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Interestingly, when there was no restriction to biomarkers based on the significance of their fitted slope, but there was a restriction to using data for studies with well-defined groups the ECIG RR estimate of 12.89 (11.7314.16) dropped dramatically to 2.06 (1.742.43), mainly because the first four of the five very high RR estimates cited above occurred in studies where the study was not classified as having well-defined groups as the definition of the smoking groups was not clearly exclusive

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