Abstracts – Page 4

Development and testing of the online probe survey and the myPROBE app and integration with the Canadian bleeding disorder registry

Germini F, Borg Debono V, Page D, Skinner MW, Zuk V, Kucher A, Sevestre M, Iorio A, on behalf of PROBE investigators. Development and testing of the online probe survey and the myPROBE app and integration with the Canadian bleeding disorder registry. Abstract P097. Haemophilia. 2020;26(S2):27-181. https://doi.org/10.1111/hae.13911

Introduction

Advances to support accessibility and robust data collection are important in a world of rapidly changing technology.

Methods

To assess future development of software infrastructure of the Patient Reported Outcomes Burdens and Experiences(PROBE) project, we conducted a series of semi-structured interviews of relevant stakeholders, including PROBE investigators, people with hemophilia, and representatives of the sponsors. The Health Information Research Unit team at McMaster University andDesign2Code Inc. developed an online survey using Windows.net technologies and a mobile application for iOS and Android usingreact-native, in collaboration with the PROBE investigators. A user group evaluated the final product using the system usability scale (SUS) and an open feedback framework.

Results

The online survey was updated, a myPROBE app for mobile devices and a new application programming interface were developed. The app was tested and modified according to user feedback over multiple cycles. The final version of the app wasreleased in July 2019. Seventeen users aged 23 to 67 years evaluated the final version of the app using the SUS. The median (first, third quartile) SUS score for the app was 85 (68, 88) out of 100. The newly introduced functionalities are: 1) the capability oflongitudinal tracking repeated fillings of the questionnaire at different time points by the same patients (as opposed to anonymous completion); 2) linking of the questionnaire with hemophilia registries, starting with the Canadian Bleeding Disorders Registry (CBDR) as a proof of concept; 3) removing or adding questions as needed; 4) sending notifications to the users (e.g. reminders). A new secure database was built for securely storing personal information separately from the questionnaire data. Seven hundred and twelve users completed the PROBE questionnaire, 165 of whom used their CBDR credentials. The PROBE online survey is currently available in 60+ countries and 75+ languages.

Discussion/Conclusion

The online survey was updated successfully, and the myPROBE app was developed. In the first months after the product’s release, the responses from testers and users have been largely positive. The median SUS compares well with the top 10 most used and popular apps across all categories (78).

Disclosure of Interest

F. Germini Grant/Research support from: The author’s institution received research supportfrom Roche to conduct this project., V. Borg Debono: None Declared, D. Page: None Declared, M. Skinner Grant/Research support from: Research support as the PROBE study principal investigator from Bayer, CSL, Novo Nordisk, Roche, Sanofi, Sobi and Takeda., V. Zuk: None Declared, A. Kucher: None Declared, M. Sevestre: None Declared, A. Iorio Grant/Research support from: Research support as PROBE study investigator from Bayer, CSL,Novo Nordisk, Roche, Sanofi, Sobi and Takeda.

View Poster: Online PROBE survey and the myPROBE app: integration with the Canadian bleeding disorder registry

Association Between Aging and Health Status in Persons Leaving with Hemophilia and Controls Without a Bleeding Disorder – Insights from the PROBE Study

Background: People with hemophilia (PWH) have a life expectancy disadvantage as compared to the general population but little is known about the impact of aging on health status and health-related quality of life (HRQL).

Aims

Assessing the characteristics of the association between aging, health status and HRQL in PWH and people with no bleeding disorders (PWNoBD).

Methods

A cross-sectional, multinational study was conducted as part of the Patient Reported Outcomes, Burdens and Experiences (PROBE) project. PWH and PWNoBD were asked to complete the PROBE questionnaire. Measures of health status and HRQL were the PROBE score, the EQ-5D-5L utility index, and the EuroQol visual analog scale (EQ-VAS) of global health. The association between these measures and the age of participants was explored using a multivariable model adjusting for sex (all) and disease severity (PWH only) and stratifying by country.

Results

1157 PWH and 690 PWNoBD completed the questionnaire in 33 countries from 2016 to 2019. Study population demographics are reported in Table 1. Eight percent of the PWH and 12% of the PWNoBD were aged ≥65 years. Multivariable analysis results are reported in Table 2. As expected, the EQ-5D utility index and EQ-VAS did not show a variation with aging in PWNoBD, while in PWH they were reduced respectively by 0.031 (95% confidence interval [CI] 0.021-0.041) and 0.030 (95% CI 0.014-0.047) every 10 years. Aging was associated with a mean reduction in the PROBE score of 0.010 (95% CI 0.004 to 0.017) every 10 years in PWNoBD. PWH showed an additional reduction in the PROBE score of 0.015 (95% CI 0.008 to 0.022) every 10 years.

Conclusions

Aging is associated with a steeper decrease in health status and HRQL in PWH than in PWNoBD. PROBE is more sensitive than EQ5D in measuring the association of aging for the specific domains measured in both PWH and PWNoBD.

View Presentation: Association Between Aging and Health Status

Association Between Aging and Health Status in Persons Leaving with Hemophilia and Controls Without a Bleeding Disorder – Insights from the PROBE Study

Germini F, O’Callaghan S, Chai-Adisaksopha C, Curtis R, Frick N, Nichol M, Noone D, O’Mahony B, Page D, Stonebraker J, Skinner M, Iorio A, investigators P. Association Between Aging and Health Status in Persons Leaving with Hemophilia and Controls Without a Bleeding Disorder – Insights from the PROBE Study [abstract]. Res Pract Thromb Haemost. 2020;4(Suppl 1). https://abstracts.isth.org/abstract/association-between-aging-and-health-status-in-persons-leaving-with-hemophilia-and-controls-without-a-bleeding-disorder-insights-from-the-probe-study/. Accessed June 29, 2020.

Background and aim

People with hemophilia (PWH) have a life expectancy disadvantage as compared to the general population but little is known about the impact of ageing on health status and health-related quality of life (HRQL). The aims of this study were to assess the characteristics of the association between ageing, health status and HRQL in PWH and persons without hemophilia (PWOH).

Methods

A cross-sectional, multinational study was conducted as part of the Patient Reported Outcomes, Burdens and Experiences (PROBE) project. PWH and PWOH were included. Participants were asked to complete the PROBE questionnaire, which contains haemophilia-related, general health and HRQL questions. Measures of health status and HRQL were the PROBE score, the EQ-5D-5L utility index, and the EuroQol visual analog scale (EQ VAS) of global health. The association between these measures and the age of participants was explored using a multivariable generalized linear model adjusting for sex (all) and disease severity (PWH only) and stratifying by country.

Results

1264 PWH and 694 PWOH completed the questionnaire in 33 countries from June 2016 to December 2019. Study population demographics are reported in Table 1. Seven percent of the PWH and 12% of PWOH were aged ≥ 65 years. Multivariable analysis results are reported in Table 2. As expected, the EQ-5D utility index and EQ VAS did not show a variation with ageing in PWOH, while in PWH they were reduced respectively by 0.021 (95%CI 0.015 to 0.028) and 0.033 (95 CI 0.018 to 0.049) every 10 years. Aging was associated with a mean reduction in the PROBE score of 0.01 (95% confidence interval [CI] 0.003 to 0.016) every 10 years in PWOH. PWH showed an additional reduction in the PROBE score of 0.02 (95% CI 0.013 to 0.027) every 10 years.

Conclusions

Ageing is associated with a steeper decrease in health status and HRQL in PWH than in persons without bleeding disorders. PROBE is more sensitive than EQ5D in measuring the association of aging for the specific domains measured in both PWH and PWOH.

View Poster: Association Between Aging and Health Status

3 apps in 1: MyCBDR, myWAPPS and myPROBE

Page D. 3 apps in 1: MyCBDR, myWAPPS and myPROBE. MTD-MP-025 (377). Haemophilia. 2020;26(Suppl. 4):3-140. https://doi.org/10.1111/hae.13941

Introduction and Objective

MyCBDR is the patient/caregiver bleed and infusion reporting app connected to the Canadian Bleeding Disorder Registry. myWAPPS is an app that enables patients to see their personalized predicted plasma factor levels in real-time. These two apps were connected in July 2019 such that an infusion reported in MyCBDR instantly updates factor levels in myWAPPS. myPROBE is an app that allows people with hemophilia to complete the PROBE survey on-line and, through anonymous registration, be followed longitudinally. It, too, was linked in July 2019 such that the MyCBDR login can be used and MyCBDR users can be followed over time, receive yearly reminders to complete the PROBE survey and receive reports on changes to their PROBE score. The objective of this connectivity is to make data collection more user-friendly, useful and attractive.

Materials and Methods

The Health Information Research Unit team at McMaster University and Design2Code Inc. developed an online survey using Windows.net technologies and a mobile application for iOS and Android using react-native, in collaboration with the PROBE investigators. A user group evaluated the final product using the system usability scale (SUS) and an open feedback framework. In addition, the number of Canadian patients who, after undergoing a previous WAPPS pharmacokinetics study, registered through MyWAPPS was measured.

Results

Seventeen users aged 23 to 67 years evaluated the final version of the PROBE app using the SUS. The median (first, third quartile) SUS score for the app was 85 (68, 88) out of 100. The median SUS compares well with the top 10 most used and popular apps across all categories (78). 165 Canadians with hemophilia used their CBDR credentials to complete the PROBE study. 37 Canadian patients registered for myWAPPS via MyCBDR.

Conclusions

In the first months after the apps were linked, the responses from testers and users have been largely positive. Over time, the inter-connectivity will lead to increased patient/caregiver engagement with their care and improved data collection.

View Poster: 3 apps in 1

Relationship of PROBE Pain Domain and EQ-5D: Insights from the PROBE study

Skinner M, Noone D, Curtis R, Frick N, Germini F, Kucher A, Nichol M, O’Mahony B, Page D, Stonebraker J, Iorio A. P-019 (1035680) Relationship of EQ-5D Pain Domain and Bleeds – Insights from the PROBE Study. (2021), ABSTRACTS. Haemophilia, 27: 3-20. https://doi.org/10.1111/hae.14385

Introduction

Bleeding in people living with haemophilia (PWH) has a significant impact on Health-Related Quality of Life (HRQoL). This impact has been used in terms of disutilities in cost-effectiveness analysis. The aim was to assess the impact on overall HRQoL by severity for a bleed being reported in the last two weeks and assess the level of impact on outcomes.

Methods

Data collected between 2018-2021, was analyzed to determine the relationship of bleeding events being reported within the past two weeks and the PROBE and EQ-5D-5L utility scores. 1168 questionnaires from male PWH A and B ≥ Age 18 (mean[SD] age 41.1[14.5]), were collected in 50 countries. Descriptive analysis and generalised linear models were produced using Stata 13.

Results

The level of pain reported using the EQ-5D-5L pain domain increased across all severities when a PWH reported having a bleed in the past two weeks. Overall, the EQ-5D utility scores were 0.077 (p=0.029), 0.058 (p=0.087) and 0.092 (p< 0.001) higher for mild, moderate and severe patients, respectively, when a bleed was reported in the last two weeks. Using the PROBE score, they were 0.074 (p=0.074), 0.080 (p< 0.001) and 0.089 (p< 0.001) higher. Using a generalised linear model accounting for age, severity and current treatment regimen the disutility associated with a bleed in the last 2 weeks was 0.08 (p< 0.001) for EQ-5D-5L and 0.086 (p< 0.001) for the PROBE score.

Conclusion

Bleeding has a significant impact on PWH HRQoL. A disutility in HRQoL measured by the EQ-5D and PROBE score is evident even two-weeks after a bleeding event. The temporal limitations of the EQ-5D may mask the length of impact of bleeding events unless the context of recent bleeding events is considered. The resulting utility scores may lead to a misrepresentation of the true impact of pain within the severe haemophilia population.

View Poster: PROBE Pain Domain and EQ-5D

Aging and health status in persons leaving with hemophilia and controls without a bleeding disorder

Germini F, O’Callaghan S, Chai-Adisaksopha R, Curtis R, Frick N, Nichol M, Noone D, O’Mahony B, Page D, Stonebraker J, Skinner M, Iorio A. Aging and health status in persons leaving with hemophilia and controls without a bleeding disorder. Abstract (20). NHF 2022.

Objective

People with hemophilia (PWH) have a life expectancy disadvantage as compared to the general population but little is known about the impact of aging on health status and health-related quality of life (HRQL). The aim of the analysis was to assess the characteristics of the association between aging, health status and HRQL in PWH and people with no bleeding disorders (PWNoBD).

Methods

Summary

Conclusions

View Poster: Aging with Hemophilia

A Comparative Study of Different Methods of Handling Missing Data in Patient Reported Outcomes, Burdens and Experiences (PROBE) Score Algorithm among People with Hemophilia

Ibrahim Q, Iorio A, Curtis R, Nichol M, Noone D, Stonebraker J, Skinner M, Germini F, and the PROBE Investigators. A Comparative Study of Different Methods of Handling Missing Data in Patient Reported Outcomes, Burdens and Experiences (PROBE) Score Algorithm among People with Hemophilia. (2022), Abstratc. THSNA. 2022.

Background

The Patient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire measures quality of life (QoL) in people with hemophilia (PWH) and people with no bleeding disorder (NoBD). A score is calculated as the average of nine core item score (0=worst and 1=best reported health status). There is currently no validated method for calculating the PROBE score when some item scores are missing. Grouping highly correlated question scores into a domain and then treating missing values within a domain could be an effective strategy.

Objective

Our objectives were to identify domains within PROBE and compare four strategies of estimating the score as an average of the available item scores when the availability of scores were:

≥50% item scores within a domian,
only one item score within a domain,
≥50% item scores irrespective of any domain,
8 out of 9 item scores.

Method

The observational PROBE phase 3 study data (2018/10/10 – 2021/10/29) were used. Item scores with intra-class correlation (ICC) ≥0.5 were grouped into a domain. We created 36 data sets with artificially generated missing PROBE and item scores from each combination of i) 3 types of hypothetical missing data: Missing Completely At Random (MCAR), Missing At Random (MAR): missing among aged >45 years, and Missing Not At Random (MNAR): missing from the lower quartile of the score, ii) 3 percentages of missing values: 10, 15, and 20% , and iii) the 4 scenarios of missing item scores. A strategy with mean of absolute errors (MAE) (Standard Deviation (SD)) <0.05, and calibration intercepts and slopes not systematically different from 0 and 1, respectively, was considered acceptable.

Results

Among 3217 participants, 48% were PWH, 9% were hemophilia carriers, and 43% were NoBD. 20% of the participants were female, and the mean (SD) age was 41 (15) years. Chronic pain score had ICC ≥0.5 with each of acute pain; pain medication; and difficulty of activities of daily living (ADLs). These four item scores were grouped into a domain. Internal consistency within the domain was shown (Cronbach’s alpha=0.8). For MCAR and MAR data, the closest estimates of PROBE were observed for strategies 1 and 4 (MAE ± SD: 0.02 ± 0.02), followed by strategies 2 and 3. Strategy 1 estimated PROBE score accurately for MCAR and MAR data, and slightly underestimated the score in case of MNAR data. Strategies 2 and 4 slightly underestimated the score for MCAR and MAR data and considerably underestimated the score for MNAR data. Strategy 3 substantially underestimated the score for all missing data types.

Conclusion

Chronic pain was correlated with acute pain, pain medication, and difficulty of ADLs for participants of the PROBE study, indicating that pain is an important contributer to QoL and the PROBE score. We recommend estimating PROBE scores as a simple average of available item scores if at least one item within pain/difficulty in ADLs domain is available or 8 out of 9 items are available irrespective of the domain. This algorithm allows for calculation of the PROBE score for those with missing data.

View Poster: Missing Data Algorithm

Exploring the Quality Of Life And Self‐Reported Outcomes Of Patients With Hemophilia A In A Cross‐Sectional Study In Colombia

Franco J-S, Torres L, Peñuela O, Forero MDR, Rivera M, Vizcaya D. Exploring the Quality Of Life And Self‐Reported Outcomes Of Patients With Hemophilia A In A Cross‐Sectional Study In Colombia. Abstract 110. Haemophilia, 2021;27(S2):18-181. https://doi.org/10.1111/hae.14236

Introduction

Collecting and interpreting patient‐reported outcomes in Hemophilia A supports the understanding of patients’ perspec‐tives on the burden of their disease and its treatment to improve their comprehensive care. However, in Colombia, this information is limited.

Methods

Cross‐sectional study conducted in the context of a he‐mophilia educational bootcamp held November 29 to December 1, 2019 in Medellin, Colombia. The bootcamp was organized by a hemo‐philia patient organization (Liga Antioqueña de Hemofilia) responsible for contacting and inviting patients with Hemophilia A (PwHA), inde‐pendently of their treatment. The objective of this 3‐day bootcamp was to obtain information on patient’s health beliefs, treatment ex‐perience, and Health‐Related Quality of Life (HRQoL) through focus groups, individual interviews and the Patient Reported Outcomes Burdens and Experiences (PROBE) questionnaire that includes the EuroQol five‐dimension (EQ‐5D‐5L).

Results

A total of 25 moderate or severe PwHA (age range 10‐59 yrs) were enrolled in the study and completed the PROBE questionnaire. Acute pain was the most frequently reported symptom (80%) with 88% of the patients reporting use of pain medication. Chronic pain was reported by 55%. Difficulty with activities of daily living was reported by 48% and 32% reported requiring use of mobility aids or assistive devices. Furthermore, 28% of the patients have been told they have clinically significant inhibitors, 52% reported having more than 2 spontaneous bleeding events in the past 12 months and 76% of the patients reported target joints. Treatment was administered at home in 72% of patients, with regular prophylaxis as the most common treatment regimen. In terms of overall HRQoL, measured by EQ‐5D VAS, the mean score reported by the patients was 82.7 (SD 14.6), reporting worse health state in the EQ‐5D‐5L dimensions of pain/discomfort (24% moderate and 4% severe problems) and usual activities (16% moderate problems).

Discussion/Conclusion

Patients with Hemophilia A in Colombia still suffer from the complications of the disease related with bleeding events, mainly pain and disability affecting their HRQoL, which high‐lights the need of developing patient‐centered initiatives to improve the health of this population. Further efforts are required to ensure an appropriate prophylaxis treatment regimen among patients.

Disclosure of Interest

J.‐S. Franco Employee of: Bayer S.A. Colombia, L. Torres Employee of: Bayer S.A. Colombia, O. Peñuela Employee of: Bayer S.A. Colombia, M. D. R. Forero Employee of: Bayer S.A. Colombia, M. Rivera Employee of: Bayer Hispania, Spain, D. Vizcaya Employee of: Bayer Hispania, Spain.

View Presentation: EAHAD21-ABS-1393

Characteristics and Self‐Reported Outcomes of Children and Adults with Severe Hemophilia A from Colombia

Vizcaya D, Torres L, Peñuela O, Forero MDR, Rivera M, Franco J-S. Characteristics and Self‐Reported Outcomes of Children and Adults with Severe Hemophilia A from Colombia. Abstract 060. Haemophilia. 2021;27(S2):18-181. https://doi.org/10.1111/hae.14236

Introduction

Patient-reported outcomes are useful to optimize care of persons with hemophilia, but little is known of the differences between adult and children reported outcomes.

Methods

Cross-sectional study conducted in the context of a hemophilia educational bootcamp held November 29 to December 1, 2019 in Medellin, Colombia. A hemophilia patient organization (Liga Antioqueña de Hemofilia), organized the bootcamp, contacted and invited people with Hemophilia A (PwHA), independently of their treatment prescribed. The objective was to provide a patient-centered framework to collect information on patients’ beliefs and perceptions of their disease. During the 3 days, focus groups, individual interviews and 2 questionnaires were administered: the EuroQoL five-dimension (EQ-5D-5L) and the Patient Reported Outcomes Burdens and Experiences (PROBE).

Results

Overall, 24 of 25 were severe PwHA and 15 (60%) came from urban areas. Thirteen patients (52%) were aged ≥ 18 years (mean age 32.4 yrs), 12 (48%) were ≤ 17 years old (mean age 13.4 yrs). When comparing PROBE results between adults and children, adults reported worse outcomes including acute pain in the last 12 months (100% vs 58%, respectively) and chronic pain in the last 12 months (61% vs 17%, respectively). With regards to bleeds in the past year, 42% of children reported no bleeds and the remainder reported less than three bleeds, whereas only 15% (2/3) of adults reported no bleeds and more than half reported four bleeds or more. All children reported being on a prophylactic treatment 2-3 times weekly, compared to 77% (10/13) of adults in this same treatment regimen. Self-reported overall health-related QoL, measured by EQ-5D VAS, was lower in adults than children (mean (SD): 75.5 (15.5) vs 90.4 (8.6), respectively). Adults also reported a worse health state than children in the EQ-5D dimensions of pain, mobility and usual activities. However, children reported greater anxiety/depression than adults: 100% moderate and 77% slight or no anxiety/depression, respectively in children and adults.

Discussion/Conclusion

Adults with severe Hemophilia A in Colombia report worse outcomes and a greater impact on their QoL compared to children except for the emotional disorders’ domain. Additional strategies must be implemented to ensure an early intervention with appropriate prophylaxis treatment regimen across all ages.

Disclosure of Interest

D. Vizcaya Employee of: Bayer Hispania, L. Torres Employee of: Bayer S.A. Colombia, O. Peñuela Employee of: Bayer S.A. Colombia, M. D. R. Forero Employee of: Bayer S.A. Colombia, M. Rivera Employee of: Bayer Hispania, J.-S. Franco Employee of: Bayer S.A. Colombia.

View Presentation: EAHAD21-ABS-1390

Assessment of quality of life of patients in Kyrgyzstan using the PROBE tool

Vizcaya D, Torres L, Peñuela O, Forero MDR, Rivera M, Franco J-S. Characteristics and Self‐Reported Outcomes of Children and Adults with Severe Hemophilia A from Colombia Tool. Abstract 060. Haemophilia. 2021;27(S2):18-181. https://doi.org/10.1111/hae.14236

Introduction

In resource constrained countries such as the Kyrgyz Republic, there is very limited availability of clotting factor concentrates which has a determinantal effect on the long-term health-related quality of life (HRQoL) of people with haemophilia (PWH).

Methods

HRQoL data was collected from PWH > age 10 using the PROBE questionnaire which also collects haemophilia related sequalae, socioeconomic variables, and EQ-5D-5L. Descriptive methods were used to analyse the data set.

Results

37 PWH with a mean age (SD) of 22.76 (8.25) years participated. 29.7% (n=11), 50.5% (n=15), 2.7% (n=1) and 27.0% (n=10) were severe, moderate, mild or of those whom reported they do not know their severity level. 18.9% (n=7) reported access to some prophylaxis; 59.5% (n=22) and 16.2% (n=6) reported episodic (on-demand) or no treatment availability respectively. 35.1% (n=13) of adults (≥age 18) who did not otherwise report that they were a student reported they were either unemployed or on long-term disability. Overall, 70.3% (n=26) reported an impact on activities of daily living. PWH reporting acute or chronic pain in the past 12 months were 56.8% (n=21) and 75.7% (n=28) respectively. 67.6% (n=25) reported having a “target joint”. 41.5% (n=17) reported chronic pain in their target joint(s). 83.8% (n=31) reported having a joint(s) with reduced range of motion. 24.3% (n=9) reported having had life- or limb-threatening bleeds in the past 12 months. Overall HRQoL utility scores (SD) measured by EQ-5D and PROBE were 0.734 (0.23) and 0.715 (0.13) respectively reflecting the significant impact on quality of life for people living with haemophilia.

Discussion

This study was carried out in a cohort of PWH who did not have consistent access to factor concentrates. Among this cohort, the data demonstrate a significant impact on quality of life, joint health, employment, and chronic / acute pain. Early in life, the lack of accessible treatment has led to early disability, impacts on independence, and work-life.

Conclusion

There is evidence of significant joint damage and reduced quality of life without consistent availability of treatment regimens such as low-dose prophylaxis early in life. The introduction of prophylactic regimen has a demonstrated benefit for PWH. Implementation in the Kyrgyz Republic could significantly improve the health of future generations of PWH.

View Poster: Kyrgyz Republic NMO