In total, 26 randomised controlled trials met the inclusion criteria and were included in this assessment. The CoaguChek system was used in 22 of the 26 trials and it was unclear which model of the system was used in 6 of these trials. In 2 of the remaining 4 trials either the CoaguChek S system or the INRatio monitor were used for INR measurement (results were not reported according to the type of point-of-care monitor, and the model of the INRatio monitor used in the trials was not reported). No trials that exclusively assessed the clinical effectiveness of INRatio were identified. The ProTime microcoagulation system was used in the other 2 trials. In all 6 trials based in the UK, the CoaguChek system (either CoaguChek or version ‘S’) was used for the INR measurement. The prothrombin time (PT) test is a general coagulation test to monitor Vitamin K Antagonist therapy.

Relative treatment effects were estimated and applied separately for self-testing and self-management. Atrial fibrillation is the most common heart arrhythmia and affects around 800,000 people in the UK. It can affect adults of any age but it is more common in older people; 0.5% of people aged 50–59 years and around 8% of people aged over 65 years are estimated to be affected. Atrial fibrillation is also more common in men than women, and is more common in people with other conditions, such as high blood pressure, atherosclerosis and heart valve problems. Wan, Y., Heneghan, C., Perera, R., Roberts, N., Hollowell, J., et al. (2008). Anticoagulation control and prediction of adverse events in patients with atrial fibrillation: a systematic review. Circ Cardiovasc Qual Outcomes 1, 84–91 The Committee considered the similarities between self-monitoring coagulation status and self-managing diabetes. The Committee heard from a patient expert that some patients are used to self-testing for conditions such as diabetes, hypertension and heart conditions. The Committee also heard from a clinical specialist that although there were similarities between self-testing for different conditions, there were intrinsic differences between self-testing for diabetes and coagulation. Vitamin K antagonists are more sensitive to diet and exercise, and act over a longer period of time than insulin. Therefore, the dose response for vitamin K antagonists is less predictable than for insulin and the risk of adverse events is perceived to be higher. The clinical specialist also reported that some patients were successfully self-monitoring their coagulation status but not all people receiving vitamin K antagonist therapy will be able to self-monitor and some may not wish to. The Committee noted that some groups of patients who may have difficulty with self-monitoring, such as children or those with a disability, may be able to self-test or self-manage with the help of a carer. The Committee concluded that there are different considerations for self-monitoring of coagulation status to those made for self-testing for diabetes, and that the decision for a patient to self-monitor should be made after a thorough discussion and subsequent agreement between the patient and the healthcare professional.

exclusive self-testing or self-management compared with standard monitoring in primary and secondary care New oral anticoagulants are an alternative to vitamin K antagonists and can be administered to reduce the risk of thrombosis or stroke. The new oral anticoagulants have fewer food and drug interactions than vitamin K antagonists and they do not involve therapeutic monitoring. However, they may be unsuitable for some people such as people with mechanical heart valves, people with renal or liver dysfunction and those taking concurrent drugs that cannot be taken with the new oral anticoagulants. NICE technology appraisal guidance recommends the use of 3 new oral anticoagulants: apixaban, rivaroxaban and dabigatran etexilate, for preventing stroke and systemic embolism in people with non-valvular atrial fibrillation. The comparator used in this assessment is INR testing in primary or secondary care using laboratory analysers or point-of-care tests. 5 Outcomes Approximately 47% of people with atrial fibrillation currently receive vitamin K antagonist therapy. It is estimated that a further 30% of people with atrial fibrillation could receive this therapy but currently do not. People with atrial fibrillation are at a 5–6 times greater risk of stroke, with 12,500 strokes directly attributable to atrial fibrillation occurring every year in the UK. Treatment with warfarin reduces this risk by 50–70%. Heart valve disease Data from the UK heart valve registry indicate that approximately 0.2% of the UK population has prosthetic heart valves. Around 6500 adult heart valve replacements (using mechanical or biological valves) are carried out each year, of which around 5000 are aortic valve replacements.

The results indicated that over a 10-year period, introducing self-monitoring would reduce the proportion of people experiencing a thromboembolic event by 2.5%, whilst slightly increasing the proportion having a major haemorrhagic event by 1.4%.

Heneghan, C., Ward, A., Perera, R., Bankhead, C., Fuller, A., et al. (2012). Self-monitoring of oral anticoagulation: systematic review and meta-analysis of individual patient data. Lancet 379, 322–334 Apixaban for preventing stroke and systemic embolism in people with nonvalvular atrial fibrillation. NICE technology appraisal guidance 275 (2013). April 2022, Roche Diagnostics will partner with Williams Medical We’re pleased to announce that from 4th April 2022, Williams Medical and Roche Diagnostics will be joining forces The test strip comprises 2 layers of transparent plastic laminated to each other that contain 1 sample well, 3 clot cells, and narrow channels connecting the sample well and the clot cells. The top side of the bottom layer is printed with 3 pairs of silver electrodes (1 pair per cell) that start from inside the clot cells to the end of the strip where they are connected to the monitor main circuitry. One trial reported more than 98% adherence with self-testing and of those who did not adhere, 2 had difficulties doing the test or experienced disruption caused by hospitalisation, and 1 lost the CoaguChek meter. In another trial 75% (30/40) of participants did not report any problems with using the device and expressed willingness to continue with self-monitoring. The remaining participants who did not adhere to the testing procedure (25%) reported difficulties with the technique or problems placing the fingertip blood drop on the right position on the test strip. This resulted in the need to use multiple strips to achieve a single reading. Evidence on clinical outcomes Bleeding

Patients who spend a high proportion of time (> 70%) in the therapeutic range achieve better clinical outcomes.2,3 Studies show that this can be achieved through self-testing using CoaguChek technology. 1,4 Bussey, H.I., Bussey M., Bussey-Smith K.L., Frei, C.R. (2013). Evaluation of warfarin management with international normalized ratio self-testing and online remote monitoring and management plus low-dose vitamin k with genomic considerations: a pilot study. Pharmacotherapy 33, 1136–1146 Patients who self-test are more engaged in their own care, test more often and spend more time in therapeutic range. 4,5 One trial reported the time for each INR monitoring (that is, time from INR measurement to test results) and the total time spent for anticoagulant management during the 4-month follow-up period. The time spent for each INR measurement by self-managed participants was statistically significantly lower (mean 5.3 minutes, standard deviation [SD] 2.6 minutes) compared with the time spent by participants receiving standard care (mean 158 minutes, SD 67.8 minutes, p<0.001). During the 4-month follow-up, the total time spent for anticoagulation monitoring by participants in standard care was statistically significantly higher (mean 614.9 minutes, SD 308.8 minutes) than the total time spent by participants who self-managed their therapy (mean 99.6 minutes, SD 46.1 minutes, p<0.0001). Patient compliance with testing The Committee considered the clinical evidence on the use of point-of-care coagulometers in people with atrial fibrillation or artificial heart valves. The Committee noted that 26 randomised controlled trials compared the use of point-of-care coagulometers for self-monitoring with standard anticoagulation control. The Committee noted that self-monitoring nearly halved the risk of thromboembolic events and substantially reduced the risk of mortality in people with artificial heart valves compared with standard monitoring. However, the Committee also noted that self-monitoring did not result in a significant reduction in the number of major and minor bleeding events compared with standard monitoring. The Committee discussed the heterogeneity in the trials and the applicability of the pooled results from the meta-analysis of the trial data to the UK population. It noted that the meta-analysis results showed low statistical heterogeneity and concluded that self-monitoring offered clinical benefit because it was likely to result in a significant reduction in thromboembolic events. The Committee concluded that the pooled effect estimates from the meta-analysis were likely to be applicable to the UK because there are no confounding biological differences between people receiving vitamin K antagonist therapy in the UK and those in other countries.Eighteen trials reported INR time in therapeutic range (TTR) although there was variation in the measures used for reporting TTR so pooling the data was not appropriate. TTR ranged from 52% to 80% for self-monitoring and from 55% to 77% for standard care. In 15 of the 18 trials TTR was higher in self-monitoring participants compared with those in standard care and, in 5 of these trials, the difference between intervention groups was statistically significant. Three of the UK-based trials reported no statistically significant differences between self-monitoring and standard care.

After consultation, the Committee will meet again to consider the evidence, this document and comments from the consultation. After considering these comments, the Committee will prepare its final recommendations, which will be the basis for NICE’s guidance on the use of the technology in the NHS in England. Heneghan, C., Alonso-Coello, P., Garcia-Alamino, J.M., Perera, R., Meats, E., Glasziou, P. (2006). Self-monitoring of oral anticoagulation: a systematic review and meta-analysis. Lancet 367, 404–411 Vice Chair, Diagnostics Advisory Committee and Consultant in Public Health Medicine, PHG Foundation, Cambridge and UK Genetic Testing Network

Brand

The Committee considered the benefits for patients receiving vitamin K antagonist therapy of using point-of-care coagulometers. It heard from a patient expert on the Committee that self-monitoring is important to psychological wellbeing because it provides a sense of control for the patient and removes the need to frequently attend clinics or hospitals, which serve as a constant reminder of their condition. The Committee also heard that self-monitoring allows people to travel to visit, or act as a carer for, other family members, without having to worry about attending testing appointments or if testing facilities are available in other countries. The Committee also heard that the current variation in access to self-testing strips on prescription for self-monitoring was of concern to patients because it restricted their freedom to move GP practice or move house to a different area in case the testing strips would no longer be prescribed. The Committee concluded that the benefits of self-monitoring for patients were not fully captured in the cost-effectiveness analyses. Initially, the electrode impedance is infinite but drops to a minimum value when the blood sample fills the clot cells. The time when this initial minimum impedance is achieved is registered by the monitor as the start of the coagulation. As the reaction progresses, the sample impedance increases to a maximum and then gradually drops as the clotting proceeds. The elapsed time, in seconds, from the start until the clotting end point is reached is the prothrombin time. The monitor software calculates the INR of the sample using prothrombin time and calibration coefficients. The evidence on the clinical effectiveness of the coagulometers for monitoring coagulation status was summarised by the External Assessment Group in 3 categories: intermediate outcomes, clinical outcomes, and patient-reported outcomes. Evidence on intermediate outcomes Time and values in therapeutic range The systematic review identified 12 relevant economic evaluations. All of these evaluations compared INR self-monitoring strategies with standard care and were assessed against the NICE reference case by the External Assessment Group. The results of the studies included in the systematic review varied widely and showed that the cost effectiveness of self-monitoring was dependent on a number of key factors. The baseline utility value for people with atrial fibrillation or mechanical heart valve who were stable was taken as the baseline EQ-5D value from trial data, 0.738. This value was applied to 65–70 year old people and adjusted by the External Assessment Group to estimate age-specific baseline utilities in the model.