LETTER
CD4 Counts as Surrogate Markers for Progression to AIDS
Stephen D. Nightingale, MD
1 January 1994 | Volume 120 Issue 1 | Pages 87-88
TO THE EDITOR:
Dr. Choi and colleagues [1] found CD4 percent to be a better surrogate marker for progression to the acquired immunodeficiency syndrome (AIDS) than the CD4 count, particularly in patients who had not progressed to AIDS after 16 weeks of therapy. In our patients, the logarithm of the CD4 count can account for 97% of the variation in 1-year survival and 89% of the variation in 1-year progression to AIDS [2]. How does this compare with the CD4 percent?
The Cox proportional-hazards model used by the authors assumes a constant risk for progression to AIDS over time [3]. The difference observed by the authors in the association between CD4 count compared with percent and progression to AIDS before and after 16 weeks of therapy suggests that this assumption may have been violated. Did the authors formally test this assumption of uniform hazard?
Furthermore, the criterion for a surrogate marker adopted by Choi and colleagues—that the effect of a drug on a disease should be explained by its effect on the surrogate marker—is reasonable but ambiguous. Should 20%, 60%, 100% of the effect of a study drug on a disease be explainable before the marker is accepted as a valid surrogate? When the choice of end point in a clinical trial is between a surrogate marker and a life-threatening (or fatal) event, a less-than-perfect correlation between marker and event may be acceptable.
|
Author and Article Information
|
|---|
University of Texas Southwestern Medical Center; Dallas, TX 75235
1. Choi S, Lagakos SW, Schooley RT, Volberding PA. CD4+ lymphocytes are an incomplete surrogate marker for clinical progression in persons with asymptomatic HIV infection taking zidovudine. Ann Intern Med. 1993; 118:674-80.
2. Nightingale SD, Jockusch JD, Haslund I, Cal SX, Peterson DM, Loss SD. Logarithmic relationship of the CD4 count to survival in patients with human immunodeficiency virus infection. Arch Intern Med. 1993; 153:1313-8.
3. Lee ET. Statistical Methods for Survival Data Analysis. Second edition. New York: John Wiley and Sons; 1992:250.
About Letters
The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:
•Include no more than 300 words of text, three authors, and five references
•Type with double-spacing
•Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.
Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.
Annals welcomes electronically submitted letters.
Top
Author & Article Info
References
Article
