Alternative subgroup joint analysis proposal of nonlinear longitudinal and time-to-event data for modeling pregnancy miscarriage
Résumé
Pregnancies achieved through in-vitro fertilization (IVF) are associated with adverse first
trimester outcomes in comparison to spontaneously achieved pregnancies. Human chorionic
gonadotrophin β subunit (β-HCG) is a well-known and accurate biomarker for the diagnosis and monitoring of pregnancy after IVF. Low levels of β-HCG during the first trimester
of pregnancy are related to miscarriage, ectopic pregnancy and failure of IVF procedure.
Longitudinal profiles of β-HCG can be utilized to distinguish between normal and abnormal
pregnancies, and to assist and guide the clinician in better management and monitoring of
post-IVF pregnancies. Therefore, being able to assess the association between longitudinally
measured β-HCG and time to early miscarriage is of crucial interest to clinicians. A common
joint modeling approach proposal to achieve this objective is to use subject-specific random
effects in a mixed effects model for longitudinal β-HCG data as predictors in a model for the
time-to-event (TTE) data. This work was motivated by an observational study with normal
and abnormal pregnancies where serum concentrations of β-HCG were measured in 173
young women during a gestational age of 9-86 days at a private clinic in Santiago, Chile.
Some women experienced a miscarriage event but the rest did not. For those women who
experienced miscarriage, their exact event times were unknown, in such case we have interval censored data, assuming that the event occurred between the last time of the observed
β-HCG measurement and ten days after. For our dataset we consider a nonlinear mixed
effects (NLME) model for both normal and abnormal pregnancies, but the joint model is
considered only for the subgroup of miscarriage women. All the estimation procedures are
based on the Stochastic Approximation of the EM (SAEM) algorithm implemented in the
Monolix software.
Domaines
Statistiques [math.ST]Origine | Fichiers produits par l'(les) auteur(s) |
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