Original Title: Determinación por quimioluminiscencia del dominio I de los anticuerpos anti-beta2 glicoproteína IgG en el síndrome antifosfolipídico

Authors' objectives: The main objective of this Health Technology Assessment report is to evaluate the effectiveness, cost-effectiveness and ethical, legal, organizational, social and patient, and environmental aspects of the incorporation of the detection of aD1 IgG by CLIA in the identification of patients with APS at high-risk of thrombosis or morbidity during pregnancy.

Authors' results and conclusions: RESULTS: EFFECTIVENESS: No RCTs, non-RCTs, observational studies with a control group, or studies that validate prognostic models were found that could be finally included according to the pre-established selection criteria. Therefore, diagnostic performance studies with an observational design were considered. Twelve studies were included. In the 12 studies, a total of 3,570 patients were recruited, of which 1,512 (42.25%) presented a diagnosis of APS and 1,140 (31.85%) a diagnosis of APS with high thrombotic or obstetric risk. The overall prevalence rates of thrombotic and obstetric events were 34.25% (N=1,226) and 21.39% (N=543), respectively. In all the studies, aD1 IgG determination by CLIA, as well as the aPL criteria panel, to identify patients with APS at high-risk of thrombosis or morbidity during pregnancy were carried out. However, only one study evaluated the detection of aD1 IgG by CLIA together with the aPL criteria panel, while the rest of the studies evaluated the detection of aD1 IgG by CLIA. With the detection of aD1 IgG added to the aPL criteria panel for thrombotic and obstetric manifestations, with a cut-off value of 20 CU, sensitivity ranged from 16% (95%CI: 11% to 21%; I²= NA; k= 1; n= 851) to 15% (95%CI: 9% to 22%; I²= NA; k= 1; n= 481), and specificity was 97% (95%CI: 11% to 21%; I²= NA; k= 1; n= 851) and 94% (95%CI: 91% to 96%; I²= NA; k= 1; n= 481) for thrombotic and obstetric events, respectively. Regarding the diagnostic performance of the detection of aD1 IgG in isolation for thrombotic and obstetric manifestations, the sensitivity was 29% (95%CI: 18% to 41%; I²= 0%; k= 6; n= 1,545) and 48% (95%CI: 38% to 59%; I²= 0%; k= 3; n= 690); and specificity was 60% (95%CI: 38% to 79%; I²= 0%; k= 6; n= 1,545) and 72% (95%CI: 26% to 94%; I²= 95.30; k= 3; n= 690), respectively. The AUC was 34% (95%CI: 30% to 39%; I²= 0%; k= 6; n= 1,545) for thrombotic events and 52% (95%CI: 47% to 56%; I²= 95.30; k= 3; n= 690) for obstetric events. No publication bias was detected in the analyses performed. The overall quality of the evidence was considered low. COST-EFFECTIVENESS: The SR did not identify any economic evaluation according to the pre-established selection criteria. The cost analysis revealed that the strategy under evaluation here (determination of aD1 IgG by CLIA added to the aPL criteria panel) involves a higher cost per patient than the usual clinical practice in Spain (determination of the aPL criteria panel). The cost of the aforementioned stands at 194.38 and 170.34 euros per patient, respectively, and an incremental difference of 24.04 euros. Sensitivity analyses confirmed the robustness of the base case results. The estimates obtained in the budget impact analysis show that the incorporation of this technology in the NHS would mean an annual increase of approximately 17.29 million euros if a time horizon of three years is considered. ETHICAL, LEGAL, ORGANIZATIONAL, SOCIAL AND PATIENT, AND ENVIRONMENTAL ASPECTS: The SR did not identify any study for the evaluation of ethical, legal, organizational, social and patient, and environmental aspects. CONCLUSIONS: Based on the SR on effectiveness and cost-effectiveness, the economic evaluation and the analysis of the ethical, legal, organizational, social, patient-related and environmental aspects, carried out for this HTA report, the following conclusions can be established on the incorporation of the detection of aD1 IgG by CLIA in the identification of patients with APS at high-risk of thrombosis or morbidity during pregnancy: • The following conclusions can be drawn from the best available evi-dence for effectiveness, which comes from 12 studies with a total of 3,572 included patients evaluating the diagnostic accuracy of the de-tection of aD1 IgG by CLIA. Only one study evaluated detection of aD1 IgG by CLIA added to the aPL criteria panel, while the rest of the studies evaluated the detection of aD1 IgG by CLIA: aD1 IgG by CLIA together with the aPL criteria panel - For the thrombotic events, with a cut-off value of 20 CU, the de-tection of aD1 along with the aPL criteria panel gives a sensitivity of 16% (134 of every 1,000 patients are incorrectly classified as low thrombotic risk and 160 patients with high thrombotic risk) and a specificity of 97% (25 out of 1,000 patients are incorrectly clas-sified as high thrombotic risk and 840 as low thrombotic risk) (quality of evidence: low ⊕⊕⊖⊖). - For the obstetric events, with a cut-off value of 20 CU, the detec-tion of aD1 along with the aPL criteria panel gives a sensitivity of 15% (140 out of 1,000 patients are incorrectly classified as low obstetric risk and 165 patients with high obstetric risk) and a spec-ificity of 94% (50 out of 1,000 patients are incorrectly classified as high obstetric risk and 835 as low obstetric risk) (quality of evi-dence: low ⊕⊕⊖⊖). aD1 IgG determination by CLIA - For the thrombotic events, with a cut-off value between 13.80 and 32.40 CU, the detection of aD1 shows a sensitivity of 29% (114 out of 1,000 patients are incorrectly classified as low thrombotic risk and 160 patients as high thrombotic risk) and a specificity of 60% (336 out of 1,000 patients are incorrectly classified as high thrombotic risk and 840 as low thrombotic risk) (quality of evi-dence: very low ⊕⊖⊖⊖). - For the obstetric events, with a cut-off value between 14.20 and 32.40 CU, the detection of aD1 panel shows a sensitivity of 48% (86 out of 1,000 patients are incorrectly classified as low obstetric risk and 165 patients as high obstetric risk) and a specificity of 72% (243 out of 1,000 patients are incorrectly classified as high obstetric risk and 835 as low obstetric risk) (quality of evidence: low ⊕⊖⊖⊖). • No economic evaluation was identified that met the pre-established selection criteria. • The cost analysis conducted out for this report concludes that the strategy that includes the detection of aD1 IgG by CLIA added to the aPL criteria panel is more expensive than usual clinical practice (€194.38 and €170.34/patient, respectively), with an incremental differ-ence of €24.04 per patient. • The budget impact analysis shows that the adoption of the evaluated diagnostic strategy in all the NHS would imply a net budgetary impact of 17.29 million euros. • No studies were identified on the evaluation of ethical, legal, organiza-tional, social and patient aspects of the evaluated technology. • No studies were identified on the environmental impact generated by the manufacture, transport, use, and recycling or elimination of the technology.

Authors' methods: EFFECTIVENESS: A systematic review (SR) of the literature published up to March 2021 was conducted in the following databases: Medline, EMBASE and Cochrane. A comprehensive search strategy was applied that included controlled vocabulary and free text terms. The search was completed with the manual examination of the bibliographic list of the included articles, as well as with the verification in Google Scholar of the studies citing the selected studies. Original studies published in English or Spanish were selected that evaluated the effectiveness of the incorporation of the detection of aD1 IgG by CLIA in the identification of patients with APS at high-risk of thrombosis or morbidity during pregnancy. Randomized clinical trials (RCTs) were selected. Failing that, non-randomized clinical trials (non-RCTs) and observational studies with a control group were considered. In the additional absence of this evidence, prospective and retrospective longitudinal studies were considered that performed an evaluation of the diagnostic validity of the test and developed and/or validated prognostic models. The outcome measures considered were: change in the treatment decision, patient risk stratification, comorbidity, thrombotic events, maternal morbidity and mortality, patient reported outcomes measures and patient reported experience measures. When diagnostic performance studies were included, the following outcome measures were considered: sensitivity, specificity and area under the curve (AUC). The RoB-2 tool and the ROBINS-I tool were used to assess the risk of bias of the RCTs, non-RCTs and observational studies with a control group. The risk of bias of the prognostic or diagnostic studies was assessed according to the QUIPS or QUADAS-2 scale, respectively. Quantitative synthesis of the results and publication bias analysis were performed by meta-analysis using version 17 of the statistical program STATA. The evaluation of the quality of the evidence and the grading of the strength of the recommendation were carried out following the methodology of the international working group Grading of Recommendations Assessment, Development and Evaluation (GRADE). COST-EFFECTIVENESS: An SR of cost-effectiveness studies was conducted from the search described above. Selection criteria included economic evaluations developed in parallel with primary studies and economic models. Outcome measures could be incremental cost-effectiveness ratio (ICER), incremental cost-utility ratio, costs expressed in monetary units, and benefits expressed in quality-adjusted life years (QALYs), life years gained (LY), monetary units, or any of the other measures selected in the effectiveness review. Two reviewers (economists) selected the identified references. The methodological quality was assessed with the list of criteria of Drummond et al. and the recommendation guide by López-Bastida et al. Finally, a narrative synthesis of the results was carried out. In addition, a cost analysis evaluation was performed where a diagnostic strategy of APS for patients with a high risk of thrombus and/or morbidity during pregnancy, consisting of the detection of aD1 IgG by CLIA, together with classical aPL criteria, using dilute Russell's viper venom time, activated partial thromboplastin time and enzyme linked immunosorbent assay was compared with usual clinical practice in Spain (the aPL panel test). A decision tree was designed to model the short term (three months), from the perspective of the National Health System (NHS), including direct health costs. The costs are expressed in 2021 euros, without applying a discount rate. The target population was patients between the ages of 15-50 with suspected high-risk APS. A deterministic sensitivity analysis and a probabilistic sensitivity analysis were carried out to quantify the uncertainty surrounding the decision to be made. As a complementary measure, a budget impact analysis was conducted to estimate the cost for the NHS of implanting this diagnostic strategy. This analysis was carried out for a time horizon of three years and its sensitivity to variations in the susceptible population of starting the procedure and the cost of CLIA. ETHICAL, LEGAL, ORGANIZATIONAL, SOCIAL AND PATIENT, AND ENVIRONMENTAL ASPECTS: The scope of the evaluation of these aspects was based on the same population, intervention and comparison described above for the evaluation of the effectiveness and cost effectiveness. The same electronic databases were systematically searched for articles. A narrative synthesis of the results was planned, taking into account the criteria of relevance and coherence of the results.

Project Status: Completed

Year Published: 2023

URL for published report: https://sescs.es/determinacion-por-quimioluminiscencia-de-los-anticuerpos-contra-el-dominio-i-de-la-beta2-glicoproteina-igg-en-el-sindrome-antifosfolipidico/

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Spain

Organisation Name: Canary Health Service

Contact Address: Dirección del Servicio. Servicio Canario de la Salud, Camino Candelaria 44, 1ª planta, 38109 El Rosario, Santa Cruz de Tenerife

Contact Name: sescs@sescs.es

Contact Email: sescs@sescs.es