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 %O  =pRELATIVE RISK ESTIMATION IN RANDOMISED CONTROLLED TRIALS: A COMPARISON OF METHODS FOR INDEPENDENT OBSERVATIONSqp p ZLisa N Yelland, Amy B Salter, Philip Ryan The University of Adelaide, Adelaide, Australia [P+0.  L  Background  Binary outcomes traditionally analysed using logistic regression Effect of treatment described as odds ratio Odds ratio difficult to interpret Often misinterpreted as relative risk which will overstate treatment effect$@ <Example US study* on effect of patient race on physician referrals Referral rate: white 90.6% vs black 84.7% Reported odds ratio of 0.6 Interpreted by media as referral rates 40% lower for black vs white Relative risk is actually 0.93**$@@V  c  ( Relative Risks }Growing preference for relative risk Log binomial regression recommended Generalised linear model Convergence problems common~$@~ ~ Relative Risks ,Growing preference for relative risk Log binomial regression recommended Generalised linear model Convergence problems common pi = exp(0 + 1x1i + & )~$@%H ( ( ( @    Relative Risks ,Growing preference for relative risk Log binomial regression recommended Generalised linear model Convergence problems common pi = exp(0 + 1x1i + & )~$@%H ( ( ( @     Relative Risks ,Growing preference for relative risk Log binomial regression recommended Generalised linear model Convergence problems common pi = exp(0 + 1x1i + & )~$@%H ( ( ( @    Alternative Methods Many different methods proposed Few comparisons between methods Unclear which method is  best Further research is neededz$@zy 6Aim  +Methods rLog binomial regression Constrained log binomial regression COPY 1000 method Expanded logistic GEE Log Poisson GEEs$PZs s  Simulation Scenarios Simulated data assuming log binomial model 170 simulation scenarios 200 or 500 subjects Blocked or stratified randomisation Different treatment and covariate effects Binary and/or continuous covariate Different covariate distributions6D$@$@D ' Size of Study  1000 datasets per scenario 10 different methods 2000 resamples used for bootstrapping Unadjusted and adjusted analyses SAS grid computing$@.6   L >SAS Grid Computing   Comparing Methods OComparisons based on: Convergence Type I error Power Bias Coverage probability6$@:$@:O 8Results - Overall  Results - Convergence   ,Results  Type I Error  $@ 4$Results  Coverage  $@  Results  Bias  $@ ) The Winner  Log Poisson approach Performed well relative to other methods Simple to implement Most used in practice Invalid predicted probabilities (max 6%) Problematic if prediction is of interest$@ # Conclusion  Log binomial regression useful when it converges Many alternatives available if it doesn t Alternatives not all equal Log Poisson approach recommended if log binomial regression fails to converge Performance with clustered data remains to be investigated$PZ :Acknowledgements International Biometric Society for financial assistance sponsored by CSIRO Professor Philip Ryan and Dr Amy Salter for supervising my research$@ 0  /   $(*,1579;=?  0` 33` Sf3f` 33g` f` www3PP` ZXdbmo` \ғ3y`Ӣ` 3f3ff` 3f3FKf` hk]wwwfܹ` ff>>\`Y{ff` R>&- {p_/̴>?" dd@,|?" dd@   " @ ` n?" dd@   @@``PR    @ ` ` p>> f(    6  `}  T Click to edit Master title style! !  0  `  RClick to edit Master text styles Second level Third level Fourth level Fifth level!     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NEJM 1999; 341: 279-283d H  0޽h ? 3380___PPT10.V| 0 d\p (  \  C 4Aualogo_colourIDgx  c $g` }  ` x  c $Xh` ` ` XB  0DԔ H  0޽h ? 3380___PPT10.V| 0 d\` (  \  C 4Aualogo_colourIDgx  c $ n` }  ` x  c $n` ` ` XB  0DԔ H  0޽h ? 3380___PPT10.V|! 0 @ !(  \  C 4Aualogo_colourIDgx  c $s` }  ` x  c $8T ` ` XB  0DԔ   0`  Q(0,1)  lr  6"`f 1 H  0޽h ? 3380___PPT10.V|Q 0  Q(   \  C 4Aualogo_colourIDgx  c $` }  ` x  c $` ` ` XB  0DԔ   0`  Q(0,1)    6̏`G@ p N>0  lr  6"`f 1 lr  6"`f  H  0޽h ? 3380___PPT10.V| 0 d\P(  \  C 4Aualogo_colourIDgx  c $` }  ` x  c $` ` ` XB  0DԔ H  0޽h ? 3380___PPT10.V| 0 ?7 (  \  C 4Aualogo_colourIDgx  c $` }  ` XB  0DԔ S  0`GS To determine how the different methods for estimating relative risk compare under a wide range of scenarios relevant to RCTs with independent observations    H  0޽h ? 3380___PPT10.V|7 0 7(  \  C 4Aualogo_colourIDgx  c $,` }  ` x  c $`   ` XB  0DԔ ;  0` m  oLog normal GEE Logistic regression with marginal or conditional standardisation delta method or bootstrapping<)$PZG$PZ)G p H  0޽h ? 3380___PPT10.V| 0 d\((  (\ ( C 4Aualogo_colourIDgx ( c $` }  ` x ( c $` ` XB ( 0DԔ H ( 0޽h ? 3380___PPT10.V| 0 d\P(  \  C 4Aualogo_colourIDgx  c $8` }  ` x  c $` ` ` XB  0DԔ H  0޽h ? 3380___PPT10.V| 0  (  \  C 4Aualogo_colourIDgx  c $` }  ` XB  0DԔ tB  8ETFHQ&UVWUUJGOEDKB5KBOEJGOEJGOEKJIGG JKJKJPP(PM%M/ %Mz (PPP(PPP(P KBH?H?r7r7.FF0*Fr7@r7@H?|EH?sJOERMSYNySO`TP`T]Q`TQ`TR`T+S`T+SSSySSR`TR`T*`T`T8`TSQS+Sj+SjRjQj]QPQOYNMM0*  KB KB KB>D VKM KB @ @h.h. 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BBBr7@r7@H?H?r7!$@`@@`@@`@@-@@`@@`@@`@0*0*0*`TF0* ?-computr3#" `U F ^B  6DjJV -- ^B  6DjJ--`  T! ?"6@ NNN?N=W  ]Run SAS program dB  <7DjJ  dB  <DjJP 2 PdB  <DjJ @ w dB  <ZDjJ @ w    < !4 <  PTask   <P` \  RResult dB  <1DjJ m dB  <}DjJ9 @ w 9 H  0޽h ? 3380___PPT10.V| 0 d\$(  $\ $ C 4Aualogo_colourIDgx $ c $! }  ! x $ c $\! ` ! XB $ 0DԔ H $ 0޽h ? 3380___PPT10.V| 0 ` (  \  C 4Aualogo_colourIDg~  s *! `}  ! XB  0DԔ   0``  ` .$@g  0!!  Differences between methods Convergence problems Differences in type I error rates and coverage probabilities Large bias for some methods under certain conditions Little difference in power$@  H  0޽h ? 3380___PPT10.V|b  0 xb(  x\ x C 4Aualogo_colourIDg~ x s *'! `}  ! XB x 0DԔ   x <\)!/uv {/Percentage of Simulations where Model Converged00/   x <H/!% l  M%   x <P3!Pm  RMethod j x C BA*IBS convergence plot ;H x 0޽h ? 3380___PPT10.V|  0 h` $0(  0\ 0 C 4Aualogo_colourIDg~ 0 s *:! `}  ! ~ 0 s *(;!   ! XB 0 0DԔ  0 <Finally I would just like to acknowledge the international biometric society for providing me with financial assistance to attend this conference through the generous sponsorship provided by CSIRO and also my supervisors, professor philip ryan and dr amy salter at the university of adelaide for supervising this work.             H  0޽h ? 3380___PPT10.JX@J30 /(  ^  S H   K  c $tKH 0  K %As an example of what can go wrong when odds ratios are misinterpreted, there is a rather famous study conducted in the US which looked at the effect of race on whether physicians recommended referring patients who presented with chest pain for cardiac catheterisation. The study found that the referral rate was 90.6% for white patients compared to 84.7% for black patients and the odds ratio of 0.6 was reported. This study generated quite a bit of interest from the media who went on to say that referral rates were 40% lower for black patients compared to white patients and you can just imagine the kind of response a headline like this would receive. In other words, the media interpreted the odds ratio as a relative risk. The actual relative risk was 0.93 which indicates that referral rates were only 7% lower for black patients compared to white patients. By incorrectly interpreting the odds ratio as a relative risk, this effect of race was severely overstated in the media. .   H  0޽h ? 3380___PPT10.DX`Uu;0 K(  ^  S H   K  c $ KH 0  K AThe basic idea with grid computing in SAS is that you connect a bunch of computers up in a grid and then you run a program on one computer which will then distribute tasks to all computers in the grid and these run in parallel, allowing you to get the results much faster.  H  0޽h ? 3380___PPT10.HX W=r'e79:GPBA>DcKqu[ ^jc1ңAĶ6޽A|U# 8j'`^<zWR0 0(4^6Smx4e>=qa # ?1Oh+'0l `hx  Slide 1 a1069947 a106994779Microsoft Office PowerPoint@0&@"FV@k Ghg  ,V'&" WMFC <8?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijklmnopqrstuvwxyz{|}~      !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijklmnopqrstuvwxyz{|}~      !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijklmnopqrstuvwxyz{|}~      !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghijlmnopqrstuvwxyz{|}~Root EntrydO)PicturesRCurrent UserSummaryInformation(kPowerPoint Document(DocumentSummaryInformation8Root EntrydO)`'%l@PicturesRCurrent User,SummaryInformation(k_UserUser