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. 2014 Oct 23;1(11):938–952. doi: 10.1002/acn3.131

Table 2.

Targetable components of trial design to maximize likelihood of seeing an effect in adjuvant therapy trials for HAND

Case ascertainment Cannot define a target population or an outcome measure without a clear framework for defining the various subtypes of HAND.
Target population and goals of therapy Inclusion/exclusion criteria must be determined independently for each candidate drug based on the proposed case definitions, mechanism of action, and goal of therapy. There is a high risk of a falsely negative trial if attention is not paid to focusing the primary question of efficacy on a specific population
Dose selection Dose selection must be based on preclinical data and PK/PD in HIV-infected subjects and samples. If it is not, investigators cannot know if the appropriate concentrations of therapies are being achieved for the proposed mechanism of action
Primary outcome Primary outcome measures of clinical efficacy should be standardized across trials. Readers must be careful not to use a trial powered to assess safety and tolerability to determine clinical efficacy in HAND. Outcome measures examining secondary endpoints such as changes in neuroimaging may be useful in select circumstances based on the proposed mechanism of action of a candidate therapy
Confounders and interactions Covariates that act as confounders or interactions in the proposed mechanism of action of a candidate drug must be accounted for to avoid masking a true treatment effect. Thought should be given in particular to covariates that have a known biological effect on HAND or HIV immunology (including, but not limited to, gender, age, CD4 nadir, etc.)
Study duration Study durations must be defined based on the primary question of a trial. Durations of less than a year may not be long enough to see a true effect on cognitive function. In addition, results of too frequent neuropsychological testing may confound results by introducing a practice effect

HAND, human immunodeficiency virus-associated neurocognitive disorder.