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Biosta’s’cs Group Biosta’s’cs Group July 28, 2015 Atul Sharma MD, MSc, FRCPC Biosta’s’cs Group, George and Fay Yee Center for Health Care Innova’on Department of Pediatrics and Child Health, University of Manitoba

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Page 1: Biostas’cs)Group)) - University of Manitoba cs)Group) Biostas’cs)Group))) July28,2015) Atul)SharmaMD,)MSc,)FRCPC)) Biostas’cs)Group,) George)and)Fay)Yee)Center)for)Health)Care)Innovaon)

Biosta's'cs  Group  

Biosta's'cs  Group      

July  28,  2015    

Atul  Sharma  MD,  MSc,  FRCPC    

Biosta's'cs  Group,  George  and  Fay  Yee  Center  for  Health  Care  Innova'on  

 Department  of  Pediatrics  and  Child  Health,    

University  of  Manitoba  

Page 2: Biostas’cs)Group)) - University of Manitoba cs)Group) Biostas’cs)Group))) July28,2015) Atul)SharmaMD,)MSc,)FRCPC)) Biostas’cs)Group,) George)and)Fay)Yee)Center)for)Health)Care)Innovaon)

Biosta's'cs  Group  

The  Biosta's'cs  Group  is  one  of  three  expert  groups  within  the  Data  Science  Pla4orm  in  the  George  and  Fay  Yee  Centre  for  Health  Care  Innova'on.  The  two  others  groups  are:  Clinical  Research  Data  and  Bioinforma'cs/Computa'onal  Biology  •  PlaRorm  Director:  Lisa  Lix  PhD  

Biosta's'cs  Group  Members:  •  Group  Leader:  Depeng  Jiang  PhD  •  Rasheeda  Rabbani  PhD  •  Brenden  Dufault  MSc  •  Atul  Sharma  MD,  MSc,  FRCPC  •  Kris'ne  Kroecker,  BSc  (Trainee)  

Page 3: Biostas’cs)Group)) - University of Manitoba cs)Group) Biostas’cs)Group))) July28,2015) Atul)SharmaMD,)MSc,)FRCPC)) Biostas’cs)Group,) George)and)Fay)Yee)Center)for)Health)Care)Innovaon)

Biosta's'cs  Group  

Our  Mission:  •  Support  for  clinical  inves'gators  and  pa'ent-­‐oriented  clinical  research  (consul'ng  service)  

•  Independent  ‘innova've  and  cu[ng  edge’  research  •  Training  and  educa'on  of  the  next  genera'on  of  health-­‐care  researchers  

Page 4: Biostas’cs)Group)) - University of Manitoba cs)Group) Biostas’cs)Group))) July28,2015) Atul)SharmaMD,)MSc,)FRCPC)) Biostas’cs)Group,) George)and)Fay)Yee)Center)for)Health)Care)Innovaon)

Biosta's'cs  Group  

Training  Ini'a'ves:  Established  Inves'gators  •  Workshop  series  in  advanced  sta's'cal  methods  •  Propensity  score  methods  for  non-­‐randomized,  observa'onal  data  (A.  Sharma)  

•  Hierarchical/  longitudinal  models  (D.  Jiang)  •  Latent  class  models  (B.  Dufault,  L.  Lix)  

Page 5: Biostas’cs)Group)) - University of Manitoba cs)Group) Biostas’cs)Group))) July28,2015) Atul)SharmaMD,)MSc,)FRCPC)) Biostas’cs)Group,) George)and)Fay)Yee)Center)for)Health)Care)Innovaon)

Biosta's'cs  Group  

Training  Ini'a'ves:  Clinical  Trainees  •  Academic  half-­‐day  teaching  for  clinical  trainees  to  sa'sfy  the  new  Royal  College  ‘scholarly  competency’  (CanMEDS  2015)  I.  Introduc'on  to  biosta's'cs  II.  Study  design  and  sample  size  calcula'ons  III.  Introduc'on  to  data  analysis  with  the  generalized  linear  model  IV.  Introduc'on  to  sta's'cal  compu'ng  (computer  lab)  

Page 6: Biostas’cs)Group)) - University of Manitoba cs)Group) Biostas’cs)Group))) July28,2015) Atul)SharmaMD,)MSc,)FRCPC)) Biostas’cs)Group,) George)and)Fay)Yee)Center)for)Health)Care)Innovaon)

Biosta's'cs  Group  

Training  Ini'a'ves:  Clinical  Trainees  •  Open  House:    •  Each  month,  our  consultants  meet  with  trainees  •   Opportunity  to  discuss  their  research  design  and  analysis  ques'ons  in  an  informal  se[ng  with  mul'ple  consultant  

 

•  One-­‐on-­‐one  advisory  sessions  with  trainees  

Page 7: Biostas’cs)Group)) - University of Manitoba cs)Group) Biostas’cs)Group))) July28,2015) Atul)SharmaMD,)MSc,)FRCPC)) Biostas’cs)Group,) George)and)Fay)Yee)Center)for)Health)Care)Innovaon)

•  Canadian  Pediatric  Endocrine  Group  (CPEG)  working  commibee  for  na'onal  growth  charts  and  its  methodology  subcommibee,  now  a  permanent  member  of  the  PHAC’s  Growth  Chart  Collabora've  Group    

 

Anatomy  of  a  Consulta'on  

CPEG  working  commibee:  •  J.P.  Chanoine  BC  Children’s    (Vancouver)  •  Dan  Metzger,  BC  Children’s  (Vancouver)  •  Mark  Palmert,  Hospital  Sick  Children  (Toronto)  •  Sarah  Lawrence,  CHEO  (Obawa)  •  Celia  Rodd,  HSC  (Winnipeg)  •  Beth  Cummings,  IWK  (Halifax)  •  Atul  Sharma,  HSC  (Winnipeg)  

 

Page 8: Biostas’cs)Group)) - University of Manitoba cs)Group) Biostas’cs)Group))) July28,2015) Atul)SharmaMD,)MSc,)FRCPC)) Biostas’cs)Group,) George)and)Fay)Yee)Center)for)Health)Care)Innovaon)

•  1977 CDC growth charts → revised 2000 •  Public Health Agency of Canada (PHAC) released “2010

WHO Growth Charts adapted for Canada” •  A collaborative process involving Canadian Pediatric

Society (CPS), College of Family Physicians of Canada, Community Health Nurses of Canada, Dietitians of Canada

Anatomy  of  a  Consulta'on  

Page 9: Biostas’cs)Group)) - University of Manitoba cs)Group) Biostas’cs)Group))) July28,2015) Atul)SharmaMD,)MSc,)FRCPC)) Biostas’cs)Group,) George)and)Fay)Yee)Center)for)Health)Care)Innovaon)

2010 WHO GROWTH CHARTS for CANADA

Page 10: Biostas’cs)Group)) - University of Manitoba cs)Group) Biostas’cs)Group))) July28,2015) Atul)SharmaMD,)MSc,)FRCPC)) Biostas’cs)Group,) George)and)Fay)Yee)Center)for)Health)Care)Innovaon)

Reaction from clinicians was immediate  

•  Posi%on  statement  of  the  Canadian  Pediatric  Endocrine  Group  (CPEG)  on  the  WHO  growth  curves.  Canadian  Pediatric  Endocrine  Group;  2011    

 •  Use  of  growth  charts.  2012  results.  Canadian  Pediatric  Surveillance  Program  (Paediatr  Child  

Health,  2014)  

•  Canadian  Pediatric  Endocrine  Group  extension  to  WHO  growth  charts:  Why  bother?  Paediatr  Child  Health  2013,  18(6):295–297.    

 •  Rodd  C,  Metzger  D,  Sharma  A  for  the  Canadian  Pediatric  Endocrine  Group.  Extending  World  

Health  Organiza%on  weight-­‐for-­‐age  reference  curves  to  older  children.  BMC  Pediatrics  2014  14:32  

2010 WHO Growth Charts for Canada

Page 11: Biostas’cs)Group)) - University of Manitoba cs)Group) Biostas’cs)Group))) July28,2015) Atul)SharmaMD,)MSc,)FRCPC)) Biostas’cs)Group,) George)and)Fay)Yee)Center)for)Health)Care)Innovaon)

No weight-for-age >age 10y, to promote BMI: •  Charts  are  tools  for  both  popula'on  health  

(obesity  screening)  and  individual  pa'ent  care  (longitudinal  surveillance,  simultaneous  ht/wt)  

•  Assessment of medical conditions like IBD, CRF

•  Even for population, BMI is not

sufficient; weight Z is an independent predictor of mortality  

CPEG POSITION STATEMENT

Page 12: Biostas’cs)Group)) - University of Manitoba cs)Group) Biostas’cs)Group))) July28,2015) Atul)SharmaMD,)MSc,)FRCPC)) Biostas’cs)Group,) George)and)Fay)Yee)Center)for)Health)Care)Innovaon)

WHO  charts  include  cen'les  0.1,  99.9%  (-­‐3,  +3  SD)  

CPEG POSITION STATEMENT

Page 13: Biostas’cs)Group)) - University of Manitoba cs)Group) Biostas’cs)Group))) July28,2015) Atul)SharmaMD,)MSc,)FRCPC)) Biostas’cs)Group,) George)and)Fay)Yee)Center)for)Health)Care)Innovaon)

Fewer  cen'les  in  normal  range  •  CDC    3,  10,  25,  50,  75,  90,  97  •  WHO  3          15          50          85          97    •  z  =      -­‐2        -­‐1            0            +1          +2  

CDC  cen'les  for  diagnosis  of  FTT,  hypertension,  FASD…  

CPEG POSITION STATEMENT

Page 14: Biostas’cs)Group)) - University of Manitoba cs)Group) Biostas’cs)Group))) July28,2015) Atul)SharmaMD,)MSc,)FRCPC)) Biostas’cs)Group,) George)and)Fay)Yee)Center)for)Health)Care)Innovaon)

Reaction from clinicians was immediate  

•  Posi%on  statement  of  the  Canadian  Pediatric  Endocrine  Group  (CPEG)  on  the  WHO  growth  curves.  Canadian  Pediatric  Endocrine  Group;  2011    

 •  Use  of  growth  charts.  2012  results.  Canadian  Pediatric  Surveillance  Program  (Paediatr  Child  

Health,  2014)  

•  Canadian  Pediatric  Endocrine  Group  extension  to  WHO  growth  charts:  Why  bother?  Paediatr  Child  Health  2013,  18(6):295–297    

 •  Rodd  C,  Metzger  D,  Sharma  A  for  the  Canadian  Pediatric  Endocrine  Group.  Extending  World  

Health  Organiza%on  weight-­‐for-­‐age  reference  curves  to  older  children.  BMC  Pediatrics  2014  14:32  

2010 WHO Growth Charts for Canada

Page 15: Biostas’cs)Group)) - University of Manitoba cs)Group) Biostas’cs)Group))) July28,2015) Atul)SharmaMD,)MSc,)FRCPC)) Biostas’cs)Group,) George)and)Fay)Yee)Center)for)Health)Care)Innovaon)

CPSP SURVEY: Limitations of WHO curves  

50%  

24%  

13%  

Page 16: Biostas’cs)Group)) - University of Manitoba cs)Group) Biostas’cs)Group))) July28,2015) Atul)SharmaMD,)MSc,)FRCPC)) Biostas’cs)Group,) George)and)Fay)Yee)Center)for)Health)Care)Innovaon)

Reaction from clinicians was immediate  

•  Posi%on  statement  of  the  Canadian  Pediatric  Endocrine  Group  (CPEG)  on  the  WHO  growth  curves.  Canadian  Pediatric  Endocrine  Group;  2011.    

•  Use  of  growth  charts.  2012  results.  Canadian  Pediatric  Surveillance  Program.    

•  Canadian  Pediatric  Endocrine  Group  extension  to  WHO  growth  charts:  Why  the  fuss?  Paediatr  Child  Health  2013,  18(6):295–297  

 •  Aoer  much  discussion  with  PHAC,  Collabora've  Group,  WHO:  

•  WHO  agrees  to  share  core  NCHS  data  for  re-­‐analysis  of  weight-­‐for-­‐age    •  In  Dec  2012,    CPEG  releases  2012  CPEG  growth  charts    

2010 WHO Growth Charts for Canada

Page 17: Biostas’cs)Group)) - University of Manitoba cs)Group) Biostas’cs)Group))) July28,2015) Atul)SharmaMD,)MSc,)FRCPC)) Biostas’cs)Group,) George)and)Fay)Yee)Center)for)Health)Care)Innovaon)

2012 CPEG Growth Charts for Canada

Rodd C, Metzger D, Sharma A: Extending World Health Organization weight-for-age reference curves to older children. BMC Pediatrics 2014 14:32 Re-analysis of NCHS data, N = 22917 •  Strict applications of WHO exclusions

and LMS methods to extend weight-for-age to ages 10-19y

•  Increased granularity of centiles in the normal range (7 vs 5)

•  Dropped centiles 0.1, 99.9%

Page 18: Biostas’cs)Group)) - University of Manitoba cs)Group) Biostas’cs)Group))) July28,2015) Atul)SharmaMD,)MSc,)FRCPC)) Biostas’cs)Group,) George)and)Fay)Yee)Center)for)Health)Care)Innovaon)

HOW PRECISE ARE THE EXTREME CENTILES    

•  Ques'on:  How  precise  are  es'mates  of  1:1000  cen'le  based  on  only  673 ± 204  boys  646 ± 185  girls/yearly  interval?  

 

Page 19: Biostas’cs)Group)) - University of Manitoba cs)Group) Biostas’cs)Group))) July28,2015) Atul)SharmaMD,)MSc,)FRCPC)) Biostas’cs)Group,) George)and)Fay)Yee)Center)for)Health)Care)Innovaon)

HOW PRECISE ARE THE EXTREME CENTILES    

•  Fibed  smoothed  cen'les  to  1000  non-­‐parametric  bootstrap  replicates;  N  =  11106  boys,  11193  girls    •  Es'mated  bias  and  95%  CI  (0.1,  3,  50,  97,  99.9%iles)  at  biannual  intervals      •  Demonstrated  sample  size  requirement  of  60k  of  each  gender  

6 8 10 12 14 16 18

10

15

20

25

30

35

40

Age(y)

BM

I kg

/m

6 8 10 12 14 16 18

20

40

60

80

10

0

Age(y)

We

igh

t kg

6 8 10 12 14 16 18

10

01

40

18

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BMI,  weight,  height:  Bootstrap  confidence  intervals    

Page 20: Biostas’cs)Group)) - University of Manitoba cs)Group) Biostas’cs)Group))) July28,2015) Atul)SharmaMD,)MSc,)FRCPC)) Biostas’cs)Group,) George)and)Fay)Yee)Center)for)Health)Care)Innovaon)

•  AnthroCalcCPEG  to  calculate  percen'les,  Z  scores  hOp://www.cpeg-­‐gcep.net  

LMS PARAMETERS

Page 21: Biostas’cs)Group)) - University of Manitoba cs)Group) Biostas’cs)Group))) July28,2015) Atul)SharmaMD,)MSc,)FRCPC)) Biostas’cs)Group,) George)and)Fay)Yee)Center)for)Health)Care)Innovaon)
Page 22: Biostas’cs)Group)) - University of Manitoba cs)Group) Biostas’cs)Group))) July28,2015) Atul)SharmaMD,)MSc,)FRCPC)) Biostas’cs)Group,) George)and)Fay)Yee)Center)for)Health)Care)Innovaon)

•  Feb  2014:  PHAC  re-­‐convenes  Growth  Chart  Collabora've  Group,  adding  CPEG  to  permanent  membership  

 •  Sept  2014:  PHAC  released  2014  WHO  Growth  Charts  for  Canada,  adding    weight-­‐

for-­‐age  10-­‐19y,  de-­‐emphasizing  cen'les  0.1  and  99.9,  and  restoring  7  cen'les  familiar  to  CDC  chart  users  

•  June  2014:  CPEG  receives  CPS’s  Noni  MacDonald  Award  for  clinical  impact    

Response to CPEG efforts:

Page 23: Biostas’cs)Group)) - University of Manitoba cs)Group) Biostas’cs)Group))) July28,2015) Atul)SharmaMD,)MSc,)FRCPC)) Biostas’cs)Group,) George)and)Fay)Yee)Center)for)Health)Care)Innovaon)
Page 24: Biostas’cs)Group)) - University of Manitoba cs)Group) Biostas’cs)Group))) July28,2015) Atul)SharmaMD,)MSc,)FRCPC)) Biostas’cs)Group,) George)and)Fay)Yee)Center)for)Health)Care)Innovaon)

•  Canadian  Paediatric  Society  (Growth  and  Nutri'on)  •  College  of  Family  Physicians  of  Canada  •  Community  Health  Nurses  of  Canada  •  Dietitians of Canada •  Canadian  Pediatric  Endocrine  Group  •  Canadian Association of Pediatric Nephrologists •  Public Health Agency of Canada •  World Health Organization

A collaborative effort

Page 25: Biostas’cs)Group)) - University of Manitoba cs)Group) Biostas’cs)Group))) July28,2015) Atul)SharmaMD,)MSc,)FRCPC)) Biostas’cs)Group,) George)and)Fay)Yee)Center)for)Health)Care)Innovaon)

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