title: Studies on the variation in clinical laboratory data and safety evaluation of pharmaceuticals.
abstract: The safety of pharmaceuticals has become increasingly important not only in daily medical treatment but also in clinical trials. Although clinical laboratory data are more objective than clinical symptoms, the determination as to whether they indicate abnormal variations depends largely upon the clinical judgment of physicians. The process of determination has not been sufficiently objectified. The present study investigated the indices of criteria for variations in clinical laboratory data obtained in clinical trials. Then, detection rates of abnormal variations were compared between our determination method that employs the reference change value (RCV) expressing the width of biological variation for each test component and conventional determination methods. The study also demonstrated that by combining standard values and the RCV for determination, abnormal variations were found at a rate greater than 50%. The method we propose was applied to the safety evaluation of pharmaceuticals. In clinical trials on the antiviral drug ribavirin administered alone, components of laboratory tests were selected that should be noted in studies on its effects. Expect for decreases in red blood cell counts and hemoglobin values, which are closely associated with anemic symptoms and well known to hepatologists, the increasing trend in platelet counts and decreasing trend in albumin were found to be laboratory test components that should be paid attention to, even though they may not be obvious.
authors.affiliation: Department of Pharmacy, Kinki University Hospital, Japan. mnomura@med.kindai.ac.jp
authors.forename: Morihiro
authors.initials: M
authors.lastname: Nomura
authors.forename: Taeko
authors.initials: T
authors.lastname: Hata
authors.forename: Shouchi
authors.initials: S
authors.lastname: Naitoh
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kuwano
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kuwao
authors.forename: Kenzo
authors.initials: K
authors.lastname: Moriyama
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukuoka
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kudo
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tohda
mesh_terms: D000998:Antiviral Agents / Q000009:adverse effects; D002984:Clinical Laboratory Information Systems / Q000941:ethics; D019411:Clinical Laboratory Techniques; D002986:Clinical Trials as Topic; D003627:Data Interpretation, Statistical; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D004364:Pharmaceutical Preparations; D012016:Reference Values; D012254:Ribavirin / Q000009:adverse effects; D012680:Sensitivity and Specificity
chemical_list: D000998:Antiviral Agents; D004364:Pharmaceutical Preparations; D012254:Ribavirin