Genedrive kit for detecting single nucleotide polymorphism m.1555A>G in neonates and their mothers: a systematic review and cost-effectiveness analysis

• Published in: Health technology assessment (Winchester, England) England), 2024-10, Vol.28 (75), p.1-75
• Main Authors: Shabaninejad, Hosein, Kenny, Ryan Pw, Robinson, Tomos, Stoniute, Akvile, O'Keefe, Hannah, Still, Madeleine, Thornton, Christopher, Pearson, Fiona, Beyer, Fiona, Meader, Nick
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - therapeutic use; Cost-Benefit Analysis; Cost-Effectiveness Analysis; Female; Gentamicins - therapeutic use; Humans; Infant, Newborn; Mothers; Polymorphism, Single Nucleotide; Quality-Adjusted Life Years
• ISSN: 2046-4924; 1366-5278; 2046-4924
• DOI: 10.3310/TGAC4201

Neonates with suspected sepsis are commonly treated with gentamicin, an aminoglycoside. These antibiotics are associated with high risk of ototoxicity, including profound bilateral deafness, in people with the m.1555A>G mitochondrial genetic variant. This early value assessment summarised and critically assessed the clinical effectiveness and cost-effectiveness of the Genedrive MT-RNR1 ID Kit for identifying the gene m.1555A>G variant in neonates and mothers of neonates needing antibiotics or anticipated to need antibiotics. Following feedback from the scoping workshop and specialist assessment subgroup meeting, we also considered the Genedrive MT-RNR1 ID Kit for identifying the m.1555A>G variant in mothers prior to giving birth. For clinical effectiveness, we searched three major databases in October 2022: MEDLINE, EMBASE and CINAHL (Cumulative Index to Nursing and Allied Health Literature). For cost-effectiveness, in addition to the three mentioned databases we searched Cochrane and RePEc-IDEAS. Study selection and risk-of-bias assessment were conducted by two independent reviewers (Ryan PW Kenny and Akvile Stoniute for clinical effectiveness and Hosein Shabaninejad and Tomos Robinson for cost-effectiveness). Any differences were resolved through discussion, or by a third reviewer (Nick Meader). Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies-2. One study (  = 751 neonates recruited) was included in the clinical effectiveness review and no studies were included in the cost-effectiveness review. All except one outcome (test failure rate: low risk of bias) were rated as being at moderate risk of bias. The study reported accuracy of the test (sensitivity 100%, 95% confidence interval 29.2% to 100%; specificity 99.2%, 95% confidence interval 98% to 99.7%), number of neonates successfully tested (  = 424/526 admissions), test failure rate (17.1%, although this was reduced to 5.7%), impact on antibiotic use (all those with a m.1555A>G genotype avoided aminoglycosides), time taken to obtain a sample (6 minutes), time to genotyping (26 minutes), time to antibiotic treatment (55.18 minutes) and the number of neonates with m.1555A>G (  = 3). The economic component of this work identified key evidence gaps for which further data are required before a robust economic evaluation can be conducted. These include the sensitivity of the Genedrive MT-RNR1 ID Kit for identifying the gene m.1555A>G variant in neonates, the magnitude of risk