Table 1.

Comparison of previous classification schemas that assign clinical utility to molecular alterations used to select targeted therapies in cancer

Data type and classification variable	Andre et al., Ann Oncol 2014	Van Allen et al., Nat Med 2014	Meric-Bernstam et al., JNCI 2015	Chakravarty et al., JCOPO 2017 (OncoKB)
Data have been generated in randomised clinical trials	Yes, but allow into the same level of evidence targets supported by multiple non-randomised trials	Does not discriminate between clinical data generated by randomised versus non-randomised trials	Does not discriminate between clinical data generated by randomised versus non-randomised trials	Does not discriminate between clinical data generated by randomised versus non-randomised trials
Data come from prospective clinical trials	Does not discriminate prospective versus retrospective clinical studies	Not specifically considered	Data from prospective versus retrospective study are assigned different levels of evidence	Not specified, refers to ‘compelling clinical data’
Regulatory approval (FDA/EMA) for the drug	Not specifically considered	FDA approval is the principal variable to assign category	FDA approval is the criteria for top evidence level (1A) assignment	FDA approval is the principal variable to assign category
Validation of the assay used for biomarker detection	Not specifically considered	Not specifically considered	Not specifically considered	Accounts for FDA recognition of the biomarker under consideration
Clinical data have been generated in same or different tumour types	Includes specific category IC for level I supportive data generated in a different tumour type, recommending treatment different tumour type in the context of clinical trials	Use different categories depending on supportive data generated in the same or different tumour types	Use different categories based on data generated in the same or different tumour types	Categories 2 and 3 are subdivided based on whether data were generated in same or different tumour types
Considers magnitude of benefit (OS, PFS, RR)	Not specifically considered	Not specifically considered	Not specifically considered	Not specifically considered
Considers preclinical data	Includes specific category for predictions of actionability based on preclinical data	Includes specific category for predictions of actionability based on preclinical data	Includes specific category for predictions of actionability based on preclinical data	Includes specific category for predictions of actionability based on preclinical data
Considers if clinical efficacy is known for the biomarker negative population	Yes, but effect in marker-negative group does not impact clinical recommendation	Not specifically considered	Not specifically considered	Not specifically considered
Other comments		Considers predictive versus prognostics versus diagnostic value evidence	Considers data coming from case reports as level 3A	Includes grading of evidence for resistance biomarkers