Table 3: Summary of PICO to define the question for public funding that assessment will investigate Patients tests Intervention Comparator Reference Standard Outcomes to be (for diagnostic tests) assessed Patients Histological EGFR gene No agreed reference Primary comparator Safety  with diagnosis of mutation testing standard currently No EGFR gene mutation Toxic effects of  previously non- and, after testing and use of available, but treatment untreated squamous presenting with comparisons should treatment with platinum- Adverse events  non- or locally advanced be made against the based doublet from biopsies squamous NSCLC not or metastatic chemotherapy after specific tests used to Rate of re-biopsy  NSCLC or otherwise disease, use of generate the evidence presenting with locally NSCLC not classified first-line erlotinib to support the advanced or metastatic Effectiveness otherwise in patients with disease effectiveness of first- Progression free  classified tumours line erlotinib (the survival expressing EGFR “evidentiary”  Overall survival standard), specifically: exon 19 deletions Objective tumour  or exon 21 point PCR followed by  response rate mutation L858R length analysis in an Quality of life  and use of ABI Prism 3130 DNA Comparison of  platinum-based analyser for exon 19 test performance doublet deletions and a 5’ chemotherapy in nuclease PCR Cost patients not (Taqman) assay for effectiveness expressing these exon 21 point Cost per QALY  EGFR gene mutations (EURTAC mutations and in trial) those patients PCR-based direct  whose EGFR sequencing gene mutation (OPTIMAL trial) status is unknown No agreed reference Secondary comparator  standard currently EGFR gene mutation testing and, after available, but comparisons should presenting with locally be made against the advanced or metastatic disease, use of gefitinib specific tests used to generate the evidence in patients with tumours expressing EGFR exon to support the 19 deletions or exon 21 effectiveness of gefitinib point mutation L858R and use of platinum-based doublet chemotherapy in patients not expressing these EGFR gene mutations and in those whose EGFR gene mutation status is unknown
Table 3: Summary of PICO to define the question for public funding that assessment will investigate Patients tests Intervention Comparator Reference Standard (for diagnostic tests) Outcomes to be assessed Patients with previously untreated non- squamous NSCLC or NSCLC not otherwise classified Histological diagnosis of non- squamous or NSCLC not otherwise classified EGFR gene mutation testing and, after presenting with locally advanced or metastatic disease, use of first-line erlotinib in patients with tumours expressing EGFR exon 19 deletions or exon 21 point mutation L858R and use of platinum-based doublet chemotherapy in patients not expressing these EGFR gene mutations and in those patients whose EGFR gene mutation status is unknown  Primary comparator No EGFR gene mutation testing and use of treatment with platinum- based doublet chemotherapy after presenting with locally advanced or metastatic disease No agreed reference standard currently available, but comparisons should be made against the specific tests used to generate the evidence to support the effectiveness of first- line erlotinib (the “evidentiary” standard), specifically:  PCR followed by length analysis in an ABI Prism 3130 DNA analyser for exon 19 deletions and a 5’ nuclease PCR (Taqman) assay for exon 21 point mutations (EURTAC trial)  PCR-based direct sequencing (OPTIMAL trial) Safety  Toxic effects of treatment  Adverse events from biopsies  Rate of re-biopsy Effectiveness  Progression free survival  Overall survival  Objective tumour response rate  Quality of life  Comparison of test performance Cost effectiveness  Cost per QALY  Secondary comparator EGFR gene mutation testing and, after presenting with locally advanced or metastatic disease, use of gefitinib in patients with tumours expressing EGFR exon 19 deletions or exon 21 point mutation L858R and use of platinum-based doublet chemotherapy in patients not expressing these EGFR gene mutations and in those whose EGFR gene mutation status is unknown No agreed reference standard currently available, but comparisons should be made against the specific tests used to generate the evidence to support the effectiveness of gefitinib