Hypothesised effects of potential gene therapy for haemophilia on domains of the Haemophilia Activities List (HAL)
| HAL domain | LYING-DOWN / SITTING / KNEELING / STANDING | FUNCTION OF THE LEGS | FUNCTION OF THE ARMS | USE OF TRANSPORTATION | SELF-CARE | HOUSEHOLD TASKS | LEISURE ACTIVITIES |
|---|---|---|---|---|---|---|---|
| Hypothesised directionality* and magnitude of domain scores | |||||||
| Score interpretation | Higher/increased scores = Less functional limitation | ||||||
| Hypothesis rationale | Impact of rehabilitative therapy not likely to be seen after 1 month (recall period) | Over time, chance for greater functioning of legs after therapy | Improved function of arms is likely to occur concurrently with improved function of legs | Use of transport is unlikely to change as PWH are not more or less likely to use transport as a result of any treatment regimen | Dated list of self-care activities, thus difficult to accurately measure this HRQoL domain with this instrument | Dated list of household tasks, thus difficult to accurately measure this HRQoL domain with this instrument | Large expected impact of gene therapy after 12 months of therapy |
| Comments from expert working group | Rehabilitative physiotherapy would have more of an impact on this domain compared with the haemophilia treatment itself | The lower extremities are more commonly affected by this condition, such as the ankles and the knees | The elbows would be the most impacted area in the upper extremities | Confidence to partake in activities would improve opportunity for self-care | Important to consider that PWH adapt well to their condition as they would have been dealing with it their whole life | Ability to take part in activities is important to emotional wellbeing | |
Hypothesised effects of potential gene therapy for haemophilia on domains of the Haemophilia-specific Quality of Life Questionnaire for Adults (Haemo-QoL-A)
| Haemo-QoL-A domain | PHYSICAL/ROLE FUNCTIONING | WORRY | CONSEQUENCES OF BLEEDING | EMOTIONAL IMPACT | TREATMENT CONCERNS |
|---|---|---|---|---|---|
| Hypothesised directionality* and magnitude of domain score | |||||
| Score interpretation | Higher/increased scores = Better HRQoL or less impairment | ||||
| Hypothesis rationale | Physical functioning expected to improve due to stabilised factor levels and fewer joint bleeds | Worries expected to decrease and HRQoL to increase in the long term as factor levels expected to improve with gene therapy | Consequences of bleeding will decrease (and therefore domain score will improve) with treatment advancement as number of bleeds are likely to decrease | The emotional impact of treatment outcomes may either positively impact a patient (e.g., new sense of freedom, ability to partake in rigorous activities) or negatively impact a patient (e.g., loss of identity, reflection of time lost) | Items within domain were considered dated and not fit for purpose in the context of novel treatment regimens, such as gene therapy |
| Comments from expert working group | Patients will not need to infuse prior to physical activity | Worry may be engrained and long-lasting, therefore perhaps unlikely to change rapidly in the short term | Although bleeding consequences reduce with treatment advancement, PWH will remain aware/conscious of needing to be compliant with treatment in order to reduce consequences | There could be a deterioration in emotional wellbeing in the short term on gene therapy, but an improvement in the long term | Advanced or novel treatments can be more costly and are not necessarily covered by insurance or national health service, which could be a potential treatment concern |
Hypothesised effects of potential gene therapy for haemophilia on domains of the Patient Reported Outcomes, Burdens and Experiences (PROBE)
| PROBE domain | DEMOGRAPHIC DATA | PATIENT-REPORTED OUTCOMES – GENERAL HEALTH PROBLEMS | HAEMOPHILIA-RELATED HEALTH | EQ-5D-5L AND EQ-VAS |
|---|---|---|---|---|
| Hypothesised directionality* and magnitude of domain score | ||||
| Score interpretation | Higher/increased scores = Better health status | |||
| Hypothesis rationale | Gene therapy expected to have strong impact on this domain, such as weight change, education level (ability to stay within education) and relationships | Strong impact expected on this domain assuming treatment will result in normal factor levels (40–50%) | Strong impact expected on this domain as ABR, ‘target’ or damaged joints, range of motion and life-threatening bleeds expected to improve due to higher factor levels | Strong impacts expected on mobility, anxiety and depression, and on EQ-VAS scores |
| Comments from expert working group | Improved educational status may only be evident at older ages as gene therapy is not available to children | Large impact expected on acute and chronic pain due to decrease in bleeds, anxiety and depression, activities of daily living and school/work | Potential for improvement in ABR is dependent upon patient's baseline ABR, which will be different according to geographical location, i.e., PWH in developed countries may report 0–1 ABR (no room for improvement), whereas PWH in developing countries may report 20–30 ABR (room for improvement) | Increased granularity in the detail of the various subdomains is needed |