Missing Data Methods in Hiv Clinical Trials: Regulatory Guidance and Alternative Approaches

• Published in: Drug information journal Vol. 35; no. 4; pp. 1363 - 1371
• Main Authors: Kelleher, Thomas, Thiry, Alexandra, Wilber, Richard, Cross, Anne
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.10.2001; Pergamon Press; Springer Nature B.V
• Subjects: Biological and medical sciences; Clinical trial. Drug monitoring; Clinical trials; General pharmacology; HIV; Human immunodeficiency virus; Medical sciences; Missing data; Pharmacology. Drug treatments; Ribonucleic acid; RNA; Clinical trials; Missing data; HIV; Regulatory guidance; Human; Drug; Immunopathology; Drug combination; AIDS; Immune deficiency; Infection; Statistical method; Chemotherapy; Treatment; Viral disease; Antiviral; Clinical trial; Comparative study
• ISSN: 2168-4790; 0092-8615; 2168-4804; 2164-9200
• DOI: 10.1177/009286150103500432

Efficacy in HTV clinical trials is measured by changes in HIV RNA levels over time as well as the proportion of subjects with HIV RNA levels below an assay's threshold of reliable quantification at a single time point. Missing data arise naturally due to missed visits and premature discontinuations of treatment. The available data are then analyzed using repeated measures models and univariate comparisons of proportions, assuming missing data occur at random or considering missing values as treatment failures (worst case scenario). These and other methods recently proposed by regulatory authorities are presented along with alternative approaches. Advantages and disadvantages of each method are discussed. Data from a recent comparison of ‘standard-of-care’ triple combination regimens are used for illustration.