Evidence of relative effectiveness derived from modelling final outcomes (effectiveness) from trial outcomes (efficacy) may be considered weak or unacceptable. This may be because the association between final (model) and surrogate (trial) and final outcomes is weak, and therefore estimated with low confidence (wide uncertainty). More technically, the relationship may be poorly specified statistically, or not well validated. The modelling approach itself may be inadequately described or justified. The data sources (especially sources other than trials) may not be considered relevant to the population under consideration, or are of poor quality (missing data, potential biases in their analysis). In some healthcare systems the use of modelling per se may be inadmissible or considered to be (only) supportive evidence.
RWE Navigator / Introduction to developing medicines / Effectiveness issues: challenges in demonstrating effectiveness / Late / Modelling of final outcomes from trial efficacy is not robust