In the GBD CRA approach, the TMREL is the level of risk exposure that leads to minimum risk for individuals. In principle, the TMREL could vary by location, age, and sex. To date, the TMREL in the GBD work has been selected to be universal. For more detail on TMREL, see appendix 1 (p 22). The analysis of alcohol, where for IHD there is a protective effect at mild to moderate consumption but a harmful effect for neoplasms and injuries, is a good example of where it would be desirable to vary TMREL by age. In younger ages, injuries will be more important than cardiovascular diseases, pushing the TMREL toward zero consumption of alcohol, whereas at older ages, the TMREL might be higher. Letting the TMREL vary by age and sex and even location will add an extra analytical step to GBD; like all other estimation steps, this can have estimation error. To date, we have thought the estimation error associated with a TMREL that varies may not make the effort worthwhile. As evidence accumulates on some risks like alcohol, we will carefully evaluate this position.
