|Methodological areas||Issues identified in the current practice of economic evaluations||Possible solutions/suggestions|
|Methodological approaches||Data requirements|
|Target population||Pre-selected population group with known biomarker status was targeted in EEs.||Target the entire patient group including biomarker positive, negative, and unknown.||Clinical data on all patients including false positive, false negative, unknown biomarker status.|
|Perspective||Payer perspective was mostly used following the HTA guidelines by the reimbursement authority.||Holistic viewpoint desired (e.g. societal perspective). However, if infeasible, biomarker testing related cost items should be included in evaluations.||Cost data collected from administrative database or real-world setting.|
|Comparator||With versus without the use of biomarker testing compared in evaluations yet in the context of the same targeted therapy.||SOC in current routine clinical practice should be employed as a comparator in the context of treating the disease condition of interest and the target patient population.||Evidence on standard of care being routinely practiced for the target patient population with the disease condition in a country-specific setting.|
|Comparison structure||No consistency in structuring strategies to be compared in comparative analysis of companion biomarkers for targeted therapies.||Test-treat versus treat-all with SOC is suggested as a base-case comparison structure.||
Clinical data on patients treated all with SOC without biomarker tested.|
Clinical data on patients tested negative.
|Clinical effectiveness||Clinical value of companion biomarkers was limited to sensitivity/specificity. Often, biomarker prevalence data was ignored. Sensitivity /specificity was often assumed to be 100% or excluded completely from the economic model inputs.||Clinical value of companion biomarkers beyond sensitivity /specificity should be incorporated in economic evaluations of biomarker-guided therapies.||Clinical evidence generated from clinical trials on both the drug and the diagnostic. If possible, separate RCTs in test positive and test negative patients respectively treated with guided therapy and non-guided therapy. In addition, the clinical utility values including the change of clinician’s behavior in choosing this treatment option over SOC should be captured.|
|Preference-based outcome||Utility and/or disutility values related to biomarker testing were not considered.||Biomarker related patient preferences should be incorporated in economic evaluations of biomarker-guided therapies.||Individual patient utility (or disutility) values on the use of a companion biomarker test prior to the administration of targeted therapy. Patient preference data can be acquired along the clinical trials, reflecting all biomarker relevant preference items.|
|Timing of the test use||The timing of the use of companion biomarker testing is often not incorporated and not reported in economic evaluations.||The value of companion biomarkers should be understood throughout the clinical pathways applicable to the decision-making of clinicians.||The timing of the test use in clinical routine settings is preferred over the RCT setting.|
|Uncertainty analysis||Many economic evaluations did not examine the characteristics of a test separately from that of the corresponding therapy.||The characteristic components relevant to a companion biomarker diagnostic should be tested separately as part of uncertainty analysis of biomarker-guided therapy.||Value of information analysis can be useful to inform the uncertainty around current information/data against perfect or partial perfect information.|
|Information and model inputs to be incorporated in economic evaluations of companion biomarkers||Limited number of model parameters pertinent to biomarker testing was incorporated into the economic assessment of companion biomarkers.||Model inputs relevant to companion biomarker testing should all be captured and incorporated in economic evaluations of biomarker-guided therapies.||
Name/type of biomarker testing diagnostic/kit.|
Resource use of testing.
Unit cost of testing.
Capital cost if the testing device is not currently available in current clinical settings.
Prevalence of biomarker status in patient population.
Utility and/or disutility values of performing the test in relation to preference-based outcomes.
Clinical pathways including the test (for example, when the test is performed in routine clinical settings).