Early Genomic Testing for Inherited Bleeding Disorders

Официальное название

Early Genomic Testing for Inherited Bleeding Disorders in Patients Without a Diagnosis After First Line Testing: a Randomized Controlled Trial

Обзор

The investigators aim to test the introduction of genomic testing early in the diagnostic pathway for inherited bleeding disorders in patients who have not received a diagnosis after first-line testing. The goal of this clinical trial is to test the introduction of genomic testing early in the diagnostic pathway for patients referred to Hematology for a suspected inherited bleeding disorder. The main questions it aims to answer are: 1. Does adding early genomic testing increase the number of patients who are diagnosed? 2. Does adding early genomic testing decrease the overall time to diagnosis? 3. Is it cost-effective to include early genomic testing in the diagnostic pathway? The investigators will compare with a control group of participants who are receiving standard care (no early genomic testing). Participants will randomized to a standardized diagnostic testing plus early genomic testing group or to the standardized diagnostic testing group only (with the possibility of being offered genomic testing after 1 year in the study).

Подробное описание

With the current standardized diagnostic testing process up to 50% of people referred with significant bleeding symptoms will be classified as bleeding disorder of unknown cause (BDUC), defined as those with a positive bleeding score but in whom all current diagnostic test results are repeatedly normal. Incorporating genomic testing early in the diagnostic pathway could significantly improve diagnostic yield, reduce diagnostic delay, alleviate patient anxiety, and allow for more prompt symptom recognition and targeted treatment.

Вмешательства

• Генная терапия Genetic testing for inherited bleeding disorders
  Gene panel for bleeding: This analysis will look at a list of genes known to be associated with rare coagulation, platelet, connective tissue, and bleeding disorders. There are currently 318 genes on the panel however this list may be updated throughout the study. Genes of study include those on the the International Society of Thrombosis and Haemostasis (ISTH) TIER-1 (the first group of genes are the diagnostic-grade) and TIER-2 gene list, as well as additional genes identified in published res

Первичные конечные точки

• Diagnostic yield [Срок оценки: One year]

Вторичные конечные точки (5)

• Time to diagnosis [Срок оценки: One year]
• Patient Burden [Срок оценки: One year]
• Health Related Quality of Life [Срок оценки: One year]
• Cost-effectiveness analysis [Срок оценки: 2 years]
• Budget Impact Analysis [Срок оценки: 2 years]

Критерии участия

Критерии включения

• New patient referred for abnormal bleeding.
• Hemostasis expert clinician determined abnormal bleeding history AND family history of bleeding
• OR no family history of bleeding but hemostasis expert clinician determined severe bleeding history.

Критерии исключения

• Prior diagnosis of an inherited bleeding disorder.
• Acquired cause of bleeding (i.e., medication known to cause bleeding, significant renal or hepatic disease)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Диагностика

Центры проведения

Канада · 3 центра

• Queen's University/Kingston Health Sciences Centre — Kingston
• The Ottawa Hospital — Ottawa
• Unity Health — Toronto

Публикации

• Elbatarny M, Mollah S, Grabell J, Bae S, Deforest M, Tuttle A, Hopman W, Clark DS, Mauer AC, Bowman M, Riddel J, Christopherson PA, Montgomery RR; Zimmerman Program Investigators; Rand ML, Coller B, James PD. Normal range of bleeding scores for the ISTH-BAT: adult and pediatric data from the merging project. Haemophilia. 2014 Nov;20(6):831-5. doi: 10.1111/hae.12503. Epub 2014 Sep 6. PMID 25196510
• Castle D, Desborough MJR, Kemp M, Lowe G, Thomas W, Obaji S. Outcomes and management of pregnancy in women with bleeding disorder of unknown cause. J Thromb Haemost. 2022 Nov;20(11):2519-2525. doi: 10.1111/jth.15871. Epub 2022 Sep 21. PMID 36053176
• Arya S, Wilton P, Page D, Boma-Fischer L, Floros G, Winikoff R, Teitel J, Dainty K, Sholzberg M. "Everything was blood when it comes to me": Understanding the lived experiences of women with inherited bleeding disorders. J Thromb Haemost. 2020 Dec;18(12):3211-3221. doi: 10.1111/jth.15102. Epub 2020 Oct 21. PMID 32979008
• Andres O, Konig EM, Althaus K, Bakchoul T, Bugert P, Eber S, Knofler R, Kunstmann E, Manukjan G, Meyer O, Strauss G, Streif W, Thiele T, Wiegering V, Klopocki E, Schulze H; THROMKIDplus Study Group of the Society of Paediatric Oncology Haematology (Gesellschaft fur Padiatrische Onkologie und Hamatologie, GPOH) and the Society of Thrombosis Haemostasis Research (Gesellschaft fur Thrombose- und Hamo PMID 31249973
• Downes K, Borry P, Ericson K, Gomez K, Greinacher A, Lambert M, Leinoe E, Noris P, Van Geet C, Freson K; Subcommittee on Genomics in Thrombosis, Hemostasis. Clinical management, ethics and informed consent related to multi-gene panel-based high throughput sequencing testing for platelet disorders: Communication from the SSC of the ISTH. J Thromb Haemost. 2020 Oct;18(10):2751-2758. doi: 10.1111/jth PMID 33079472
• Kim SH, Kim SO, Lee SI, Jo MW. Deriving a mapping algorithm for converting SF-36 scores to EQ-5D utility score in a Korean population. Health Qual Life Outcomes. 2014 Sep 24;12:145. doi: 10.1186/s12955-014-0145-9. PMID 25248494
• Briggs A, Sculpher M, Claxton K. Decision modelling for health economic evaluation. Oup Oxford; 2006.
• Sullivan SD, Mauskopf JA, Augustovski F, Jaime Caro J, Lee KM, Minchin M, Orlewska E, Penna P, Rodriguez Barrios JM, Shau WY. Budget impact analysis-principles of good practice: report of the ISPOR 2012 Budget Impact Analysis Good Practice II Task Force. Value Health. 2014 Jan-Feb;17(1):5-14. doi: 10.1016/j.jval.2013.08.2291. Epub 2013 Dec 13. PMID 24438712

Идентификаторы

NCT: NCT06736158 · 4909 · RDP-193724

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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