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Statistical Comments on Retrospective Analysis

Statistical Comments on Retrospective Analysis. Girish Aras, Ph.D. Jonathan Ma, Ph.D. Center for Drug Evaluation and Research, FDA. Data Analysis Plan. Logistic Regression model

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Statistical Comments on Retrospective Analysis

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  1. Statistical Comments on Retrospective Analysis Girish Aras, Ph.D. Jonathan Ma, Ph.D. Center for Drug Evaluation and Research, FDA

  2. Data Analysis Plan • Logistic Regression model • Dependent variable (Virological Failure) is ‘explained’ with independent variables ( baseline covariates ).

  3. BaselineCovariates • Baseline Log (HIV-1 RNA) • New Drug Covariate • Genotypic Measures • Genotypic Sensitivity Score • No. of PI, NRTI and NNRTI mutations • Phenotypic Measures • Overall Sensitivity Score • No. of PI, NRTI and NNRTI drugs with Phenotypic sensitivity

  4. Relative Risk (Risk Ratio, RR) • P0 = Probability of virological failure when a covariate is at a given level • P1 = Probability of virological failure when a covariate is at one unit higher than the previous level • RR = P1/ P0

  5. Oddsratio • RR is the quantity of interest but typically not estimable from a retrospective study • OR (Odds Ratio) = P1/(1-P1) ÷ P0/(1-P0) • OR can be estimated from a retrospective study, but may not of interest in itself • When P1 and P0 are small,RR  OR

  6. Odds Ratios for Various Relative Risks P0=0.25 P0=0.2 P0=0.15 Odds Ratio or Relative Risk P0=0.1 P0=0.05 P1 — Relative Risk — Odds Ratio

  7. Odds Ratios for Various Relative Risks RR=3 RR=2.5 RR=1.5 RR=2 Odds Ratio P0

  8. Mutation-Drug Resistance Table • Table 1 in DAP titled ‘mutations associated with resistance to specific antiretroviral drugs’ is largely based on in vitro data and/or exploratory subgroup analyses • A general consensus is yet to emerge on this table.

  9. Mutation-Drug Resistance Table • Most of the studies were available to the resistance collaborative group before the DAP was developed

  10. 95% Confidence Interval for Odds Ratio for Overall Genotypic Sensitivity Score: Model C (Univariate) and E (Multivariate)

  11. 95% confidence interval for Odds ratio for Number of PI Mutations: Model D andF

  12. 95% Confidence Interval for Overall Phenotypic Score: Model C (Univariate) and Model G (Multivariate)

  13. Conclusions • These exploratory analyses suggest predictive link between virological failure and genotypic and phenotypic measures at the baseline • They will provide insight in generating specific hypotheses to be tested in future confirmatory studies

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