Neuropad for detecting preclinical diabetic peripheral neuropathy

The evidence for the accuracy of Neuropad in diagnosing preclinical diabetic peripheral neuropathy (DPN) comprises longitudinal observational studies that mainly compared testing in terms of neuropathy scoring systems (most commonly the neuropathy disability score). The committee was aware that the external assessment centre (EAC) had rejected the study by Tsapas et al. (2014; a meta-analysis identified by the company) because of overlapping populations in the studies included and differences in the reference standards used, and had, instead, done its own meta-analysis. The results from the EAC's meta‑analysis showed that Neuropad has a sensitivity of 89.4% (95% confidence interval [CI] 83.2 to 93.5) and a specificity of 60.3% (95% CI 50.9 to 69.0), when using a neuropathy disability score of 5 or more as a reference standard for the diagnosis of DPN. Based on this, the committee concluded that Neuropad demonstrates good sensitivity but poor specificity as a diagnostic test for DPN. Although no direct comparative data were available for 10 g monofilament, the committee and EAC agreed that it was appropriate to use the sensitivity (84%) and specificity (83%) estimates for 10 g monofilament that were used in NICE's medical technologies guidance on VibraTip. The committee concluded, therefore, that the current evidence for Neuropad is insufficient to support its effectiveness as an alternative test to 10 g monofilament for detecting DPN.

The clinical experts advised the committee that patients with diabetes are offered foot checks every year, during which physical examination, 10 g monofilament testing and vibration testing are used to test for DPN and therefore the clinical risk of future complications. The clinical experts explained that patients who test positive for DPN at these foot checks (and who are therefore at moderate or high risk of foot complications) are referred to community podiatrists for ongoing foot care.

The clinical experts explained that Neuropad tests different nerve fibres and functions to a 10 g monofilament test: Neuropad tests sudomotor dysfunction, which is a feature of small fibre, preclinical DPN, whereas 10 g monofilaments are used to test for the loss of fine touch, which is a distinctive symptom of clinically apparent DPN. They explained that because it is uncertain how well autonomic testing (such as testing for sudomotor dysfunction) predicts progressive neuropathy or the development of complications, it is not included in current DPN scoring systems. This means that it would be difficult to understand, on the basis of current evidence, how Neuropad testing may affect diabetic foot risk assessment and referral practice. Specifically, the clinical experts advised that a positive Neuropad test alone would currently not lead to a change in management, because it would not alter the definition of risk status in a patient with diabetes. A patient diagnosed with preclinical DPN using Neuropad testing could be offered more attentive foot care, but it is unclear to what extent this would lead to beneficial clinical consequences.

The clinical experts explained that Neuropad has particular promise for patients who have difficulty in engaging with testing for DPN. Monofilament testing requires the patient to confirm when they feel a fine touch on their foot or toes, but for some people with cognitive impairment or communication difficulties, this may not be possible. The clinical experts estimated that between 5% and 10% of all patients with diabetes may have difficulty engaging with 10 g monofilament testing for these reasons. The committee acknowledged that because Neuropad testing does not need patient feedback, it may be of particular value for patients with cognitive impairment or communication difficulties if future evidence supports its case for adoption in the NHS.

The committee also heard that some patients, such as older and frailer people, may not be able to easily access foot clinics. The clinical experts explained that type 2 diabetes, which accounts for 90% of all diabetes, is much more common in older people. Many of these patients do not always attend their yearly foot checks and so do not have the benefit of foot care programmes. The clinical experts also explained that DPN progression may be prevented if it is detected early and appropriate treatment is started. Consequently, limited access to regular testing may increase the risks of progressive DPN and its clinical complications in a vulnerable patient group. The committee acknowledged that a test such as Neuropad, which can be done easily in the community, may be of particular value to people with limited access to foot clinics but concluded that this has not been tested in clinical studies and cannot be inferred from the evidence available.

The clinical experts stated that Neuropad might be considered as part of a community-delivered DPN detection and management service. However, they acknowledged that for this to be successful, changes would be needed to other important parts of the community package of care for people with diabetes. Having heard from the experts about the existing deficiencies in DPN detection and foot care services in the UK, the committee concluded that addressing these deficiencies in the current pathway would be needed before any potential benefits associated with detecting preclinical DPN could be realised.

The committee considered the importance of foot preparation before Neuropad testing in order to ensure a reliable result. It heard from the clinical experts that the foot needs to be completely dry and that the test strip should not be placed on calluses or dry skin for the result to be meaningful. It concluded that, were Neuropad introduced into the community, clear guidance on its use would be needed to avoid misleading results.

The committee noted the differences between the company's and EAC's revised cost models and their base-case estimates. It agreed with the EAC's changes and concluded that the revised model most accurately represented the cost consequences of adopting Neuropad.

The committee noted that Neuropad's low diagnostic specificity (based on the evidence presented and current diagnostic criteria) means that its use alone would increase the rate of false-positive results for DPN. Because of the current uncertainty about whether patients with diagnosed preclinical DPN would benefit from referral to a foot care service, the committee concluded that a positive result with Neuropad would probably lead to further 10 g monofilament testing. The committee understood that the results of this dual-testing strategy in the EAC model should be treated with caution, because it assumed that the 2 tests are done completely independently (that is, the sensitivity and specificity of the 10 g monofilament test are not affected by the results of the Neuropad test). The committee was also aware there is no evidence to support the merits of such a dual-testing approach. It concluded that the cost modelling for Neuropad is uncertain, but that it is most likely that Neuropad testing alone would be cost incurring compared with conventional testing with a 10 g monofilament.

In its assessment report, the EAC identified a number of possible priorities for future research on the comparative effectiveness of Neuropad and 10 g monofilament testing, and on the effectiveness of foot care programmes. The clinical experts also highlighted areas for future research that could be considered. They proposed a multicentre, longitudinal study with at least 5 years' follow up, comparing point-of-care testing strategies (including Neuropad) in predicting future diabetic complications, including DPN, using a reference standard (such as the neuropathy disability score). The experts also proposed a community-based study to explore the benefits of using Neuropad to detect preclinical DPN in populations that include vulnerable people, in whom 10 g monofilament testing is not possible. Such a study could also define the benefits to people with diabetes of improved access to DPN diagnostic and treatment services.

The committee considered that research into the wider benefits of detecting preclinical DPN and how to address the deficiencies in the current care pathway would be valuable but acknowledged that these are issues beyond the scope of this assessment. Such research would also help to clarify Neuropad's effectiveness in detecting preclinical DPN.