Consequences of prolonged inhalation of ozone on F344/N rats: collaborative studies. Part X: Robust composite scores based on median polish analysis.
This report describes some of the statistical methods used to analyze data from the National Toxicology Program/Health Effects Institute Collaborative Ozone Project. The purpose of the collaborative study was to assess the health effects of chronic ozone inhalation. Data were obtained from a subset of 164 F344/N rats dedicated to use by the Health Effects Institute from a standard ozone inhalation study conducted by Battelle Pacific Northwest Laboratories for the National Toxicology Program. The study involved eight groups of investigators, each assessing different types of ozone-related health effects. These included studies of respiratory function and of structural, cellular, and biochemical changes in the lungs and airways. Designing and analyzing a study with several groups of investigators raises many statistical challenges. The highest design priority for this study was that each investigation be individually interpretable as an independent study. This meant that each investigator had to receive an adequate number of animals, balanced with respect to level of ozone exposure and other factors such as the gender of the rats and the time they were killed. Another feature of the collaborative study was the opportunity it provided to assess and quantify the effect of ozone exposure on a broad spectrum of endpoints, and to explore the relations between the different types of effect. Maximizing the potential to assess these correlations required that the individual animals studied by the different groups of investigators overlap as much as possible. This aspect of the statistical design required careful consideration of the compatibility between various investigations. Fortunately, the degree of compatibility was substantial. In many cases, for example, it was possible to assess respiratory function in the animals before they were killed, and then to divide the tissue among several different investigators. This report concentrates on the methods that were specially developed to analyze the data for multiple endpoints collected in the study. Nonstandard techniques were required to accommodate the complex pattern of missing data that was inherent in the study design because no animals were measured by all investigators.
Catalano
P J
PJ
Harvard School of Public Health, Boston, MA, USA.
Rogus
J
J
Ryan
L M
LM
D000280:Administration, Inhalation; D000402:Airway Obstruction / Q000139:chemically induced*; D000704:Analysis of Variance; D000818:Animals; D003094:Collagen / Q000378:metabolism; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D015233:Models, Statistical; D015999:Multivariate Analysis; D009297:Nasal Mucosa / Q000503:physiopathology; D010126:Ozone / Q000008:administration & dosage / Q000009:adverse effects*; D011237:Predictive Value of Tests; D011658:Pulmonary Fibrosis / Q000139:chemically induced*; D051381:Rats; D011916:Rats, Inbred F344; D015203:Reproducibility of Results; D012129:Respiratory Function Tests; D012220:Rhinitis / Q000139:chemically induced*; D013997:Time Factors
D010126:Ozone; D003094:Collagen