Assessing Health Consequences of Vitamin D Fortification Utilizing a Societal Experiment Design: Methodological Lessons Learned from the D-Tect Project.

By utilizing historical changes in Danish legislation related to mandatory vitamin D fortification of margarine, which was implemented in the mid 1930s and abruptly abandoned in June 1985, the studies in the D-tect project investigated the effects of vitamin D on health outcomes in individuals, who during gestation were exposed or unexposed to extra vitamin D from fortified margarine. This paper reviews and narratively summarizes the analytic approaches alongside the results of the societal fortification experiment studies from the D-tect project and addresses the challenges in designing societal experiment studies and evaluating their results. The latter are discussed as lessons learned that may be useful for designers of similar studies, expected to be extensively utilized while researching the health consequences of the COVID-19 pandemic by comparing individuals born before and after the epidemic. In the D-tect project, 16 articles based on the societal fortification experiment were published analyzing 10 different outcomes and using different statistical approaches. Lessons learned included the detail of the analysis of the historical information on the exposure, availability and validity of the outcome data, variety of analytical approaches, and specifics concerning vitamin D effect evaluation, such as consideration of the influence of sunshine or season. In conclusion, the D-tect project clearly demonstrated the cost-effectiveness and research potential of natural- or societal-experiment-based studies.