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. 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 over 1,000 people taking direct oral anticoagulants.
The evidence base comprises 1 multicentre, prospective observational study published as a full text article, a single-centre, prospective, observational study and a case report of 1 patient (both published as conference abstracts).
A review was identified that described the functionality of the DOAC Dipstick, the testing procedure and the available evidence for the test (Harenberg et al. 2019). An abstract was also identified that described the design of an ongoing prospective, single cohort study in people with atrial fibrillation or history of venous thromboembolism on DOAC therapy who need treatment interruption (Tafur et al. 2019). These have not been reviewed further in this briefing.
The clinical evidence and its strengths and limitations is summarised in the overall assessment of the evidence.
Overall assessment of the evidence
The available evidence for the DOAC Dipstick is relatively limited in terms of quality and quantity. Two of the 3 studies included in this briefing were presented in abstract form with limited information, which made thorough critical appraisal difficult (Jilma et al. 2019 and Harenberg et al. 2017). Results from Harenberg et al. (2020), a multicentre observational study, suggest that the sensitivity and specificity of the technology in detecting DOACs in urine is non-inferior to that of liquid chromatography-tandem mass spectrometry (LC-MS/MS) for factor Xa inhibitors and superior to that of LC-MS/MS for thrombin inhibitors.
Most of the studies were done in Germany and there was no evidence from the UK, which may limit generalisability to the NHS. The managing director and founder of the DOAC Dipstick test was an author for all the studies. There were no independent studies identified using the technology. There is currently no evidence assessing the effect of the test on resource use and clinical outcomes for patients.
Harenberg et al. (2020)
Key outcomes
Of the 914 people in the study, 880 people were included in the per-protocol analysis (451 in the direct oral factor Xa inhibitor group and 429 in the direct oral thrombin inhibitor group). The sensitivity, specificity, accuracy, and predictive values were non-inferior to that of LC-MS/MS for detecting factor Xa inhibitors (at least 95% with a 0.5% margin, p<0.04) and superior to that of LC-MS/MS for detecting thrombin inhibitor (significant at a proportion of 97.5%; p<0.001). The agreement (kappa value) between results of the dipstick test and LC-MS/MS were 0.945 for detecting factor Xa inhibitors and 0.987 for detecting thrombin inhibitor. Receiver operating curves showed c‑values of 0.989 for factor Xa inhibitor detection and 0.995 for thrombin inhibitor detection (a c‑value of 1 indicates a 'perfect' test result). The intention-to-analyse analysis confirmed the results of the per-protocol analysis. Visual evaluation of the factor Xa and thrombin inhibitor pads were not different between centres.
Strengths and limitations
The study author is the managing director and founder of the DOAC Dipstick. The time since the bladder was previously emptied was not considered or standardised in the study. The thrombin pad served as a negative control for the factor Xa inhibitor test and vice versa. The study did not involve people not taking direct oral anticoagulants. The design of this study was previously described in an abstract by Harenberg et al. (2019).
Jilma et al. (2019)
Key outcomes
The patient, who was included in an ongoing cohort study, was taking rivaroxaban 20 mg once daily and was also diagnosed with acute pre-renal kidney injury (plasma creatinine 5 mg/dl, blood urea nitrogen 130 mg/dl). The DOAC Dipstick results were interpreted to be negative for the presence of rivaroxaban and normal for levels of creatinine in the urine. The control test pad (which is designed to detect abnormal urine colour) turned yellow, indicating that the person had dark-coloured urine. The case report highlights the effect of dark-coloured urine on the DOAC Dipstick results.
Strengths and limitations
This was a single person case report, which is regarded as relatively low-grade level of evidence. The results were presented in abstract form with limited information, which made thorough critical appraisal difficult. The case report was from a person treated in Austria, which may limit generalisability to the NHS. One of the authors is the managing director and founder of the DOAC Dipstick.
Harenberg et al. (2017)
Intervention and comparator
The DOAC Dipstick test compared with liquid chromatography-tandem mass spectrometry.
Key outcomes
The authors stated that the reliability (kappa index) and validity of the test were 100% (95% confidence intervals 74% to 100%) for detecting apixaban, rivaroxaban or dabigatran. The ranges of results analysed by ImageJ software did not overlap for negative or positive results on the point-of-care test pads for either DOAC type. Validity was calculated using concentrations of DOACs measured with LC-MS/MS. Concentrations were below 10 ng/ml in control samples, 202 ng/ml to 6.667 ng/ml in samples from people taking apixaban, 169 ng/ml to 9.579 ng/ml in samples from people taking rivaroxaban and 1.057 ng/ml to 15.996 ng/ml in samples from people taking dabigatran.
Strengths and limitations
Results suggest that the point-of-care test could offer a rapid, reliable and valid detection of DOACs. Results were presented in abstract form and are also described in Harenberg et al. (2019). There was limited information on the demographics of the people involved and possible confounding factors. Two independent observers visually assessed the coloured test pads using a CMYK scale. The test strips were also photographed in a lightbox and colours analysed by the ImageJ software program.
Sustainability
The technology's external packaging and dipstick container are made from recyclable materials. The dipstick container is made from polypropylene and is free from bisphenol A. The company claims that adopting the DOAC Dipstick point-of-care test may help reduce the environmental impact by decreasing the number of laboratory tests needed. There is no published evidence to support this claim.
Recent and ongoing studies
No ongoing or in-development trials were identified by NICE when searching key clinical trial registries. The company stated that there are a total of 5 ongoing studies evaluating the DOAC Dipstick. These are being done in Germany, France, Austria, the US and Croatia. They include people having major orthopaedic surgery, outpatients with venous thromboembolism and people admitted to emergency departments.