title: The cost-effectiveness of screening lung cancer patients for targeted drug sensitivity markers.
abstract: BACKGROUND
  New oncology drugs are being developed in conjunction with companion diagnostics with approval restricting their use to certain biomarker-positive subgroups. We examined the impact of different predictive biomarker screening techniques and population enrichment criteria on the cost-effectiveness of targeted drugs in lung cancer, using ALK and crizotinib to build the initial model.
  
  
  METHODS
  Health economic modeling of cost per Quality Adjusted Life Year was based on literature review and expert opinion. The modeled population represented advanced non-small cell lung cancer (NSCLC), eligible for predictive biomarker screening with prescribing restricted to biomarker-positive patients.
  
  
  RESULTS
  For assays costing $1400 per person, cost per quality-adjusted life year (QALY) gained for ALK screening all advanced NSCLC, excluding treatment cost, is $106,707. This falls to $4756 when only a highly enriched population is screened (increasing biomarker frequency from 1.6 to 35.9%). However, the same enrichment involves missing 56% patients who segregate within the unscreened group. Cheaper screening tests that miss some true positives can be more cost-effective if proportional reductions in cost exceed proportion of subjects missed. Generic modeling of idealised screening assays, including treatment cost, reveals a dominant effect of screening cost per person at low biomarker frequencies. Cost-effectiveness of <$100,000 per QALY gained is not achievable at biomarker frequencies <5% (with drug costs $1-5000 per month and screening costs $600-1400 per person).
  
  
  CONCLUSIONS
  Cost-effectiveness of oncology drugs whose prescribing is restricted to biomarker-positive subgroups should address the cost of detecting marker-positive patients. The cost of screening dominates at low frequencies and strategies to improve cost-effectiveness based on the assay cost, drug cost and the group screened should be considered in these scenarios.
authors.affiliation: Department of Health Systems, Management and Policy, Colorado School of Public Health, University of Colorado, Aurora, CO, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Atherly
authors.forename: D R
authors.initials: DR
authors.lastname: Camidge
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000191:economics / Q000201:enzymology; D003362:Cost-Benefit Analysis; D000077547:Crizotinib; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000191:economics / Q000201:enzymology; D008954:Models, Biological; D058990:Molecular Targeted Therapy / Q000191:economics; D057285:Precision Medicine / Q000191:economics; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D011788:Quality of Life; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases