??????????? Real World Study

1
???????????Real World Study

• ????????????
• ??????????
• ???
• wushx_at_sina.com

2
??????????
CER ????????(comparative effectiveness research,
CER),??RCT?????????????????????,?????????(RWS)?
CER???????GRACE????????????????,??????????????
RCT?? ?????? ,??????,?????????,??????,??????,????
??,?????????
PSS ?? PSS(Post-market Safty Study,??????????),??
???????????????????????
2
3
??????????
PER ?? PER(Pharmacoeconomic Research,???????),???
?-???????-???????-?????
???? ?????,??????,??????????,????????,????????
?????????????
????? ???????????????(1)CER ??(2)RCT??(3)????-
??? ??????????????????????
3
4
???????

• ???????,????,?????
• (????)
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• (????)
• ???????,????,?????????
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5
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• ?????,?????,????,????,????,????,??????,?????
  ???????,????,???????,??????
• ??????????

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• ????????????????,????????????????
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7
????

• ??????,??????,??????,???,???????,???????,?????
  ?,??????
• ????????

8
????

• ????????????????????(MISPSTCM)??
• ?????
• ???????????(CCSPS)
• ?????

9
????--- REVERSAL

• ????????????
• ?????????(IVUS)????????70??,654????34?-78???????
  ???????
• ????????
• ?????????80mg VS ????40mg
• ??18??
• ?????????????????????
• ATP? ,PROVE-IT, A to Z, TNT,IDEAL
• ???????????????????????????

10
???????

• ????????????????????
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• ?????????????????
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11
??CER

• 20???,???????????CER?
• 07?, ???????CER??????????????
• 09?2?,?????????????,???????????11 ?????CER,
  ??????????????CER ?????????
• 09?6?,????????????,??CER??,??CER????????
• 10 ?, ???????????????????, ????????????????
  ????????????CER??????????????????????????CER?????,
  ???????????????

12
??CER

• ???????, ??????????CER ?????????
• ????????????CER ???, ?????????????????????????????
  CER ?????, ?????????????????
• 2011 ?3 ?, ?????????????????, ??????????????,?CER?
  
• 2011 ?5 ???????????????????,??????????????????
• 2011 ?6 ?, ???????????????????,??????????????????

13
???????CER 100 ???????

• ??6 ???
• ????
• ????
• ????
• ????
• ??
• ????

14
???????CER 100 ???????
????29 ????? ???10??????? ????????
?????? ??????? ?????
??? ???? ???
?? ??? ??????
15
CER????

• ???????( pragmatic trials)
• ??????( adaptive designs)
• ??????( clinical registries)
• ??????????????( clinical data registries)
  ??????CER, ???????(The Real World Study)

16
????????

• ????????
• GRACEGlobal Registry of Acute Coronary
  Events(?????????????)
• ????????
• ??????????????????

17
GRACE??Global Registry of Acute Coronary Events

• ????,?????,????????????????????,????????????(????
  ???),??????????????????,???????,????????????,?????
  ?????????,???????,?????,???????????????????,??????
  ????,???????????????????,??????????????

18
GRACE??Global Registry of Acute Coronary Events

• ???????????(?????????ST????????)?????????????????
  ?????????,??????????????????????????
• ?????????????????????(??????)

19
GRACE??Global Registry of Acute Coronary Events

• ????1999?4?,???????
• ????14??????????????????????
• Cluster Sites(??)18?(??5?),??????????????(????)?
  ????????????????????

20
GRACE??Global Registry of Acute Coronary Events

• ??47??
• ???????????,??????????????????????
• ??????????????????????????
• ?????????????????????,?????????????????????

21
GRACE??Global Registry of Acute Coronary Events

• Population-based Cluster(?????????)
• USA
• Massachusetts
• Boston
• Residents of Falmouth and Hyannis (n108,800)
• Cape Cod Hospital, Falmouth Hospital
• ????(???)

22
GRACE??Global Registry of Acute Coronary Events

• ????10,000,????????????????????????
• ????
• ???????????
• 18???
• ???????
• ??????????,???????????????????????????????????????
  ?????
• ??????????
• ?????????????,????????
• ??????6?????,????????,??,??????????
• ?????????????????,???????,????1?????,???????,?????
  ?????????????

23
GRACE??Global Registry of Acute Coronary Events

• ????
• ?????????
• ????????????
• ????????
• ???????????
• ?????????????????????,??????????
• ?????????????600?,????????????????
• ????????

24
GRACE??Global Registry of Acute Coronary Events

• ????
• 6?????????,???????????????????????????????????????
  ?
• ????
• ?????
• ???6????

25
GRACE??Global Registry of Acute Coronary Events

• ??(????????)
• ???????????????
• ???????
• ?????????
• ????????????????
• ????
• ????(Premier Research, Philadelphia, PA, USA)
• ??GRACE????(Center for Outcomes Research,
  University of Massachusetts Medical School,
  Worcester, MA, USA)
• ????????????

26
GRACE????Global Registry of Acute Coronary Events

• A comparison between B-type natriuretic peptide,
  global registry of acute coronary events (GRACE)
  score and their combination in ACS risk
  stratification.
• Prehospital Delay in Patients With Acute Coronary
  Syndromes (from the Global Registry of Acute
  Coronary Events GRACE).
• N-terminal pro B type natriuretic peptide
  complements the GRACE risk score in predicting
  early and late mortality following acute coronary
  syndrome
• Thrombocytopenia in patients with an acute
  coronary syndrome (from the Global Registry of
  Acute Coronary Events GRACE).

27
GRACE????Global Registry of Acute Coronary Events

• Magnitude and prognosis associated with
  ventricular arrhythmias in patients hospitalized
  with acute coronary syndromes (from the GRACE
  Registry).
• Time course of events in acute coronary
  syndromes implications for clinical practice
  from the GRACE registry.
• Predictive factors of recurrent angina after
  acute coronary syndrome the global registry
  acute coronary events from China (Sino-GRACE).

28
GRACE????Global Registry of Acute Coronary Events

• Treatment of the acute coronary syndrome in
  Germany experiences in a German cluster of the
  GRACE registry
• Predicting outcome in patients with acute
  coronary syndrome evaluation of B-type
  natriuretic peptide and the global registry of
  acute coronary events (GRACE) risk score.
• Interactions between heparins, glycoprotein
  IIb/IIIa antagonists, and coronary intervention.
  The Global Registry of Acute Coronary Events
  (GRACE).
• Bleeding events with antithrombotic therapy in
  patients with unstable angina or non-ST-segment
  elevation myocardial infarction insights from a
  large clinical practice registry (GRACE).
• Global Registry of Acute Coronary Events (GRACE)
  hospital discharge risk score accurately predicts
  long-term mortality post acute coronary syndrome.

29
2007?GRACE???????????????????????????????????????

• ????????????????????????????????????????????,????
  ????????????(??????????) ????????????????????????
• ??800????????????????????????,????????
  ??????(n580) ???????????(n220) ,?????????????
• ????????????????????????????????????????,?????6??
  ????????????

30
2011?GRACE??????????????????????????

• ????????????????????????????????ACS??????????????
  ????????ACS?????????,??????
• ???????1999??2007??14????123??????,???55189???,57
  9????????????
• ??
• 1????????????????? ????????,????,?????????,????
  ????,???,??,?????
• 2?579??????50???S-T????????,????????????33???S-T
  ?????????

31
2011?GRACE??????????????????????????

• ??
• 3????????????2???3????
• 4????????????????????ACS????????S-T???????????????
  ?????
• 5??????????????????(12 vs 4.8)?
• 6????????????,????????????????????????(13vs
  4.2),????(31 vs 18)?????????(7.6 vs
  2.9)????????,???GRACE?????????????????????????

32
GRACE?????Global Registry of Acute Coronary
Events

• ?????
• ?????????
• ?????????????????
• ???????????????????
• ???????

33
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34
??????????????????????????

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• 9??????????????????????

35
??????????????????????????

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  ???????????????,???????,????????????????????????

36
????

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• ??CER????(??????,RWS)?????????
• ????
• ??????????5000??

37
??

• ?????????????????????,?????????????????,?????????
  ?,???????????????????????????
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  ????????????????????????

38
????

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• ?????????2010?????????????
• ??????
• ????????????,?????????????????
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• ???????????(??????,RWS)????????,??????????????????
  ?????????
• ????????,????????????????????,????????,?????????,?
  ?????????????
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• ???????????(??????,RWS)????????,??????????????????
  ?????????,???????

39
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40
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  ??????

41
????

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• ??????
• ??????(???????)(???????????????????,?????????8
  00 - 10 00????,????5 min?,????????????????,????3?
  ,?????2 min,???2????????5mmHg?????)
• ??????
• 1???????(???????)
• 2?????(???????)
• 3??????(???????)
• 4??????(?????)
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• 6??????????(???????)
• 7??????(???????)
• 8???(??????????,??????)

42
????(1000?)
?? ???? ?? FAS PP ??
1 ????? 38 38 38 0
2 ???? 90 90 88 2
3 ?????? 200 200 198 2
4 ??????? 24 24 24 0
5 ???????? 96 96 96 0
6 ??416?? 25 25 25 0
7 ????????? 40 40 34 6
8 ????????? 58 58 58 0
9 ????????? 50 50 48 2
10 ??????? 80 80 79 1
11 ??????? 13 13 11 2
12 ??????? 79 79 54 25
13 ?????? 124 124 91 33
14 ????? 35 35 28 7
15 ??????? 48 48 25 23
?? 1000 1000 897 103

• ???????2011?9??2012?1???,15???,???1000???,???????

43
????(1000?)
1000??????????????

• 1000????1?????310?,?31.0,2?????486??48.6,3?????2
  04??20.4?
• ??????????210??21.0,???397??39.7,???186??18.6,?
  ???207??20.7?
• ?????2??????????????????

44
????(1000?)
1000??????????

• ???????,?261??26.1,?111??11.1,??283??28.3,?112?
  ?11.2,??????157??15.7?
• ?????????20??2,?????????????12??1.2,????????????
  ?50??1.9,??????????174??17.4?
• ?????????74??7.4,??????????11??1.1?

45
????(1000?)
1000????????????

• 1000????,??????163??16.3,???????378??37.8,??????
  209??20.9,??????223??22.3?
• ???230??23,????????????13.22(?)?
• ?????350??35.0?

46
????(1000?)
1000???????????

• 1000????,??????????348??34.8,?????122??12.2,????
  ?55??5.5,?????35??3.5,????(??????????)440??44?

47
????(1000?)
???????????

• ??????2????4????6????8?????????????,Plt0.05

1??? 2??2? 3??4? 4??6? 5??8?
48
????(1000?)
???????????????????????
49
????(1000?)
????????????????????
?? ?? ???(mmHg) ???(mmHg) ???(mmHg) ???(mmHg) ???(mmHg) ???(F) P
?? ?? ??? ??2? ??4? ??6? ??8? ???(F) P
????? 601 90.2011.367 85.2410.497 82.54?9.543 81.519.067 80.208.426 355.803 .000
?????? 399 89.8110.802 85.269.085 83.028.082 81.477.674 80.236.958 244.984 .000
50
????(1000?)
???????????????????????
51
????(1000?)
????????????????????
?? ?? ???(mmHg) ???(mmHg) ???(mmHg) ???(mmHg) ???(mmHg) ???(F) P
?? ?? ??? ??2? ??4? ??6? ??8? ???(F) P
????? 601 156.7116.495 147.1714.931 141.8813.540 138.5513.191 135.5212.071 630.818 .000
?????? 399 152.4013.847 145.4612.240 140.2411.215 137.2410.258 133.62 9.539 568.063 .000
52
????(1000?)
1000???????????????????,????411??41,??572??57,??
?17??2?
53
????(1000?)
?????????134??13.4,????866??86.6????????862??86
.2,????138??13.8?
54
????(1000?)

• ???????????????
• ??????288??28.8
• ??????????554??55.4
• ??????147??14.7
• ??2??0.2
• ??2??0.2

55
????(1000?)

• ????
• ????????,??????12?
• 2??????,???????,?????,????????????,???????????
• 5???????,??????,?????,????????????,???????????
• ??2?,???????,?????,????????????,???????????
• ??2?,???????,1????????,1????????,????????????,????
  ???????
• ??1?,????

56
???????????????

• ??
• ??????????,??????????,????????????????????????????
  ??????????,???????????,????????????????????
• ??
• CER???
• ???????
• ?????????????(?????????????)
• ECRF(???????)?????????????????????????????,???????
  ???????????(??????CER??),???????????????????

57
Songlingxuemaikang Capsule(SLXMK)
2010
Chinese Pharmacopoeia
2009
1994
National essential drugs list Class A
2000
Marked
National essential drugs list Class A
1998
National essential drugs list

58
Main components

• Fresh pine needles

Kudzu root
Pearl
59
Treatment of hypertension

• Headache
• Vertigo
• Insomnia

60
clinical trial of SLXMK on hypertension

• Object of study
• 2009/92010/3
• Stroke patients after discharge, 48 cases
• hypertension patients Class 2-3
• Dosing regimens
• Treatment GroupAmlodipine2.5mg/d Valsartan
  80mg/d SLXMK 3,Tid
• Control GroupAmlodipine 2.5mg/d Valsartan
  80mg/d
• course of treatment 8 weeks
• Evaluation index
• Ambulatory blood pressure

61
clinical trial of SLXMK on hypertension
Effect of Hypetension
C T P
24 hour average systolic blood pressure 29.677.86 36.885.50 lt0.01
24 hour average diastolic blood pressure 14.008.65 18.507.97 0.067
Daytime average systolic blood pressure 29.837.49 37.135.28 lt0.01
Daytime average diastolic blood pressure 14.508.19 18.508.93 lt0.05
Nocturnal mean systolic blood pressure 28.048.78 37.135.02 lt0.01
Nocturnal mean diastolic blood pressure 13.338.60 21.137.76 lt0.01
62
clinical trial of SLXMK on hypertension
trough/peak ratio
63
clinical trial of SLXMK on hypertension
Smoothness index
64
The Real Word Study of SLXMK on hypertension

• Research topics
• A practical hospital registration clinical
  research of Songling Xuemaikang Capsule in
  treatment of essential hypertension
• Study objective
• Safety, effectiveness and satisfaction evaluation
• Overall design
• Drug epidemiology (The Real Word Study )
• Sample size
• 5000 Cases
• Treatment programs
• SLXMK 3,Tid, course of treatment 8 weeks
• Research progress
• This test is under study, has selected 980 cases

65
Planned clinical trial

• Research topics
• Effects of Songling Xuemaikang Capsule on blood
  pressure variability(BPV) , A randomized, double
  blind, multicenter parallel controlled study
• Study objective
• Evaluation of Songling Xuemaikang Capsule on
  blood pressure variability
• Overall design
• A randomized, double blind, multicenter parallel
  controlled study
• Treatment programs
• Treatment GroupAmlodipine2.5mg/d SLXMK 3,Tid
• Control GroupAmlodipine 2.5mg/d Placebo 3,Tid
• course of treatment 12 weeks
• Evaluation index
• Variability of blood pressure
• Heart rate variability
• systolic pressure
• diastolic pressure

66
Look forward to cooperation

• China's pharmaceutical enterprises, traditional
  Chinese medicine, urgent need
• Evidence based Data
• International Journals (For example
  Hypertension)
• Look forward to cooperation
• Research design
• Quality control

67
Thanks for Attention