Estimating measures of interaction on an additive scale for preventive exposures

Abstract

Measures of interaction on an additive scale (relative excess risk due to interaction [RERI], attributable proportion [AP], synergy index [S]), were developed for risk factors rather than preventive factors. It has been suggested that preventive factors should be recoded to risk factors before calculating these measures. We aimed to show that these measures are problematic with preventive factors prior to recoding, and to clarify the recoding method to be used to circumvent these problems. Recoding of preventive factors should be done such that the stratum with the lowest risk becomes the reference category when both factors are considered jointly (rather than one at a time). We used data from a case-control study on the interaction between ACE inhibitors and the ACE gene on incident diabetes. Use of ACE inhibitors was a preventive factor and DD ACE genotype was a risk factor. Before recoding, the RERI, AP and S showed inconsistent results (RERI = 0.26 [95%CI: −0.30; 0.82], AP = 0.30 [95%CI: −0.28; 0.88], S = 0.35 [95%CI: 0.02; 7.38]), with the first two measures suggesting positive interaction and the third negative interaction. After recoding the use of ACE inhibitors, they showed consistent results (RERI = −0.37 [95%CI: −1.23; 0.49], AP = −0.29 [95%CI: −0.98; 0.40], S = 0.43 [95%CI: 0.07; 2.60]), all indicating negative interaction. Preventive factors should not be used to calculate measures of interaction on an additive scale without recoding.

The synergic effect of BRAF^V600E mutation and multifocality on central lymph node metastasis in unilateral papillary thyroid carcinoma

“…When there is no additive interaction, the 95% CI of RERI and AP include 0, or S includes 1. RERI > 0, AP > 0, or S > 1 is considered to signify the existence of biological interaction [19]. SPSS statistical software (version 18.0) was used for all the analyses.…”

Effects of Smoking, Depression, and Anxiety on Mortality in COPD Patients: A Prospective Study

“…In the absence of additive interactions, RERI and attributable proportion are equal to zero. 34 In the present study we refined the criteria as either a statistically significant RERI Ͼ 0, attributable proportion Ͼ 0, or synergy index Ͼ 1 to indicate biological interactions.…”

Dosage of Sulfadoxine–Pyrimethamine and Risk of Low Birth Weight in a Cohort of Zambian Pregnant Women in a Low Malaria Prevalence Region

“…We also calculated the attributable proportion of LBW infants prevented by the additive interaction between SP and ART, adjusting for all other covariates. 23 Because women who present for a first antenatal visit later in pregnancy may have fewer opportunities to receive three doses of SP, we performed a subanalysis by restricting the cohort to those HIV-infected women whose first ANC occurred at or before 22 weeks gestation. In a final analysis, we compared our results to a model restricted to HIV-uninfected women from the original cohort.…”