Limitations and strengths
cardiovascular disease
CARDIOVASCULAR DISEASE
Limitations in our study include, first, that our participants were at high risk of cardiovascular disease and they belonged to a Mediterranean country, thus reducing generalizability. Nevertheless, external validity should take into account biological plausibility and not only representativeness in the merely statistical interpretation used for surveys. Secondly, even though we accounted for many potential confounders, a potential for residual confounding exist; however, previous intention-to-treat results were reasonably free of residual confounding and also showed strong benefits. Thirdly, a certain degree of measurement error using MEDAS may have occurred; however, the face-to-face interviews by expert and well-trained dietitians to collect the MEDAS questionnaires may miminize this risk; also, the use of cumulative averages is known to reduce measurement errors [Strengths of our study included addressing the important issue of the assessment of the effect of actual compliance with a dietary intervention in a large randomized trial. Secondly, those variables which met the requirements as to be considered major potential confounders were appropriately controlled for in the statistical analyses (we did not adjust for intermediate links in the causal pathway, to avoid overadjustment). In any case, it was reassuring that the results did not materially change after a variety of multivariable adjustments. Thirdly, we used cumulative averages of diet scores, which accounted for previous dietary exposures and reduced measurement errors. Fourth, biomarkers of adherence in a large subset of participants were used to confirm the validity of results.