A Statistician Reads JAMA: A Futile Issue

On the latest episode of "In the Interim…", Dr. Scott Berry provides an empirical examination of two recent JAMA trials: TRACK (low-dose rivaroxaban in advanced kidney disease) and VICTORY (IV vitamin C in severe burn injury). The TRACK trial lacked any pre-specified futility criteria, with a DSMB-initiated stop based on conditional power calculations. Scott argues that conditional power, especially in this interim context, is a poor, misleading tool—contrasting it against a Bayesian predictive probability calculation that produced a much lower and more realistic estimate of success. In VICTORY, a pre-specified risk ratio threshold for futility was incorporated, with simulation confirming minimal effect on bias and statistical power. Scott underscores the practical and ethical importance of rigorously pre-specified, simulation-based futility rules and operationalizes the case for Bayesian predictive probability as a decision metric in interim monitoring. He reiterates that responsibility for defining futility belongs to trial designers, not left to ad hoc DSMB judgment, and calls for precise statistical planning in adaptive trial protocols.

Key Highlights

• TRACK: No pre-specified futility rule; DSMB stopped for futility using conditional power post hoc.
• Technical critique of conditional power as misguided at interim, supporting Bayesian predictive probability instead.
• VICTORY: Pre-specified futility threshold, with simulation confirming minimal operational bias and power reduction.
• Emphasizes pre-specified, simulation-based futility planning and predictive probability monitoring as standards for all trials.

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