Estimating measures of interaction on an additive scale for preventive exposures

• Published in: European journal of epidemiology Vol. 26; no. 6; pp. 433 - 438
• Main Authors: Knol, Mirjam J., VanderWeele, Tyler J., Groenwold, Rolf H. H., Klungel, Olaf H., Rovers, Maroeska M., Grobbee, Diederick E.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer 01-06-2011; Springer Netherlands; Springer Nature B.V; Springer Verlag
• Subjects: Angiotensin converting enzyme inhibitors; Biological and medical sciences; Cardiology; Case-Control Studies; Causality; Confidence interval; Data Interpretation, Statistical; Diabetes; Drug interactions; Epidemiologic Research Design; Epidemiology; Estimating techniques; General aspects; Genotypes; Humans; Infectious Diseases; Infinity; Inhibitors; Life Sciences; Medical sciences; Medicine; Medicine & Public Health; METHODS; Miscellaneous; Oncology; Predisposing factors; Prevention and actions; Primary Prevention; Public Health; Public health. Hygiene; Public health. Hygiene-occupational medicine; Ratios; Risk Assessment - methods; Risk Assessment - statistics & numerical data; Risk Factors; Santé publique et épidémiologie; Type 2 diabetes mellitus; Relative excess risk due to interaction; Synergy index; Preventive factors; Interaction; Human; Evaluation scale; Estimation; Exposure; Index; Epidemiology; Relative risk; Prevention; Additive; Public health
• ISSN: 0393-2990; 1573-7284
• DOI: 10.1007/s10654-011-9554-9

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.