Estimating Additive Interaction in Two-Stage Individual Participant Data Meta-Analysis

Authors: Maartje Basten, Lonneke A van Tuijl, Kuan-Yu Pan, Adriaan W Hoogendoorn, Femke Lamers, Adelita V Ranchor, Joost Dekker, Philipp Frank, Henrike Galenkamp, Mirjam J Knol, Nolwenn Noisel, Yves Payette, Erik R Sund, Aeilko H Zwinderman, Lützen Portengen, Mirjam I Geerlings Journal: American Journal of Epidemiology Abstract: Individual participant data (IPD) meta-analysis provides important opportunities to study interaction and effect modification for which individual studies often lack power. While previous meta-analyses have commonly focused on multiplicative interaction, additive interaction holds greater relevance for public health and may in certain contexts better reflect biological interaction. Methodological literature on interaction in IPD meta-analysis does not cover additive interaction for models including binary or time-to-event outcomes. We aimed to describe how the Relative Excess Risk due to Interaction (RERI) and other measures of additive interaction or effect modification can be validly estimated within two-stage IPD meta-analysis. First, we explain why direct pooling of study-level RERI estimates may lead to invalid results. Next, we propose a three-step procedure to estimate additive interaction: 1) estimate effects of both exposures and their product term on the outcome within each individual study; 2) pool study-specific estimates using multivariate meta-analysis; 3) estimate an overall RERI and 95% confidence interval based on the pooled effect estimates. We illustrate this procedure by investigating interaction between depression and smoking and risk of smoking-related cancers using data from the PSYchosocial factors and Cancer (PSY-CA) consortium. We discuss implications of this procedure, including the application in meta-analysis based on published data. doi: https://doi.org/10.1093/aje/kwae325

New Article – The mediating role of health behaviors in the association between depression, anxiety and cancer incidence: an individual participant data meta-analysis

Congratulations to Dr. Kuan-Yu Pan and the Psychosocial Factors and Cancer Incidence (PSY-CA) Consortium team members on their latest publication, “The mediating role of health behaviors in the association between depression, anxiety and cancer incidence: an individual participant data meta-analysis.” PSY-CA includes 18 international cohorts with 320,000 participants, including Atlantic PATH, the Ontario Health Study and CARTaGENE. Article: https://bit.ly/3weFXXP

The mediating role of health behaviors in the association between depression, anxiety and cancer incidence: an individual participant data meta-analysis

Authors: Kuan-Yu Pan , Lonneke van Tuijl, Maartje Basten, Judith J. M. Rijnhart, Alexander de Graeff, Joost Dekker, Mirjam I. Geerlings, Adriaan Hoogendoorn, Adelita V. Ranchor, Roel Vermeulen, Lützen Portengen, Adri C. Voogd, Jessica Abell, Philip Awadalla, Aartjan T. F. Beekman, Ottar Bjerkese, Andy Boyd, Yunsong Cui, Philipp Frank, Henrike Galenkamp, Bert Garssen, Sean Hellingman, Monika Hollander, Martijn Huisman, Anke Huss, Melanie R. Keats, Almar A. L. Kok, Steinar Krokstad, Flora E. van Leeuwen, Annemarie I. Luik, Nolwenn Noisel, Yves Payette, Brenda W. J. H. Penninx, Susan Picavet, Ina Rissanen, Annelieke M. Roest, Judith G. M. Rosmalen, Rikje Ruiter, Robert A. Schoevers, David Soave, Mandy Spaan, Andrew Steptoe, Karien Stronks, Erik R. Sund, Ellen Sweeney, Alison Teyhan, Emma L. Twait, Kimberly D. van der Willik and Femke Lamers. Journal: Psychological Medicine Abstract: Background – Although behavioral mechanisms in the association among depression, anxiety, and cancer are plausible, few studies have empirically studied mediation by health behaviors. We aimed to examine the mediating role of several health behaviors in the associations among depression, anxiety, and the incidence of various cancer types (overall, breast, prostate, lung, colorectal, smoking-related, and alcohol-related cancers). Methods – Two-stage individual participant data meta-analyses were performed based on 18 cohorts within the Psychosocial Factors and Cancer Incidence consortium that had a measure of depression or anxiety (N = 319 613, cancer incidence = 25 803). Health behaviors included smoking, physical inactivity, alcohol use, body mass index (BMI), sedentary behavior, and sleep duration and quality. In stage one, path-specific regression estimates were obtained in each cohort. In stage two, cohort-specific estimates were pooled using random-effects multivariate meta-analysis, and natural indirect effects (i.e. mediating effects) were calculated as hazard ratios (HRs). Results – Smoking (HRs range 1.04–1.10) and physical inactivity (HRs range 1.01–1.02) significantly mediated the associations among depression, anxiety, and lung cancer. Smoking was also a mediator for smoking-related cancers (HRs range 1.03–1.06). There was mediation by health behaviors, especially smoking, physical inactivity, alcohol use, and a higher BMI, in the associations among depression, anxiety, and overall cancer or other types of cancer, but effects were small (HRs generally below 1.01). Conclusions  – Smoking constitutes a mediating pathway linking depression and anxiety to lung cancer and smoking-related cancers. Our findings underline the importance of smoking cessation interventions for persons with depression or anxiety.   doi: DOI: https://doi.org/10.1017/S0033291724000850