Definition serious adverse reaction (SAR):
An unintended response, including a communicable disease, in the donor or in the recipient associated with the procurement or human application of tissues and cells that is fatal, life threatening, disabling, incapacitating or which results in, or prolongs, hospitalisation or morbidity.
Adverse reaction imputability:
| Definite, certain | Conclusive evidence beyond reasonable doubt for attribution to donation or infusion of the cell product |
| Probably, likely | Evidence in favour of attribution to donation or infusion of the cell product |
| Possible | Evidence is indeterminate |
| Unlikely | Evidence is clearly in favour of attribution to alternative causes |
| Excluded | Conclusive evidence beyond reasonable doubt for attributing adverse reaction to alternative causes |
| Not Assessable | Insufficient data for imputability assessment |
Adverse reaction severity grade
The WMDA follows the Common Terminology Criteria for Adverse Events (CTCAE) guidance for severity assessment.
| Grade 1 | Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. |
| Grade 2 | Moderate; minimal, local or noninvasive intervention indicated; limiting age appropriate instrumental ADL* |
| Grade 3 | Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL** |
| Grade 4 | Life-threatening consequences; urgent intervention indicated |
| Grade 5 | Death related to AE |
Activities of Daily Living (ADL)
*Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc.
**Self care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden.
Definition serious adverse event (SAE):
Any untoward occurrence associated with the procurement, storage and distrubution of tissues and cells that might lead to the transmission of a communicable disease, to death or life-greatening, disabling or incapacitating conditions for donors or patients or which might result in, or prolong, hospitalisation or morbidity.
Criteria for serious adverse event (SAE):
The event (could have) led to inappropriate use of tissues or cells
The event (could have) resulted in loss of the complete or significant quantity of irreplaceable cells
The event (could have ) led to a serious adverse reaction (grade 2, 3 or 4)
The event (could have) led to misidentification or an unintended switch of cells
The event (could have) led to (an unforeseen) transmission of disease from donor to recipient
IMPACT: A product of the the likelihood of recurrence and severity of (potential) reaction on donor/patient, the system and the cell supply. A method to determine what the urgency is and what type of action is warranted.
| Likelyhood of recurrence | ||
|---|---|---|
| 1 | Rare | Difficult to believe it could happen again |
| 2 | Unlikely | Not expected to happen again |
| 3 | Possible | May occur occasionally |
| 4 | Likely | Expected to happen again but not persistent |
| 5 | Probably | Expected to happen again on many occasions |
| Severity | On donor/patient; potential in case of SAE, actual in case of SAR | On system | On cell supply | |
|---|---|---|---|---|
| 0 | Insignificant | Nil | No effect | Insignificant |
| 1 | Minor | Non-serious | Minor change | Some applications postponed |
| 2 | Moderate | Serious | Damage for a short period | Many cancellations or postponements |
| 3 | Major | Life threatening | Major damage to system-significant delay to repair | Significant cancellations-importation required |
| 4 | Catastrophic | Death | System destroyed - need to rebuild | All allogeneic applications cancelled |
IMPACT MATRIX: grades from 0 to 20
Likelihood of recurrence from left to right Severity grade from top to bottom | Rare 1 | Unlikely 2 | Possible 3 | Likely 4 | Probable 5 |
|---|---|---|---|---|---|
| Insignificant 0 | 0 | 0 | 0 | 0 | 0 |
| Minor 1 | 1 | 2 | 3 | 4 | 5 |
| Moderate 2 | 2 | 4 | 6 | 8 | 10 |
| Major 3 | 3 | 6 | 9 | 12 | 15 |
| Catastrophic 4 | 4 | 8 | 12 | 16 | 20 |
IMPACT and the necessity of actions: to be discussed.
| 0-3 | The registry manages the corrective and preventive actions. Voluntary reporting to WMDA is encouraged. |
| 4-9 | Report to health authority which may request an inspection and corrective and preventive actions to be followed up. Reporting to WMDA is required for accredited registries. |
| 10-20 | Health authority will generally designate representatives to participate in corrective and preventive action plan. Reporting to WMDA is required for accredited registries within 24 hours after registry is informed. |
IMPUTABILITY ASSESSMENT of SAR: WMDA examples
| Imputability | Definite | Probable | Possible | Unlikely | Excluded |
|---|---|---|---|---|---|
| 0-30 days after donation | Anemia occurring immediately after bone marrow donation Local trauma as a result of Central Venous Catheter placement Anaphylactic reaction occurring 10 minutes after first G-CSF administration Pulmonary edema during intubation for bone marrow collection Transmission of rare chromosomal abnormalitity found in donor and recipient Severe rejection of graft after unintended infusion of completely mismatched stem cells. | Exacerbation of psoriasis 2 days after G-CSF administration Hematuria due to IgA nephropathy during mobilization Back pain lasting 2 weeks after bone marrow harvest | Varicella zoster occuring 3 weeks post PBSC donation. | Rheumatoid Arthritis Car accident 1 week post donation | |
| long-term follow up | Back pain lasting more than 6 weeks | Colorectal cancer, 2 years after PBSC donation First symptoms of Rheumatoid Arthritis 3 months post PBSC | Breast carcinoma 3 years post bone marrow harvest | ||