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Semicompeting risks in aging research: methods, issues and needs

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Abstract

A semicompeting risks problem involves two-types of events: a nonterminal and a terminal event (death). Typically, the nonterminal event is the focus of the study, but the terminal event can preclude the occurrence of the nonterminal event. Semicompeting risks are ubiquitous in studies of aging. Examples of semicompeting risk dyads include: dementia and death, frailty syndrome and death, disability and death, and nursing home placement and death. Semicompeting risk models can be divided into two broad classes: models based only on observables quantities (class \(\mathcal {O}\)) and those based on potential (latent) failure times (class \(\mathcal {L}\)). The classical illness-death model belongs to class \(\mathcal {O}\). This model is a special case of the multistate models, which has been an active area of methodology development. During the past decade and a half, there has also been a flurry of methodological activity on semicompeting risks based on latent failure times (\(\mathcal {L}\) models). These advances notwithstanding, the semicompeting risks methodology has not penetrated biomedical research, in general, and gerontological research, in particular. Some possible reasons for this lack of uptake are: the methods are relatively new and sophisticated, conceptual problems associated with potential failure time models are difficult to overcome, paucity of expository articles aimed at educating practitioners, and non-availability of readily usable software. The main goals of this review article are: (i) to describe the major types of semicompeting risks problems arising in aging research, (ii) to provide a brief survey of the semicompeting risks methods, (iii) to suggest appropriate methods for addressing the problems in aging research, (iv) to highlight areas where more work is needed, and (v) to suggest ways to facilitate the uptake of the semicompeting risks methodology by the broader biomedical research community.

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Acknowledgments

Ravi Varadhan is a Brookdale Leadership in Aging Fellow and would like to thank the Brookdale Foundation for their support. The authors would also like to thank the support from the Johns Hopkins Older Americans Independence Center under the NIA/NIH contract P30-AG02133 and the Johns Hopkins Alzheimer’s Disease Research Center, NIA P50 AG005146.

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Correspondence to Ravi Varadhan.

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Varadhan, R., Xue, QL. & Bandeen-Roche, K. Semicompeting risks in aging research: methods, issues and needs. Lifetime Data Anal 20, 538–562 (2014). https://doi.org/10.1007/s10985-014-9295-7

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