Use of the likelihood reduction factor in a path analysis framework to quantify surrogacy in clinical trials.

In clinical trials, surrogate endpoints are useful when the endpoint of interest is difficult to measure or requires a long follow-up time. Current methodology for validating surrogate endpoints encounters challenges in the presence of collinearity between the treatment and surrogate endpoint, which is often present in clinical trials. The proposed methods adapt current methodology in the structural framework of path analysis to quantify the validity of a surrogate endpoint. The path analysis framework provides an improved interpretation of treatment effect. Through derivation and simulation we show the proposed path likelihood reduction factor (LRF P ), is less biased and more robust than current methodology in cases of collinearity between the treatment and surrogate endpoint, with notable improvement when surrogacy is weak or moderate. LRF P can be expanded to evaluate multiple correlated surrogate endpoints, which as shown through simulation, is also less biased and more robust than current methodology in the case of collinearity between the treatment and surrogate endpoint.

Purpose in Life Among Centenarian Offspring.

OBJECTIVES: Purpose in life (PIL), a feeling of meaning and direction in life, is associated with favorable health outcomes including lower mortality and reduced risk of disease, disability, and cognitive impairment. Since centenarian offspring have been shown to have long health spans we sought to examine whether they have higher PIL than individuals without familial longevity. METHOD: We compared PIL scores from the Ryff Scales of Psychological Well-Being in centenarian offspring from the New England Centenarian Study (N = 361, mean age = 82.0 years) with 3 referent groups: spouses, birth cohort-matched referents, and Health and Retirement Study (HRS) participants. RESULTS: Logistic regression analyses adjusted for age, sex, education, and marital status indicated greater odds of high PIL among centenarian offspring compared with spouse (adjusted odds ratio [aOR] = 1.92, 95% confidence interval [CI] = 1.002-3.68, p = .049) and birth cohort referents (aOR = 2.64, 95% CI = 1.36-5.14, p = .004). Offspring had an almost 3 times greater odds of having high PIL than HRS participants (odds ratio [OR] = 2.93, 95% CI = 2.17-3.96, p < .0001). DISCUSSION: Higher PIL is associated with being an offspring of a long-lived parent and may play a role in the ability to delay age-associated illnesses and functional decline. Increasing purposefulness may be a target for interventions to promote healthy aging.