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Heterogeneity's ruses: the neglected role of between-individual variability in longitudinal studies of COPD exacerbations.

Sadatsafavi M, FitzGerald JM - Thorax (2014)

Bottom Line: Standard survival analysis techniques often used in such studies typically produce results that pertain to the overall population, whereas the greatest interest is in the study of associations within individuals.A factor that can lead to profound discrepancies between population-level and individual-level survival patterns is the between-individual heterogeneity in the rate of exacerbations.We caution on the distinction between population and individual-level associations in survival analysis, and recommend accounting for heterogeneity in future studies.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Medicine, Institute for Heart and Lung Health, The University of British Columbia, Vancouver, British Columbia, Canada.

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Related in: MedlinePlus

Heterogeneity's ruses: an illustrative example of discrepancies between the population and individual hazards. This is a hypothetical population consisting of two subgroups (each 50% of the population) with regard to the hazard of an absorbing event (such as death or ‘next’ exacerbation): a frail subgroup that experiences the event at a high rate and a robust subgroup that experiences the event at a lower rate. While the hazard is constant within each subgroup, the population hazard decreases over time. This is because at any given point in time, the population hazard is the weighted average of subgroup hazards, with weights being the proportion of each subgroup in the event-free population. At first, everyone is event free, so the overall hazard is the midpoint between the subgroups’ hazards. As time passes, more individuals in the frail than the robust subgroup experience the event, thus, the event-free population becomes predominantly of the robust subgroup, lowering the population hazard. If the population hazard is interpreted at the individual level, one might erroneously conclude that the hazard of the event decreases over time. Phenomena similar to this can be responsible for the findings of both the studies discussed in this paper. For other examples refer to reference 1.
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THORAXJNL2013205061F1: Heterogeneity's ruses: an illustrative example of discrepancies between the population and individual hazards. This is a hypothetical population consisting of two subgroups (each 50% of the population) with regard to the hazard of an absorbing event (such as death or ‘next’ exacerbation): a frail subgroup that experiences the event at a high rate and a robust subgroup that experiences the event at a lower rate. While the hazard is constant within each subgroup, the population hazard decreases over time. This is because at any given point in time, the population hazard is the weighted average of subgroup hazards, with weights being the proportion of each subgroup in the event-free population. At first, everyone is event free, so the overall hazard is the midpoint between the subgroups’ hazards. As time passes, more individuals in the frail than the robust subgroup experience the event, thus, the event-free population becomes predominantly of the robust subgroup, lowering the population hazard. If the population hazard is interpreted at the individual level, one might erroneously conclude that the hazard of the event decreases over time. Phenomena similar to this can be responsible for the findings of both the studies discussed in this paper. For other examples refer to reference 1.

Mentions: There is great interest in studying the impact of exacerbations on the course of COPD. Such studies often rely on survival analysis of longitudinal data. Standard survival analysis techniques produce results that pertain to the population, whereas the real interest is in within-individual associations. A crucial issue in this context is the heterogeneity in the exacerbation rate across individuals. Estimates of hazard function from survival analysis are particularly associated with surprisingly conflicting and potentially misleading patterns when heterogeneity is not taken into account.1figure 1 provides an illustrative example.


Heterogeneity's ruses: the neglected role of between-individual variability in longitudinal studies of COPD exacerbations.

Sadatsafavi M, FitzGerald JM - Thorax (2014)

Heterogeneity's ruses: an illustrative example of discrepancies between the population and individual hazards. This is a hypothetical population consisting of two subgroups (each 50% of the population) with regard to the hazard of an absorbing event (such as death or ‘next’ exacerbation): a frail subgroup that experiences the event at a high rate and a robust subgroup that experiences the event at a lower rate. While the hazard is constant within each subgroup, the population hazard decreases over time. This is because at any given point in time, the population hazard is the weighted average of subgroup hazards, with weights being the proportion of each subgroup in the event-free population. At first, everyone is event free, so the overall hazard is the midpoint between the subgroups’ hazards. As time passes, more individuals in the frail than the robust subgroup experience the event, thus, the event-free population becomes predominantly of the robust subgroup, lowering the population hazard. If the population hazard is interpreted at the individual level, one might erroneously conclude that the hazard of the event decreases over time. Phenomena similar to this can be responsible for the findings of both the studies discussed in this paper. For other examples refer to reference 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4215271&req=5

THORAXJNL2013205061F1: Heterogeneity's ruses: an illustrative example of discrepancies between the population and individual hazards. This is a hypothetical population consisting of two subgroups (each 50% of the population) with regard to the hazard of an absorbing event (such as death or ‘next’ exacerbation): a frail subgroup that experiences the event at a high rate and a robust subgroup that experiences the event at a lower rate. While the hazard is constant within each subgroup, the population hazard decreases over time. This is because at any given point in time, the population hazard is the weighted average of subgroup hazards, with weights being the proportion of each subgroup in the event-free population. At first, everyone is event free, so the overall hazard is the midpoint between the subgroups’ hazards. As time passes, more individuals in the frail than the robust subgroup experience the event, thus, the event-free population becomes predominantly of the robust subgroup, lowering the population hazard. If the population hazard is interpreted at the individual level, one might erroneously conclude that the hazard of the event decreases over time. Phenomena similar to this can be responsible for the findings of both the studies discussed in this paper. For other examples refer to reference 1.
Mentions: There is great interest in studying the impact of exacerbations on the course of COPD. Such studies often rely on survival analysis of longitudinal data. Standard survival analysis techniques produce results that pertain to the population, whereas the real interest is in within-individual associations. A crucial issue in this context is the heterogeneity in the exacerbation rate across individuals. Estimates of hazard function from survival analysis are particularly associated with surprisingly conflicting and potentially misleading patterns when heterogeneity is not taken into account.1figure 1 provides an illustrative example.

Bottom Line: Standard survival analysis techniques often used in such studies typically produce results that pertain to the overall population, whereas the greatest interest is in the study of associations within individuals.A factor that can lead to profound discrepancies between population-level and individual-level survival patterns is the between-individual heterogeneity in the rate of exacerbations.We caution on the distinction between population and individual-level associations in survival analysis, and recommend accounting for heterogeneity in future studies.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Medicine, Institute for Heart and Lung Health, The University of British Columbia, Vancouver, British Columbia, Canada.

Show MeSH
Related in: MedlinePlus