Proposed structure of economic evaluation (decision-analytic) The extended PICO to be used for the economic evaluation are provided in Table 10. Table 10 Summary of extended PICO to define research questions that economic evaluation will investigate Patients Intervention Comparator Outcomes to be Healthcare assessed resources to be considered Patients suspected ECG (Schwartz ECG (Schwartz Effectiveness: see Table 9 of having long QT score) ± exercise score) ± Direct evidence syndrome, who are stress test ± Holter exercise stress classified as monitoring plus test ± Holter Primary outcomes – intermediate or molecular genetic monitoring Mortality/survival; quality high risk (Schwartz testing for LQTS of life; incidence of life- score threatening events ≥3) including cardiac arrest and ventricular fibrillation. Linked evidence Clinically Molecular genetic ECG (Schwartz Effectiveness: see 9 unaffected testing for LQTS ± score) ± Direct evidence relatives of a ECG (Schwartz exercise stress patient with a Primary outcomes ± exercise test ± Holter – known long QT Mortality/survival; quality stress test ± Holter monitoring syndrome of life; incidence of life- monitoring threatening events including cardiac arrest and ventricular fibrillation. Linked evidence Research Questions 1. Is molecular testing for the genetic mutations associated with LQTS cost-effective when used in addition to clinical diagnostic approaches in the diagnosis of patients presenting with symptoms suggestive of long QT syndrome? 2. Is molecular testing for the genetic mutations associated with LQTS cost- effective when used as a triage for clinical assessment, treatment and life-long monitoring of family members of patients who are known to have LQTS? Two main analyses will be performed, assessing: 1) the consequences of adding the genetic test into clinical practice for the proband (index case) alone (diagnostic setting; Figure 3); and and 2) the consequences of using the genetic test for both the proband their family members (predictive setting; Figure 4). A stepped analysis will be performed to determine whether the genetic test is cost-effective when restricted to index cases and first degree relatives alone, and subsequently, if it is cost-effective when broadened to the index case plus first and second degree relatives.
Proposed structure of economic evaluation (decision-analytic) The extended PICO to be used for the economic evaluation are provided in Table 10. Table 10 Summary of extended PICO to define research questions that economic evaluation will investigate Patients Intervention Comparator Outcomes to be assessed Healthcare resources to be considered Patients suspected of having long QT syndrome, who are classified as intermediate or high risk (Schwartz score ≥3) ECG (Schwartz score) ± exercise stress test ± Holter monitoring plus molecular genetic testing for LQTS ECG (Schwartz score) ± exercise stress test ± Holter monitoring Effectiveness: Direct evidence Primary outcomes – Mortality/survival; quality of life; incidence of life- threatening events including cardiac arrest and ventricular fibrillation. Linked evidence see Table 9 Clinically unaffected relatives of a patient with a known long QT syndrome Molecular genetic testing for LQTS ± ECG (Schwartz ± exercise stress test ± Holter monitoring ECG (Schwartz score) ± exercise stress test ± Holter monitoring Effectiveness: Direct evidence Primary outcomes – Mortality/survival; quality of life; incidence of life- threatening events including cardiac arrest and ventricular fibrillation. Linked evidence see 9 Research Questions 1. Is molecular testing for the genetic mutations associated with LQTS cost-effective when used in addition to clinical diagnostic approaches in the diagnosis of patients presenting with symptoms suggestive of long QT syndrome? 2. Is molecular testing for the genetic mutations associated with LQTS cost- effective when used as a triage for clinical assessment, treatment and life-long monitoring of family members of patients who are known to have LQTS? Two main analyses will be performed, assessing: 1) the consequences of adding the genetic test into clinical practice for the proband (index case) alone (diagnostic setting; Figure 3); and 2) the consequences of using the genetic test for both the proband and their family members (predictive setting; Figure 4). A stepped analysis will be performed to determine whether the genetic test is cost-effective when restricted to index cases and first degree relatives alone, and subsequently, if it is cost-effective when broadened to the index case plus first and second degree relatives.
1151_FinalDAP.docx