临床试验设计的类型(1)ppt课件

1、Lea Drye, PhDJohns Hopkins UniversityTypes of Trial DesignCopyright 2019 Johns Hopkins University and Lea Drye. All Rights Reserved.; P h a s e I :F i r s t s t a g e i t e s t i g a e w i t e r v e t i o i h u m a sU s u a l l y 1 0 - 3 0 p e o p l eI d e t i f y t o l e r a b l e d o s e , p r o v

2、 i d e i f o r m a t i o o d r u g m e t a b o l i s m ,e x c r e t i o , a d t o x i c i t yO f t e o t c o t r o l l e d P h a s e I I :U s u a l l y 3 0 - 1 0 0 p e o p l eP r e l i m i a r y i f o r m a t i o o e f f i c a c y , a d d i t i o a l i f o r m a t i o o s a f e t y a d s i d e e f f

3、 e c t s P h a s e I I I :U s u a l l y 1 0 0 + p e o p l eA s s e s s e f f i c a c y a d s a f e t yC o t r o l l e d , u s u a l l y r a d o m i z e d2Phases of trials;Lecture Outline D i s c u s s v a r i o u s t r i a l d e s i g t y p e sP a r a l l e lC r o s s o v e rG r o u p a l l o c a t

4、i o F a c t o r i a lL a r g e s i m p l eE q u i v a l e c yN o - i f e r i o r i t yA d a p t i v e3;Comparison Structure: Parallel, Crossover, and GroupAllocation DesignsSection AThe material in this video is subject to the copyright of the owners of the material and is being provided for educati

5、onal purposes under rules of fair use for registered students in this course only. No additional copies of the copyrighted work may be made or distributed.;Parallel Design5 S i m u l t a e o u s t r e a t m e t a d c o t r o l g r o u p s E a c h p e r s o i s r a d o m l y a s s i g e d t o o e t r

6、 e a t m e t g r o u p R a d o m i z a t i o r e m o v e s t r e a t m e t s e l e c t i o b i a s a d p r o m o t e s c o m p a r a b i l i t y o f t r e a t m e t g r o u p s S t a t i s t i c a l c o m p a r i s o s m a d e b e t w e e t r e a t m e t g r o u p s;|P叫 eG巾Randomized占v1，白6iJHSPH;Par

7、allel Design Example: NETTSource: NETT Research Group (2019). Chest 1999; 116: 1750-61; NETT Research Group (2019). J Thorac Cardiovasc Surg, 118: 518-528; Fishman, A., & Martinez, F., et al. (2019). N Engl J Med 348: 2059-73.7 N a t i o a l E m p h y s e m a T r e a t m e t T r i a l ( N E T T

8、)- P h a s e I I I t r i a l , u m a s k e dPopulationPeople with severe emphysemaSample size1,200Allocation to treatmentRandomizedTreatmentsLung volume reduction surgery plus medical therapyMedical therapy (standard therapy control);Parallel Design Example: NETTSource: NETT Research Group (2019). C

9、hest 1999; 116: 1750-61; NETT Research Group (2019). J Thorac Cardiovasc Surg, 118: 518-528; Fishman, A., & Martinez, F., et al. (2019). N Engl J Med 348: 2059-73.8Hypothesis testingSuperiorityOutcomesPrimary: mortality, exercise capacitySecondary: quality of life, symptoms,lung function and mec

10、hanics, functional capacityFollow-upUp to 7.5 yearsNumber of recruiting centersMulti-center (17);Crossover Design9 R a d o m i z a t i o o f o r d e r i w h i c h t r e a t m e t s a r e r e c e i v e dA B o r B AR a d o m i z a t i o p r o m o t e s b a l a c e b e t w e e t r e a t m e t g r o u p

11、 s i t i m i g o f e x p o s u r e T e s t i g o f b o t h t r e a t m e t s i e a c h p a t i e tE a c h p a t i e t s e r v e s a s h i s / h e r o w c o t r o lV a r i a b i l i t y r e d u c e d b e c a u s e l e s s v a r i a b i l i t y w i t h i p a t i e t t h a b e t w e e p a t i e t s F e

12、 w e r p a t i e t s e e d e d;Crossover Design GraphWashout10Group 1, Tx AGroup 1, Tx BGroup 2, Tx BGroup 2, Tx A;Crossover Design: Disadvantages11 T r e a t m e t c a t h a v e p e r m a e t e f f e c t s o r c u r e s P o t e t i a l c a r r y - o v e r e f f e c t s o f f i r s t - p e r i o d t

13、 r e a t m e t t o s e c o d p e r i o dW a s h o u t e e d s t o b e l o g e o u g hU e q u a l c a r r y - o v e r e f f e c t sT r e a t m e t d u r i g w a s h o u t T e s t f o r p e r i o d b y t r e a t m e t i t e r a c t i o s o t p o w e r f u l D r o p o u t s m o r e s i g i f i c a t A

14、a l y s i s m a y b e m o r e d i f f i c u l t;Crossover Design: Uses12 C o s t a t i t e s i t y o f u d e r l y i g d i s e a s eC h r o i c d i s e a s e s a s t h m a , h y p e r t e s i o , a r t h r i t i s S h o r t - t e r m t r e a t m e t e f f e c t sR e l i e f o f s i g s o r s y m p t

15、 o m s o f d i s e a s e M e t a b o l i c , b i o a v a i l a b i l i t y , o r t o l e r a b i l i t y s t u d i e s;Crossover Design: Examples13 E v e i g - d o s e v s . m o r i g - d o s e d t r a v o p r o s t i o p e - a g l e g l a u c o m a f o r 2 4 - h o u r i t r a o c u l a r p r e s s

16、u r e c o t r o l M o t e l u k a s t v s . s a l m e t e r o l a s a d j u v a t t o i h a l e d f l u t i c a s o e f o r e x e r c i s e - i d u c e d a s t h m a i c h i l d r e T o p i c a l o i l v s . p l a c e b o f o r e u r o p a t h i c p a i ;Group Allocation Design14 A l s o k o w a s “

17、 c l u s t e r r a d o m i z a t i o R a d o m i z a t i o u i t i s a g r o u p o f i d i v i d u a l s ( c o m m u i t y , s c h o o l , c l i i c ) I d i v i d u a l r a d o m i z a t i o a d i t e r v e t i o i s o t f e a s i b l e o r i s u a c c e p t a b l eT r a c k i gC o t a m i a t i o I

18、 f t h e r e i s a c o r r e l a t i o i t h e r e s p o s e s w i t h i a g r o u p , d e s i g l o s e s s o m e e f f i c i e c y ( m o r e i d i v i d u a l s r e q u i r e d );lIj川臼15Randomized;Group Allocation Example: Sommer Vit A trial16Lancet. 1986 May 24;1(8491):1169-73 P o p u l a t i o P r e s c h o o l c h i l d r e i o r t h e r S u m a t r a i 1 9 8 2 - 8 3 T r e a t m e