Illustrations of Delamanid and STREAM 1 Phase III Trial Results
Explore the results of Delamanid and STREAM 1 Phase III trials showcasing superiority and non-inferiority in TB treatment modalities. Dive into the comparison of time to conversion, risk differences, and conclusions from the study. Gain insights into the potential new treatment algorithms for RR/MDR-TB.
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Presentation Transcript
The results are in! Now what? The results are in! Now what? Illustrations of results from Delamanid (superiority) and STREAM 1 (non-inferiority) Phase III Trials Carole Mitnick Meredith Brooks
Superiority Example: Time to conversion 95% CI 95% CI Superior H0: time to conversion is not different between the experimental and control regimens 95% CI Control arm Experimental arm Not superior 95% CI 0 Median days to culture conversion
DLM phase III Results: primary analysis 95% CI Treatment arm (mITT) Control (n=101) Experimental (n=226) Crude difference Days to conversion (95% CI) 57 (56-64) 51 (43-57) 6 days 95% CI 0 Median days to culture conversion P-value 0.056 H0: time to conversion is equal between the experimental and control regimens
Superiority vs. Non-inferiority: risk difference example Inferior Not superior Inconclusive Non- inferior Superior 0 0 10 Difference in unfavorable outcomes between the experimental and control regimens Difference in unfavorable outcomes between the experimental and control regimens H0: difference in unfavorable outcomes between the experimental and control arms=0 HA: difference in unfavorable outcomes between the experimental and control arms<0 H0: difference in unfavorable outcomes between the experimental and control arms>=10 HA: difference in unfavorable outcomes between the experimental and control arms<10
STREAM Results Treatment arm (mITT) Experimental (n=210) Control (n=108) Crude difference % unfavorable outcome 21.9% 19.4% 2.5% Adjusted difference = 10 Conclusion: 95% CI includes (10%), inconclusive for non-inferiority 2.1 (95% CI: -6.9, +11.2) 95% confident that true difference between the control and experimental treatments is between -6.9% and +11.2% 0 H0 (experimental regimen is >= 10% worse than the control), cannot be ruled out
Simplified example of possible algorithm integrating all new treatment modalities for RR/MDR-TB
Rapid molecular (or conventional) test positive for TB and RR/MDR Conventional regimen + 2 of 3: BDQ, LZD, DLM Continue shortened regimen Known (or suspected) R to FQ and/or inject or HIV infected? No Yes Yes Is R documented? No Known R to PZA? >=50% PZA R among FQ-S in jurisdiction? Shortened regimen, pending conventional DST Yes No PZA-R, XDR, pre-XDR among known contacts of patient? No Yes No Conventional regimen + BDQ and/or DLM Known or suspected R to other drugs in shortened regimen? Yes No Yes
