Treatment Effects ARE Heterogeneous What Should We Do About It?

Transcript

1 Treamen Effecs AE Heerogeneous Wha Should We Do Abou I? Sco L. Zeger Professor of Bosascs and Medcne codrecor for Daa Scence, Hopkns nhealh FDA Symposum on Treamen Heerogeney November 28, 208 esearch repored n hs lecure was parally funded by a generous gf from he Greene Foundaon and hrough a PaenCenered Oucomes esearch Insue (PCOI) Award (ME ). The vews expressed are solely he responsbly of he auhor and do no necessarly represen he vews of he PaenCenered Oucomes esearch Insue (PCOI), s Board of Governors or Mehodology Commee.

2 Talk Oulne The Sew All reamens have heerogeneous effecs Paen s Vew Wha s my healh sae? Wha s my healh rajecory;? W Wha s he expeced effec of my rajecory for each of he avalable nervenons? Wha To Do? Sascal scence Clncal scence Healh Sysems FDA/Governmen evew Nov 28, 208 FDA 2

3 The Sew

4 Axom: All reamens have heerogeneous effecs Wllam Osler sad so: Varably s he law of lfe, and as no wo faces are he same, so no wo bodes are alke, and no wo ndvduals reac alke and behave alke under he abnormal condons whch we know as dsease. Assymery of he null hypohess: falure o rejec null of no heerogeney s no evdence n favor of he null. Sudes rarely powered o esmae dfferen reamen effecs n subgroups, especally less common subgroups. Because hey are dffcul o esmae does no mean hey are no crcal o clncal medcne Nov 28, 208 FDA 4

5 Boole a Bayes Thomas Bayes 7076 George Boole Nov 28, 208 FDA 5

6 Ths mage canno currenly be dsplayed. Boullabasse Boole a Bayes Nov 28, 208 FDA 6

7 Paen s Vew

8 Is my umor ndolen or lfehreaenng? Should I ge a bopsy oday or wa a year? Should I connue annual checkups or have my prosae removed or rradaed? Nov 28, 208 FDA 8

9 Common Generc Quesons. Wha s my healh sae? 2. Wha s my rajecory? 3. Wha oher measuremens mgh help clarfy my sae? 4. Whch nervenon s bes for me oday? Nov 28, 208 FDA 9

10 Herarchcal Model for Healh Sae/Trajecory ( ) wh Personspecfc Indcaor ( ) Nov 28, 208 FDA 0

11 Effecs of Exogenous () and Endogenous (x) Covaraes on Healh Sae/Trajecory wh Personspecfc egresson Coeffcens ( ) x x x Nov 28, 208 FDA

12 Observaons () ha Inform abou Healh Sae hrough Coeffcens ( ) x x x Nov 28, 208 FDA 2

13 Treamen Decsons Depend on Pas Measured Oucomes hrough Parameers ( ) x x x Nov 28, 208 FDA 3

14 Nov 28, 208 FDA 4

15 , Σ ϑ CTs Nov 28, 208 FDA 5

16 , Σ ϑ Ζ Nov 28, 208 FDA 6

17 Nov 28, 208 FDA 7, Σ ϑ Ζ, Σ ϑ Ζ, Σ ϑ Ζ, Σ ϑ Ζ, Σ ϑ Ζ

18 Nov 28, 208 FDA 8, Σ ϑ Ζ, Σ ϑ Ζ, Σ ϑ Ζ, Σ ϑ Ζ, Σ ϑ Ζ andomzed clncal rals resuls

19 Sascal Commens When unverfable assumpons are added, many call hese causal models or srucural equaon models; we prefer predcng nervenon effecs (pe or π) models Models can be parally denfable Wellconrolled, embedded clncal rals daa are core daa for hese predcons Communcaon o paens and clncans s hard, bu crcal

20 Wha o Do? Sascans: Predcng nervenon effecs (π) models for populaons and people Clncal esearch Groups: Clncal cohor daabases Healh Sysems: Delver essenal evdence relevan o each decson o he pon of care

21 PMAP Precson Medcne Analycs Plaform DATA SOUCES DISCOVE Epc Pah Genomcs adology. DATA COMMONS IB Approvals ESEACH ENVIONMENT Valdaon /Process TEATMENT PLATFOM Feedback Nov 28, 208 FDA 2

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23 Pr(Aggressve Tumor) = 8% Nov 28, 208 FDA 23

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25 Seps for More Coheren Healh Decsons. Frame unme healh need 2. Specfy bomedcal model of curren knowledge 3. Wrangle relevan daa no a clncal cohor daabase (CCDB) (CTs, Clncal observaons) 4. Predcng nervenon effecs models 5. Desgn and es users nerface for populaon healh manager, clncan and/or paen 6. Desgn and es ongong ool evaluaon/curaon 7. Devse busness model o susan/mprove ool 8. Scale hrough consora Nov 28, 208 FDA 25

26 3 Opporunes for FDA/ Oher egulaory Agences. andomzed Consumer Trals o mprove safey rang and esmae reamen heerogeney 2. Incen publc avalably of paenlevel clncal rals daa 3. Promulgae mehods for approvng, hen curang clncal decson suppor ools Nov 28, 208 FDA 26

27 The Sew Man Pons Once Agan All reamens have heerogeneous effecs Paen s Vew Wha s my healh sae? Wha s my healh rajecory? Wha s he expeced effec of my rajecory for each of he avalable nervenons? Wha To Do?. Sascal scence: parner wh clncal nvesgaors o buld models ha use scenfc evdence o address he paens quesons as accuraely and precsely as he daa wll allow 2. Clncal scence: creae and use research qualy clncal cohor daabases 3. Healh Sysems: nform decsons wh relevan evdence a he pon of care 4. Governmen: hgh sandards for evdence abou he ATE for nal lcensng; ncen poslcensng, andomzed Cusomer Trals (CoTs) and publc access daa ses o drve 3 above. Nov 28, 208 FDA 27

28 Thank you

29 Two Ideas o Generae More Knowledge abou Heerogeneous Effcacy and Safey Faser Drop safe n favor of safelevel k Drop he complee separaon of produc research from produc use Already beng done n observaonal research Why no n expermenal research andomzed Consumer Trals Nov 28, 208 FDA 29