American Journal of Epidemiology Vol. 91, No. 6: 568-574
Copyright © 1970 by The Johns Hopkins University School of Hygiene and Public Health
research-article |
A DESIGN FOR THE EVALUATION OF ANTIVIRAL DRUGS IN HUMAN INFLUENZA1
2Division of Clinical Pharmacology, Departments of Medicine and Pharmacology and Therapeutics, University of Cincinnati College of Medicine Eden and Bethesda Avenues, Cincinnati, Ohio 46219
3USPHS Research Career Development Awardee HE-16,008
Bloomfield, S. S. (Div. of Clinical Pharmacology, Univ. of Gncinnati College of Medicine, Gndnnati, Ohio 45219), T. E Gaffney and G. M. Schiff. A design for the evaluation of antiviral drugs in human influenza. Amer. J. Epid., 1970, 97; 568–574.—The evaluation of antiviral drugs in experimental influenza has frequently involved hundreds of subjects to demonstrate prophylactic efficacy in reducing illness and antibody response. This report describes a double-blind study using only 18 highly susceptible volunteers in a matched-pairs design. Nine subjects randomly received amantadine 200 or 300 mg orally daily for 10 days; their partners, a placebo. On the 2nd day a challenge dose of 64, 000 TCID50 of Rockville A2 strain influenza virus was administered to the nasopharynx. Four of the placebo-treated subjects developed typical influenza; no cases occurred in the amantadine group. Illness scores were significantly higher (p =.05) in placebo-treated subjects than In the amantadine-treated partners. In addition, 14 and 21 days after viral challenge placebo subjects had a greater antibody rise than their amantadine partners (p <.01). Despite the attenuated antibody response to viral challenge in subjects treated with amantadine, a significant increase (p <.05) in titer did occur. A positive, significant correlation between illness score and antibody response suggested that the illness scoring technique could predict the degree of immunologic response to vims In highly susceptible subjects. These statistically significant differences in 18 volunteers confirmed investigations involving much larger numbers. Success was related in large part to 3 design features: a homogenous sample, accurate measurement techniques and matched pairing of subjects. This approach minimizes the number of subjects exposed to the risks of an investigational treatment and also may save time and money.
amantadine; antibodies; antiviral agents; drug therapy; influenza, Asian; influenza viruses; serology; therapeutics
1From the University of Cincinnati College of Medicine. Supported by a grant-in-aid from E. I. duPont de Nemours and Company.
4Section of Clinical Virology, Division of Infectious Diseases, Department of Medicine, and Department of Microbiology, University of Cincinnati College of Medicine. USPHS Research Career Development Awardee HE-13, 666. The authors gratefully acknowledge the co-operation and assistance of the late R. W. Alvis, Superintendent, David Hirst, M.D., Medical Officer, and the inmates of Lebanon Correctional Institution, Lebanon, Ohio, and the technical assistance of Mrs. Susan Kogon