Developing a Surrogate Endpoint for AIDS Clinical Trials

Abstract

When it comes to the process of developing new treatments, the choice of an endpoint is very crucial because this endpoint will be used to assess the effects of the treatments. However the most sensitive and clinically relevant endpoint which is called the ‘true endpoint’ is difficult to use in a clinical trial because the measurement of the true endpoint can be costly and difficult to measure. In such cases the most feasible solution is to replace the true endpoint by another endpoint termed ‘surrogate endpoint’ which can be measured earlier and frequently.CD4 and viral loads are used in majority of AIDS clinical trials as surrogate endpoints, however, no surrogate endpoint has yet been shown to be suitable in forecasting the effectiveness of anti-HIV treatments. As a solution, the current study is intended on developing a surrogate endpoint for AIDS based on a combination of variables. This study consists of 16 variables measured in 1151 HIV infected patients. From descriptive statistics, variables CD4 cell count and Karnofsky score were identified as potential candidates for surrogate. However a model with a combination of variables named score consisting of CD4, Karnofsky score and age yielded positive results in the log rank test and conventional statistics. Validation of the scoring model using Prentice’s criteria fulfilled all four criteria of Prentice and the model was also successful in identifying the difference between the two treatments. When a comparison was made between CD4 cell count and the combined variable model as possible surrogate endpoints for AIDS, the combined variable model http://doi.org/10.4038/sljastats.v18i2.7955