Principles and performance: assessing the evidence

Despite the apparent rigour of the systematic review process there are a nu mber of reasons why it may not accurately reflect the true state of current knowledge. For inborn errors of intermediary metabolism in general, the fo rmal quality of literature on treatment is poor, partly because the rarity of the conditions makes systematic study difficult, partly because of the s elf-evident evidence paradox with treatments that are so obviously life-sav ing, and partly because of the widespread use of biochemical normalisation as a proxy outcome. In the field of newborn screening there is a paucity of formal trials so that assessment must be either by the 'causal pathway' ap proach or by reference to screenings "criteria". The causal pathway approac h may be misleading in that there are discontinuities, for example in proje cting from known incidence (clinically diagnosed cases) to the incidence ex pected on screening. The criteria-based approach suffers from qualitative d escriptors, such as "important" and "adequate", with no clear end-points, w hilst in the context of neonatal screening some of the Wilson and Jungner c riteria conflict with current evidence-based views. These problems are illu strated by reference to two reviews recently produced as part of the UK Hea lth Technology Assessment Programme.