Advice

Clinical and technical evidence

Clinical and technical evidence

A literature search was carried out for this briefing in accordance with the interim process and methods statement for medtech innovation briefings. This briefing includes the most relevant or best available published evidence relating to the clinical effectiveness of the technology. Further information about how the evidence for this briefing was selected is available on request by contacting mibs@nice.org.uk.

Published evidence

Three studies are summarised in this briefing, involving a total of 956 pregnant women. All studies were prospective, non-randomised observational studies.

The clinical evidence and its strengths and limitations is summarised in the overall assessment of the evidence.

Overall assessment of the evidence

The current published evidence for Lumella is limited to 3 prospective observational studies. All studies were funded or supported by the company and some of the authors were employees or shareholders of the company.

Across all 3 studies, glycosylated fibronectin (GlyFn) showed good biomarker performance to detect pre-eclampsia. The reported area under the receiver-operating characteristic curve (AUROC) for GlyFn was between 0.94 and 0.99, and numerically higher than that reported for other pre-eclampsia biomarkers tested (soluble fms‑like tyrosine kinase‑1 [sFlt‑1] and placental growth factor [PlGF], sFlt‑1, PlGF and PAPPA2). Only 1 of the studies evaluated GlyFn biomarker performance primarily using the commercially available Lumella test (Nagalla et al. 2020). In this study (n=798), the Lumella test had a sensitivity of 98.5% and a specificity of 92.8% (at a threshold of 263 microgram/ml GlyFn or higher). The other 2 studies mainly used a GlyFn plate immunoassay but showed that the performance (AUROC) was similar to the Lumella point-of-care test using a small subset of samples.

The studies included recommended biomarkers sFlt‑1 and PlGF or PlGF alone but the immunoassays used in the studies are not the commercial assays currently used in the NHS (Triage PlGF test and Elecsys immunoassay sFlt‑1/PlGF ratio). Studies were done in India, Finland and Switzerland. There is currently no evidence in an NHS setting. Further evidence comparing the diagnostic accuracy of the Lumella test with standard care testing in the NHS is needed. Future research evaluating the impact of the test on clinical outcomes and resource use compared with standard care testing would also be helpful.

Nagalla et al. (2020)

Study size, design and location

Prospective, multicentre observational study of 798 pregnant women in India. Of these, 469 tested as normotensive with no proteinuria, 135 had pre-eclampsia and 194 had gestational hypertension at 20 weeks or more of pregnancy.

Intervention and comparators

The Lumella test compared with immunoassays for sFlt‑1, PlGF, and PAPPA2.

Key outcomes

The Lumella test showed the highest test performance, followed by PAPPA2, PlGF and sFlt‑1. AUROC values were 0.99 (95% confidence interval [CI] 0.98 to 0.99) with the Lumella test, 0.96 (95% CI 0.94 to 0.98) with PlGF, 0.86 (95% CI 0.83 to 0.89) with sFlt‑1 and 0.96 (95% CI 0.94 to 0.97) with PAPPA2. Overall and relative biomarker performance were not different between early- and late-onset pre-eclampsia or between non-severe and severe pre-eclampsia.

Strengths and limitations

The study included a relatively large number of people and had well-defined inclusion and exclusion criteria. However, the study was done in India which may limit the generalisability of results to the NHS. The prevalence of pre-eclampsia in the study was 17%, higher than that reported in the UK. The study does however present diagnostic accuracy data based on a theoretical prevalence of 5% or 7%. All people in the study had new-onset hypertension and were being evaluated for pre-eclampsia so results may not be generalisable to a screening population of women with no symptoms. Although Lumella was compared with immunoassays for other biomarkers, the study did not use standard care tests in the NHS (Triage PlGF test and Elecsys immunoassay sFlt‑1/PlGF ratio). The study was funded by the company and a number of the authors are either employees or shareholders of the company.

Rasanen et al. (2015)

Intervention and comparators

GlyFn immunoassay compared with other pre-eclampsia biomarkers (PlGF, sFlt‑1 and PlGF/SFlt‑1 ratio). The diagnostic accuracy of the GlyFn immunoassay was also compared with that of the point-of-care GlyFn test (Lumella version 1.0).

Key outcomes

There were 45 women with normotension and 62 who were diagnosed with pre-eclampsia. Compared with women with normotension, women with pre-eclampsia had significantly high levels of GlyFn in the first semester which remained high throughout pregnancy (p<0.01). All biomarkers tested were associated with pre-eclampsia status (p<0.01). The AUROC was 0.99 (95% CI 0.98 to 1.00) for GlyFn, 0.96 (95% CI 0.89 to 1.00) for sFlt‑1, 0.94 (95% CI 0.86 to 1.00) for PlGF and 0.98 (95% CI 0.94 to 1.00) for sFlt‑1/PlGF ratio. At a cut-off value of 176.4 micrograms/ml, GlyFn had a sensitivity of 0.97 (95% CI 0.85 to 1.00) and a specificity of 0.93 (95% CI 0.66 to 1.00). With an estimated population prevalence of 5% for pre-eclampsia, the positive predictive value was 47% (95% CI 23% to 72%) and the negative predictive value was 89% (95% CI 80% to 98%). Increased GlyFn levels were statistically significantly associated with length of pregnancy, birthweight, blood pressure, uric acid and alanine transaminase (p≤0.01). The point-of-care GlyFn test (Lumella) showed similar diagnostic performance to the plate assay (AUROC of 0.93; 95% CI 0.85 to 1.00). Authors state that it outperformed the plate assay for the ability to distinguish between mild and severe pre-eclampsia (AUROC 0.78 compared with 0.68).

Strengths and limitations

The study included a small number of people, and the primary outcomes were measured using a GlyFn plate assay, not the commercially available Lumella test. The Lumella test was compared with the plate assay using a small subset of samples, but it is not clear from the study how many this was. There were 13 people who were unable to be assessed for sFlt‑1 because of the large serum sample needed. The PlGF assay was only done in 57 people because of inadequate serum sample. The study was funded by the company and some of the authors are employees or shareholders of the company, or consultants for the company.

Huhn et al. (2020)

Intervention and comparators

GlyFn immunoassay compared with other biomarkers for pre-eclampsia (including PAPPA2, PlGF, and sFlt-1). The diagnostic accuracy of the GlyFn immunoassay was also compared with that of the point-of-care GlyFn test (Lumella).

Key outcomes

Serum samples were collected from women between 20 and 37 weeks of pregnancy. There were 32 out of 151 women (21%) who developed a clinical diagnosis of pre-eclampsia within 4 weeks. All biomarkers exhibited good classification performance (GlyFn AUROC 0.94, 91% sensitivity, 86% specificity; PAPPA2 AUROC 0.92, 87% sensitivity, 77% specificity; PlGF AUROC 0.90, 81% sensitivity, 83% specificity; sFlt-1 AUROC 0.92, 84% sensitivity, 91% specificity). The GlyFn immunoassay and the rapid point-of-care test showed a correlation of r=0.966.

Strengths and limitations

The study's primary outcomes were measured using the GlyFn plate immunoassay and not the point-of-care Lumella test. The Lumella test was compared with the GlyFn immunoassay only in a small subset of randomly selected samples (25 control and 25 cases). The study was not able to test the diagnostic accuracy of the biomarkers in pre-existing proteinuria without hypertension. The diagnostic performance of the biomarkers in late-onset pre-eclampsia was not evaluated by the study. The study used simplified cut-off values for the biomarkers that may need validating in different populations before being integrated into clinical practice. The study was partly supported by the company.

Sustainability

The company states that compared with standard care the Lumella test has a lower environmental impact. It states that adopting the test may help to reduce the need for people to travel if the test is done locally by midwives. The company also states that the test reader uses less energy than the instruments needed to process standard care tests. There is no published evidence to support these sustainability claims.

Recent and ongoing studies

Glycosylated fibronectin test in first trimester to predict chances of preeclampsia. Trial identifier: CTRI/2021/04/033066. Status: not yet recruiting (last modified on 20 April 2021). Indication: unspecified pre-eclampsia. Device: Lumella. Date: trial was registered on 23 April 2021 with planned date of first enrolment of 30 April 2021. Country: India.

The company also states that a retrospective study of 6,546 people is planned at the Prince of Wales hospital in Hong Kong to evaluate the effectiveness of Lumella as a first trimester screening test for pre-eclampsia. The samples for this study are from the ASPIRE trial (Rolnik et al. 2017), which was a multicentre randomised trial of women screened for pre-eclampsia at 11 to 13 weeks of pregnancy.