Lack of Quality Control for Point of Care INR devices can have far reaching consequences
We read with interest the recent BMJ editorial “Rivaroxaban:Can we trust the evidence”.1 which questions the conclusions from the ROCKET AF clinical trial on Rivaroxaban 2. Cohen raises questions about the accuracy of the INRs used for monitoring patients in the warfarin control arm and suggests that they may have compromised the validity of the published conclusions. The ROCKET investigators have defended their conclusions after re assessing the data in light of these concerns 3. The device used for INR testing in the warfarin control arm was not identified in the original publication but subsequently has been revealed as the INRatio Point of Care (POC) device. This device was the subject of a safety recall notice by FDA in 2014 due to “clinically significantly lower” readings compared to laboratory values, with the fault going back to 2002 (before the Rocket AF trial started). The BMJ editorial points out that a falsely low INR reading could mean that patients in the control arm may have had their warfarin dose unnecessarily increased leading to a greater risk of bleeding.
To ensure accuracy, POC INR testing should be subjected to the same level of quality control (QC) and quality management systems that laboratory INR testing has to meet. Appropriate and effective External Quality Assessment (EQA) for POC INR testing devices is possible 4 and there has been a POC INR EQA programme available in the UK for 20 years. In the UK NEQAS for Blood Coagulation EQA programmes we provide suitable material for several different devices and have over 4500 users enrolled in the programmes (January 2016). The POC device used in the warfarin control arm of the ROCKET AF study 2 is one which we evaluated to assess our EQA material suitability in 2010 but found we were unable to provide any suitable EQA material for this technology. To our knowledge no other programme provides EQA for this device. The lack of EQA and internal quality control (IQC) makes it difficult to assess the reliability of INR results obtained with this device.
Laboratory based INR testing in many countries is subject to accreditation, often against international ISO standards (ISO 15189) 5 which require participation in regular EQA as part of the quality management system. Currently the vast majority of POC INR testing in many countries is not subject to such accreditation and not all POC sites participate in EQA even when this is available. Although such participation for POC sites is not currently mandated by regulation, we believe it should be obligatory. Non-participation despite availability could have serious medico-legal implications in the event of untoward incidents. If the use of INR methods in the laboratory or in point of care was restricted to those for which satisfactory participation in EQA can be demonstrated, the issues of clinically significant problems in INR testing such as those which have led to the questioning of the ROCKET AF study could be more easily avoided.
POC INR testing has been in use for over two decades and in our view is safe, providing continuous QC assessment is in place in order to ensure that the INR results produced are valid and accurate 6.There are several published national and international guidelines stating the essential requirement for QC to ensure reliable results 7-9 when using POC INR devices. It would be inappropriate to view all POC devices for INR testing to be inferior to the laboratory measurements as this is not usually the case. POC devices can be accurate and precise giving reliable results in a very quick turnaround time. The key is to ensure the accuracy and precision of all INR results, whether derived from a POC device or from a laboratory method, with the use of both internal control and external quality assessment.
1.Cohen D. Can we trust the evidence? BMJ 2016,352,179-180
2. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, Breithardt G, Halperin JL, Hankey GJ, Piccini JP, Becker RC, Nessel CC, Paolini JF, Berkowitz SD, Fox KAA, Califf RM, and the ROCKET AF Steering Committee, for the ROCKET AF Investigators* N Eng J Med 2011:365; 883-891
3.Patel MR, Hellkamp AS, Fox KAA, and the ROCKET AF executive committee and investigators. Point–of–Care Warfarin monitoring in the ROCKET AF Trial. N Eng J Med 2016:374-378
4 Kitchen DP, Kitchen S, Jennings I, et al. Point of Care INR testing devices: performance of the Roche CoaguChek XS and XS Plus in the UK NEQAS BC external quality assessment programme for healthcare professionals: four years’ experience. J Clin Pathol 2012;65(12):1119–1123
5 The British Standards : Medical laboratories- Requirements for quality and competence ISO 15189
6. Kitchen S, Kitchen DP , Jennings I, Woods TAL, Walker ID , Preston FE. Point of Care INRs : UK NEQAS experiences demonstrates necessity for proficiency testing of three different monitors. Thromb Haemost 2006 : 96; 590-6.
7.CLSI Point –of –Care monitoring of anticoagulation therapy: Approved guideline. CLSI document POCT14-A Wayne PA:Clinical and laboratory standards institute 2004
8. Keeling D, Baglin T, Tait C, et al; British Committee for Standards in
Haematology. Guidelines on oral anticoagulation with warfarin -fourth edition. Br J Haematol 2011;154(3):311–324
9. Jennings I, Kitchen D, Keeling D, et al; BCSH Committee. Patient self-testing and self-management of oral anticoagulation with vitamin K antagonists: guidance from the British Committee for Standards in Haematology. Br J Haematol 2014;
Competing interests: No competing interests