Twenty Five Years Designing Clinical Trials . and Still Learning - - PowerPoint PPT Presentation

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Nov 05, 2023 227 likes •326 views

Twenty Five Years Designing Clinical Trials . and Still Learning Roy N. Tamura Health Informatics Institute University of South Florida Career Timeline Type 1 Diabetes, Rare Diseases USF - Health Informatics Strattera Cymbalta Zyprexa

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Twenty Five Years Designing Clinical Trials …. and Still Learning Roy N. Tamura

Health Informatics Institute University of South Florida

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Career Timeline

Started at NCSU Finished PhD ! Eli Lilly Non-Clinical Eli Lilly Clinical Zyprexa Strattera Cymbalta USF - Health Informatics Type 1 Diabetes, Rare Diseases 1978 1983 1992 2012

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1. Group Sequential Designs: alpha spending functions,

efficacy monitoring futility analyses

2. Adaptive Designs:

sample size, randomization, stratification

3. Enriched Designs:

biomarker based, response based

4. Multi-stage Designs:

SMART (sequential multiple assignment randomized trials) and many other useful proposals.

Clinical Trial Design Advancements – Past 25 Years

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Isolated Skin Vasculitis: No current effectiveness information on any drug Trial: Compare dapsone, colchicine, azathioprine over six month period. Goal: Find the best drug and compare that drug with the next best drug.

NIH Rare Disease Network Project

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ARAMIS - Small n Sequential Multiple Assignment Randomized Trial (snSMART)

Enrollment Randomization n=90 (1:1:1) Azathioprine N = 30 Dapsone N = 30 Colchicine N = 30

Stage 1 Stage 2

responders M6 continue Azathioprine non-responders randomized 1:1 Dapsone Colchicine responders M6 continue Colchicine non-responders randomized 1:1 Azathioprine Dapsone responders M6 continue Dapsone non-responders randomized 1:1 Azathioprine Colchicine

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Weighted Z Statistic

Let d1 and d2 be the difference in response rates between Drugs A and B in Stages 1 and 2 respectively. Let Var1 and Var2 be the usual pooled variances in Stage 1 and Stage 2. Zw = (wd1 + (1-w)d2) / (w2Var1 + (1−w)2Var2) w is the weight for each Stage. See Tamura, et al. 2016, Contemporary Clinical Trials on how to chose w).

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U Michigan Biostatistics (Kelley Kidwell – PI) and U South Florida Rare Disease Network (me) Consolidate information from both stages of an snSMART to make overall drug recommendation Investigate incorporation of adaptive design elements into snSMART Develop user friendly app for power, sample size

PCORI Improving Methods Contract

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Role models for both research and application. Emphasis on experimental design / collaboration with researchers. Support, advice, and encouragement throughout my career. Best wishes to the Department for their Next 75 Years!