Experimental design and analysis is an effective and commonly used tool in scientific investigations and industrial applications. Orthogonal arrays, such as factorial and fractional factorial designs, are popular experimental plans for identifying important factors. Motivated by an antiviral drug experiment, we introduce a new class of composite designs based on a two-level factorial design and a threelevel orthogonal array. These designs have many desirable features and are effective for factor screening and response surface modeling. Some advantages are that they can use resolution IV designs in the screening stage, they can perform in-depth analyses, and they can be used in either a single or a sequential experiment. We study the construction method and compare the new composite designs with existing ones. We illustrate the methodology with data from an experiment that studies the effects of five antiviral drugs on the Herpes simplex virus type 1.
Herpes simplex virus type 1 (HSV-1) is known to cause diseases of various severities. There is increasing interest to find drug combinations to treat HSV-1 by reducing drug resistance and cytotoxicity. Drug combinations offer potentially higher efficacy and lower individual drug dosage. In this paper, we report a new application of fractional factorial designs to investigate a biological system with HSV-1 and six antiviral drugs, namely, Interferon-alpha, Interferon-beta, Interferon-gamma, Ribavirin, Acyclovir, and TNF-alpha. We show how the sequential use of two- and three-level fractional factorial designs can screen for important drugs and drug interactions, as well as determine potential optimal drug dosages through the use of contour plots. Our initial experiment using a two-level fractional factorial design suggests that there is model inadequacy and drug dosages should be reduced. A follow-up experiment using a blocked three-level fractional factorial design indicates that TNF-alpha has little effect and HSV-1 infection can be suppressed effectively by using a right combination of the other five antiviral drugs. These observations have practical implications in the understanding of antiviral drug mechanism that can result in better design of antiviral drug therapy.
Discrete choice experiments (DCEs) are increasingly used for studying and quantifying subjects preferences in a wide variety of health care applications. They provide a rich source of data to assess real-life decision making processes, which involve trade-offs between desirable characteristics pertaining to health and health care, and identification of key attributes affecting health care.
The choice of the design for a DCE is critical because it determines which attributes’ effects and their interactions are identifiable. We apply blocked fractional factorial designs to construct DCEs and address some identification issues by utilizing the known structure of blocked fractional factorial designs. Our design techniques can be applied to several situations including DCEs where attributes have different number of levels. We demonstrate our design methodology using two health care studies to evaluate (1) asthma patients’ preferences for symptom-based outcome measures, and (2) patient preference for breast screening services.
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