Author Affiliations: Department of Biostatistics, Harvard School of Public Health, Boston, Mass (Drs Gilbert and DeGruttola); Division of Infectious Diseases, Columbia Presbyterian Center, New York, NY (Dr Hammer); and University of Colorado Health Sciences Center, Denver (Dr Kuritzkes).
Suppression of plasma human immunodeficiency virus (HIV) RNA levels
has been widely accepted as an appropriate surrogate end point for HIV disease
progression, and it is currently used as the primary end point to determine
efficacy in many antiretroviral trials. However, this end point does not always
measure other important effects of treatment, such as inducement of multidrug
resistance, which depletes future therapy options, and toxic effects. An alternative
that directly factors in these treatment costs is a composite regimen termination end point, defined as a protocol-determined change
in regimen due to either virologic failure or treatment-related toxic effects.
Pros and cons for using purely virologic vs various composite primary end
points are discussed. Conclusions include (1) a trial's clinical objective
guides the choice of primary end point, (2) a purely virologic end point is
often preferable, (3) it may be important to analyze both end point types
in interpreting study results, and (4) long-term clinical outcome studies
are needed for identifying the most predictive surrogate end points.
Gilbert PB, DeGruttola V, Hammer SM, Kuritzkes DR. Virologic and Regimen Termination Surrogate End Points in AIDS Clinical Trials. JAMA. 2001;285(6):777-784. doi:10.1001/jama.285.6.777