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| ID | Type | Description | Link |
|---|---|---|---|
| RDP-193724 | Other Grant/Funding Number | Canadian Institutes of Health Research |
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| Name | Class |
|---|---|
| Unity Health Toronto | OTHER |
| The Ottawa Hospital | OTHER |
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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:
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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Early Genomic Testing Diagnostic Pathway | Experimental | Participants will receive early genomic testing in addition to standard diagnostic testing. |
|
| Standard Diagnostic Pathway | No Intervention | Participants will receive standard diagnostic testing with the option of receiving genomic testing after 12 months. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Genetic testing for inherited bleeding disorders | Genetic | 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 research. |
| Measure | Description | Time Frame |
|---|---|---|
| Diagnostic yield | Defined as the proportion of patients who achieve a final diagnosis at one year. | One year |
| Measure | Description | Time Frame |
|---|---|---|
| Time to diagnosis | The amount of time in weeks and/or months between initial Hematology visit and achieving a diagnosis of an inherited bleeding disorder | One year |
| Patient Burden | This will be captured by patient reported survey. Will include data on: number of appointments for diagnosis, number of blood draws, travel (distance, mode, associated costs) and productivity loss questions (e.g. time spent away from work, wages lost, child/elder care costs). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Julie Grabell, CCRP | Contact | 1 613 533 6000 | 75223 | grabell@queensu.ca |
| Megan Chaigneau, RN | Contact | 1 613 533 6000 | 75223 | megan.chaigneau@queensu.ca |
| Name | Affiliation | Role |
|---|---|---|
| Paula D James, MD, FRCPC | Queen's University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Queen's University/Kingston Health Sciences Centre | Recruiting | Kingston | Ontario | K7L 3N6 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25196510 | Background | 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. | |
| 36053176 |
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all (Individual Participant Data) IPD that underlie results in a publication
IPD and supporting information will be available once manuscript is accepted for publication and will be available indefinitely.
Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA)
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| ID | Term |
|---|---|
| D020141 | Hemostatic Disorders |
| D001778 | Blood Coagulation Disorders |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D006474 | Hemorrhagic Disorders |
| D006402 | Hematologic Diseases |
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| ID | Term |
|---|---|
| D005820 | Genetic Testing |
| ID | Term |
|---|---|
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D008919 | Investigative Techniques |
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|
| One year |
| Health Related Quality of Life | Will be determined using the PROMIS (Patient Reported Outcome Measurement Information System) Profile CAT (Computer Adaptive Testing) v1.0 - 29 for participants 18 and older, and the PROMIS Pediatric Profile GenPop (General Population) v3.0 - Profile-25 for participants 12-17. Each section consists of four items with five-point descriptive scales, except for pain intensity which has a 0-10 numerical rating scale. The sum of the item responses for each multi-item category is converted to a T-score where a score of 50 is the average for the US general population with a standard deviation of 10. Higher scores represent more of something. Therefore, for physical function, higher scores represent better health whereas for anxiety, higher scores represent poorer health. | One year |
| Cost-effectiveness analysis | Will be measured by estimating the cost-effectiveness of the early genomic testing pathway compared with the standard diagnostic pathway (cost per diagnosis). This will be done by calculating the costs for each pathway along with the number of cases detected. | 2 years |
| Budget Impact Analysis | Economic Impact will be measured by a budget impact analysis. This will be conducted from the healthcare system's perspective using standard techniques. In this model-based analysis, the incremental cost of testing for both the control and intervention arm will be determined, which will allow for detailed analysis on the economic impact of inserting genomic testing at different time points along the diagnostic algorithm. | 2 years |
| The Ottawa Hospital | Recruiting | Ottawa | Ontario | K8N 1J4 | Canada |
|
| Unity Health | Not yet recruiting | Toronto | Ontario | M5B 1W8 | Canada |
|
| Background |
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| 28748566 | Background | Leinoe E, Zetterberg E, Kinalis S, Ostrup O, Kampmann P, Norstrom E, Andersson N, Klintman J, Qvortrup K, Nielsen FC, Rossing M. Application of whole-exome sequencing to direct the specific functional testing and diagnosis of rare inherited bleeding disorders in patients from the Oresund Region, Scandinavia. Br J Haematol. 2017 Oct;179(2):308-322. doi: 10.1111/bjh.14863. Epub 2017 Jul 27. |
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| 32537805 | Background | Srivastava A. Diagnosis of haemophilia and other inherited bleeding disorders - Is a new paradigm needed? Haemophilia. 2021 Feb;27 Suppl 3:14-20. doi: 10.1111/hae.14042. Epub 2020 Jun 14. |
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| D006425 |
| Hemic and Lymphatic Diseases |
| D005821 | Genetic Techniques |
| D033142 | Genetic Services |
| D006296 | Health Services |
| D005159 | Health Care Facilities Workforce and Services |
| D003954 | Diagnostic Services |
| D011314 | Preventive Health Services |