{"id":"AIBD-0927","title":"EMA qualified the iBox score to predict kidney graft loss in drug trials, and AQuAS found that it predicted better than transplant physicians","summary":"EMA qualified the iBox score as a secondary endpoint in kidney transplant drug trials. AQuAS found that iBox predicted seven-year graft survival better than nine transplant physicians.","date_observed":"2022-12-19","date_basis":"source publication","date_precision":"day","benefit_status":"mixed","source_collection":null,"source_entry":null,"account":"The Paris Transplant Group built iBox, a score that predicts whether a transplanted kidney will fail, from data on 4,000 patients at four French centers. The Transplant Therapeutics Consortium, which C-Path formed with two US transplant societies, asked the European Medicines Agency (EMA) to qualify it for drug trials. EMA's medicines committee adopted its opinion on 15 December 2022. It qualified the full and abbreviated scores as a secondary endpoint prognostic for graft loss in trials of new immunosuppressive medicines. In four external validation datasets, every c-statistic was 0.70 or greater. The committee found that the models predict individual graft loss with good performance. It did not qualify iBox as a surrogate primary endpoint, because too few trials and events were available. In 2025, Catalonia's assessment agency AQuAS reviewed iBox for Spain's network of assessment agencies. In the one study it found, iBox predicted seven-year graft survival better than nine transplant physicians did. Its discrimination was 0.789, against 0.638 to 0.786 for the physicians. The group that built iBox ran that study on the records of 400 past patients.","category":"aggregate result","unexpected":false,"purpose":"The Paris Transplant Group built iBox to predict the risk that a transplanted kidney will fail within three, five or seven years from routine clinical, immunological and biopsy data.","system":"iBox Scoring System (iBox prediction algorithm)","model_version":"Full and abbreviated models","developer":"Paris Transplant Group (INSERM UMR 970, AP-HP and University of Paris)","deployer":"C-Path's Transplant Therapeutics Consortium (validation for EMA) and the Paris Transplant Group (comparison with nine physicians)","location":"France (derivation data from four transplant centers), with validation in the United States, Finland and two international trials","domain":"Healthcare (kidney transplantation)","segment":null,"benefit_type":"Improved Task Accuracy","work_activities":["4.A.2.a.4"],"taxonomy_note":null,"registry_ids":{"clinicaltrials_gov":"NCT04918199"},"ratings":[{"group":"organizational","depth":null,"reason":"EMA and AQuAS assessed predictions on past cohorts and trials, and neither reports a trial result or a patient's care that depended on iBox."}],"ai_role":{"status":"assessed","statement":"iBox is a statistical prediction model. EMA describes a multivariable Cox proportional hazards model derived from prospectively collected data on 4,000 patients, with variables selected from 31 candidates and 8 retained in the full score. AQuAS calls it a classical statistical model built on Cox regression coefficients. Its marketer calls it AI, and AQuAS notes that no publication makes clear whether it has since gained more advanced AI elements. The comparison with physicians isolates the model's predictions."},"evidence":[{"kind":"regulatory document","citation":"European Medicines Agency, Committee for Medicinal Products for Human Use (CHMP). Qualification opinion for the iBox Scoring System as a secondary efficacy endpoint in clinical trials investigating novel immunosuppressive medicines in kidney transplant patients. EMADOC-1700519818-946771, 19 December 2022, adopted by CHMP on 15 December 2022. Section 1, CHMP qualification opinion statement.","title":"Qualification opinion for the iBox Scoring System as a secondary efficacy endpoint in clinical trials investigating novel immunosuppressive medicines in kidney transplant patients","url":"https://www.ema.europa.eu/en/documents/scientific-guideline/qualification-opinion-ibox-scoring-system-secondary-efficacy-endpoint-clinical-trials-investigating-novel-immunosuppressive-medicines-kidney-transplant-patients_en.pdf","date":"2022-12-19","written_by":"independent","quote":"CHMP qualifies the iBox Scoring System (Composite Biomarker Panel) as a secondary endpoint prognostic for death-censored allograft loss (allograft failure) in kidney transplant recipients to be used in clinical trials to support the evaluation of novel immunosuppressive therapy applications."},{"kind":"assessment report","citation":"Agència de Qualitat i Avaluació Sanitàries de Catalunya (AQuAS), for the Red Española de Agencias de Evaluación de Tecnologías Sanitarias y Prestaciones del SNS. Prieto Durán I, Moltó-Puigmartí C, Mestre Lleixà B, Ibeas J, Estrada Sabadell MD, Vivanco-Hidalgo RM. Algoritmo predictivo para monitorizar y evaluar el impacto de los tratamientos en trasplante de riñón. Ficha de evaluación de tecnologías nuevas y emergentes. Madrid: Ministerio de Sanidad, 2025. DOI 10.62727/DSalut.AQUAS/13303. Puntos clave.","title":"Algoritmo predictivo para monitorizar y evaluar el impacto de los tratamientos en trasplante de riñón","url":"https://redets.sanidad.gob.es/productos/buscarProductos.do?metodo=descargarFichero&idProducto=1316","date":null,"written_by":"independent","quote":"concluye que el algoritmo predice de manera más realista y homogénea el pronóstico de supervivencia del aloinjerto renal, en comparación con las predicciones de los profesionales sanitarios, que son más heterogéneas y menos fiables."},{"kind":"peer-reviewed study","citation":"Divard G, Raynaud M, Tatapudi VS, et al. Comparison of artificial intelligence and human-based prediction and stratification of the risk of long-term kidney allograft failure. Communications Medicine 2022, 2:150. doi:10.1038/s43856-022-00201-9. Written by the Paris Transplant Group, which developed iBox. One author declares shares in Cibiltech.","title":"Comparison of artificial intelligence and human-based prediction and stratification of the risk of long-term kidney allograft failure","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9684574/","date":"2022-11-23","written_by":"makers","quote":"The iBox system demonstrates the best predictive performance with a discrimination of 0.79 and a median calibration error of 5.79%, while physicians tend to overestimate the risk of graft failure."}],"replication":{"produced_by":["iBox combines kidney function (eGFR), proteinuria, donor-specific antibodies, biopsy findings and the time since transplant, and the abbreviated score leaves out the biopsy.","For trials, the score is measured one year after transplant to predict death-censored graft loss at five years.","In the study that AQuAS reviewed, iBox and nine physicians worked from the same anonymized records of 400 past patients."],"must_hold":["Trial sponsors use iBox as a secondary endpoint, since EMA did not qualify it as a surrogate primary endpoint.","The required measurements are available between 6 and 24 months after transplant.","Physicians use the prediction as support alongside their own clinical judgment."],"echoes":[]},"paired_incident":null,"headline":"EMA backs the *iBox* score to forecast kidney graft loss in trials","metric":"every c-statistic was 0.70 or greater","comparator":{"against":"Predictions of nine transplant physicians from the same 400 records (study reviewed by AQuAS)","before":"0,638 to 0,786 discrimination for the physicians","after":"0,789 for iBox","basis":"measured","quote":"fue mayor en el algoritmo de predicción iBox™ (0,789), mientras que la discriminación de los diferentes profesionales sanitarios fue menor y heterogénea","url":"https://redets.sanidad.gob.es/productos/buscarProductos.do?metodo=descargarFichero&idProducto=1316"},"later":{"status":"scaled","date":null,"note":"In 2025 AQuAS identified six ongoing randomized trials that use iBox as a secondary endpoint to test treatments for kidney transplant patients.","quote":"Sin embargo, se han identificado 6 estudios en curso que están utilizando el algoritmo de predicción iBox™ como variable secundaria en ECA para evaluar la superioridad de diferentes tratamientos farmacológicos para el manejo de los pacientes con trasplante renal.","url":"https://redets.sanidad.gob.es/productos/buscarProductos.do?metodo=descargarFichero&idProducto=1316"},"value":null,"developer_country":"France","deployer_country":"Multiple: United States, France","unrated_because":"Both bodies assessed iBox on past data, and its benefit to drug trials and patient care is still to come.","brief_notes":null,"brief":null,"revisions":[{"date":"2026-10-31","change":"Added the record from the findings of the European Medicines Agency and AQuAS.","source":"https://www.ema.europa.eu/en/documents/scientific-guideline/qualification-opinion-ibox-scoring-system-secondary-efficacy-endpoint-clinical-trials-investigating-novel-immunosuppressive-medicines-kidney-transplant-patients_en.pdf","editor":"AIBD"}],"confidence":"found","shade":"high","claim_status":"Found by a regulator","claim_basis":"Sources: one independent regulatory document, one independent assessment report and the makers' peer-reviewed study. 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