Table 2.

Summary of evidentiary challenges when evaluating NGS technologies

Challenges	Examples	Addressed	Gaps
1) Accounting for all NGS outcomes	- Health outcomes - Non-health outcomes:  ○ Information  ○ Process  ○ Test characteristics	- Preference studies include non-health attributes	- Should economic evaluations incorporate non-health outcomes? - If so, how?
2) Addressing uncertainty	- Limited data available:  ○ Accuracy  ○ Clinical outcomes  ○ Canadian context - Heterogeneity of NGS - Future changes in services and outcomes	- Parameter uncertainty  ○ Probabilistic and deterministic analysis - Decision uncertainty  ○ Value of information - Model uncertainty  ○ Scenario analysis	- Accuracy in economic evaluations - Uncertainty in stated preference studies
3) Improving consistency	- Difficult to capture benefits of NGS:  ○ Diagnostic odyssey  ○ Comparison strategies  ○ Downstream effects (e.g., cascade testing) - Study design and methods in the absence of RCT data	- Transparency around ad hoc decisions	- Guidance on:  ○ Data collection  ○ Study designs  ○ Statistical methods

NGS, next-generation sequencing; RCT, randomized controlled trial