LECTURE 25 2011

LECTURE 25 2011 - Interim Analyses of Clinical Trials A...

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Interim Analyses of Clinical Trials A Requirement
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Outline Background and how DSMBs function Group sequential methods Examples
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Suggested Reading DeMets DL, Furberg CD, Friedman LM Data Monitoring in Clinical Trials. A Case Studies Approach Springer, 2006
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Examples (1) A trial stopped early for efficacy A trial that might have been stopped too soon except for attention to monitoring boundaries A trial stopped for a secondary outcome A trial with multiple outcomes A trial stopped 2, maybe 3 times
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Examples (2) Blinding treatments to the DMC – not a good idea Sharing data between DMCs Two similar trials with one stopped early A trial with a safety concern A trial in which the DSMB may have over- stepped their role A trial that should have stopped early???
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Beta-Blocker Heart Attack Trial Propranolol Placebo Deaths 138/1916 188/1921 7.2% 9.8% Early Termination for Efficacy Planned termination: June 1982 Early termination: October 1981 JAMA 1982
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Beta-Blocker Heart Attack Trial Observed Meeting z-value O-Brien/ No. (Log-Rank) Fleming Boundary* 1 1.68 5.46 2 2.24 3.85 3 2.37 3.15 4 2.30 2.73 5 2.34 2.44 6 2.82 2.23 Trial terminated; significant at 5% level Pocock’s critical value = 2.49 Peto’s critical value = 3.0 *Jennison C and Turnbull BW, Group Sequential Methods With Applications to Clincal Trials; C B (7,0.05)=2.063.
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1.96
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Fleming TR, Neaton JD, et al, JAIDS , 1995. Relative Risk of AIDS/Death by Date of DSMB Review – Good Thing We Did Not Stop 5.7 3.6 0.80 Relative Risk (on a log scale) 1.00 1.25 FINAL 9/20/92 157:152 (ddI:ddC) DSMB #5 8/21/92 130:130 (ddI:ddC) DSMB #4 2/13/92 77:91 (ddI:ddC) DSMB #3 11/08/91 50:66 (ddI:ddC) DSMB #2 8/29/91 19:39 (ddI:ddC) ddC Better ddI Better Confidence Intervals: Repeated 95%
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Physician’s Health Study Aspirin Component – CVD Mortality Was Not Going To Make It. 7-86 28 33 .52 75 122 .0007 1-87 37 42 .57 89 154 <.0001 12-87 44 44 .99 104 189 <.0001 Date of DSMB Review No. Events Cairns et al. Annals Epid , 1991. Aspirin Placebo P-value CVD Death Aspirin Placebo P-value Fatal/Non-fatal MI + + Largely non-fatal events Unconditional power and conditional power assessed for CVD mortality. Unconditional power was approximately 50% and conditional power was about 30%.
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Women’s Health Initiative Multiple Clinical Outcomes Event Estrogen/ Progestin Placebo HR CHD 164 122 1.29* Stroke 127 85 1.41 Pulmonary Emb. 70 31 2.13* Breast cancer 166 124 1.26* Hip fracture 44 62 0.66* Death 231 218 0.98 Total No. Patients * P<0.05; Global index 8,506 Z = -1.62 8,102 Writing Group for WHI, JAMA 2002.
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Prevention Trial of Toxoplasmic Encephalitis in Patients with Advanced HIV (TOXO Trial): Design and Recruitment Goals
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This note was uploaded on 11/21/2011 for the course PUBH 7420 taught by Professor Ph7420 during the Spring '07 term at Minnesota.

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LECTURE 25 2011 - Interim Analyses of Clinical Trials A...

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