Covariate-adjusted survival analyses in propensity-score matched samples: Imputing potential time-to-event outcomes

Matching on an estimated propensity score is frequently used to estimate the effects of treatments from observational data. Since the 1970s, different authors have proposed methods to combine matching at the design stage with regression adjustment at the analysis stage when estimating treatment effects for continuous outcomes. Previous work has consistently shown that the combination has generally superior statistical properties than either method by itself. In biomedical and epidemiological research, survival or time-to-event outcomes are common. We propose a method to combine regression adjustment and propensity score matching to estimate survival curves and hazard ratios based on estimating an imputed potential outcome under control for each successfully matched treated subject, which is accomplished using either an accelerated failure time parametric survival model or a Cox proportional hazard model that is fit to the matched control subjects. That is, a fitted model is then applied to the matched treated subjects to allow simulation of the missing potential outcome under control for each treated subject. Conventional survival analyses (e.g., estimation of survival curves and hazard ratios) can then be conducted using the observed outcome under treatment and the imputed outcome under control. We evaluated the repeated-sampling bias of the proposed methods using simulations. When using nearest neighbor matching, the proposed method resulted in decreased bias compared to crude analyses in the matched sample. We illustrate the method in an example prescribing beta-blockers at hospital discharge to patients hospitalized with heart failure.

Statins as Potential Antimalarial Drugs: Low Relative Potency and Lack of Synergy with Conventional Antimalarial Drugs

ABSTRACT The in vitro sensitivity of Plasmodium falciparum to atorvastatin and rosuvastatin was assessed using chloroquine-sensitive and chloroquine-resistant strains. Although atorvastatin was more potent, it had weak activity (mean 50% inhibitory concentration of ≥17 μM) and an indifferent interaction with chloroquine and dihydroartemisinin. Bioassay of plasma from an atorvastatin-treated subject showed similar results.

Comment

The scarcity of skilled professional manpower in developing nations has given rise, of necessity, to a formidable array of para-professional personnel. Khare's description of the touts of Lucknow and the ‘sea-lawyers’ of Gopalpur serves as a useful starting point for discussion in this vastly important but little-treated subject. From a lawyer's point of view, most of the crucial questions are not answered here. How much actual legal business, in terms of letter-writing, negotiations and simple giving of advice, is in fact carried out in the village by the para-legal individuals described? To what extent are their opinions, and ways of operating, similar? Do they, by virtue of pervasive and agreed practice, in fact ‘make’ law? Are they possibly, being closer to the people, more acceptable to the people, more efficient than ordinary lawyers, and cheaper?