CPIC’s therapeutic recommendations are based on weighing the evidence from a combination of preclinical functional and clinical data, as well as on some existing disease-specific consensus guidelines. Some of the factors that are taken into account in evaluating the evidence supporting therapeutic recommendations include: in vivo pharmacokinetic and pharmacodynamic data, in vitro enzyme activity of tissues expressing wild-type or variant-containing protein, in vitro enzyme activity from tissues isolated from individuals of known genotypes, and in vivo pre-clinical and clinical pharmacokinetic and pharmacodynamic studies.
Overall, the therapeutic recommendations are simplified to allow rapid interpretation by clinicians. CPIC uses a slight modification of a transparent and simple system for just three categories for recommendations adopted from the rating scale for evidence-based recommendations on the use of antiretroviral agents¹:
Strong recommendation for the statement: The evidence is high quality and the desirable effects clearly outweigh the undesirable effects.
Moderate recommendation for the statement: There is a close or uncertain balance as to whether the evidence is high quality and the desirable clearly outweigh the undesirable effects.
Optional recommendation for the statement: The desirable effects are closely balanced with undesirable effects, or the evidence is weak or based on extrapolations. There is room for differences in opinion as to the need for the recommended course of action.
No recommendation: There is insufficient evidence, confidence, or agreement to provide a recommendation to guide clinical practice at this time.
¹Adolescents PoAGfAa. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. 2011. p. 1-166.