Studies on the variation in clinical laboratory data and safety evaluation of pharmaceuticals.
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.
Nomura
Morihiro
M
Department of Pharmacy, Kinki University Hospital, Japan. mnomura@med.kindai.ac.jp
Hata
Taeko
T
Naitoh
Shouchi
S
Kuwano
Hiroyuki
H
Kuwao
Hiroyuki
H
Moriyama
Kenzo
K
Fukuoka
Masahiro
M
Kudo
Masatoshi
M
Tohda
Yuji
Y
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
D000998:Antiviral Agents; D004364:Pharmaceutical Preparations; D012254:Ribavirin