Atrial fibrillation and heart valve disease: self-monitoring coagulation status using point-of-care coagulometers (the CoaguChek XS system)

Evidence-based recommendations on the CoaguChek XS system for self-monitoring coagulation status in adults and children. The recommendations originally included the InRatio2 PT/INR, but this was withdrawn from the market in October 2016 and is not currently available.

# Recommendations
The CoaguChek XS system is recommended for selfmonitoring coagulation status in adults and children on longterm vitamin K antagonist therapy who have atrial fibrillation or heart valve disease if:
the person prefers this form of testing and
the person or their carer is both physically and cognitively able to selfmonitor effectively.
This recommendation has been removed because the InRatio2 PT/INR monitor is no longer available.
Patients and carers should be trained in the effective use of the CoaguChek XS system and clinicians involved in their care should regularly review their ability to selfmonitor.
Equipment for selfmonitoring should be regularly checked using reliable quality control procedures, and by testing patients' equipment against a healthcare professional's coagulometer which is checked in line with an external quality assurance scheme. Ensure accurate patient records are kept and shared appropriately.
For people who may have difficulty with or who are unable to selfmonitor, such as children or people with disabilities, their carers should be considered to help with selfmonitoring.# The technologies
Three CEmarked pointofcare coagulometers for selfmonitoring coagulation status were identified during scoping as being relevant to this assessment. One of these coagulometers, the ProTime microcoagulation system, was included in the assessment but has been removed from this guidance because it is no longer available to the NHS and its successor model is not intended for patient selfmonitoring. Additional details of the coagulometers included in the guidance are provided in section 4.# Clinical need and practice

# The problem addressed
The pointofcare coagulometers are designed to monitor the clotting tendency of blood in people on longterm vitamin K antagonist therapy, such as those with atrial fibrillation or artificial heart valves who are at risk of thrombosis. The tests allow monitoring by 2 different methods of care: selftesting and selfmanaging. Both methods are based on the international normalised ratio (INR), which is a standardised unit for measuring the time it takes for blood to clot. Selftesting refers to the user doing the INR test themselves and then contacting their healthcare professional with the reading for advice on any change to the dosage of the anticoagulant that may be needed. Selfmanaging refers to the user doing the INR test themselves and then selfadjusting the dosage of their anticoagulant medication by following an agreed care protocol. Together, these methods of care are referred to as selfmonitoring.
The use of these coagulometers may reduce the frequency of visits to hospital or clinics for patients and enable them to be monitored more regularly. This may improve health outcomes by enabling the dose of therapy to be adjusted more accurately, thereby avoiding adverse events that can result from an over or underdose of longterm vitamin K antagonist therapy, such as stroke and major haemorrhage.
The purpose of this assessment is to evaluate the clinical and cost effectiveness of using the CoaguChek XS system and the INRatio2 PT/INR monitor for selfmonitoring (selftesting or selfmanaging) coagulation status in people on longterm vitamin K antagonist therapy who have atrial fibrillation or heart valve disease.

# The condition
There are a number of conditions that can result in people having an increased risk of thrombosis and consequently, receiving longterm vitamin K antagonist therapy. These conditions include atrial fibrillation and heart valve disease. Guidance on selfmonitoring the coagulation status of people who have had a venous thromboembolism and are receiving longterm vitamin K antagonist therapy is included in the NICE guideline on venous thromboembolic diseases and so this population is not included in the scope of this diagnostics assessment of selfmonitoring coagulometers.

## Atrial fibrillation
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 5059 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.
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 56 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 5070%.

## Heart valve disease
Valve disease can affect blood flow through the heart in 2 ways: valve stenosis, in which the valve does not open fully, and valve regurgitation (or incompetence) in which the valve does not close properly, allowing blood to leak backwards. Disease can occur in any of the 4 heart valves, although disorders of the aortic and mitral valves are more serious.
The main causes of heart valve disease are congenital heart disease and other diseases such as rheumatic fever, lupus, cardiomyopathy and endocarditis. Aortic stenosis is the most common type of valve disease and it affects around 1 in 20 adults over the age of 65 years in the UK.
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.
Patients with mechanical heart valves (and some patients with bioprosthetic valves) are susceptible to thromboembolism and need lifelong anticoagulant therapy.

# The diagnostic and care pathways
Nonvitamin K antagonist oral anticoagulants are an alternative to vitamin K antagonists and can be administered to reduce the risk of thrombosis or stroke. The nonvitamin K antagonist oral anticoagulants have fewer food and drug interactions than vitamin K antagonists and they do not need therapeutic monitoring. However, they may be unsuitable for some people, such as people with mechanical heart valves, certain people with renal or liver dysfunction and those taking concurrent drugs that cannot be taken with the nonvitamin K antagonist oral anticoagulants. The individual summary of product characteristics should be consulted for specific details when prescribing a nonvitamin K antagonist oral anticoagulant. NICE technology appraisal guidance recommends 3 nonvitamin K antagonist oral anticoagulants (see the NICE guidance on apixaban, rivaroxaban and dabigatran etexilate) for preventing stroke and systemic embolism in people with nonvalvular atrial fibrillation.
Guidelines on oral anticoagulation with warfarin, published by the British Committee for Standards in Haematology (Keeling et al. 2011), outline the process for INR monitoring for those receiving warfarin. The NICE clinical knowledge summary for oral anticoagulation states that INR can be most accurately measured in venous blood samples, but that capillary blood samples are also used because they are more convenient. People being tested should receive a written copy of their INR result including any necessary dose adjustments and a date for the next check.
The summary states that the INR should be measured:
daily, or on alternate days, until it is within the therapeutic range (usually between 2.0 and 3.0, ideally 2.5) on 2 consecutive occasions
then twice weekly for 12 weeks, followed by weekly measurements until the INR is stable within the therapeutic range
thereafter, depending on the stability of the INR, at longer intervals (for example, up to every 12 weeks, if agreed locally).
More frequent monitoring of the INR is recommended for patients at risk of overcoagulation or bleeding, or those having problems adhering to treatment. Intravenous drug users, and people with hepatitis B, hepatitis C, or HIV, may be referred to a specialist clinic according to local arrangements.
INR monitoring can be managed by local anticoagulant clinics in primary care, but sometimes clinics are based in secondary care, involving travel to hospital. The NICE anticoagulation commissioning guide (2013) states that anticoagulation therapy services can be delivered in a number of different ways, and that mixed models of provision may be needed across a local health region. This could include full service provision in secondary or primary care, shared provision, domiciliary provision and selfmanagement. Services may be managed by a range of healthcare professionals including nurses, pharmacists and general practitioners.# The diagnostic tests

# The interventions

## The CoaguChek XS system
The CoaguChek XS system (Roche Diagnostics) comprises a meter and specifically designed test strips that can analyse a blood sample (fresh capillary blood or fresh untreated whole venous blood) and calculate the prothrombin time and the international normalised ratio (INR). These measures indicate the rate at which the blood clots. If the INR is too low, there is a higher risk of blood clots that can lead to a heart attack or a stroke. If the INR is too high, there is a higher risk of bleeding, which in severe cases can be gastrointestinal or intracerebral bleeding.
A code chip, which contains calibration data and the expiry date of the test strips, is inserted into the meter before it is switched on. Once the device is switched on, a test strip is inserted and the blood sample is applied. The test result is displayed approximately 1 minute after applying the sample and the monitor automatically stores the result in its memory. The user is guided through the process by onscreen graphical instructions.
The CoaguChek XS test strip contains a lyophilised reagent consisting of thromboplastin and a peptide substrate. When a blood sample is applied, thromboplastin activates coagulation, which leads to the formation of thrombin. The enzyme thrombin cleaves the peptide substrate, generating an electrochemical signal. Depending on the time elapsed before it first appears, this signal is then converted by means of an algorithm into customary coagulation units and the result is displayed on the screen. This can be displayed as prothrombin time in seconds, Quick value, or INR.
The CoaguChek XS system has a number of inbuilt quality control functions including checks of the electric components when switched on, the test strip temperature during testing, and checks on the test strip batch such as the expiry date and quality of each strip. The CoaguChek XS test strips are packaged as single strips in resealable plastic containers in quantities of 24 and 48 test strips. The strips can be stored at room temperature or refrigerated between 2 and 8C and can be used straight from the fridge. On manufacture, the CoaguChek XS test strips have a shelflife (expiration date) of 18 months.
The CoaguChek XS meter is supplied with 4  AAA batteries, a CoaguChek Softclix finger pricker and 20 Softclix XL lancets, 6 test strips, a user manual and carry case. The system can carry out a minimum of 60 tests per set of batteries. The meter is 138 mm  78 mm  28 mm and weighs 127 g (without batteries).
An earlier model of the CoaguChek XS system is the CoaguChek S system. The CoaguChek XS system is reported to have the following advantages over the CoaguChek S system: the thromboplastin used in the prothrombin time test strips is a human recombinant thromboplastin, which is more sensitive and has a lower international sensitivity index of 1.0 compared with 1.6; test strips have inbuilt quality control that is automatically run with every test; test strips do not have to be refrigerated; a smaller blood sample can be used; and the meter is smaller and lighter. Another model of the CoaguChek XS system is the CoaguChek XS Plus system. The XS Plus model is intended for use by healthcare professionals only and is not indicated for individual INR selfmonitoring.

## The INRatio2 PT/INR monitor
The INRatio2 PT/INR monitor (Alere) does a modified version of the 1stage prothrombin time test using a recombinant human thromboplastin reagent. The clot formed in the reaction is detected by the change in the electrical impedance of the sample during the coagulation process. The system consists of a monitor and disposable test strips.
The monitor provides a user interface, heats the test strip to the appropriate reaction temperature, measures the impedance of blood samples, and calculates and reports prothrombin time and INR results. Instructions and test results are displayed on an LCD. The monitor can store the results so that past test results can be reviewed.
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. Test strips are individually foil wrapped, supplied in quantities of 12 or 48 strips and can be stored at room temperature for up to 12 months or until the expiration date.
The INRatio2 PT/INR monitor analyses fresh capillary blood and when the blood sample is applied to the sample well, it is drawn through the narrow channels by capillary action to the clot cells, where the impedance of the sample is measured by the monitor through the electrodes. Clot cells have reagents applied and the reagents are different for each channel. One channel contains the thromboplastin reagent for the prothrombin time test. The other 2 channels contain reagents that produce a low and high control time, regardless of the clotting time of the sample.
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 INRatio2 PT/INR monitor does a selftest when it is turned on and each test strip has a code that is accepted by the monitor if the strip code is in the correct format. The monitor uses 4  AA batteries or a mains adapter as a power source, and can connect to a printer or computer through the RS232 serial communication port.

# The comparator: INR testing
The comparator used in this assessment is INR testing in primary or secondary care using laboratory analysers or pointofcare tests.# Outcomes
The Diagnostics Advisory Committee (section 8) considered evidence from a number of sources (section 9).

# How outcomes were assessed
The assessment consisted of a systematic review of the evidence on test performance and clinicaleffectiveness data for the CoaguChek XS system, the INRatio2 PT/INR monitor, the ProTime microcoagulation system and comparator tests. The ProTime microcoagulation system was in the assessment but has been removed from this guidance because it is no longer available to the NHS and its successor model is not intended for patient selfmonitoring.

# Clinical effectiveness
The External Assessment Group conducted a systematic review of the evidence on the clinical effectiveness of selfmonitoring coagulation status in people on longterm vitamin K antagonist therapy who have atrial fibrillation or heart valve disease.
Studies were included if they appeared relevant to the outcomes listed in the decision problem:
Intermediate outcomes:
time and values in therapeutic range
international normalised ratio (INR) values
test failure rate
time to test result.
Patient adherence to testing and treatment:
frequency of testing
frequency of visits to primary or secondary care clinics.
Clinical outcomes:
frequency of bleeds or blood clots
morbidity (for example, thromboembolic and cerebrovascular events) and mortality from INR testing and vitamin K antagonist therapy
adverse events from INR testing, false test results, vitamin K antagonist therapy and sequelae.
Patientreported outcomes:
anxiety associated with waiting time for results and not knowing current coagulation status and risk
acceptability of the tests
healthrelated quality of life.
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: 9 trials used the CoaguChek S model, 4 trials used the CoaguChek XS model, 1 trial used the CoaguChek Plus model, and 2 trials used the CoaguChek model. It was unclear which model of the CoaguChek system was used in 6 of the 22 trials. In 2 of the remaining 4 trials either the CoaguChek S system or the INRatio monitor was used for INR measurement (results were not reported according to the type of pointofcare monitor, and the model of the INRatio monitor used in the trials was not reported). No trials that exclusively assessed the clinical effectiveness of the INRatio2 PT/INR monitor 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 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 patientreported outcomes.

## Performance of pointofcare coagulometers
The External Assessment Group did not carry out a formal evaluation of the performance of the CoaguChek system or the INRatio2 PT/INR monitor with regard to INR measurement because it was outside the scope of this assessment. However, an objective 'true' INR remains to be defined and INR determined in the laboratory is regarded as the gold standard to which all other measurement methods should be compared. Information on the precision and accuracy of these pointofcare coagulometers was therefore gathered from the available literature.
A systematic review by Christensen and Larsen published in 2012 assessed the precision and accuracy of currently available pointofcare coagulometers including CoaguChek XS, INRatio and ProTime. The authors found that the precision of CoaguChek XS varied from a coefficient of variation of 1.4% to 5.9% based on data from 14 studies. The precision of INRatio and ProTime varied from 5.4% to 8.4% based on data from 6 studies. The coefficient of correlation for CoaguChek XS varied from 0.81 to 0.98, and that for INRatio varied from 0.73 to 0.95. The review concluded that the precision and accuracy of pointofcare coagulometers were generally acceptable compared with laboratorybased INR testing. The same conclusions were drawn by the Canadian Agency for Drugs and Technologies in Health report published in 2012 on pointofcare testing. Similarly, the international guidelines prepared in 2005 by the International SelfMonitoring Association for Oral Anticoagulation stated that 'Pointofcare instruments have been tested in a number of different clinical settings and their accuracy and precision are considered to be more than adequate for the monitoring of oral anticoagulation therapy in both adults and children'.
Six studies compared the performance of CoaguChek S with that of CoaguChek XS in relation to conventional INR measurement. The studies showed a good agreement between the 2 CoaguChek models and conventional laboratorybased testing results. However, the CoaguChek XS showed more accurate and precise results than CoaguChek S in both adults and children, especially for higher INR values (>3.5).

## Evidence on intermediate outcomes
Eighteen trials (including 4 trials that used the CoaguChek XS system) reported INR time in therapeutic range although there was variation in the measures used for reporting this outcome, so pooling the data was not appropriate. Time in therapeutic range ranged from 52% to 80% for selfmonitoring and from 55% to 77% for standard care. In 15 of the 18 trials, time in therapeutic range was higher in selfmonitoring participants compared with those in standard care and, in 5 of these trials (including 2 trials using the CoaguChek XS system), the difference between intervention groups was statistically significant. Three of the UKbased trials reported no statistically significant differences between selfmonitoring and standard care.
Twelve trials reported INR values in therapeutic range and there was variation in the measures used so pooling the data was not appropriate. In 8 of these trials, the proportion of INR values in therapeutic range ranged from 43.2% to 80.8% for selfmonitoring and from 22.3% to 72.0% for standard care. In 4 trials that reported the proportion of participants in therapeutic range, the values ranged from 53.0% to 72.9% for selfmonitoring and from 43.2% to 72.0% for standard care. Ten of the trials reported higher proportions of INR values in therapeutic range or larger proportions of participants in therapeutic range for selfmonitoring than for standard care.
Among participants with artificial heart valves, selfmonitoring resulted in a statistically significant higher INR time in therapeutic range compared with standard care. In 2 trials that included participants with atrial fibrillation, no time in therapeutic range differences were found between selfmonitoring and standard care.
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 4month followup period. The time spent for each INR measurement by selfmanaged participants was statistically significantly lower (mean 5.3 minutes, standard deviation  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 4month followup, 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 selfmanaged their therapy (mean 99.6 minutes, SD 46.1 minutes, p<0.0001).
One trial reported more than 98% adherence with selftesting 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 selfmonitoring. 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
Twenty one trials reported a total of 1472 major and minor bleeding events involving 8394 participants. 476 major bleeding events were reported in a total of 8202 participants and 13 of these 21 trials reported 994 minor bleeding events in a total of 5425 participants. No statistically significant differences were seen between selfmonitoring participants (selftesting and selfmanagement) and those in standard care for any bleeding events (relative risk  0.95, 95% confidence interval  0.74 to 1.21, p=0.66), major bleeding events (RR 1.02, 95% CI 0.86 to 1.22, p=0.80) and minor bleeding events (RR 0.94, 95% CI 0.65 to 1.34, p=0.73). The results were not affected by removing the UKbased trials or by restricting the included trials to those assessing the CoaguChek system. Similarly, sensitivity analyses restricted to trials using the CoaguChek XS system showed no differences from the alltrials results. A sensitivity analysis restricted to trials at low risk of bias slightly changed the estimate of effect but did not substantially impact on the findings (RR 0.59, 95% CI 0.27 to 1.30, p=0.19).
The External Assessment Group did a subgroup analysis by type of anticoagulant management therapy. No difference between selfmanagement and standard care for any bleeding events (RR 0.94, 95% CI 0.68 to 1.30, p=0.69) was found but there was a statistically significant higher risk in selftesting participants than in those receiving standard care (RR 1.15, 95% CI 1.03 to 1.28, p=0.02). No statistically significant differences in the risk of major bleeding were seen between selfmanagement (RR 1.09, 95% CI 0.81 to 1.46, p=0.58) or selftesting (RR 0.99, 95% CI 0.80 to 1.23) compared with standard care. When only minor bleeding events were assessed, there was a statistically significant increased risk in selftesting participants (23%) compared with those in standard care (RR 1.23, 95% CI 1.06 to 1.42, p=0.005) but not in those who were selfmanaging (RR 0.84, 95% CI 0.53 to 1.35, p=0.47).
Of the 21 trials, 2 trials enrolled participants with atrial fibrillation, 6 trials enrolled participants with artificial heart valves and 13 trials enrolled participants with mixed indication. No statistically significant subgroup differences were found for bleeding events according to the type of clinical indication or the type of control standard care.
Twenty one trials reported 351 major and minor thromboembolic events in a total of 8394 participants. Selfmonitoring (selftesting and selfmanagement) showed a statistically significant reduction in the risk of thromboembolic events by 42% (RR 0.58, 95% CI 0.40 to 0.84, p=0.004) compared with standard care. The risk reduction further increased to 48% when only major thromboembolic events were considered (RR 0.52, 95% CI 0.34 to 0.80, p=0.003). The risk of thromboembolic events substantially decreased when the analyses were restricted to nonUK trials (RR 0.50, 95% CI 0.32, 0.76, p=0.001); to CoaguChek trials (RR 0.52, 95% CI 0.38, 0.71, p<0.0001); and to trials at low risk of bias (RR 0.38, 95% CI 0.16 to 0.92, p=0.03).
Selfmanagement halved the risk of thromboembolic events compared with standard care (RR 0.51, 95% CI 0.37 to 0.69, p<0.0001). In contrast, there was no statistically significant risk reduction for selftesting compared with standard care (RR 0.99, 95% CI 0.75 to 1.31, p=0.56). The subgroup difference between selfmanagement and selftesting was statistically significant (p=0.002). Selfmonitoring participants with artificial heart valves showed a statistically significant reduction in the number of thromboembolic events compared with those in standard care (RR 0.56, 95% CI 0.38 to 0.82, p=0.003). No statistically significant effect was shown among selfmonitoring participants with mixed clinical indication (atrial fibrillation, artificial heart valves, or other conditions) compared with participants receiving standard care.
Thirteen trials reported 422 deaths due to allcause mortality in a total of 6537 participants. The risk reduction for allcause mortality was not statistically significant between selfmonitoring (selftesting and selfmanagement) and standard care (RR 0.83, 95% CI 0.63 to 1.10, p=0.20).
Risk of death reduced by 32% through selfmanagement (RR 0.68, 95% CI 0.46 to 1.01, p=0.06) but not through selftesting (RR 0.97, 95% CI 0.78 to 1.19, p=0.74) even though the test for subgroup differences was not statistically significant (p=0.13). Selfmonitoring halved the risk of mortality in participants with artificial heart valves (RR 0.54, 95% CI 0.32 to 0.92, p=0.02) but not in those with mixed clinical indication for anticoagulant therapy (RR 0.95, 95% CI 0.78 to 1.16, p=0.61). The subgroup difference between participants with artificial heart valves and those with mixed indication with regard to the number of deaths was statistically significant (p=0.05). No data were available from trials that enrolled participants with atrial fibrillation. Statistically significantly fewer deaths were recorded among participants who selfmonitored their therapy compared with those who were routinely managed by their GP/doctor (RR 0.52, 95% CI 0.30 to 0.90, p=0.02).

## Evidence on patientreported outcomes
One trial (n=28) compared selfmanagement with selftesting in children and reported that 1 parent did not favour selfmanagement because of the increased anxiety about INR measurements.
Four trials conducted a questionnaire survey to assess acceptability to participants of selftesting and selfmanagement using pointofcare devices. These trials reported high rates of acceptance for both selfmanagement and selftesting (77% to 98%).
One of these trials reported that 93% of participants rated their satisfaction with regard to selfmonitoring (using either the INRatio monitor or the CoaguChek S system) as high or good. When asked about the overall relative satisfaction with the device, 43% of participants favoured the INRatio monitor, 36% the CoaguChek S system, and 21% both devices in equal way. One trial conducted in children reported that most participants (13 out of 14 participating families, 92%) opted for the CoaguChek XS device.
An unpublished review from the National Thrombosis Service in the Netherlands reported the INR values from over 5000 patients on vitamin K antagonist therapy using either the CoaguChek XS system or the INRatio2 PT/INR monitor for selfmonitoring. The review reported that the INR values within therapeutic range were comparable between the monitors. It also reported that the choice of monitor appeared to have no clinically relevant effect on the time in therapeutic range or adverse outcomes in people on longterm vitamin K antagonist therapy.

# Healthrelated quality of life
Healthrelated qualityoflife outcomes were reported in 9 trials using a variety of different measures. Four trials used Sawicki's questionnaire to measure quality of life, and substantially greater improvements in treatment satisfaction and selfefficacy were reported in the selfmanagement arm compared with the standard care arm of the trials. All 4 trials reported a reduced level of distress and daily inconvenience although 1 trial reported an increased level of distress in participants who received education but did not directly monitor their anticoagulation therapy.
Two UKbased trials reported no substantial differences in qualityoflife outcomes between selfmonitoring participants and those receiving standard care. One trial reported qualityoflife data using the UK SF36, the EuroQol scores and Lancaster's instrument. The other trial assessed themes that were adapted from the Lancaster tool, the SEIQol tool and a series of focus groups. Five common themes emerged from the interviews on selfmanagement: knowledge and management of condition and selfempowerment, increased anxiety and obsession with health, selfefficacy, relationship with healthcare professionals, and societal and economic cost. One trial, conducted in the Netherlands, measured quality of life in people with artificial heart valves by using the SF36v2. Substantial improvements in qualityoflife scores in the physical component summary were reported in people who selfmanaged their therapy compared with those receiving standard care.
Another trial measured quality of life by means of the Health Utilities Index Mark 3. It reported a statistically significant gain in health utilities at the 2year followup among selftesting participants compared with those managed in high quality anticoagulant clinics (p<0.001). The same investigators also measured anticoagulant satisfaction using Duke Anticoagulation Satisfaction Scale. They found that the degree of satisfaction was higher in selftesting participants compared with those in standard care (p=0.002).
One trial compared selfmanagement with selftesting in children and provided qualityoflife data using the KIDCLOT PAC QL parentproxy (parents' quality of life and their assessment of child's quality of life) and the child teen KIDCLOT PAC QL. The 5 common themes identified were: awareness, communication, relationship between parent and child, flexibility and anxiety.

# Costs and cost effectiveness
The External Assessment Group conducted a systematic review to identify existing economic analyses for selfmonitoring coagulation status. The review also sought to identify potentially relevant evidence sources to inform parameter values for the de novo economic model developed by the External Assessment Group. The de novo economic model constructed aimed to assess the cost effectiveness of selfmonitoring coagulation status using the CoaguChek XS system, the INRatio2 PT/INR monitor or the ProTime microcoagulation system. The ProTime microcoagulation system was included in the assessment but has been removed from this guidance because it is no longer available to the NHS and its successor model is not intended for patient selfmonitoring.

## Systematic review of costeffectiveness evidence
The systematic review identified 12 relevant economic evaluations. All of these evaluations compared INR selfmonitoring 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 selfmonitoring was dependent on a number of key factors.
The adopted perspective and the initial costs associated with selfmonitoring appeared to substantially affect the cost effectiveness. Selfmonitoring strategies appeared more favourable than standard care when a wider societal perspective was adopted, as a result of lower time costs associated with fewer health service contacts. The size of the estimates of effect applied to selfmonitoring in reducing thromboembolic and bleeding events compared with those applied to standard care also appeared to affect cost effectiveness. The 2 UKbased evaluations applied effect estimates consistent with small or negligible differences between selfmanagement and usual care with respect to time in therapeutic range and adverse thromboembolic and haemorrhagic events. This resulted in a low probability of selfmonitoring being cost effective. Several studies that applied large effect estimates resulted in a high probability of selfmonitoring being cost effective.
The 2 UKbased economic evaluations were based on data from the same trial. One evaluation adopted an NHS and wider societal perspective, and the other adopted an NHS and personal social services perspective. Selfmonitoring strategies appeared to increase the costs of INR monitoring in the short term and because these 2 evaluations applied small effect estimates, consistent with those seen in the largest UKbased trial of patient selfmanagement, selfmonitoring of INR appeared unlikely to be cost effective. However, no UKbased trials have been sufficiently powered to detect a statistically significant difference between standard INR monitoring and patient selfmonitoring in terms of major thromboembolic or haemorrhagic events. Therefore, the External Assessment Group carried out a metaanalysis of relevant trials including evidence from a number of European trials in which standard care is similar to that provided in the UK in terms of approach, frequency of testing and the level of INR control achieved.

## Economic analysis
The External Assessment Group developed a de novo economic model designed to assess the cost effectiveness of selfmonitoring (selfmanaging and selftesting) coagulation status using 2 different pointofcare coagulometers: the CoaguChek XS system and the INRatio2 PT/INR monitor.

## Model structure
The structure of the Markov model was based on the review of published models of INR selfmonitoring and previous models evaluating the cost effectiveness of new anticoagulant drugs compared with warfarin therapy in people with atrial fibrillation. A further unpublished economic model of INR selfmonitoring was provided by the manufacturer of CoaguChek XS, and this model was also used to inform the structure of the new economic model.
The Markov model compared the alternative monitoring strategies for a hypothetical cohort of people with atrial fibrillation or an artificial heart valve, and was used to simulate the occurrence of thromboembolic and bleeding events over a 10year period. People with atrial fibrillation or an artificial heart valve represent the majority of people on longterm vitamin K antagonist therapy. The model simulated transitions between the discrete health states, and accumulated costs and qualityadjusted life years (QALYs) on a quarterly (3 month) cycle. Within each cycle, the simulated cohort was exposed to a risk of the adverse events as well as death from other causes. The adverse events included in the model were ischaemic stroke (minor, nondisabling, and major, disabling or fatal), systemic embolism, minor haemorrhage, and major haemorrhage (intracranial haemorrhage, including haemorrhagic stroke, gastrointestinal bleed, and others). A constraint was applied whereby the simulated cohort in the model could only experience 1 event per cycle.

## Model inputs
The model was populated using data derived from the systematic clinical effectiveness review, other additional focused reviews to inform key parameters (for instance baseline risks), routine sources of cost data, and where necessary some studyspecific cost estimates based on expert opinion.

## Costs
Data on the resource use and costs associated with the alternative monitoring strategies were informed by published literature, existing guidance, expert opinion, manufacturers' and suppliers' prices, and other routine sources of unit cost data. Some costs were informed by expert opinion where suitable data from other sources were not available.

## Healthrelated quality of life
The baseline utility value for people with atrial fibrillation or mechanical heart valve who were stable was taken as the baseline EQ5D value from trial data, 0.738. This value was applied to 6570 year old people and adjusted by the External Assessment Group to estimate agespecific baseline utilities in the model.
Utilities associated with acute events were applied for the 3month period after the event. For postevent states with associated ongoing morbidity, the appropriate health state utilities were applied for all subsequent cycles spent in these states. Halfcycle corrections were applied, by assuming that people experienced events on average at the midpoint of the cycle. Thus a patient starting off in the well state and experiencing a major stroke in a given cycle of the model would accrue 6 weeks at the utility value for well and 6 weeks at the utility value for major stroke.

## Basecase analysis
For the purposes of decisionmaking, the incremental costeffectiveness ratios (ICERs) per QALY gained were considered. The following assumptions were applied in the basecase analysis:
% of standard care monitoring was done in primary care by practice nurses.
% of the cohort had atrial fibrillation and 40% had an artificial heart valve.
The average age of the cohort was 65 years, and 55% were male.
% of people who selfmonitored did selftesting and 50% selfmanaged.
The increase in the number of tests done per year with selfmonitoring was 23 (that is, 35 tests compared with 12 tests in standard care).
Relative treatment effects were estimated and applied separately for selftesting and selfmanagement.
% of participants did not start selfmonitoring after training (training failure).
% of participants stopped selfmonitoring within a year of starting.
Selfmonitoring device costs were annuitized over 5 years.
% of devices were reused by another patient when a patient stopped selfmonitoring.
The results indicated that over a 10year period, introducing selfmonitoring would reduce the proportion of people experiencing a thromboembolic event by 2.5%, while slightly increasing the proportion having a major haemorrhagic event by 1.4%.
The predicted monitoring costs were higher with selfmonitoring compared with standard monitoring, but the total health and social care costs were similar and in some cases lower. The QALY gains were greater for selfmonitoring than standard monitoring. For all of the selfmonitoring coagulometers there was a QALY gain of 0.027 compared with standard monitoring. Selfmonitoring with the INRatio2 PT/INR monitor was 29 cheaper than standard monitoring. Selfmonitoring with the CoaguChek XS system was 37 more expensive than standard monitoring. Therefore, in the basecase scenario, the selfmonitoring strategies compared favourably with standard care. The INRatio2 PT/INR monitor dominated standard monitoring in the analysis because it was less costly and more effective. The ICER for the CoaguChek XS system was 319 per QALY gained compared with standard monitoring. The lower cost of the INRatio2 PT/INR monitor and testing strips, coupled with the assumption of equivalent clinical effectiveness, meant that the INRatio2 PT/INR monitor also dominated the CoaguChek XS system. However, it should be noted that no direct evidence of clinical effectiveness was identified exclusively for the INRatio2 PT/INR monitor from the systematic review.

## Analysis of alternative scenarios
Several scenario analyses were done by the External Assessment Group:
exclusive selftesting or selfmanagement compared with standard monitoring in primary and secondary care
exclusive primary or secondary care clinic testing compared with selfmonitoring in primary and secondary care
different pooled risk estimates applied.
For the exclusive selfmanagement strategy, the INRatio2 PT/INR monitor and the CoaguChek XS system dominated standard monitoring under the basecase assumptions, whereas for the exclusive selftesting strategy, the ICERs were above 2 million per QALY gained compared with standard monitoring. The results also showed that for a mixed selfmonitoring strategy (50% selftesting, 50% selfmanagement), the CoaguChek XS system and the INRatio2 PT/INR monitor dominated standard monitoring when exclusively carried out in secondary care. When applying the pooled relative risk estimates for adverse events (derived from all selfmonitoring studies) to both selftesting and selfmanaging participants, the cost savings and QALY gains associated with selfmonitoring increased.
The External Assessment Group carried out alternative nonbasecase scenarios, to assess the impact of using selfmonitoring to replace standard monitoring tests (that is, no increase in the number of tests done annually). It was assumed that there was no difference in clinical effectiveness between selfmanagement, selftesting and standard care. Under most of these scenarios, standard monitoring was found to be less costly than selfmonitoring. However, selftesting and selfmanagement with the INRatio2 PT/INR monitor and the CoaguChek XS system dominated standard monitoring when carried out exclusively in secondary care.
Subgroup analyses showed the cost effectiveness of selfmonitoring compared with standard care, stratified by indication (atrial fibrillation and artificial heart valves) and cohort age. Selfmonitoring in a '65 years old with atrial fibrillation' cohort was estimated to cost 2574 per QALY gained when using the INRatio2 PT/INR monitor and 4160 per QALY gained when using the CoaguChek XS system, compared with standard monitoring. For a '65 years old with artificial heart valve' cohort, selfmonitoring with the INRatio2 PT/INR monitor and the CoaguChek XS system was found to be more effective and less costly (dominant) compared with standard monitoring.
A further analysis was carried out for the atrial fibrillation cohort using the baseline risks seen for participants with better INR control in standard care, assuming a constant relative risk reduction for thromboembolic events associated with selfmonitoring. As the INR time in therapeutic range increased in the control group, and the baseline risk of thromboembolic events consequently dropped, the cost effectiveness of selfmonitoring also decreased. However, the ICERs for the CoaguChek XS system and the INRatio2 PT/INR monitor only rose above 20,000 per QALY gained when the baseline time in therapeutic range was set at greater than 72.6%.

## Sensitivity analyses
Deterministic sensitivity analysis showed that the modelbased findings were most sensitive to the baseline risk of thromboembolic events and the effectiveness of selfmonitoring for preventing these events. The ICERs for the selfmonitoring strategies rose above 30,000 per QALY gained when the baseline risk was set to 1.15% and the upper confidence limit for the relative risk of thromboembolic events associated with selfmanagement (RR 0.69) was applied. The same was found when the lower baseline risk of thromboembolic events was coupled with the upper confidence limit of the pooled relative risk for selfmonitoring (RR 0.89). It should be noted however that selfmanagement on its own remained cost saving under the former combined scenario.
A sensitivity analysis was also conducted to approximate the cost effectiveness of selfmonitoring for a cohort of children with an artificial heart valve on longterm vitamin K antagonist therapy. For this analysis, the cohort age was set to 10, the baseline risk of thromboembolic events was reduced to 1.4%, and the standardised mortality ratio for allcause mortality after a stroke was set at 14.5. Under this scenario, selfmonitoring with the CoaguChek XS system and the INRatio2 PT/INR monitor dominated standard monitoring. However, it should be noted that the standardised mortality ratio estimated for an 1855 year old cohort of people with artificial heart valves was applied because no robust data were identified to appropriately adjust the risk of death from all causes in children with an artificial heart valve.
Probabilistic sensitivity analyses of the base case were done to examine the uncertainty in the cost effectiveness of selfmonitoring. Selfmonitoring with the CoaguChek XS system and the INRatio2 PT/INR monitor were estimated to have an 80% and 81% probability of being cost effective if the maximum acceptable ICER was 20,000 per QALY gained, respectively. However, it should be noted that there is no direct randomised controlled trial evidence to show the clinical effectiveness of the INRatio2 PT/INR monitor.# Considerations
The Diagnostics Advisory Committee reviewed the evidence available on the clinical and cost effectiveness of selfmonitoring coagulometers for selftesting or selfmanaging coagulation status in people on longterm vitamin K antagonist therapy who have atrial fibrillation or heart valve disease.
The Committee considered the clinical evidence on the use of pointofcare coagulometers in people with atrial fibrillation or artificial heart valves. The Committee noted that 26 randomised controlled trials compared the use of pointofcare coagulometers for selfmonitoring with standard anticoagulation control. The Committee noted that selfmonitoring 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 selfmonitoring did not result in a statistically 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 metaanalysis of the trial data to the UK population. It noted that the metaanalysis results showed low statistical heterogeneity and concluded that selfmonitoring 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 metaanalysis 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.
The Committee discussed that 22 of the 26 trials included in the assessment investigated the use of the CoaguChek system and considered the different versions of the CoaguChek systems used in these trials. The Committee noted that there are substantial technical differences between the CoaguChek S system and the CoaguChek XS system and heard from clinical specialists and the manufacturer that changes had been made to the different versions to improve reliability and accuracy. The Committee considered the performance of the CoaguChek S and XS systems compared with the gold standard of laboratorybased INR testing and noted that the precision and accuracy of the 2 CoaguChek versions correlated with that of laboratorybased measurements. The Committee concluded that results from the CoaguChek XS system were likely to be at least as good as those obtained from trials in which previous versions of the system were used. The Committee also noted that 4 of the 22 trials investigated the use of the CoaguChek XS system and that 2 of these trials demonstrated a significant improvement in time in therapeutic range. The Committee concluded that it was appropriate to pool the results of trials using different versions of the CoaguChek system and that these pooled results could demonstrate the clinical effectiveness of selfmonitoring using the CoaguChek XS version of the system.
The Committee considered the evidence for the 2 different selfmonitoring coagulometers: the CoaguChek XS system and the INRatio2 PT/INR monitor. The Committee noted that 22 of the 26 trials included in the assessment investigated the use of the CoaguChek system and noted that there was no direct randomised controlled trial evidence to show the clinical effectiveness of the INRatio2 PT/INR monitor. The Committee considered the evidence that showed the 2 coagulometers had a broadly similar performance in precision and accuracy with regard to time in therapeutic range measurement when compared with the gold standard of laboratorybased INR testing and therefore concluded that it was appropriate to extrapolate the clinicaleffectiveness data from the CoaguChek system to the INRatio2 PT/INR monitor.
The Committee discussed the usability of the coagulometers and noted that small differences in devices can sometimes result in large differences in behaviour. The Committee considered the results of the systematic review by Christensen and Larsen (2012) and the unpublished review of over 5000 patients from the National Thrombosis Service in the Netherlands. It noted that although the results of the unpublished review suggested that any potential differences in usability between the 2 monitors did not affect their clinical effectiveness, the unpublished review could not be considered methodologically robust. The Committee concluded that based on the systematic review, any potential differences in the usability of the coagulometers did not appear to affect their ability to measure INR.
The Committee considered the differences in clinical outcomes between people who were selfmanaging their anticoagulation control and those who were selftesting. The Committee noted that there was a statistically significantly greater reduction in thromboembolic events among people who selfmanaged compared with those who selftested. The Committee also noted that when only minor bleeding events were assessed, a statistically significantly increased risk was seen in selftesting participants compared with those in standard care. Allcause mortality was lower through selfmanagement but not through selftesting. The Committee discussed possible reasons for the differences in results between selfmanaging and selftesting, and it heard from clinical specialists that people who selfmanage their coagulation control may behave differently to those who selftest because they have greater responsibility for managing their coagulation control. The Committee noted that the largest trial in the assessment of selftesting did not show a reduction in clinical adverse events but did show an increase in the time in therapeutic range (Matchar et al. 2010). The Committee also noted that this trial had a high standard of coagulation control in the control arm, which could explain why no statistically significant difference in clinical adverse events was detected between the selftesting group and the standard care group. The Committee concluded that the high standard of coagulation control in the control arm of the trial may not reflect general UK clinical practice and so it was plausible that the increase in time in therapeutic range would lead to a statistically significant reduction in clinical adverse events if compared with UK standard coagulation control practice. The Committee concluded that selftesting and selfmanaging were likely to be clinically effective and that selftesting was often a step towards selfmanagement in clinical practice.
The Committee considered the clinical evidence for using selfmonitoring in the population group with atrial fibrillation. The Committee noted that only 2 trials investigated selfmonitoring in people with atrial fibrillation and 19 trials investigated selfmonitoring in a mixed population that included people with atrial fibrillation. The Committee heard from clinical specialists that the clinical outcomes for people with atrial fibrillation are similar to those for people with artificial heart valves. The Committee also heard that people with artificial heart valves may be a younger population than people with atrial fibrillation. The Committee noted that it was not possible to isolate the data for people with atrial fibrillation from the mixed populations investigated in the 19 trials but concluded that it was likely that selfmonitoring would result in similar clinical benefits in people with atrial fibrillation to those achieved in people with artificial heart valves.
The Committee considered the costeffectiveness analysis carried out by the External Assessment Group on selfmonitoring. In the basecase analysis, selfmonitoring with the CoaguChek XS system resulted in an incremental costeffectiveness ratio (ICER) of around 300 per qualityadjusted life year (QALY) gained (based on the pooled effect estimates from the metaanalysis) compared with standard monitoring. Selfmonitoring with the INRatio2 PT/INR monitor dominated (that is, was less expensive and more effective than) the CoaguChek XS system and standard care, although the Committee noted that there was no direct randomised controlled trial evidence for the clinical effectiveness of the INRatio2 PT/INR monitor so clinical effectiveness equivalent to the CoaguChek XS system was assumed in the base case. The Committee concluded that selfmonitoring with the CoaguChek XS system is cost effective in light of the reduction in thromboembolic events seen in the pooled results of the trial data. However, although the INRatio2 PT/INR monitor dominated standard monitoring in the basecase analysis, the Committee did not consider this result to be as robust as that for the CoaguChek XS system because there was no direct evidence of clinical effectiveness for the INRatio2 PT/INR monitor that showed a reduction in thromboembolic events. The Committee noted the similar performance of the CoaguChek XS system and the InRatio2 PT/INR monitor compared with the gold standard of laboratorybased INR testing and concluded therefore that selfmonitoring with the INRatio2 PT/INR monitor was likely to represent a costeffective use of NHS resources.
The Committee considered the cost effectiveness of selftesting and selfmanaging individually. The findings showed that selfmanagement alone is highly cost effective (dominant) but that selftesting alone is not cost effective, compared with standard monitoring. The Committee noted that these findings were based on the contrasting pooledeffect estimates obtained from the metaanalysis of randomised controlled trials, based on thromboembolic events while selftesting and selfmanaging. The Committee discussed the impact of 1 large trial by Matchar et al. (2010) (see section 6.6) on the cost effectiveness of selftesting and noted that although this trial did not show a reduction in clinical adverse events, it did show an increase in the time in therapeutic range. The Committee discussed the impact on the ICERs for selftesting if the economic model was driven by time in therapeutic range rather than adverse events. The Committee concluded that selftesting may be more cost effective if the model had been based on time in therapeutic range. The Committee also considered the costs of selfmanaging and selftesting and noted that selftesting was more expensive because of higher administration costs. The Committee heard from the External Assessment Group that if the pooledeffect estimates from selfmonitoring were applied to selftesting, selftesting would become cost effective even with the higher administration costs this incurred. The Committee concluded that it was likely that the increase in time in therapeutic range shown for selftesting in the trial would lead to a reduction in adverse events compared with standard clinical practice in the UK. The Committee therefore concluded that it was likely that the clinical benefits of selftesting had been underestimated in the economic analyses and that both selftesting and selfmanaging were cost effective.
The Committee considered the impact on people whose anticoagulation therapy is monitored by standard clinical practice. The Committee acknowledged the additional costs and inconvenience for patients of travelling to specialist clinics or hospital to be monitored. The Committee also noted the loss in productivity through absence from work or school to attend clinic appointments. The Committee acknowledged these costs were incurred outside the healthcare system and therefore not included in the reference case; however, it considered that selfmonitoring may reduce the costs and inconvenience incurred by the patient. The Committee also noted that monitoring anticoagulation therapy can have a substantial impact on the quality of life of patients and their families because of the anxiety associated with the risks of bleeding and the consequent behavioural changes such as the length of time they are willing to spend away from home or the distances they are willing to travel. The Committee concluded that the main benefits of selfmonitoring involve reducing the substantial burden associated with monitoring anticoagulation therapy for the patient and their families.
The Committee considered the different methods of selfmonitoring for people having longterm vitamin K antagonist therapy. The Committee heard from a clinical specialist that computer algorithms may be used by some services to determine dose adjustments. The Committee noted that the cost of software licensing had not been included in the costeffectiveness analyses and it discussed the implications of computerbased dosing for people who would selfmanage their coagulation status. The Committee heard that there were alternative methods to determine dose adjustments and that a lack of internet access should not restrict a person's access to selfmonitoring. The Committee considered an additional analysis by the External Assessment Group that investigated the impact of an additional cost for dose adjustment software on the basecase ICERs for selfmanaging. The Committee noted that the additional cost of software would need to be greater than 190 per patient per year to substantially affect the costeffectiveness of selfmanaging with the coagulometers. The Committee concluded that the additional cost of software was unlikely to exceed this value and therefore, even with this potential additional cost, selfmanaging with the pointofcare coagulometers would still represent a costeffective use of resources in the NHS.
The Committee considered the benefits for patients receiving vitamin K antagonist therapy of using pointofcare coagulometers. It heard from a patient expert on the Committee that selfmonitoring 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 selfmonitoring 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 selftesting strips on prescription for selfmonitoring 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 selfmonitoring for patients were not fully captured in the costeffectiveness analyses.
The Committee considered the similarities between selfmonitoring coagulation status and selfmanaging diabetes. The Committee heard from a patient expert that some patients are used to selftesting for conditions such as diabetes, hypertension and heart conditions. The Committee also heard from a clinical specialist that although there were similarities between selftesting for different conditions, there were intrinsic differences between selftesting 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 selfmonitoring their coagulation status but not all people receiving vitamin K antagonist therapy will be able to selfmonitor and some may not wish to. The Committee noted that some groups of patients who may have difficulty with selfmonitoring, such as children or those with a disability, may be able to selftest or selfmanage with the help of a carer. The Committee concluded that there are different considerations for selfmonitoring of coagulation status to those made for selftesting for diabetes, and that the decision for a patient to selfmonitor should be made after a thorough discussion and subsequent agreement between the patient and the healthcare professional.
The Committee considered the impact of the increasing use of nonvitamin K antagonist oral anticoagulant drugs, which do not involve monitoring because of their predictable dose response. It heard from clinical specialists that there are factors that may influence clinical decisions and affect the number of people receiving warfarin: people receiving warfarin who have stable INRs may be unlikely to switch to nonvitamin K antagonist oral anticoagulants, and the nonvitamin K antagonist oral anticoagulants may be unsuitable for some, such as people with mechanical heart valves, certain people with renal or liver dysfunction or those taking drugs that cannot be taken at the same time as the nonvitamin K antagonist oral anticoagulants. The Committee concluded that, because the nonvitamin K antagonist oral anticoagulants would not be suitable for all people who need anticoagulant therapy, and there are many people who will receive warfarin therapy rather than nonvitamin K antagonist oral anticoagulant therapy, selfmonitoring coagulometers are still of clinical importance to the NHS and patients.
The Committee considered the need for quality control of individual patient coagulometers. The Committee heard from a clinical specialist that the National External Quality Assessment Service runs a scheme to ensure the accuracy of coagulometers used by healthcare professionals, and coagulometers used by patients could be checked against a professional coagulometer to ensure accuracy. The Committee concluded that this was a reliable method of ensuring accuracy of individual coagulometers.