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Nonidentifiability in the presence of factorization for truncated data.

ABSTRACT: A time to event, [Formula: see text], is left-truncated by [Formula: see text] if [Formula: see text] can be observed only if [Formula: see text]. This often results in oversampling of large values of [Formula: see text], and necessitates adjustment of estimation procedures to avoid bias. Simple risk-set adjustments can be made to standard risk-set-based estimators to accommodate left truncation when [Formula: see text] and [Formula: see text] are quasi-independent. We derive a weaker factorization condition for the conditional distribution of [Formula: see text] given [Formula: see text] in the observable region that permits risk-set adjustment for estimation of the distribution of [Formula: see text], but not of the distribution of [Formula: see text]. Quasi-independence results when the analogous factorization condition for [Formula: see text] given [Formula: see text] holds also, in which case the distributions of [Formula: see text] and [Formula: see text] are easily estimated. While we can test for factorization, if the test does not reject, we cannot identify which factorization condition holds, or whether quasi-independence holds. Hence we require an unverifiable assumption in order to estimate the distribution of [Formula: see text] or [Formula: see text] based on truncated data. This contrasts with the common understanding that truncation is different from censoring in requiring no unverifiable assumptions for estimation. We illustrate these concepts through a simulation of left-truncated and right-censored data.

SUBMITTER: Vakulenko-Lagun B

PROVIDER: S-EPMC6690171 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Nonidentifiability in the presence of factorization for truncated data.

Vakulenko-Lagun B B Qian J J Chiou S H SH Betensky R A RA

Biometrika 20190513 3

A time to event, [Formula: see text], is left-truncated by [Formula: see text] if [Formula: see text] can be observed only if [Formula: see text]. This often results in oversampling of large values of [Formula: see text], and necessitates adjustment of estimation procedures to avoid bias. Simple risk-set adjustments can be made to standard risk-set-based estimators to accommodate left truncation when [Formula: see text] and [Formula: see text] are quasi-independent. We derive a weaker factorizat ...[more]

PMID: 31427826

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Project description:BACKGROUND:Calibration is the process of estimating parameters of a mathematical model by matching model outputs to calibration targets. In the presence of nonidentifiability, multiple parameter sets solve the calibration problem, which may have important implications for decision making. We evaluate the implications of nonidentifiability on the optimal strategy and provide methods to check for nonidentifiability. METHODS:We illustrate nonidentifiability by calibrating a 3-state Markov model of cancer relative survival (RS). We performed 2 different calibration exercises: 1) only including RS as a calibration target and 2) adding the ratio between the 2 nondeath states over time as an additional target. We used the Nelder-Mead (NM) algorithm to identify parameter sets that best matched the calibration targets. We used collinearity and likelihood profile analyses to check for nonidentifiability. We then estimated the benefit of a hypothetical treatment in terms of life expectancy gains using different, but equally good-fitting, parameter sets. We also applied collinearity analysis to a realistic model of the natural history of colorectal cancer. RESULTS:When only RS is used as the calibration target, 2 different parameter sets yield similar maximum likelihood values. The high collinearity index and the bimodal likelihood profile on both parameters demonstrated the presence of nonidentifiability. These different, equally good-fitting parameter sets produce different estimates of the treatment effectiveness (0.67 v. 0.31 years), which could influence the optimal decision. By incorporating the additional target, the model becomes identifiable with a collinearity index of 3.5 and a unimodal likelihood profile. CONCLUSIONS:In the presence of nonidentifiability, equally likely parameter estimates might yield different conclusions. Checking for the existence of nonidentifiability and its implications should be incorporated into standard model calibration procedures.

Dataset Information

Nonidentifiability in the presence of factorization for truncated data.

Publications

Nonidentifiability in the presence of factorization for truncated data.

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