Work

Lots of considerations when evaluating the FujiLAM assay

Year: 2023

Type: article

Abstract: Point-of-care non-sputum-based tests for tuberculosis are an international research priority,1WHOHigh-priority target product profiles for new tuberculosis diagnostics: report of a consensus meeting. World Health Organization, Geneva2014Google Scholar particularly for populations for whom bacteriological confirmation is difficult, such as children or people who are immunocompromised and living with HIV. The urine-based Alere Determine TB LAM Ag (Abbott, Waltham, MA, USA) test partly meets these criteria, however, the test has important shortcomings that must be overcome. SILVAMP TB-LAM (FujiLAM; Fujifilm, Tokyo, Japan), which is no longer available, targeted the same biomarker (lipoarabinomannan) and showed promise in initial evaluations.2Broger T Sossen B du Toit E et al.Novel lipoarabinomannan point-of-care tuberculosis test for people with HIV: a diagnostic accuracy study.Lancet Infect Dis. 2019; 19: 852-861Summary Full Text Full Text PDF PubMed Scopus (125) Google Scholar However, a post-hoc analysis of a large multicentre study later showed wide lot-to-lot variability that affected sensitivity and specificity estimates.3Székely R Sossen B Mukoka M et al.Multicentre accuracy trial of FUJIFILM SILVAMP TB LAM test in people with HIV reveals lot variability.medRxiv. 2022; (published online Sept 9.) (preprint).https://doi.org/10.1101/2022.09.07.22278961Google Scholar This work concluded the test was inappropriate for clinical management.3Székely R Sossen B Mukoka M et al.Multicentre accuracy trial of FUJIFILM SILVAMP TB LAM test in people with HIV reveals lot variability.medRxiv. 2022; (published online Sept 9.) (preprint).https://doi.org/10.1101/2022.09.07.22278961Google Scholar The manufacturer subsequently cancelled the long-awaited launch of the assay and a WHO policy review on the test, planned for the third quarter of 2022, was postponed. We hope Fujifilm redesign their test and that the next generation of the assay is improved. In light of this situation, the recent study published in The Lancet Global Health by Helena Huerga and colleagues4Huerga H Bastard M Lubega AV et al.Novel FujiLAM assay to detect tuberculosis in HIV-positive ambulatory patients in four African countries: a diagnostic accuracy study.Lancet Glob Health. 2023; 11: e126-e135Summary Full Text Full Text PDF PubMed Scopus (5) Google Scholar on FujiLAM is noteworthy. The authors confirmed accuracy varied between lots.3Székely R Sossen B Mukoka M et al.Multicentre accuracy trial of FUJIFILM SILVAMP TB LAM test in people with HIV reveals lot variability.medRxiv. 2022; (published online Sept 9.) (preprint).https://doi.org/10.1101/2022.09.07.22278961Google Scholar For example, sensitivity differed by about 28% and specificity by about 21% (point absolute difference). If the authors had received other lots, their findings could have been very different. Furthermore, intra-lot variability was unexamined. We do understand how doing research in the context of a constantly shifting technological landscape is challenging but presenting pooled accuracy estimates as part of the primary analysis is, in our opinion, inappropriate. It risks fuelling misinterpretation of the findings by scientific and lay audiences around a test that might not become available in the short term (if at all). This situation is especially precarious as the Alere Determine TB LAM Ag test, which is the only rapid tuberculosis test with evidence from a randomised controlled trial of a mortality benefit,5Peter JG Zijenah LS Chanda D et al.Effect on mortality of point-of-care, urine-based lipoarabinomannan testing to guide tuberculosis treatment initiation in HIV-positive hospital inpatients: a pragmatic, parallel-group, multicountry, open-label, randomised controlled trial.Lancet. 2016; 387: 1187-1197Summary Full Text Full Text PDF PubMed Scopus (184) Google Scholar remains underused after almost a decade. The lot variability, although acknowledged by the authors, should have been more central to the manuscript. This study, however, raises broader questions. Should results be published if, through no fault of the authors, a defective version of a test was used? Should a test be considered for implementation if, as in this case, lot-to-lot variation is unstudied? How useful are evaluations involving the test if it will not be available? Do such findings create false hope, leading to unmet expectations and frustration from the tuberculosis community, who desperately need better non-sputum tests? Will this situation further damage confidence in lipoarabinomannan, which remains one of our most promising biomarkers for the diagnosis of tuberculosis? Conversely, how do researchers fulfil their obligations to publish the data they have generated? Crucially, what is the role of the journal and peer reviewers in moderating and answering these questions? GT's institution has received funding to provide urine for the analysis of LAM-based tests from Biopromic, FIND, and PATH. All other authors declare no competing interests. Novel FujiLAM assay to detect tuberculosis in HIV-positive ambulatory patients in four African countries: a diagnostic accuracy studyNext-generation, higher sensitivity urine-lipoarabinomannan assays are potentially promising tests that allow rapid tuberculosis diagnosis at the point of care for HIV-positive patients. However, the variability in accuracy between FujiLAM lot numbers needs to be addressed before clinical use. Full-Text PDF Open AccessLots of considerations when evaluating the FujiLAM assay – Author's replyWe thank Alberto Garcia-Basteiro and colleagues for their response to our research Article on the novel FujiLAM assay to detect tuberculosis in HIV-positive ambulatory patients in four African countries.1 Full-Text PDF Open Access

Source: The Lancet Global Health

DOI: 10.1016/s2214-109x(23)00114-6

Authors: Alberto L Garcia-Basteiro, Frank Cobelens, Willy Ssengooba, Grant Theron