臨床試験における症例数設定とガイドライン 5F 4F 5F

1 2016 (6 15 5F ) (7 27 5F ) (8 24 5F ) (11 2 4F 1) (11 16 5F ) (11 30 4F 1) (12 28 5F ) (2 1 4F 1) (2 22 5F ) (3 22 4F 1) p 40% Study AStudy B 40 , 20 ( ) p = ( ) 80 , 40 ( ) p = * ( ) Study A negative study Study B positive study Study A Positivestudy Study A Study B 80 (50%) 40 (55%) Study AStudy B80 40 ( ) The required sample size was estimated based on a threshold RR of 35% and an expected RR of 50%, 80% power, and an alpha value of (one-sided) using the binomial test.

2 Given 2% of ineligible patients, the target sample size was determined to be at least 50 patients. Phase II study of trastuzumab in combination with S-1 plus cisplatin in HER2-positive gastric cancer (HERBIS-1)(Kurokawa et al., British Journal of Cancer, 110, 1163 68, 2014) Phase II Study ( ) (RR: Response Rate) 35% 50% 1 (type I error, ) = 2 (1 type II error, ) 1 = (80%) = 50 1 ( ) 2 ( ) H0 [H1 ]H [H0 ]H0 [H1 ] 1 (H0 ) 1 (H0 )H0 [H1 ] 1 (H1 ) 2 (H1 ) 2 ( ) ( positive negative ) 1 ( ) ( negative positive ) H0 [H1 ]H [H0 ]H0 [H1 ] 1 ( )

3 1 [H1 ] 1 2 H0 35% H1 35% = 50 50% ( ) HERBIS 1 ToGA (Y J Bang, et al. The Lancet, 28, 687 697, 2010 .) ToGA (5 FU/CDDP Capecitabine/CDDP) 35% (or HR=1) ( ) ( ) HERBIS 1 ToGA (1) Trastuzumab 47% (2) HER2 (IHC 3+ or FISH positive + IHC 2+) (3) 50% ( ) ( ) Agree ( ) ( ) ( ) ( ) (censoring )

4 = or 1 = = , 1 = or WEB SITE (1/2) (One Arm BInomial) (One Arm Normal) (One Arm Survival)(One Arm Non parametric / KM ) 2 ( , Two Stage)2 (Two Arm BInomial) (Two Arm Normal) (One Arm Survival) (Two Arm BInomial) (Two Arm Normal) (Survival Noninferority) (Expected Deaths WEB SITE (2/2) Chinese University of Hong Kong EZREZR R( ) R (AHRQ.))

5 CONSORT CONSORT(Consolidated Standards of Reporting Trials ) CONSORT2010 CONSORT2010 Check List CONSORT Flow Diagram CONSORT 2010 checklist (1/4) (Title and Abstract)1a 1b (trial design) (method) (result) (conclusion) (Introduction) (Background and Objective)2a (rationale) 2b (hypothesis) Method (Trial Design)3a ( , ), 3b ( eligibility criteria ) (Participant)4a (eligibility criteria)4b (setting) (Intervention)5 CONSORT 2010 checklist (2/4) (Outcome)6a 6b (Sample size)7a 7b (Randomization) (Sequence generation)8a (allocation) (generate) 8b.

6 ( ) (Allocation concealment mechanism)9 ( ) (Implementation)10 (enrollment) (assign) (Blinding)11a ( )11b (Statistical method)12a 12b CONSORT 2010 checklist (3/4) Results (Participant flow)( )13a 13b (Recruitment)14a 14b (Baseline data)15 (demographic) (Number analyzed)16 ( ) (Outcome and estimation)17a (95 )17b2 (Ancillary analysis)18 (Harm)19 (harm) CONSORT 2010 checklist (4/4) Discussion (Limitation)20 (Generalisability)21 ( ) (Interpretation)22 Other information (Registration)23 (Protocol)24 (Funding)25 ( )

7 CONSORT UMIN 2 1 2 1 2 ( ) ( ) ( ) ( ) 3 ICH-E9 (1) ( A, B) ( ( 65, 65) PS(0,1,2)) A B ( 4) (AABB), (ABAB), (ABBA), (BAAB), (BABA), (BBAA)A B A B B A B A B B A A B B A A (2) A B A B B A B A B B A A A B B A A B A B A A B B A A B B B B A A B A B A B A A B A B A B A B B A ( 65) PS(0) ( 65) PS(1)

8 ( 65) PS(0) ( 65) PS(1) ( ) ( A, B) ( ( 65, 65) PS(0,1,2)) (1) Taves (Taves, 1974) ( ,2003) A B 65 33 665 121325 151631 A B A33 6B4 8C8917 151631 A B 54 9 8917 23 5 151631 , , 2003. ( ) ( ) 65 =D = 65 =D = A B 1213 89 54 2526A 65 =D = 65 =D = A B 33 89 54 16 16 CONSORT Flow Diagram STROBE (STROBE.)

9 Strengthingthe Reporting of Observational Studies in Epideology) STROBE Checklist 22 18 4 3 STROBE STROBE (1/4) (title and abstract)1(a) (b) (introduction) (background) (rationale)2 (objective)3 methods (study design)4 (setting)5 (participant)6(a) (b) (variable)7 (data source) 8* (bias)9 (study size)10 ( ) (quantitative variable)11 (statistical analysis)12(a) (b) (c) (d)

10 (e) STROBE (2/4) result (participant)13*(a) ( ) (b) (c) (descriptive data)14*(a) ( ) (b) (c) (Outcome data)15* (main result)16(a) ( 95% ) (b) (c) STROBE (3/4) (other analysis)17 ( ) discussion