RELATIVE RISK ESTIMATION IN RANDOMISED CONTROLLED TRIALS A
- Slides: 23
RELATIVE RISK ESTIMATION IN RANDOMISED CONTROLLED TRIALS: A COMPARISON OF METHODS FOR INDEPENDENT OBSERVATIONS Lisa N Yelland, Amy B Salter, Philip Ryan The University of Adelaide, Australia
Background • Binary outcomes traditionally analysed using logistic regression • Effect of treatment described as odds ratio • Odds ratio difficult to interpret • Often misinterpreted as relative risk which will overstate treatment effect
Example • US study* on effect of patient race on physician referrals • Referral rate: white 90. 6% vs black 84. 7% • Reported odds ratio of 0. 6 • Interpreted by media as referral rates 40% lower for black vs white • Relative risk is actually 0. 93** References: * Schulman et al. NEJM 1999; 340: 618 -626. ** Schwartz et al. NEJM 1999; 341: 279 -283
Relative Risks • Growing preference for relative risk • Log binomial regression recommended • Generalised linear model • Convergence problems common
Relative Risks • Growing preference for relative risk • Log binomial regression recommended • Generalised linear model • Convergence problems common pi = exp(β 0 + β 1 x 1 i + …)
Relative Risks • Growing preference for relative risk • Log binomial regression recommended • Generalised linear model • Convergence problems common pi = exp(β 0 + β 1 x 1 i + …) (0, 1)
Relative Risks • Growing preference for relative risk • Log binomial regression recommended • Generalised linear model • Convergence problems common pi = exp(β 0 + β 1 x 1 i + …) (0, 1) >0
Alternative Methods • Many different methods proposed • Few comparisons between methods • Unclear which method is ‘best’ • Further research is needed
Aim To determine how the different methods for estimating relative risk compare under a wide range of scenarios relevant to RCTs with independent observations
Methods • Log binomial regression • Constrained log binomial regression • COPY 1000 method • Expanded logistic GEE • Log Poisson GEE • Log normal GEE • Logistic regression with – marginal or conditional standardisation – delta method or bootstrapping
Simulation Scenarios • Simulated data assuming log binomial model • 170 simulation scenarios – 200 or 500 subjects – Blocked or stratified randomisation – Different treatment and covariate effects – Binary and/or continuous covariate – Different covariate distributions
Size of Study • 1000 datasets per scenario • 10 different methods • 2000 resamples used for bootstrapping • Unadjusted and adjusted analyses • SAS grid computing
SAS Grid Computing Run SAS program Task Result Combined Results
Comparing Methods • Comparisons based on: – Convergence – Type I error – Power – Bias – Coverage probability
Results - Overall • Differences between methods • Convergence problems • Differences in type I error rates and coverage probabilities • Large bias for some methods under certain conditions • Little difference in power
Results - Convergence Percentage of Simulations where Model Converged % Method
Results – Type I Error Percentage of Simulation Scenarios where Type I Error Problems Occurred % Method
Results – Coverage Percentage of Simulation Scenarios where Coverage Problems Occurred % Method
Results – Bias Median Bias in Estimated Relative Risk Bias Method
The Winner • Log Poisson approach • Performed well relative to other methods • Simple to implement • Most used in practice • Invalid predicted probabilities (max 6%) • Problematic if prediction is of interest
Conclusion • Log binomial regression useful when it converges • Many alternatives available if it doesn’t • Alternatives not all equal • Log Poisson approach recommended if log binomial regression fails to converge • Performance with clustered data remains to be investigated
Acknowledgements • International Biometric Society for financial assistance sponsored by CSIRO • Professor Philip Ryan and Dr Amy Salter for supervising my research
Questions?
- Rbd design layout
- Rcbd example
- Absolute risk vs relative risk
- Relative risk and attributable risk
- Relative risk and attributable risk
- Relative risk calculation
- Liquidity measures
- Cash flow estimation and risk analysis
- Return portofolio adalah
- 2 way relative frequency table
- Relative pronouns
- Relative adverbs and pronouns
- Relative clauses and relative pronouns stage 15
- How to calculate relative risk
- Jenis penelitian kedokteran
- Relative risk interpretation
- Calculate prevalence rate
- Relative risk
- Ukuran asosiasi
- Relative risk dan odds ratio
- Interpreting relative risk
- Relative risk reduction formula
- Relative risk
- Interpreting relative risk