title: Sharp bounds on causal effects using a surrogate endpoint.
abstract: This paper considers a problem of evaluating the causal effect of a treatment X on a true endpoint Y using a surrogate endpoint S, in the presence of unmeasured confounders between S and Y. Such confounders render the causal effect of X on Y unidentifiable from the causal effect of X on S and the joint probability of S and Y. To evaluate the causal effect of X on Y in such a situation, this paper derives closed-form formulas for the sharp bounds on the causal effect of X on Y based on both the causal effect of X on S and the joint probability of S and Y under various assumptions. In addition, we show that it is not always necessary to observe Y to test the null causal effect of X on Y under the monotonicity assumption between X and S. These bounds enable clinical practitioners and researchers to assess the causal effect of a treatment on a true endpoint using a surrogate endpoint with minimum computational effort.
authors.affiliation: The Institute of Statistical Mathematics, 10-3, Midori-cho, Tachikawa, Tokyo, 190-8562, Japan. mkuroki@ism.ac.jp
authors.forename: Manabu
authors.initials: M
authors.lastname: Kuroki
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers; D001699:Biometry / Q000379:methods*; D015984:Causality; D015331:Cohort Studies; D015986:Confounding Factors, Epidemiologic; D004359:Drug Therapy, Combination; D006513:Hepatitis B e Antigens / Q000097:blood; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D019259:Lamivudine / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000188:drug therapy; D019370:Observation; D011336:Probability; D016032:Randomized Controlled Trials as Topic / Q000191:economics / Q000379:methods*; D012107:Research Design; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine
keywords: linear programming (LP) method; potential outcome approach; surrogate paradox