefficients obtained
from the additive hazards model 04 049 0.10 006 0.02 002 03 xD © J 7 © “4 © oO ° 00 01 02
Trang 39Criminals and Fugitives
Identified by Robotcop Glasses
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A whole hospitalization course, cost,
Trang 42Asymptomatic patients could be scanned
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The new draft guidance, on the basis of the
EXCELLENT and PRODIGY studies, recommend a reduced duration of DAT after
DES: six months, instead of 6 to 12
The draft guidelines also specify, however, that “more than six months" is preferable in
Trang 47Study in NVAF patients undergoing PC!
À rrospertice Ra ndo m zed, o pen b |, hlinded
endpoint (PROBE) study to Eva lua te DUAL antithrombotic thera py with dabeatr n etexibte (11Ong h.id.a nd 150mg b.i.d.] re c lo ndce rel or bf tte es) es each eee al (INR 20—-3.0 pluschpdogrelorticagrelor with aspirin in patients with non valvularatral †ibril tien (Nv ÀF] that ha+e underponea
D1 50 plus a P2Y12 inhibitor is:
Nor-infe nor with respect tothe
combined thrombotic event rate [TE: death+ Ml+stmle/SE]
0|,
N¬arr-irfe đnar? 0ith spectto clinically mlevant blaeding relitive to a tripk combiration of arfarin plus DiiO plusa P2¥12 inhibitor 6:
Non- inferior with respect to the
co mì b ned thro bat &¿e nt ra tế (TE: - C0 10214204 13,
AND
Non-inferior ' th respset to c lin ca lhy
relsva mt hl£edinp reb tiee to a trí rk= combination of warfarin plusa P2V12
Pe'cutaneous corona ry inte rvention (PCI) wíth inhibitor (clo pidogrelor ticagrelor) plus a P2¥12 inhibitor (clopidogrel or
stenting (RE-OUAL FOI) <
^ ị oan ticagrelor) plus ASA
Paroxysmal, persistent or
permanent AF
(PCI with stenting [BMS
or DES] elective or ACS)
Dabigatran 150mg BID + P2¥12 inhibitor¥**
dbo Soc
Time to first combired thrombotic event ordeath
falldeath, MI, Stroke/SE)
Dabigatran 110mg BID + P2¥12 inhibitor¥**
Screening
0-72 hours
post-PC! Plus Time to first clinica lh reevant bleeding rate 18/24/30M (ISTH Majp r) bm 8M 12M or EOT n = 2840 patients perarm (Total = 8520 patients) |
' (GA Gdecontiwed inmedetey otters worst! pod rin pote ots endomaord to eeewe dobeten =
"(G8 willbe decontimed inthe warferinerm 8hS: Decontinustionof (GA st month 4 ; DES: d&continustionof (GA at month?
Trang 48Figure 3 Cumulative coefficients obtained
from the additive hazards model 04 049 0.10 006 0.02 002 03 xD © J 7 © “4 © oO ° 00 01 02
Trang 49Criminals and Fugitives
Identified by Robotcop Glasses
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A whole hospitalization course, cost,
Trang 52Asymptomatic patients could be scanned