title: On the use of propensity scores in case of rare exposure.
abstract: BACKGROUND
  Observational post-marketing assessment studies often involve evaluating the effect of a rare treatment on a time-to-event outcome, through the estimation of a marginal hazard ratio. Propensity score (PS) methods are the most used methods to estimate marginal effect of an exposure in observational studies. However there is paucity of data concerning their performance in a context of low prevalence of exposure.
  
  
  METHODS
  We conducted an extensive series of Monte Carlo simulations to examine the performance of the two preferred PS methods, known as PS-matching and PS-weighting to estimate marginal hazard ratios, through various scenarios.
  
  
  RESULTS
  We found that both PS-weighting and PS-matching could be biased when estimating the marginal effect of rare exposure. The less biased results were obtained with estimators of average treatment effect in the treated population (ATT), in comparison with estimators of average treatment effect in the overall population (ATE). Among ATT estimators, PS-weighting using ATT weights outperformed PS-matching. These results are illustrated using a real observational study.
  
  
  CONCLUSIONS
  When clinical objectives are focused on the treated population, applied researchers are encouraged to estimate ATT with PS-weighting for studying the relative effect of a rare treatment on time-to-event outcomes.
authors.affiliation: APHP, Hôpital Louis Mourier, Département d'Epidémiologie et Recherche Clinique, 178 Rue des Renouillers, Colombes, 92700, France. david.hajage@aphp.fr.|APHP, Hôpital Bichat, Centre de Pharmacoépidémiologie (Cephepi), 46 Rue Henri Huchard, Paris, F-75018, France. david.hajage@aphp.fr.|Univ Paris Diderot, Sorbonne Paris Cité, UMR 1123 ECEVE, Paris, F-75018, France. david.hajage@aphp.fr.|INSERM, UMR 1123 ECEVE, Paris, F-75018, France. david.hajage@aphp.fr.|INSERM, CIE-1425, Paris, F-75018, France. david.hajage@aphp.fr.
authors.forename: David
authors.initials: D
authors.lastname: Hajage
authors.affiliation: APHP, Hôpital Bichat, Département d'Epidémiologie et Recherche Clinique, 46 Rue Henri Huchard, Paris, F-75018, France.|APHP, Hôpital Bichat, Centre de Pharmacoépidémiologie (Cephepi), 46 Rue Henri Huchard, Paris, F-75018, France.|Univ Paris Diderot, Sorbonne Paris Cité, UMR 1123 ECEVE, Paris, F-75018, France.|INSERM, UMR 1123 ECEVE, Paris, F-75018, France.|INSERM, CIE-1425, Paris, F-75018, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Tubach
authors.affiliation: FACT, DHU FIRE, Univ Paris-Diderot, Sorbonne Paris-Cité, Paris, F-75018, France.|LVTS, INSERM U-1148, Hôpital Bichat, HUPNVS, AP-HP, Paris, F-75018, France.|NHLI, Imperial College, Royal Brompton Hospital, London, UK.
authors.forename: Philippe Gabriel
authors.initials: PG
authors.lastname: Steg
authors.affiliation: Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Deepak L
authors.initials: DL
authors.lastname: Bhatt
authors.affiliation: APHP, Hôpital Bichat, Département d'Epidémiologie et Recherche Clinique, 46 Rue Henri Huchard, Paris, F-75018, France.|APHP, Hôpital Bichat, Centre de Pharmacoépidémiologie (Cephepi), 46 Rue Henri Huchard, Paris, F-75018, France.|Univ Paris Diderot, Sorbonne Paris Cité, UMR 1123 ECEVE, Paris, F-75018, France.|INSERM, UMR 1123 ECEVE, Paris, F-75018, France.|INSERM, CIE-1425, Paris, F-75018, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: De Rycke
mesh_terms: D002318:Cardiovascular Diseases / Q000188:drug therapy*; D003198:Computer Simulation; D005260:Female; D006801:Humans; D008297:Male; D015233:Models, Statistical; D009010:Monte Carlo Method; D064887:Observational Studies as Topic / Q000379:methods*; D057216:Propensity Score; D016016:Proportional Hazards Models; D053778:Thiazolidines / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D053778:Thiazolidines
keywords: Hazard ratio; Monte Carlo simulations; Observational studies; Pharmacoepidemiology; Propensity scores; Rare exposure