Methods for handling treatment switching - MRC Network of Hubs for ...

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My talk: introduction to the methods1. Intention-to-treat analysis2. Per-protocol analysis3. Inverse-probability-of-censoring weighting (IPCW)4. Marginal structural models (MSMs)5. Rank-preserving structural nested failure time models(RPSFTMs)6. Brief comparisons6
Defining the question• What is the effect of assignment to treatment A in thecircumstances of the trial? (effectiveness)– could be: A immediately vs. A on progression• What will be the effect of assignment to treatment A inother circumstances? (alternative effectiveness)– could be: A immediately (for as long as tolerated)vs. no A• What is the effect of treatment A per se (efficacy)?– i.e. while actually given7
Page 1 and 2: Methods for handling treatmentswitc
Page 3 and 4: Note on terminology• I’ve calle
Page 5: Plan of the dayIan WhiteSusie DoddJ
Page 9 and 10: A hypothetical (& simplistic) trial
Page 11 and 12: Intention-To-Treat (ITT) Analysis
Page 13 and 14: Per Protocol (PP) Analysis• Censo
Page 15 and 16: Inverse-probability-of-censoring we
Page 17 and 18: Inverse probability weights• Half
Page 19 and 20: Choice of covariates for IPCW• Re
Page 21 and 22: Note on IPCW• Can handle more tha
Page 23 and 24: Marginal Structural Models (MSMs)
Page 25 and 26: Towards the RPSFTM• focussing on
Page 27 and 28: RPSFTM (2)• The RPSFTM relates ob
Page 29 and 30: Interpretation of ψModel: T i (0)
Page 31 and 32: G-estimation: an unusual estimation
Page 33 and 34: Hypothetical data(switches occur on
Page 35 and 36: Estimating ψ: is e ψ = 0.5?Treate
Page 37 and 38: Censoring• Censoring introduces c
Page 39 and 40: Non-standard RPSFTM-like analysisto
Page 41 and 42: Arguments used: IPCWFor• Gives HR
Page 43 and 44: Key messages: design• Collect fol
Page 45 and 46: Summary & questions• IPCW, MSM an

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