Diagnostic accuracy and clinical impact of MRI-based technologies for patients with non-alcoholic fatty liver disease: systematic review and economic evaluation.

Background: Magnetic resonance imaging-based technologies are non-invasive diagnostic tests that can be used to assess non-alcoholic fatty liver disease. Objectives: The study objectives were to assess the diagnostic test accuracy, clinical impact and cost-effectiveness of two magnetic resonance imaging-based technologies (LiverMultiScan and magnetic resonance elastography) for patients with non-alcoholic fatty liver disease for whom advanced fibrosis or cirrhosis had not been diagnosed and who had indeterminate results from fibrosis testing, or for whom transient elastography or acoustic radiation force impulse was unsuitable, or who had discordant results from fibrosis testing. Data sources: The data sources searched were MEDLINE, MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Database of Controlled Trials, Database of Abstracts of Reviews of Effects and the Health Technology Assessment. Methods: A systematic review was conducted using established methods. Diagnostic test accuracy estimates were calculated using bivariate models and a summary receiver operating characteristic curve was calculated using a hierarchical model. A simple decision-tree model was developed to generate cost-effectiveness results. Results: The diagnostic test accuracy review (13 studies) and the clinical impact review (11 studies) only included one study that provided evidence for patients who had indeterminate or discordant results from fibrosis testing. No studies of patients for whom transient elastography or acoustic radiation force impulse were unsuitable were identified. Depending on fibrosis level, relevant published LiverMultiScan diagnostic test accuracy results ranged from 50% to 88% (sensitivity) and from 42% to 75% (specificity). No magnetic resonance elastography diagnostic test accuracy data were available for the specific population of interest. Results from the clinical impact review suggested that acceptability of LiverMultiScan was generally positive. To explore how the decision to proceed to biopsy is influenced by magnetic resonance imaging-based technologies, the External Assessment Group presented cost-effectiveness analyses for LiverMultiScan plus biopsy versus biopsy only. Base-case incremental cost-effectiveness ratio per quality-adjusted life year gained results for seven of the eight diagnostic test strategies considered showed that LiverMultiScan plus biopsy was dominated by biopsy only; for the remaining strategy (Brunt grade ≥2), the incremental cost-effectiveness ratio per quality-adjusted life year gained was £1,266,511. Results from threshold and scenario analyses demonstrated that External Assessment Group base-case results were robust to plausible variations in the magnitude of key parameters. Limitations: Diagnostic test accuracy, clinical impact and cost-effectiveness data for magnetic resonance imaging-based technologies for the population that is the focus of this assessment were limited. Conclusions: Magnetic resonance imaging-based technologies may be useful to identify patients who may benefit from additional testing in the form of liver biopsy and those for whom this additional testing may not be necessary. However, there is a paucity of diagnostic test accuracy and clinical impact data for patients who have indeterminate results from fibrosis testing, for whom transient elastography or acoustic radiation force impulse are unsuitable or who had discordant results from fibrosis testing. Given the External Assessment Group cost-effectiveness analyses assumptions, the use of LiverMultiScan and magnetic resonance elastography for assessing non-alcoholic fatty liver disease for patients with inconclusive results from previous fibrosis testing is unlikely to be a cost-effective use of National Health Service resources compared with liver biopsy only. Study registration: This study is registered as PROSPERO CRD42021286891. Funding: Funding for this study was provided by the Evidence Synthesis Programme of the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 10. See the NIHR Journals Library website for further project information.

Non-alcoholic fatty liver disease includes a range of conditions that are caused by a build-up of fat in the liver, and not by alcohol consumption. This build-up of fat can cause inflammation. Persistent inflammation can cause scar tissue (fibrosis) to develop. It is important to identify patients with fibrosis because severe fibrosis can cause permanent liver damage (cirrhosis), which can lead to liver failure and liver cancer. In the National Health Service, patients with non-alcoholic fatty liver disease undergo tests to determine whether they have fibrosis. The test results are not always accurate and multiple tests can give conflicting results. Some of the tests may not be suitable for patients who have a very high body mass index. In the National Health Service, a liver biopsy may be offered to patients with inconclusive or conflicting test results or to those patients for whom other tests are unsuitable. However, liver biopsy is expensive, and is associated with side-effects such as pain and bleeding. Magnetic resonance imaging-based testing could be used as an extra test to help clinicians assess non-alcoholic fatty liver disease and identify patients who may need a liver biopsy. We assessed two magnetic resonance imaging-based diagnostic tests, LiverMultiScan and magnetic resonance elastography. LiverMultiScan is imaging software that is used alongside magnetic resonance imaging to measure markers of liver disease. Magnetic resonance elastography is used in some National Health Service centres to assess liver fibrosis; however, magnetic resonance elastography requires more equipment than just an magnetic resonance imaging scanner. We reviewed all studies examining how well LiverMultiScan and magnetic resonance elastography assess patients with non-alcoholic fatty liver disease. We also built an economic model to estimate the costs and benefits of using LiverMultiScan to identify patients who should be sent for a biopsy. Results from the model showed that LiverMultiScan may not provide good value for money to the National Health Service.

Onasemnogene Abeparvovec for Treating Pre-symptomatic Spinal Muscular Atrophy: An External Assessment Group Perspective of the Partial Review of NICE Highly Specialised Technology Evaluation 15.

As part of the National Institute for Health and Care Excellence (NICE) highly specialised technology (HST) evaluation programme, Novartis submitted evidence to support the use of onasemnogene abeparvovec as a treatment option for patients with pre-symptomatic 5q spinal muscular atrophy (SMA) with a bi-allelic mutation in the survival of motor neuron (SMN) 1 gene and up to three copies of the SMN2 gene. The Liverpool Reviews and Implementation Group at the University of Liverpool was commissioned to act as the External Assessment Group (EAG). This article summarises the EAG's review of the evidence submitted by the company and provides an overview of the NICE Evaluation Committee's final decision, published in April 2023. The primary source of evidence for this evaluation was the SPR1NT trial, a single-arm trial including 29 babies. The EAG and committee considered that the SPR1NT trial results suggested that onasemnogene abeparvovec is effective in treating pre-symptomatic SMA; however, long-term efficacy data were unavailable and efficacy in babies aged over 6 weeks remained uncertain. Cost-effectiveness analyses conducted by the company and the EAG (using a discounted price for onasemnogene abeparvovec) explored various assumptions; all analyses generated incremental cost-effectiveness ratios (ICERs) that were less than £100,000 per quality-adjusted life-year (QALY) gained. The committee recommended onasemnogene abeparvovec as an option for treating pre-symptomatic 5q SMA with a bi-allelic mutation in the SMN1 gene and up to three copies of the SMN2 gene in babies aged ≤ 12 months only if the company provides it according to the commercial arrangement (i.e. simple discount patient access scheme).