Guidance

3 Evidence

3 Evidence

Summary of clinical evidence

3.1

The evidence for Neuropad assessed by the external assessment centre (EAC) comprised 18 studies, of which 13 were full text articles and 5 were abstracts. Of the 18 studies, 17 investigated the diagnostic accuracy of Neuropad against a reference standard and 1 reported its ability to predict the risk of diabetic foot ulceration. In addition to examining diagnostic accuracy, 1 study looked at the reproducibility of results when using Neuropad and 3 assessed the association between Neuropad testing and developing foot ulcers. The most common reference standard used was the neuropathy disability score. All the studies were prospective observational, cross-sectional or longitudinal cohort studies. For full details of the clinical evidence, see section 3 of the assessment report.

EAC's analysis of the clinical evidence

3.2

The EAC considered that the 2 published UK studies (Ponirakis et al. 2014 and Quattrini et al. 2008) were fully relevant to the scope. The EAC also did a meta-analysis of 5 diagnostic accuracy studies that used a neuropathy disability score of 5 or more as the reference standard: Freitas et al. 2009, Kamenov et al. 2010, Liatis et al. 2007, Manes et al. 2016 and Tentolouris et al. 2008.

3.3

The EAC used its meta-analysis results comparing Neuropad with a neuropathy disability score of 5 or more with the results obtained for 10 g monofilament. It concluded that Neuropad may be more sensitive than 10 g monofilament testing in detecting diabetic peripheral neuropathy (DPN) but has lower specificity. In addition, the EAC noted that the current care pathway includes interventions that are triggered only by clinically apparent DPN, which would be regarded as moderate or advanced, so the benefit of detecting preclinical DPN in the current care pathway is uncertain.

2021 guidance review: summary of clinical evidence

New evidence was not robust to support the use of Neuropad as an alternative to monofilament

3.4

The EAC reviewed evidence published since April 2017. There were 8 publications, including 7 comparative clinical studies, on Neuropad. None of the studies used a single comparator, with all using multiple tests to diagnose diabetic peripheral neuropathy, which indicates variation in the care pathway. The EAC found that the new evidence was heterogeneous and did not help to clarify Neuropad's position in the care pathway. The most common comparators (reference tests) were in line with the final scope (for details see the review report – August 2022). Four studies reported the diagnostic accuracy of using Neuropad to diagnose diabetic peripheral neuropathy compared with standard care (10 g monofilament alone). Neuropad's sensitivity ranged between 24.3% (Gomez-Banoy et al. 2017, n=93) and 95% (Zografou et al. 2020, n=174) with a specificity ranging between 29% (Lorenzini et al. 2020, n=42) and 94.2% (Gomez-Banoy et al. 2017, n=93). It is unclear to the EAC why the sensitivity and specificity reported by Gomez-Banoy et al. (2017) were outliers to the other 3 studies. The EAC concluded that the new evidence was not sufficiently robust to support the use of Neuropad in people who would currently undergo testing with monofilament. This is because the evidence reported a wide variation in sensitivity and specificity for Neuropad, compared with monofilament. [2021]

None of the new evidence showed particular benefits of Neuropad for specific population groups, including people in care homes

3.5

The EAC reported that Zografou et al. (2020) claimed Neuropad was a useful screening tool for diagnosing diabetic peripheral neuropathy in terms of time saving and objectivity during clinical examination and educational benefit for the patient. However, none of the new evidence explicitly measured and compared the time taken with Neuropad against a comparator. And none of the new evidence demonstrated particular benefits for specific patient groups, including people in care homes. [2021]

Summary of economic evidence

3.6

Neither the company nor the EAC identified any relevant published economic evidence. The company submitted a Markov model with 2 comparisons: Neuropad testing compared with 10 g monofilament testing, and Neuropad testing compared with Neuropad testing then 10 g monofilament testing. The time horizon of the model was 3 years. The EAC made a number of changes, including: adding the implications of false-negative and false‑positive results; adding a death state; extending the time horizon to 10 years; and adding a third comparison of Neuropad testing with no testing. For full details of the economic evidence, see section 4 of the assessment report.

EAC's analysis of the economic evidence

3.7

The EAC disagreed with a number of the sources used to generate parameter values in the company's model. It also noted discrepancies between the values used in the model and those quoted in the referenced sources. Moreover, the EAC considered that the cost of 10 g monofilament testing in the model had been overestimated, because it included the cost of the reusable holder. For full details of the EAC's changes to the company's economic model, see sections 4.2 and 4.3 of the assessment report.

3.8

Results from the EAC's revised model showed that Neuropad testing incurs additional cost over a 10‑year time horizon compared with all other comparators:

  • £775 per patient compared with 10 g monofilament testing

  • £1,075 per patient compared with Neuropad testing then 10 g monofilament testing

  • £1,792 per patient compared with no testing.

    The EAC did sensitivity analyses which showed that Neuropad testing alone was not cost saving in any considered scenario.

2021 guidance review: summary of economic evidence

The new evidence did not address the issues in the original cost model

3.9

An economic study was published after the original guidance was published (Rodriguez-Sanchez et al. 2020). The EAC reviewed it and noted that it was a cost-effectiveness analysis. The EAC did not consider that the study fully addressed the issues outlined by the original EAC (King's College Technology Evaluation Centre [KiTEC]; for details see the review report – August 2022). It concluded that the results of Rodriguez-Sanchez et al. (2020) were consistent with the findings presented in the original assessment report, and the economic case remains unchanged. [2021]