Headlines

Clearfield, E., Ayoub, E., Ziemele, B., Delaney, M., Youttananukorn, T., Coffin, D., Brennan, F., Kucher, A., Skinner, M. W., & James, P. (2025, August). Mapping outcomes to coreVWD: Moving toward a fully reportable core outcome set to improve access to treatment for people with von Willebrand disease (VWD) [Poster presentation]. National Bleeding Disorders Foundation (NBDF) Annual Conference, Atlanta, GA, United States.

Objective

The VWD treatment landscape is expanding; to assess upcoming products for efficacy and cost-effectiveness, outcomes must be harmonized across clinical trials, registries, and post-market studies. The coreVWD Initiative (Clearfield, Haemophilia 2024) convened a multi-stakeholder group to align on a recommended core outcome set important to decision-makers across the product lifecycle. Outcomes were prioritized for prophylaxis, perioperative treatment, and for women, girls, and people with the potential to menstruate (WGPPM); adverse events were also considered. To fully utilize these recommendations, we must now identify how to most efficiently measure, collect and report them.  

 Aims

Using coreVWD as a benchmark, to map the core outcomes identified to those currently collected in prominent ongoing studies and identify points of overlap and gaps to be covered by updated or new measurement tools.  

 Methods 

We compared the coreVWD core outcomes to the World Federation of Hemophilia’s World Bleeding Disorders Registry (WBDR) and myWBDR app datasets and to variables collected in the Patient Reported Outcomes Burdens and Experiences (PROBE) Study, a quality-of-life study for people with hemophilia.   

 Results

Frequency of bleeds and bleeds requiring treatment are well covered by WBDR, myWBDR, and PROBE, but other descriptions of bleeding are only captured dependent on what Bleeding Assessment Tool (BAT) is used (Table). Information about perioperative bleed control is only collected in WBDR. All three tools could better cover the core outcomes if they enhanced or added a section for WGPPM on menstrual bleeding and pregnancy experiences. 

 Conclusion 

coreVWD prioritized outcomes important to patients; the coreVWD outcomes will require both patient and clinically reported data. This initial analysis provides a foundation to assess completeness and fitness for purpose. Future research will assess data gaps and explore possible revisions to allow WBDR, myWBDR, or PROBE to capture additional coreVWD outcomes. Comprehensively collecting patient-important outcomes will support treatment advances for people with VWD. 

Abstract: HERE (TBA)

Kucher, A., Skinner, M. W., Clearfield, E., Brennan, F., Rotellini, D., Colle, Y., & Wilton, P. A. (2025). Development of a WGPPM-Focused PROBE Survey: Addressing underrepresentation in patient-reported outcomes and quality of life research [Poster presentation]. National Bleeding Disorders Foundation (NBDF) Annual Conference, Atlanta, GA, United States.

Objective

Women, Girls, and People with the Potential to Menstruate (WGPPM), including those with von Willebrand disease (VWD), platelet function disorders, rare coagulation factor deficiencies, and other rare bleeding disorders, remain significantly underrepresented in research related to patient-reported outcomes (PROs) and health-related quality of life (HRQoL). Existing tools such as the Patient Reported Outcomes, Burdens, and Experiences (PROBE) survey—originally developed in 2012—have primarily focused on individuals with hemophilia A or B and carriers, with data also collected from individuals without a bleeding disorder (NoBD) serving as a control group. However, the unique experiences, burdens, and health impacts specific to WGPPM have not been fully captured in existing survey instruments.

 Methods 

To address this gap, a targeted literature review using PubMed was conducted to identify key concepts influencing the quality of life in WGPPM. In parallel, the study team contributed historical examples of related surveys for review. These sources were analyzed to identify novel domains and items, which were then organized into a conceptual framework. This framework was compared against the existing PROBE questionnaire to assess gaps in content coverage. Based on this analysis, the PROBE instrument was revised to include concepts relevant to WGPPM. The development process was undertaken in collaboration with key stakeholders, including the World Federation of Hemophilia, Coalition of the Americas, European Haemophilia Consortium, and the National Bleeding Disorders Foundation, all of whom contributed to a dedicated working group guiding this initiative.

 Summary

The updated framework expands the PROBE instrument with an additional 13 questions which include several WGPPM-specific concepts, such as access to healthcare (including specialty care), emergency department utilization, and bleeding episodes unique to this population, including menstruation and gynecological complications. Additional domains address reproductive decision-making, including considerations around family planning, as well as the social and emotional impact of living with a bleeding disorder—particularly as it pertains to leisure activities and interpersonal relationships. Furthermore, the revised tool allows for improved representation of individuals with rare and often overlooked bleeding disorders.

 Conclusion 

The WGPPM-specific PROBE exploratory pilot was launched in early 2025 through an online platform. It is anticipated that this pilot will generate comprehensive and representative data to better understand the lived experiences of WGPPM. These findings will inform future efforts in research, advocacy, clinical care, and health policy, while also serving as the basis for subsequent updates to the PROBE questionnaire to ensure its continued inclusivity and relevance.

Abstract: HERE

F. Germini, C. Cossa, E. Trinari, et al. “ Feasibility of Administering the Patient Reported Outcomes, Burdens and Experiences (PROBE) Questionnaire Through the Canadian Bleeding Disorders Registry (CBDR) and Comparison of Data From the Two Sources.” Haemophilia (2025): . https://doi.org/10.1111/hae.70117

Introduction

The Patient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire can be used to measure quality of life in persons with haemophilia (PWH) and is integrated in the Canadian Bleeding Disorders Registry (CBDR). This offers the opportunity to compare the same data inputted by patients in PROBE and their treating team in CBDR.

Aim

Our objectives were to assess the feasibility of collecting PROBE data through CBDR and to compare the data collected from these two sources.

Methods

We conducted a prospective observational study among PWH using MyCBDR. Participants were invited to digitally complete the PROBE questionnaire at baseline and to repeat it at 6 and 12 months. Additional data were passively collected through CBDR. Data from PROBE and CBDR were compared using Kappa agreement, intraclass correlation (ICC) and Pearson correlation.

Results

A total of 142 PWH participated. Recruitment ratios were 21.1% and 12.0% for the two phases. Retention rates were 40.8% at 6 months and 32.4% at 12 months.

Three hundred thirteen subjects were involved in the comparison between PROBE and CBDR data. The agreement was good to very good (κ > 0.75) or the correlation very strong, with the exception of the history of inhibitor (κ = 0.57), recent bleeds (κ = 0.48) and current treatment regimen (κ = 0.57).

Conclusions

The integration of PROBE with CBDR is feasible and PROBE is a reliable tool for routine PRO data collection. Its use in clinical practice may improve data quality and personalized and patient-centred care.

View Poster: HERE

Clearfield, E., Ayoub, E., Ziemele, B., Delaney, M., Youttananukorn, T., Coffin, D., Brennan, F., Kucher, A., Skinner, M. W., & James, P. (2025). Mapping outcomes to coreVWD: Moving toward a fully reportable core outcome set to improve access to treatment for people with von Willebrand Disease (VWD) [Abstract]. ISTH. https://www.rpthjournal.org/issue/S2475-0379(24)X0006-0

Background 

The VWD treatment landscape is expanding; to assess upcoming products for efficacy and cost-effectiveness, outcomes must be harmonized across clinical trials, registries, and post-market studies. The coreVWD Initiative (Clearfield, Haemophilia 2024) convened a multi-stakeholder group to align on a recommended core outcome set important to decision-makers across the product lifecycle. Outcomes were prioritized for prophylaxis, perioperative treatment, and for women, girls, and people with the potential to menstruate (WGPPM); adverse events were also considered. To fully utilize these recommendations, we must now identify how to most efficiently measure, collect and report them.  

 Aims 

Using coreVWD as a benchmark, to map the core outcomes identified to those currently collected in prominent ongoing studies and identify points of overlap and gaps to be covered by updated or new measurement tools.  

 Methods 

We compared the coreVWD core outcomes to the World Federation of Hemophilia’s World Bleeding Disorders Registry (WBDR) and myWBDR app datasets and to variables collected in the Patient Reported Outcomes Burdens and Experiences (PROBE) Study, a quality-of-life study for people with hemophilia.   

 Results 

Frequency of bleeds and bleeds requiring treatment are well covered by WBDR, myWBDR, and PROBE, but other descriptions of bleeding are only captured dependent on what Bleeding Assessment Tool (BAT) is used (Table). Information about perioperative bleed control is only collected in WBDR. All three tools could better cover the core outcomes if they enhanced or added a section for WGPPM on menstrual bleeding and pregnancy experiences. 

 Conclusion 

coreVWD prioritized outcomes important to patients; the coreVWD outcomes will require both patient and clinically reported data. This initial analysis provides a foundation to assess completeness and fitness for purpose. Future research will assess data gaps and explore possible revisions to allow WBDR, myWBDR, or PROBE to capture additional coreVWD outcomes. Comprehensively collecting patient-important outcomes will support treatment advances for people with VWD. 

Empty cells represent data gaps. Grayed cells indicate partial coverage or that outcome can be derived from data dependent on type of assessment used and/or detail provided in open text boxes.  
1 BAT Scores assessed Self-BAT
2 BAT Scores assessed by ISTH BAT
3 BAT Scores assessed by MCMDM-1
*PROBE is collected as part of the myWBDR PRO module, or can be administered independently
† PROBE is a quality-of-life study, further description of what should be included as QOL for those with VWD is needed 

Abstract: HERE

Skinner M. W., Kucher A., Clearfield E., Curtis R. G., Germini F., Iorio A., Nichol M., Page D., Stonebraker J. Development of Women, Girls, and People Who Have or Had the Potential to Menstruate (WGPPM) questionnaire for PROBE study. (2025), Book of Abstracts. Haemophilia, 31: 21-109. https://doi.org/10.1111/hae.70032

Objective

There is limited comparative quality-of-life (QoL) data for women and girls with hemophilia A or B who have the potential to menstruate (WGwH). To advance management and treatment it is essential to collect patient-reported health outcomes data.  The validated PROBE questionnaire collects health-related QoL data from WGwH, including carriers, and women and girls who have the potential to mensurate without a bleeding disorder (NoBD) who serve as a control group. We compared the QoL of WGwH with NoBD.

Methods

This was a cross-sectional study from the PROBE database. We included WGwH ≥ age 13 who self-reported hemophilia A or B, as a carrier with a factor level <40%, or NoBD that were identified in the PROBE database. We used descriptive statistics to provide a summary of participant characteristics (Table 1).

Results

From 2015 to 2024, 232 WGwH indicated that they had severe (n=70), moderate (n=26) or mild (n=136) factor deficiency and 407 NoBD were available for comparison. Prophylaxis use was 65.71% in WGwH classified as severe, 19.23% in moderate, and 5.15% in mild. Use of mobility aids was 14.29% in severe, 38.46% in moderate, 14.71% in mild WGwH, and 8.85% in NoBD. Participants with moderate and mild hemophilia reported that this condition impacted important QoL metrics for: chronic pain (CP), target/problem joints (TJ/PJ), reduced joint range of motion (ROM) and difficulties with activities of daily living (ADL) (CP 61.54%, 44.85%; TJ/PJ 50%, 21.32%; ROM 50.0%, 19.85%; ADL 46.15%, 21.32% respectively). See Table 1.

Conclusions

Our study suggests a worse QoL for WGwH compared to NoBD, with a worsening trend with increasing severity. This analysis confirms prior research (Chai-Adisakosopha Haemophilia 2020) showing that non-severe hemophilia is not benign.  WGwH are affected by their bleeding disorders. PROBE data collection for WGwH and further analysis are on-going.

Oral Presentation: HERE

Kucher A, Skinner M. W., Clearfield E., Brennan F., Rotellini D., Colle Y., Wilton P. A. Development of Women, Girls, and People Who Have or Had the Potential to Menstruate (WGPPM) questionnaire for PROBE study. (2025), Book of Abstracts. Haemophilia, 31: 21-109. https://doi.org/10.1111/hae.70032

Objective

The Patient Reported Outcomes, Burdens, and Experiences (PROBE) survey was first developed in 2012. PROBE currently collects data from people with hemophilia A or B, including carriers, and people without a bleeding disorder (NoBD) who serve as a control group. To date, there has been limited global comparative patient reported data on health outcomes and quality of life (HRQoL) about WGPPM.

Methods

A targeted PubMed literature review was conducted to identify concepts impacting WGPPM quality-of-life. The study team also provided additional examples of past surveys for review. Novel topics and items were mapped to a conceptual framework. The resulting framework was compared to the PROBE questionnaire and subsequently PROBE was updated to include missing concepts. It is anticipated that this exploratory questionnaire will lead to an expanded PROBE to more comprehensively include WGPPM. The questionnaire was developed in consultation with the World Federation of Hemophilia, Coalition of the Americas, European Haemophilia Consortium and National Bleeding Disorders Foundation who constituted the project working group. The new WGPPM questionnaire will be initiated as an on-line survey.

Results

The group identified von Willebrand Disease (VWD), platelet disorders, rare factor deficiencies, and other rare bleeding disorders for inclusion. New concepts include access to healthcare (including specialties); visits to emergency room; bleeding episodes unique to WGPPM (e.g., menstrual bleeding; gynecological problems), decision-making around having children, and impact on social and leisure life.

Conclusions

To advance management and treatment for this underserved population it is crucial to collect and report comprehensive data on WGPPM health outcomes and quality of life.  The WGPPM PROBE exploratory pilot was launched in early 2025. Through this pilot we anticipate more accurate and comprehensive data will be available to support future advocacy, research, management and treatment.  Insights from the pilot will be applied to future PROBE updates.

Poster: HERE

On the 50th Anniversary of International Women’s Day, mark this celebration with us by participating in the PROBE Study. Contributing to this study will help us to accelerate action and break the silence for women with bleeding disorders!

Let’s take a stand for the women and girls who have been overlooked in bleeding disorder research and care. Too often, women with bleeding disorders go undiagnosed or misdiagnosed, leading to unnecessary complications. It’s time to collect the data, recognize womens’ experiences, and drive change.

What is Patient Reported Outcomes Burdens and Experiences (PROBE)?

PROBE is a validated and world recognized quality of life study, designed for patients, by patients to understand key outcomes, burdens and experiences. PROBE is now adapted to be used by women with bleeding disorders. A new module, launched today, builds on the existing PROBE Study to incorporate additional questions on gynecological bleeding and complications related to women and bleeding disorders. PROBE has been translated into 5 languages: English, French, Italian, Spanish, Portuguese and Russian to reach the most of the women’s population in the world. PROBE also collaborates with the World Federation of Hemophilia (WFH), European Haemophilia Consortium (EHC), Coalitions of America (CoA) and National Bleeding Disorder Foundation (NBDF) to support women with bleeding disorders. 

Why It Matters:

• Women experience unique symptoms that require specific research and treatment.
• Accurate data helps improve diagnosis, care, and access to treatment.
• Raising awareness leads to stronger and improved policies.

What You Can Do:

• Participate in PROBE to share your experiences of living with a bleeding disorder.
• Amplify the conversation and spread awareness #IWD2025
• Partner with patient organizations and healthcare professionals to continue the conversation!

Every woman’s voice and experience matter. Let’s make bleeding disorders visible, countable, and treatable.

Join us in making a difference! LINK

#IWD2025 #AccelerateAction #DataForChange #BleedingDisorders

Skinner M, Chen E, Ibrahim Q, Kucher A, Germini F, Karimi M, Clearfield E , O’Mahony B , Jain M. Gene Therapy in Hemophilia A: the Impact of Valoctocogene Roxaparvovec on Patient Outcomes – Initial Results from Patient Reported Outcomes, Burdens and Experiences (PROBE) from the GENEr8-1 Trial. (Abstract). NHF (2023).

Objective

The Patient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire is included in the phase 3, open-label, single-arm study (GENEr8-1) as a tertiary endpoint. The aim is to assess the effect of a single intravenous administration of valoctocogene roxaparvovec on patient-reported health and life experiences using PROBE.

Methods

134 adult men with FVIII ≤1 IU/dL without history of FVIII inhibitors and AAV5 antibodies previously receiving FVIII prophylaxis were enrolled in the GENEr8-1 trial for hemophilia A. Results from baseline, week 52 and week 104 were summarized. The PROBE questionnaire comprises four sections: demographics, general health problems, hemophilia-specific problems, and health-related quality of life (HRQoL) with the 5-level EQ-5D tool. While further validation to understand the performance of PROBE in this context of use is ongoing, this study summarized the initial PROBE summary score results (based on section 2) utilizing existing scoring algorithms. Change from baseline summary score was assessed with paired t-tests.

Summary

PROBE score was available for 124/134 (93%) at baseline, 129/132 (98%) at week 52, and 129/130 (99%) at week 104. Mean PROBE scores (SDs) were 0.82 (0.13), 0.87 (0.12) and 0.86 (0.13) at the baseline, week 52 and week 104 respectively. Average changes in score of  0.05 [95% CI: (0.03, 0.07), p <0.001] and 0.05 (0.02, 0.07), p<0.001) were observed at weeks 52 and 104. Item-level analyses suggested fewer participants reported pain, limitations in activities of daily living, and target joints at weeks 52 and 104 vs. baseline. Two years after treatment, the percentage of participants working full-time increased by >10% (Table 1). Overall, these results were consistent with EQ-5D results (Table 2).

Conclusions

Valoctocogene roxaparvovec led to measurable changes in HRQoL 2 years after a single administration. Further research is necessary to interpret clinically meaningful change in PROBE scores.

Disclosures

Er Chen: Bio Marin Pharmaceutical Inc.; Federico Germini: Bayer Bio Marin Pharmaceutical Inc., Novo Nordisk, Pfizer, Roche, Takeda; Mohit Jain: Bio Marin Pharmaceutical Inc.; Milad Karimi: Bio Marin Pharmaceutical Inc.;

Brian O’Mahony BioMarin Pharmaceutical Inc.CSL Behring; Mark Skinner: Bayer, Bio Marin Pharmaceutical Inc., Blue Cross Blue Shield, ICERMASACNHFNORD, Novo Nordisk, Pfizer, Roche/Genentech, Spark, Takeda, WFH, USA

Poster: HERE

Skinner M, Chen E, Kucher A, Germini F, Karimi M, Clearfield E , O’Mahony B , Jain M. Initial results of the impact of valoctocogene roxaparvovec on pain occurrence and interference: Insights from PROBE. (Abstract). NHF (2023).

Introduction

People with severe haemophilia A (PwSHA) commonly present with intramuscular bleeding and hemarthrosis, leading to acute and chronic pain with an overall reduction in health-related quality of life. Here, we report the occurrence of pain in PwSHA before and 2 years after administration of valoctocogene roxaparvovec, and its interference on daily life.

Methods

The Patient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire was included in the phase 3, open-label, single-arm study (GENEr8-1) as a tertiary endpoint to assess the effect of a single 6 × 10¹³ vg/kg dose of valoctocogene roxaparvovec on patient-reported health and life experiences. While further validation to understand the performance of PROBE in this context of use is ongoing, this study summarized pain-related outcomes collected within the PROBE questionnaire. This analysis evaluated PROBE completions at baseline and 104 weeks post gene therapy, including any occurrence of acute and chronic pain (recall: 12 months) and during eight activities (walking, stair climbing, nighttime, resting, weight bearing, playing, after falling/trauma, other). Participants also reported pain interference in 11 aspects of life (general activity, mood, walking ability, normal work, attending school, relations with others, sleep, enjoyment of life, playing/participating in sports/exercising, lifting, other). Descriptive statistics including 95% confidence intervals (CI) were presented at baseline and Week 104.

Results

Data were available for 124 participants at baseline and 129 at 104 weeks. Median age was 34 (range 21−73 years). Reporting of acute and chronic pain was reduced post gene therapy (acute pain: 60.5% to 41.9%, chronic pain: 65.3% to 57.0%). At 104 weeks, the aggregate instances of self-reported acute pain occurrence decreased from 151 (15.2%) to 113 (10.9%) across the 8 activities (including ‘Other’) [Table 1]. Chronic pain reduced from 238 (24.0%) to 216 (20.9%) [Table 2]. At 104 weeks, the aggregate instances of self-reported acute pain interference decreased from 294 (21.4%) to 204 (14.4%) across the 11 activities (including ‘Other’) [Table 3]. Chronic pain interference was reduced from 332 (24.3%) to 262 (18.5%) [Table 3 and 4].

Conclusions

Initial analysis of PROBE data demonstrates that gene therapy may be associated with a decrease in self-reported acute and chronic pain occurrence and interference with daily life in the study cohort.  Pain is one of the core outcomes of importance to people with haemophilia. The impact of gene therapy on pain, particularly chronic pain as demonstrated from PROBE, a haemophilia-specific tool, has important implications on treatment decision-making and continued disease management.

Disclosures

Er Chen: Bio Marin Pharmaceutical Inc.; Federico Germini: Bayer Bio Marin Pharmaceutical Inc., Novo Nordisk, Pfizer, Roche, Takeda; Mohit Jain: Bio Marin Pharmaceutical Inc.; Milad Karimi: Bio Marin Pharmaceutical Inc.;

Brian O’Mahony BioMarin Pharmaceutical Inc.CSL Behring; Mark Skinner: Bayer, Bio Marin Pharmaceutical Inc., Blue Cross Blue Shield, ICERMASACNHFNORD, Novo Nordisk, Pfizer, Roche/Genentech, Spark, Takeda, WFH, USA

Poster: HERE

Skinner M, Chen E, Kucher A, Germini F, Karimi M, Clearfield E , O’Mahony B , Jain M. Initial results of the impact of valoctocogene roxaparvovec on pain occurrence and interference: Insights from PROBE. (2023), CCS_Book of abstracts. Haemophilia, 29: 3-53. https://doi.org/10.1111/hae.14781

Introduction

People with severe haemophilia A (PwSHA) commonly present with intramuscular bleeding and hemarthrosis, leading to acute and chronic pain with an overall reduction in health-related quality of life. Here, we report the occurrence of pain in PwSHA before and 2 years after administration of valoctocogene roxaparvovec, and its interference on daily life.

Methods

The Patient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire was included in the phase 3, open-label, single-arm study (GENEr8-1) as a tertiary endpoint to assess the effect of a single 6 × 10¹³ vg/kg dose of valoctocogene roxaparvovec on patient-reported health and life experiences. While further validation to understand the performance of PROBE in this context of use is ongoing, this study summarized pain-related outcomes collected within the PROBE questionnaire. This analysis evaluated PROBE completions at baseline and 104 weeks post gene therapy, including any occurrence of acute and chronic pain (recall: 12 months) and during eight activities (walking, stair climbing, nighttime, resting, weight bearing, playing, after falling/trauma, other). Participants also reported pain interference in 11 aspects of life (general activity, mood, walking ability, normal work, attending school, relations with others, sleep, enjoyment of life, playing/participating in sports/exercising, lifting, other). Descriptive statistics including 95% confidence intervals (CI) were presented at baseline and Week 104.

Results

Data were available for 124 participants at baseline and 129 at 104 weeks. Median age was 34 (range 21−73 years). Reporting of acute and chronic pain was reduced post gene therapy (acute pain: 60.5% to 41.9%, chronic pain: 65.3% to 57.0%). At 104 weeks, the aggregate instances of self-reported acute pain occurrence decreased from 151 (15.2%) to 113 (10.9%) across the 8 activities (including ‘Other’) [Table 1]. Chronic pain reduced from 238 (24.0%) to 216 (20.9%) [Table 2]. At 104 weeks, the aggregate instances of self-reported acute pain interference decreased from 294 (21.4%) to 204 (14.4%) across the 11 activities (including ‘Other’) [Table 3]. Chronic pain interference was reduced from 332 (24.3%) to 262 (18.5%) [Table 3 and 4].

Conclusions

Initial analysis of PROBE data demonstrates that gene therapy may be associated with a decrease in self-reported acute and chronic pain occurrence and interference with daily life in the study cohort.  Pain is one of the core outcomes of importance to people with haemophilia. The impact of gene therapy on pain, particularly chronic pain as demonstrated from PROBE, a haemophilia-specific tool, has important implications on treatment decision-making and continued disease management.

Disclosures

Er Chen: Bio Marin Pharmaceutical Inc.; Federico Germini: Bayer Bio Marin Pharmaceutical Inc., Novo Nordisk, Pfizer, Roche, Takeda; Mohit Jain: Bio Marin Pharmaceutical Inc.; Milad Karimi: Bio Marin Pharmaceutical Inc.;

Brian O’Mahony BioMarin Pharmaceutical Inc.CSL Behring; Mark Skinner: Bayer, Bio Marin Pharmaceutical Inc., Blue Cross Blue Shield, ICERMASACNHFNORD, Novo Nordisk, Pfizer, Roche/Genentech, Spark, Takeda, WFH, USA

Oral Presentation: HERE

Curtis R, Wu J, Iorio A, Frick N, Nichol M, Noone D, O’Mahony B, Page D, Stonebraker J, Kucher A, Clearfield E, Skinner MW, Germini F. Test-retest reliability of a mobile application of the patient reported outcomes burdens and experiences (PROBE) study. Haemophilia. 2024 May;30(3):702-708. doi: 10.1111/hae.14969. Epub 2024 Mar 4. PMID: 38439137.

Introduction

The Patient Reported Outcomes, Burdens, and Experiences (PROBE) questionnaire is a patient-reported outcome tool that assesses quality of life and disease burden in people with haemophilia (PWH).

Aim

To assesses the test-retest reliability of PROBE when completed using the mobile phone application.

Methods

We recruited PWH, including carriers, and individuals with no bleeding disorders who attended haemophilia-related workshops or via social media. Participants completed PROBE three times (twice on the app: T1 and T2, and once on the web, T3). Test-retest reliability was analysed for T1 versus T2 (app to app, time period one) and T2 versus T3 (app to web, time period two).

Results

We enrolled 48 participants (median age = 56 [range 27-78] years). Eighteen participants (37.5%) were PWH and seven (14.6%) were carriers. On general health domain questions, we found almost perfect agreement, except for a question on the frequency of use of pain medication in the last 12 months [Kappa coefficient (κ) .72 and .37 for time period one and two, respectively] and any use of pain medications (κ .75) for time period two. For haemophilia-related questions, we found substantial to perfect agreement, except for the questions on the number of joint bleeds in the previous 6 months for time period one (κ .49) and the number of bleeds in the previous two weeks for time period two (κ .34).

Conclusions

The results demonstrate the reliability of the PROBE app. The app can be used interchangeably with the paper and web platforms for PROBE administration.

Disclosures

This disclaimer relates to PubMed, PubMed Central (PMC), and Bookshelf. These three resources are scientific literature databases offered to the public by the U.S. National Library of Medicine (NLM). NLM is not a publisher, but rather collects, indexes, and archives scientific literature published by other organizations. The presence of any article, book, or document in these databases does not imply an endorsement of, or concurrence with, the contents by NLM, the National Institutes of Health (NIH), or the U.S. Federal Government.

Iorio A, Keepanasseril A, Ibrahim Q, Iserman E, Blaser H. Self-reflections, lessons learned and suggestions for data quality assurance from a retrospective data analysis from the Canadian Bleeding Disorders Registry. (2024), POSTER ABSTRACT (PP-026). (2024), Issue Information. Haemophilia, 30: 1-2. https://doi.org/10.1111/hae.15016

Introduction

Real-world evidence (RWE) is used to complement primary evidence from clinical trials on safety and efficacy and to generate clinical effectiveness data. Theoretically, RWE is not subject to ‘on trial effect’, and it shows the true impact of intervention in unselected populations. Barriers to generating RWE are mostly stemming from the incomplete availability of relevant data points in the real-world setting. Aim: Analyse strengths and limitations of the ‘Real-World Effectiveness of PEGylated, recombinant Antihaemophilic Factor (Rurioctocog alfa pegol) Prophylaxis in Patients with Haemophilia A in Canada: A Retrospective, Intra-Patient Comparison with a Before-AfterDesign’.

Methods

A retrospective study, before-after design, comparing PK, clinical and PR outcomes for patient switched from SHL-FVIII or EHL-FVIII products to Rurioctocog alfa pegol. Outcomes: individual PK parameters (half-life, time spent above factor levels of0.01, 0.03 and 0.05 IU/mL), factor utilisation, bleed rates, QoL (PROBE)and joint function (HJHS). Pre-specified subgroups: previous treatment with SHL-FVIII versus EHL-FVIII, history of inhibitors versus no inhibitors, and age ≤12 versus >12 years. Strengths and limitations of the approach, including the amount/quality of data available for the analysis of the different outcomes, were analysed.

Results

Ninety-eight severe haemophilia A inhibitor-free patients qualified for the analysis. Thirty-seven patients had available PK data. There were four patients with history of inhibitors, six <12 years and eight patients formerly treated with SHL; four had HJHS and four had PROBE data. Clinical, PK and utilisation results have been presented elsewhere.

Conclusions

PROBE data shows a good cross-section of people with Haemophilia A, B and carriers. Brazil has free Selection bias is anticipated to be lower in retrospective design versus post-marketing surveillance (PMS) studies, which also threaten national registries data integrity. Included (n = 37) and excluded (n = 61) patients were similar in terms of age distributions, BMI, and number of surgery or traumatic bleedings, confirming that the retrospective analysis did not identify a selected population. Lim-ited availability of HJHS and PROBE data suggests that routine clinical practice does not yet include standardised recording of patient centred/reported outcomes, hampering the measurement of health care interventions’ value. There is a significant opportunity to improve the breadth/quality of data generation in the future to demonstrate the true impact of factor replacement in routine clinical practice.

Disclosures

Alfonso Iorio: Bayer, CSL, Pfizer, Roche, Sanofi/Sobi, Takeda; Heiko Blaser: Takeda.

View Poster: PP_26_WFH2024

Pietrobelli T, Skinner M. PROBE: Brazil data. (2024), POSTER ABSTRACT (PP-165). (2024), Issue Information. Haemophilia, 30: 1-2. https://doi.org/10.1111/hae.15016

Introduction

The Brazilian Haemophilia Federation (FBH) carried out a campaign to increase responses to the PROBE (Patient Reported Outcomes, Burdens, and Experiences) questionnaire, which collaborates with the World Haemophilia Federation and was integrated into myWBDR and GTR. To have robust data on the quality of life, treatment and daily life of people with Haemophilia A and B. The data collected is intended to be used in FBH advocacy actions, to improve Public Policies in Brazil.

Methods

PROBE has real-life data from patients, which is why FBH has been a partner in the study since 2018 and has a specific response link that allows you to know the state where the person lives and the distance from their home to the HTC. The information collected by PROBE allows FBH to hold meetings with government authorities and propose improvements for the treatment of people with haemophilia in all 27 federative units in Brazil.

Results

PROBE has 679 contributions to the questionnaire in Brazil. With 321 people with Haemophilia A, 49 with Haemophilia B, 35 carriers and 274 people without coagulopathy, this last group is considered a comparative group for quality of life. Considering 405 people with Haemophilia A, B and carriers, 168 have Severe Haemophilia and 45 Moderate. Around 65% undergo treatment at home and 28% go tothe HTC for treatment. 75% perform 2–3 infusions per week and only 2.25% infuse daily. 41.75% do not have chronic pain and 58.25% admit to living with chronic pain, of which 85% have chronic pain in the target joints.

Conclusions

PROBE data shows a good cross-section of people with Haemophilia A, B and carriers. Brazil has free treatment through the Public Health System, which is an example for the world and, even so, there are windows of improvement that should be taken advantage of. With this data, FBH will work to improve Public Policies with government authorities to improve access to treatment and quality of life.

Disclosures

Mark Skinner: Band Therapeutics, Bayer, BioMarin, CSL Behring, Novo Nordisk, Pfizer, Roche/Genentech, Sanofi, Takeda, Vega Therapeutics.

View Poster: PP_165_WFH2024

Naccache M, Konkle B, Peyvandi F, Miesbach W, O’Mahony B, Pile S, Youttananukorn T, Coffin D, Pierce G. Global Efforts in Uniting all stakeholders in ensuring safety of hemophilia gene therapy patients: the World Federation of Hemophilia Gene Therapy Registry. (2024), POSTER ABSTRACT (MP-021). (2024), Issue Information. Haemophilia, 30: 1-2. https://doi.org/10.1111/hae.15016

Introduction

The World Federation of Haemophilia (WFH) launched the Gene Therapy Registry (GTR) aimed at gathering comprehensive data on all people with haemophilia (PWH) who receive gene therapy worldwide.

Methods

The GTR was designed to standardise and centralise global data collection for the gathering and dissemination of gene therapy data. The GTR is a prospective, observational, and longitudinal registry. Data entry occurs once, either directly from haemophilia treatment centre (HTC) into the GTR or through data transfer from National Registries. The GTR Scientific Advisory Board oversees all data entered into the GTR and its dissemination. Specificde-identified data will be shared with various stakeholders: participating patients will have access to view their own data; HTCs and National Registries will receive aggregated global safety data; industry part-ners will receive product-specific data, and regulatory agencies and health technology assessment organisations can request specific data to inform their decisions.

Results

The WFH is engaged with a broad network of collabora-tors, and the GTR National Registries & HTC Consortium has been established to foster dialogue, obtain feedback from our collaborators, and establish mutually beneficial collaboration. This group includes representatives from Brazil, Ireland, Saudi Arabia and Sweden, and registries from Australia, Canada, France, Germany, Japan, the Netherlands, Spain, the United Kingdom and the United States. The European Medicines Agency (EMA) issued a pivotal letter of support to the WFHGTR. The CHMP endorses the GTR as the worldwide registry for consolidating all international data on PWH who receive gene therapy and encourages collaboration of all HTCs and National Registries, stating that the WFH GTR is of particular value for post approval safety and efficacy studies of gene therapies and recommending its use as a planned data source for mandated Phase IV studies.

Conclusions

The GTR facilitates the accumulation of data in one registry and supports the efficient dissemination of valuable information to all stakeholders, advancing our understanding of gene therapy’s safety, efficacy, and long-term effects. In the current landscape of numerous registries in haemophilia around the world, the success of the GTR depends on collaborative relationships with all stakeholders, including patients, HTCs, National Registries, industry partners and regulatory bodies.

Disclosures

Barbara Konkle: Be Biotherapy, Biomarin, Novo Nordisk, Pfizer, Sanofi; Flora Peyvandi: BioMarin Pharmaceutical Inc., CSL Behring, F. Hoffmann-La Roche Ltd., Grifols, Sanofi, Sobi, Takeda; Wolfgang Miesbach: Bayer, BioMarin, Biotest, Chugai, CSL Behring, Free-line, LFB, Novo Nordisk, Octapharma, Pfizer, Regeneron, Roche, Sanofi, Sigilon, Sobi, Takeda/shire; Brian O’Mahony: Biomarin, CSL Behring, Freeline, Irish Haemophilia Society, Pfizer, Roche; Mike Makris: Grifols, Novo Nordisk, Sanofi, Takeda; Steven Pipe: Apcintex, ASC Therapeutics, Bayer, BioMarin, CSL Behring, HEMA Biologics, Freeline, LFB, Novo Nordisk, Pfizer, Regeneron/Intellia, Genentech/Roche, GeneVentiv and Equilibra Bioscience, Sanofi, Takeda, Spark Therapeutics, uniQure, Siemens; Mark Skinner: Band Therapeutics, Bayer, BioMarin, CSL Behring, Novo Nordisk, Pfizer, Roche/Genentech, Sanofi, Takeda, Vega Therapeutics; Glenn F. Pierce: ASC Therapeutics, Be Bio, BioMarin, Decibel Therapeutics, Frontera, Intellia, Metagenomi, Novo Nordisk, Pfizer, Regeneron, Spark Therapeutics, Third Rock Ventures.

View Poster: MP_21_WFH2024

Youttananukorn T, Konkle B, Peyvandi F, Naccache M, Miesbach W, O’Mahony B, Makris M, Pipe S, Skinner M, Coffin D, Pierce G.Long-term retention plan through myGTR – a patient engagement tool from World Federation of Hemophilia Gene Therapy Registry. (2024), POSTER ABSTRACT (PP-054). (2024), Issue Information. Haemophilia, 30: 1-2. https://doi.org/10.1111/hae.15016

Introduction

The World Federation of Haemophilia (WFH) Gene Therapy Registry (GTR) is designed to collect comprehensive clinical data on all people with haemophilia (PWH) who receive gene therapy (GT) globally. To complement data from the GTR, the WFH developed myGTR – a patient engagement tool aimed at collecting patient-reported outcome (PRO) data. PRO data are important and are part of shared decision-making process that could lead to meaningful care and treatment.

Methods

To reduce potential data gap after GT and to ensure long-term engagement between haemophilia treatment centre (HTC) and PWH, the GTR is developing a retention plan. The patient engagement plan of the GTR includes myGTR – the foundational element, data visualisation through dashboards, video/podcasts with experts, and a dedicated website with latest news about GT.

Results

Whilst developing myGTR, the WFH held focus groups to discuss which PRO data are important to collect, at which frequency, and how to capture PWH’s experience on GT. The groups indicated mobile app fatigue and requested a simple tool. myGTR is not available at any app store. It was developed as a web-based application. Patients can choose their preferred contact method – email or text message – to access myGTR and provide PRO data via an interactive digital assis-tant. The PRO data are bleeds, treatments and health related quality of life (HR-QOL) including the Patient Reported Outcomes Burdens and Experiences (PROBE), coreHEM Mental Health Outlook (core-HEM MHO) and EQ-5D-5L. At regular interval (4 times during the first year, 2 times per year thereafter), the patients will be prompted to answer two simple questions about their health status since GT infusion, and complete two out of three HR-QOL questionnaires on a rotational basis.

Conclusions

To monitor GT’s safety, efficacy and long-term effects, engagement from both HTCs and patients is critical. The GTR is a platform for HTCs whereas myGTR allows the patients to continue providing data on their health status and HR-QOL in a simple manner. When working hand-in-hand, both tools can improve patient care and treatment outcomes as well as our understanding of benefits and risks of GT.

Disclosures

Barbara Konkle: Be Biotherapy, Biomarin, Novo Nordisk, Pfizer, Sanofi; Flora Peyvandi: BioMarin Pharmaceutical Inc., CSL Behring, F. Hoffmann-La Roche Ltd., Grifols, Sanofi, Sobi, Takeda; Wolfgang Miesbach: Bayer, BioMarin, Biotest, Chugai, CSL Behring, Free-line, LFB, Novo Nordisk, Octapharma, Pfizer, Regeneron, Roche, Sanofi, Sigilon, Sobi, Takeda/shire; Brian O’Mahony: Biomarin, CSL Behring, Freeline, Irish Haemophilia Society, Pfizer, Roche; Mike Makris: Grifols, Novo Nordisk, Sanofi, Takeda; Steven Pipe: Apcintex, ASC Therapeutics, Bayer, BioMarin, CSL Behring, HEMA Biologics, Freeline, LFB, Novo Nordisk, Pfizer, Regeneron/Intellia, Genentech/Roche, GeneVentiv and Equilibra Bioscience, Sanofi, Takeda, Spark Therapeutics, uniQure, Siemens; Mark Skinner: Band Therapeutics, Bayer, BioMarin, CSL Behring, Novo Nordisk, Pfizer, Roche/Genentech, Sanofi, Takeda, Vega Therapeutics; Glenn F. Pierce: ASC Therapeutics, Be Bio, BioMarin, Decibel Therapeutics, Frontera, Intellia, Metagenomi, Novo Nordisk, Pfizer, Regeneron, Spark Therapeutics, Third Rock Ventures.

View Poster: PP_54_WFH2024

O’Callaghan S, Parikh S, Bishop L, Caris S. Physical functioning and pain in older men with haemophilia. (2024), POSTER ABSTRACT (PP-161). (2024), Issue Information. Haemophilia, 30: 1-2. https://doi.org/10.1111/hae.15016

Introduction

It is well recognised that physical functioning can be impaired and pain common as men with haemophilia (MWH) age, due to complications from their bleeding disorder. However, it can be difficult to quantify the difference between their experience and that of men without a bleeding disorder (MNBD)of equivalent age in the general population. The PROBE (Patient Reported Outcomes Burdens Experiences) questionnaire is an internationally validated tool defining the impact of haemophilia on quality of life from the patient perspective. In 2020 the PROBE Australia Study compared the experience of MWH and MNBD, all of whom were aged 45 years and over.

Methods

A total of 106 questionnaire respondents aged 45 years and over (MWH: n = 57; MNBD: n = 49) were recruited via Australian community networks. PROBE questions included use of a mobility aid or assistive device, difficulties with activities of daily liv-ing, acute and chronic pain and use of medications for pain in the last 12 months.

Results

Differences between MWH and MNBD were pronounced. Overall MWH reported that 44% (25/57) used a mobility aid, 54% (31/57) had difficulties with activities of daily living, 58% (33/57) experienced acute pain, 74% (42/57) chronic pain and 79% (45/57) used medication for pain in the last 12 months. This was markedly higher than MNBD: none reported problems with mobility, 6% (3/49) reported problems with activities of daily living, 27% (13/49) had acute pain, 41% (20/49) chronic pain, and 61% (30/49) used medication for pain. A higher proportion of men with moderate or severe haemophilia (n = 28) reported physical function problems or pain: 61% (17/28) needed mobility aids, 79% (22/28) had difficulties with activities of daily living, 79% (22/28) had acute pain, 86% (24/28) chronic pain, and 89% (25/28) had used medi-cation for pain. Men with mild haemophilia (n = 29) also reported problems and pain more often than MNBD, including 28% (8/29) reporting mobility problems and 31% (9/29) with activities of daily living.

Conclusions

Validated haemophilia-specific tools such as PROBE are an important way to quantify the substantial differences in quality of life between older men with haemophilia and men without a bleeding disorder of equivalent age.

View Poster: PP_161_WFH2024

Pipe S, Abdelkader W, Clearfield E, Kucher A, Joseph B, Braverman J, Galante N, Monahan P, Ibrahim Q, Iorio A, Germini F, Skinner M. Gene therapy with the Padua variant of a codon-optimized human factor IX gene etranacogene dezaparvovec in people with hemophilia B: effects on patient-oriented outcomes measured using thePatient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire in the HOPE-B study. (2024), POSTER ABSTRACT (PP-164). (2024), Issue Information. Haemophilia, 30: 1-2. https://doi.org/10.1111/hae.15016

Introduction

The Patient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire was used to measure patient-oriented outcomes in the HOPE-B trial. Determine the effect of a single dose of adeno-associated virus 5 (AAV5) vector expressing the Padua factor IX variant (etranacogene dezaparvovec) on the quality of life and the burden of the disease as measured by the PROBE questionnaire.

Methods

In this phase 3, open-label, single-arm trial, people with severe to moderately severe haemophilia B, after factor IX prophylaxis for ≥6 months (lead-in period), received one infusion of etranacogene dezaparvovec. The PROBE questionnaire was admin-istered at enrolment, during the lead-in period, and at 6 months, 1, 2and 3 years after the treatment. The PROBE score was calculated and ranged from 0 to 1 (worst to best health status possible). Intra-patientchanges in PROBE scores were analysed using a two-level linear mixed model (within patient repeated observations and random intercepts).

Results

Fifty-four adult males received the treatment, and PROBE data were available for 48 participants. The characteristics of the population and the mean PROBE score at the various time points are reported in Table 1. Using the baseline as a reference, there was an average change (95% confidence interval) in the PROBE score of 0.04 (0.02, 0.07) at 6 month/1 year, which persisted at 2–3 years, 0.04(0.02, 0.06). Nine (22.5%) participants had an improvement of at least0.1 in the PROBE score, five (12.5%) had a worsening of at least 0.1. Changes in the responses to the core PROBE questions are reported in Table 2. At three years, there was a 23.8% (95% CI -41.7, −5.8) reduction in the prevalence of participants having experienced acute pain in the previous 12 months. Participants with at least one target joint at baseline demonstrated a trend towards reduction in the proportion of participants experiencing difficulties with activity of daily life, without reaching the cut off for statistical significance.

Conclusions

Administering a single dose of etranacogene dezaparvovec to patients with hemophilia B led to improvement of mean Probe score maintained through at three years.

Disclosures

Steven Pipe: Apcintex, ASC Therapeutics, Bayer, BioMarin, CSL Behring, HEMA Biologics, Freeline, LFB, Novo Nordisk, Pfizer, Regeneron/Intellia, Genentech/Roche, GeneVentiv and Equilibra Bioscience, Sanofi, Takeda, Spark Therapeutics, uniQure, Siemens; Bernard Joseph: CSL Behring; Julia Braverman: CSL Behring; Nicholas Galante: CSL Behring; Paul Monahan: CSL Behring; Alfonso Iorio: Bayer, CSL, Pfizer, Roche, Sanofi/Sobi, Takeda; Federico Germini: Bayer, Biomarin, CSL Behring, Novo Nordisk, Pfizer, Roche, Takeda; Mark Skinner: Band Therapeutics, Bayer, BioMarin, CSL Behring, Novo Nordisk, Pfizer, Roche/Genentech, Sanofi, Takeda, Vega Therapeutics

View Poster: PP_164_WFH2024

WFH 2024 – PROBE and Slovenia PosterKucher A, Clearfield E, Kavčič M, Urbančič M, Živić Kavčič M and Skinner M. Summary data from the first collaboration of PROBE and Drustvo Hemofilikov Slovenije (DHS) – an ongoing quality of life study. (2024), POSTER ABSTRACT (PP-162). (2024), Issue Information. Haemophilia, 30: 1-2. https://doi.org/10.1111/hae.15016

Introduction

Drustvo Hemofilikov Slovenije (DHS) and the Patient Reported Outcomes Burdens and Experiences (PROBE) study have initiated a collaboration to discover the quality of life (QoL) for people with hemophilia (PWH) in Slovenia.

Methods

Data was collected using PROBE’s web-based questionnaire. PROBE collects data in four categories: personal demographics, general health problems, hemophilia-specific health problems, and the Euro-QoL 5 dimensions 5 levels (EQ-5D-5L). Summary descriptive statistics are provided.  

Results

Twenty-four PWH A and B participated (Table 1); 91.7% (n=22) were PWHA. The average age (SD) was 44.3 (18.4) years. Most participants had severe hemophilia 62.5% (n=15), moderate and mild hemophilia were reported by 16.7% (n=4) and 20.8% (n=5), respectively. Nineteen (79.2%) reported access to prophylaxis treatment, and two (8.3%) reported using on-demand treatment. One person reported that treatment was not available. In the family section, 58.3% (n=14) reported being married/in a long-term relationship and 54.2% (n=13) have children. Frequency of use of pain medication was low: 45.8% (n=11) reported using it “rarely” (1-5% of the time), and 25% (n=6) selected that they did not use any pain medication. The presence of acute pain and chronic pain was reported by 50% (n=12) and 70.8% (n=17), respectively. Fifty percent (n=12) indicated their chronic pain is due to target joint/s. Seventeen people (70.8%) indicated they had a target joint. PROBE and EQ-5D-5L scores range from 0 to 1, with a score closer to 1 meaning better QoL. Mean (SD) scores for PROBE and EQ-5D-5L were 0.803 (0.16) and 0.841 (0.14), respectively.

Conclusions

Collaboration between DHS and PROBE launched recently, with a goal to administer PROBE to at least half of the severe and moderate population of PWH in Slovenia. These data from the first set of participants shows the impact and importance of QoL data collection for the patient organization. PROBE can be used to measure access to the treatment, one of the most valuable indications of positive impact on QoL for PWH. PROBE also measures other key outcomes affecting QoL for PWH. Data collection is ongoing, and further analyses will be completed to understand the impact of living with hemophilia in Slovenia.

View Poster: PROBE and Slovenia Poster

Kucher A, Clearfield E, Skinner M and PROBE Investigators. National Member Organization’s PROBE Data Dashboard Update – Adding A Pain Dashboard Page for Better Understanding of the Pain Impact in People with Hemophilia. (2024), POSTER ABSTRACT (PP-167). (2024), Issue Information. Haemophilia, 30: 1-2. https://doi.org/10.1111/hae.15016

Introduction

The Patient Reported Outcomes, Burdens and Experience (PROBE) study has been implemented in 105+ countries and translated into 50+ languages. How does the study benefit national member organizations (NMO)? The PROBE team has developed an interactive dashboard utilizing data from the pain elements of the PROBE questionnaire, a hemophilia-specific quality of life instrument. This dashboard can be provided upon request to participating NMOs for analysis and study of their country’s data with options to aggregate data, generate graphs, and utilize filters to support and specify data analyses.

Methods

The first development of the PROBE NMO Dashboard started in 2017. The dashboard was developed using Power BI, Microsoft software. Since then, the dashboard has been modified to provide better data picture for NMOs to report to health policy decision makers or for use to test and analyze hypotheses for publications. The PROBE questionnaire asks about the use of pain medication, the presence of acute and chronic pain, when pain occurs, and whether pain causes interference in a person’s life for things such as activity, mood, relationship with others.

Results

The importance of detailed PROBE responses regarding pain has been discussed among the PROBE Investigator team and approved for modification. The newest upgrade to the dashboard is a specific Pain page that covers detailed data about acute and chronic pain interference and occurrences, activities of daily living, the EQ-5D-5L pain dimension, PROBE anxiety and depression items, PROBE score and EQ-5D-5L score.

Conclusions

The pain dashboard demonstrates that a person’s experiences with pain are highly important for reporting on quality of life for people with hemophilia. Having the ability to compare both a control group and hemophilia group with pain occurrences and interferences can support claims of better or worse quality of life that could be addressed through healthcare management or and improved access to treatment. Analyzing PROBE and EQ-5D-5L together demonstrates the importance of using both generic and disease specific quality of life instruments. The pain dashboard will be a valuable asset for NMOs for pain reports and management for people with hemophilia.

View Poster: Pain Dashboard Page

Curtis R, Wu J, Iorio A, Nichol M, Germini F, Kucher A, Skinner M. Test-Retest Reliability Analysis of the Patient Reported Outcomes Burdens and Experiences (PROBE) Study. (2023), POSTER ABSTRACTS (PO077). Haemophilia, 29: 24-202. https://doi.org/10.1111/hae.14715

Objective

To investigate the test-retest reliability of the PROBE questionnaire mobile application (MyPROBE).

Methods

People with hemophilia (PWH) including carriers and individuals without a bleeding disorder who attended hemophilia related workshops were invited to participate in this study. Additional participants were recruited through social media. Participants completed PROBE anonymously 3 times: twice on the MyPROBE app (Time 1 and Time 2, ~24 hours apart) and once on the web portal (Time 3, ~14 days after T1). Test-retest reliability was measured calculating the Cohen’s Kappa coefficient for categorical variables, and the correlation coefficient for continuous variables. 

Results

Forty-eight participants were enrolled with a median age (range) of 56 (27-78) years. Of these, 13 (27.1%) were PWH, 12 (25.0%) were carriers of hemophilia A or B and 23 (47.9%) were individuals without a bleeding disorder. On general health domain questions, Kappa coefficients ranged from 0.72 to 1.00, indicating substantial to almost perfect agreement using Cohen’s Kappa for all items (T1 vs T2). T2 vs T3 values ranged from 0.64 to 0.97 with only the acute pain-related questions scoring less than almost perfect agreement. For hemophilia-related domain questions (T1 vs T2), Kappa coefficients ranged from 0.49 to 1.00. Of these, 5 of 8 items were in almost perfect agreement. Values for T2 vs T3 ranged from 0.34 to 1.00, with the time-based bleeding question showing the only coefficient that scored below substantial agreement. For overall health-related quality of life, EQ-5D-5L index scores had a paired mean difference of -0.01 for T1 to T2 and 0.01 for T2 to T3 indicating a near perfect correlation. The correlation coefficients for these two time points were 0.89 and 0.83 respectively. Reliability of the MyPROBE app showed substantial to almost perfect agreement with the web version (T2 to T3). Correlation coefficient of the EQ-visual analog scale (EQ-VAS) for T1 to T2 was 0.90 (0.83 – 0.94) and 0.71 (0.53 – 0.83) for T2 to T3.

Conclusions

The test-retest exercise showed substantial to almost perfect agreement in a majority of questions for the app vs app, and a high correlation for the web vs app. The results suggest the MyPROBE app is a reliable tool to assess patient reported outcomes for PWH and control populations independently of the platform used for its completion.

View Poster: HERE

Curtis R, Wu J, Iorio A, Nichol M, Germini F, Kucher A, Skinner M. Test-Retest Reliability Analysis of the Patient Reported Outcomes Burdens and Experiences (PROBE) Study. (2023), POSTER ABSTRACTS (PO077). Haemophilia, 29: 24-202. https://doi.org/10.1111/hae.14715

Objective

To investigate the test-retest reliability of the PROBE questionnaire mobile application (MyPROBE).

Methods

People with hemophilia (PWH) including carriers and individuals without a bleeding disorder who attended hemophilia related workshops were invited to participate in this study. Additional participants were recruited through social media. Participants completed PROBE anonymously 3 times: twice on the MyPROBE app (Time 1 and Time 2, ~24 hours apart) and once on the web portal (Time 3, ~14 days after T1). Test-retest reliability was measured calculating the Cohen’s Kappa coefficient for categorical variables, and the correlation coefficient for continuous variables. 

Results

Forty-eight participants were enrolled with a median age (range) of 56 (27-78) years. Of these, 13 (27.1%) were PWH, 12 (25.0%) were carriers of hemophilia A or B and 23 (47.9%) were individuals without a bleeding disorder. On general health domain questions, Kappa coefficients ranged from 0.72 to 1.00, indicating substantial to almost perfect agreement using Cohen’s Kappa for all items (T1 vs T2). T2 vs T3 values ranged from 0.64 to 0.97 with only the acute pain-related questions scoring less than almost perfect agreement. For hemophilia-related domain questions (T1 vs T2), Kappa coefficients ranged from 0.49 to 1.00. Of these, 5 of 8 items were in almost perfect agreement. Values for T2 vs T3 ranged from 0.34 to 1.00, with the time-based bleeding question showing the only coefficient that scored below substantial agreement. For overall health-related quality of life, EQ-5D-5L index scores had a paired mean difference of -0.01 for T1 to T2 and 0.01 for T2 to T3 indicating a near perfect correlation. The correlation coefficients for these two time points were 0.89 and 0.83 respectively. Reliability of the MyPROBE app showed substantial to almost perfect agreement with the web version (T2 to T3). Correlation coefficient of the EQ-visual analog scale (EQ-VAS) for T1 to T2 was 0.90 (0.83 – 0.94) and 0.71 (0.53 – 0.83) for T2 to T3.

Conclusions

The test-retest exercise showed substantial to almost perfect agreement in a majority of questions for the app vs app, and a high correlation for the web vs app. The results suggest the MyPROBE app is a reliable tool to assess patient reported outcomes for PWH and control populations independently of the platform used for its completion.

View Poster: HERE

Kucher A, Clearfield E, Germini F, Dubé E, Merlen C, Bonnefoy A, St-Louis J, Rivard G.E, Skinner M. Impact on Pain and Activities of Daily Living after Switching to Emicizumab: Insight from PROBE.(2023), POSTER ABSTRACTS (PO177). Haemophilia, 29: 24-202. https://doi.org/10.1111/hae.14715 

Introduction

Emicizumab for treatment of people with severe hemophilia A (SHA) was recently approved by Health Canada. A prospective observational study was initiated to evaluate the efficacy of emicizumab and assess health-related quality of life (HRQoL).

Methods

HRQoL outcomes were collected using the Patient Reported Outcomes Burdens and Experiences (PROBE) questionnaire. Eight male SHA (median age 22.5, range 17-55 years) completed PROBE pre- and ≥ 10 months post-switching to emicizumab. Acute and chronic pain were assessed as any occurrence (recall: 12 months) and during 8 activities (walking, stair climbing, nighttime, resting, weight bearing, playing, after falling/trauma, other). Participants reported pain interference in 11 aspects of life (general activity, walking ability, normal work, attending school, relations with others, sleep, enjoyment of life, playing/participating in sports/exercising, lifting, other). PROBE also includes a 24-item activities of daily living (ADL) list; current difficulty is reported. Descriptive statistics present results for pain outcomes and difficulty with ADL.

Results

The number of SHA reporting any acute pain, chronic pain, or ADL impairment was reduced post switch (7
[87.5%] to 4 [50.0%], 5[62.5%] to 4 [50%], 8 [100%] to 3 [37.5%], respectively). Switching was associated with improvement on self-reported acute and chronic pain occurrence during activities post-switch. Pre-switch SHA reporting acute pain indicated “yes” to the acute pain occurrence in 22 vs 8 cases post-switch. Chronic pain was similarly reduced from 20 to 7. No SHA reported acute or chronic pain occurrences for nighttime and resting post-switch. Reports of pain interference were also reduced: there were more affirmative reports of acute and chronic pain interfering pre-switch compared to post (42 vs 12 and 28 vs 15, respectively). Data also show an association with improvements in ADL from 72 activities reported difficult to perform pre-switch vs 20 post-switch. The most improved ADL post-switch were getting up from sitting, playing games or participating in sport, sleeping/resting, doing heavy domestic tasks.

Discussion/Conclusion

PROBE demonstrated that the introduction of emicizumab is associated with a significant decrease in self-reported acute and chronic pain, as well as reduced interference with activities of daily living.

Disclosure of Interest: Noone D.

View Poster: HERE

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. THSNA 2022.

Background

The patient reported outcomes, burdens and experiences (PROBE) questionnaire measures quality of life in people with hemophilia and healthy controls. A score is calculated as the average of nine core questions. There is currently no validated method for calculating the PROBE score when data are missing.

Objective

Our objectives were to identify domains within the questionnaire and compare strategies for estimating the PROBE score when:
1. ≥50% item scores within a domian were available,
2. only one item score within a domain was available,
3. ≥50% item scores were available irrespective of any domain,
4. 8 out of 9 item scores were available.

Method

Scores with ICC ≥0.5 were grouped into a domain. We created one simulated data set for each combination of 1) types of missing data: MCAR, MAR, and MNAR, 2) 10, 15, and 20% missing values, and 3) the four strategies described above. A strategy with mean of absolute errors (MAE) + SD <0.05, and calibration intercepts and slopes not systematically different from 0 and 1, respectively, was considered acceptable.

Results

Among 3217 participants four item scores had ICC ≥0.5 and were grouped into a domain, pain or difficulty in daily activities (Cronbach’s alpha of 0.8). Strategies 1 and 4 performed better (MAE ± SD: 0.02 ± 0.02 for MCAR and MAR) followed by strategies 2 and 3 (Table 1). Strategy 1 estimated PROBE score accurately for MCAR and MAR data (Table 2), and slightly under-estimated the score in case of MNAR data.

Conclusion<

We recommend estimating PROBE scores as a simple average of the available item scores if at least one item within pain/difficulty in daily activities domain is available or 8 out of 9 items are available irrespective of the domain.

View Poster: HERE

Chai‐Adisaksopha C, Noone D, Curtis R, Frick N, Nichol M, O’Mahony B, Page D, Stonebraker J, Iorio, A, Skinner MW. Exploring Regional Variations in the Cross‐cultural, International Implementation of the Patient Reported Outcomes Burdens and Experience (PROBE) Study. Abstract PB189. Res Pract Thromb Haemost. 2018;2(S1):1-368. https://doi.org/10.1002/rth2.12125

Background

The Patient Reported Outcomes Burdens and Experience (PROBE) study has developed and validated the multilingual PROBE questionnaire for assessing patient reported outcomes in people living with hemophilia (PWH) and participants without bleeding disorders (NOBD). The PROBE questionnaire translations into local languages account for site specific language and cultural peculiarities in the management and life experience of hemophilia.

Aims

To explore the regional variations in the international implementation of the PROBE questionnaire and examine the hypothesis that the PROBE score will not be confounded by cross-cultural aspects.

Methods

Data were collected from participants in four regions (Western Pacific, South America, North America and Europe). Participants were able to select from 23 localized language versions of the PROBE questionnaire based on their first language. We used analysis of variance methods and multivariable regression to determine the relative contribution of the variance explained by region controlling for hemophilia diagnosis, age group and level of education. We also explored interactions between region and the other components.

Results

We analyzed 862 questionnaires from 21 countries. Mean age of participants was 40.03 years (SD 13.89) and 65.20% were PWH and 34.80% were NOBD. After adjusting for hemophilia diagnosis, age group and level of education, region contributed 0.44% to 7.98% of the variance component in sub-item scores and 0.26% in the PROBE score. Years of education contributed 0.34% in the PROBE score. Age and diagnosis (NOBD, mild, moderate, severe) contributed 3.42% and 22.42% of the PROBE score. 70.74% of the variance was explained by inter-individual variation.

Conclusions

Variance partitioning for the PROBE score is similar to that for EQ5D. The results demonstrate that the PROBE questionnaire is valid to implement for assessing health status among PWH and participants without bleeding disorders across regions.

Skinner M, Chai-Adisaksopha C, Noone D, Curtis R, Frick N, Nichol M, O’Mahony B, Page D, Pastarnak A, Stonebraker J, Iorio A and the Patient Reported Outcomes Burdens and Experiences (PROBE) Study Investigator Group. The Patient Reported Outcomes Burdens and Experiences (PROBE) Study Questionnaire Development and Validation (Abstract). NHF (2019).

Objectives

The health status of people living with hemophilia (PWH) has not been systematically investigated globally. There is a substantial need to improve capacity to collect and interpret relevant patient-reported outcomes (PRO) data to support patient-centered research and optimal care of PWH. PROBE aimed to: 1) implement a structured data collection of PRO across countries to build a robust evidence base for comparative effectiveness research, evidence-based decision making, and advocacy, 2) explore the measurement properties of the PROBE questionnaire and 3) assess the feasibility of PROBE for assessing health status among PWH and participants without bleeding disorders across regions. Three intermediate objectives were identified: develop a patient-led research network; develop a standardized questionnaire to gather PRO; and perform a feasibility study of implementing the PROBE questionnaire.

Methods

Data collection from April 2015 to February 2017. 2,101 surveys were collected through all study phases across 24 countries. 1,541 met study criteria for analysis. Clinical Trial registration: NCT02439710.

Summary

The PROBE questionnaire consists of four major sections: demographic data, general health problems, hemophilia-related health problems and health-related quality of life. Outcomes of importance to PWH and metrics to consider for measurement were determined.

Domains for outcomes of importance to measure reduced burden of living with hemophilia include (metrics): Life and Family (family life, marital status, children, current health status); Education/School and Employment (attendance, educational attainment, employment duration, underemployment) and Activities (impact on activities of daily living, mobility impairment, assistance required).

Domains for reduced complications associated with hemophilia and treatment (metrics): Joint Disease (joint status); Pain, Depression/Anxiety (chronic/acute pain, pain interference, pain occurrence, pain medication, depression); and Other Comorbidities (HIV/HCV, obesity, resource utilization, mortality, longevity).

PROBE questionnaire validation studies established face validity, relevance, clarity and completeness (Skinner, Pilot and Feasibility Studies 2018); test-retest reliability (reproducibility) (Chai‐Adisaksopha, Haemophilia 2019); a core analytic framework (psychometric properties) (Chai‐Adisaksopha BMJ Open2018); and cross-cultural validation (Chai‐Adisaksopha, Haemophilia 2019).

Conclusions

The PROBE questionnaire established and assessed patient-important outcomes in PWH and control participants, with a demonstrated short completion time using both paper and electronic versions. PROBE proved the feasibility to engage diverse patient communities in the structured generation of real-world outcome research at all stages. Results demonstrate that the PROBE questionnaire is valid for assessing PROs and health status among PWH and participants without bleeding disorders across regions. The known group property of PROBE will allow its use in future clinical trials, longitudinal studies, health technology assessment studies, routine clinical care or registries. Longitudinal PRO data collection using an instrument such as PROBE will be useful within clinical development programs, clinical management settings and to support access to care initiatives.

View Poster: PROBE Study questionnaire development and validation

Skinner M, Chai-Adisaksopha C, Noone D, Curtis R, Frick N, Nichol M, O’Mahony B, Page D, Pastarnak A, Stonebraker J, Iorio A and the Patient Reported Outcomes Burdens and Experiences (PROBE) Study Investigator Group. Validation of the Patient Reported Outcomes Burdens and Experiences (PROBE) Study Questionnaire (Abstract). HAAB (2019).

Introduction

Objectives

The aims were to implement a structured data collection of PRO across countries to build a robust evidence base for comparative effectiveness research, evidence-based decision making, and advocacy. Three intermediate objectives were identified:

• develop a patient-led research network;
• develop a standardized questionnaire to gather PRO; and
• perform a feasibility study of implementing the PROBE questionnaire.

Additional aims were to explore the measurement properties of the PROBE questionnaire and demonstrate PROBEis valid to implement for assessing health status among PWH and participants without bleeding disorders acrossregions.

Methods:

Clinical Trial registration: NCT02439710.

Results

Validation studies for the PROBE questionnaire have been completed. The questionnaire was assessed for face validity, relevance, clarity and completeness(i); test-retest reliability (reproducibility) confirmed(ii); a core analytic framework (psychometric properties) established(iii); and cross-cultural validation demonstrated(iv). Outcomes of importance to PWH and metrics to consider for measurement were determined. The PROBEquestionnaire consists of four major sections (demographic data, general health problems, hemophilia-related healthproblems and health-related quality of life). PROBE questionnaire validation studies establish:

• Face validity, relevance, clarity and completeness
• Test-retest reliability (reproducibility)
• A core analytic framework (psychometric properties)
• Cross-cultural validation

Conclusions

The PROBE questionnaire is a valid and reliable tool for assessing health status among PWH and participants without bleeding disorders across regions. PROBE assesses patient-important PROs with ademonstrated short completion time. PROBE proved the feasibility to engage diverse patient communities instructured generation of real-world outcome data. The web‐based questionnaire and the paper‐based version maybe used interchangeably. The known group property of PROBE will allow its use in future clinical trials, longitudinalstudies, health technology assessment studies, routine clinical care or registries. Additional studies are planned totest responsiveness and sensitivity to change.

References

View Poster: Validation of the PROBE Study Questionnaire

Skinner M, Chai-Adisaksopha C, Noone D, Curtis R, Frick N, Nichol M, O’Mahony B, Page D, Pastarnak A, Stonebraker J, Iorio A and the Patient Reported Outcomes Burdens and Experiences (PROBE) Study Investigator Group. Comparison of the Measurement Properties of the PROBE and EQ5D on Pain [Oral Presentation]. HTAi (2019).

Background

The Patient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire has been developed for assessing patient reported outcomes in people living with hemophilia (PWH). The PROBE questionnaire consists of 29 questions involving the following domains: hemophilia-related problems, general health problems and health-related quality of life. The PROBE questionnaire contains 3 questions assessing pain (current use of pain medications, occurrence and interference of acute and chronic pain).

Objectives

This study aims to investigate the measurement properties of pain assessment of the PROBE questionnaire compared with the pain and discomfort domain of EQ5D-5L.

Methods

The participants of the PROBE study were recruited via national patient organizations from 21 countries. Participants who did not state status of hemophilia (having hemophilia or not) or those who did not report severity of disease were excluded from the analysis. Descriptive data were reported as a proportion and mean (standard deviation) as appropriate. We calculated the correlation coefficient between EQ5D-5L (pain domain) and the occurrence and inference of acute pain and chronic pain from the PROBE questionnaire. We investigated the discriminative property of the pain domain of the PROBE questionnaire and EQ5D-5L.

Results

A total of 1675 participants were included in the analysis (PWH 68.7%, 31.3% participants without bleeding disorders). Mean age was 37.5 years (SD 17.4). Data from the PROBE revealed that during the past 12 months, 60.5% and 51.1% of participants reported they have acute and chronic pain, respectively. 79.6% of participants reporting the use of pain medications. Acute pain occurred when walking (30.5%) followed by night time and weight bearing. Acute pain interfered with general activities the most (38.3%) followed by walking ability and mood. Chronic pain occurred when walking (38.9%), followed by stairclimbing and weight bearing. Chronic pain interfered with general activities the most (35.7%), followed by walking ability and mood. Table 1 shows the correlation coefficient of the counts of occurrence and inference of acute and chronic pain (PROBE) versus the pain domain of the EQ5D-5L. The correlations were moderate between acute pain (PROBE) and the pain domain on EQ5D-5L, whereas the correlations were strong between chronic pain (PROBE) and the pain domain on EQ5D-5L. When classifying participants to 4 groups (controls, mild-, moderate- and severe hemophilia), the discriminative property of PROBE (figure 1) and EQ5D-5L-pain (figure 2) was excellent. Both tools can differentiate participants with hemophilia (varied severity) and without hemophilia, ANOVA p-value<0.05.

Conclusions

The pain questions on the PROBE questionnaire are well correlated with the pain domain on EQ5D-5L. The discriminative property of both tools is found to be excellent to separate people with various severities of hemophilia as well as people without bleeding disorders. The strength of the pain domain on the PROBE questionnaire is that it provides more informative data on the use of pain medication, occurrence and interference of acute and chronic pain. Therefore, the PROBE questionnaire is a disease-specific patient reported outcome measure, which will provide more insightful information regarding pain status in PWH.

View Presentation: PROBE and EQ5D-5L on pain assessment

Skinner M, Chai-Adisaksopha C, Noone D, Curtis R, Frick N, Nichol M, O’Mahony B, Page D, Pastarnak A, Stonebraker J, Iorio A and the Patient Reported Outcomes Burdens and Experiences (PROBE) Study Investigator Group. Part-Time Employment and Early Retirement In People With Severe Haemophilia: Insights From The PROBE Study. Poster Presentations #P204 Haemophilia. 2019;25(S1):35-188. https://doi.org/10.1111/hae.13666

Introduction

Despite treatment advances economic, social and educational barriers still remain for people with severe haemophilia. Contextual factors such as the lifetime impact of haemophilia on employment and overall work life are not well understood.

Methods

People with severe haemophilia A/B (PwSH) and controls with no bleeding disorder (NoBD) reporting working part-time or havingretired early due to their health were compared with those reporting working full-time. Patient Reported Outcome Burdens and Experiences (PROBE) Study data of 1008 participants age 18 and over from 21 countries were analyzed (550 PwSH, 458 NoBD). Descriptive statistics were used to present results as n (%), and odds ratio (95% CI) were calculated for the associations for participants with any health problems—use of mobility aids, use of pain medication, having acute or chronic pain, difficulties with activities of daily living and history of joint surgery—and assessed for their statistical significance.

Results

250 PwSH (45.5%) and 263 NoBD (57.4%) reported working full time. 86 PwSH (15.6%) and 80 NoBD (17.5%) reported working part-time. 27 of the 86 PwSH (31.4%) and 3 of the 80 NoBD (3.8%) reported working part-time due to health. 52 PwSH (9.5%) and 28 NoBD (6.1%) reported taking early retirement. 25 of the 52 PwSH (48.1%) and 1 of the 28 NoBD (3.6%) reported taking early retirement due to health. Association between reporting a health-related problem and working part-time or taking early retirement due to health were[n (%), Odds Ratio (95% CI), p-value]: use of mobility aids 77.7 (3.8-1645) 0.0005, having acute pain 41.2 (2-831.8) 0.01, use of pain medication 23 (2.05-258.1) 0.01, participants experiencing any health problems 22.5 (2-252.6) 0.01, having chronic pain 16.5 (1.5-179.2) 0.02, difficulty with activities of daily living (ADL) 16.5 (1.5-179.2) 0.02, and history of joint surgery 7.3 (0.4-148) 0.197. Mean participant age: PwSH 39 (14.4 SD) and NoBD 45.3 (13.7 SD).

Discussion/Conclusion

Haemophilia has a significant negative impact on work life. PwSH report a higher rate of retiring early or working part-time due to health than age-matched controls. Use of mobility aids, acute / chronic pain, difficulty with ADL and history of joint surgery are associated with retiring early or working part-time. The lifetime impact of haemophilia on employment should be more fully considered within health technology assessments.

Disclosure of Interest

M. Skinner Grant/Research support from: PROBE is an independent investigator led research project with grant / research support from: Baxalta, now part of Shire; Bayer; Bioverativ, a Sanofi Company; CSLBehring; Novo Nordisk, Roche and Sobi and the collaboration of the US National Hemophilia Foundation., C. Chai-Adisaksopha: None Declared, D. Noone: None Declared, R. Curtis: None Declared, N. Frick: None Declared, M. Nichol: None Declared, B. O’Mahony: None Declared, D. Page: None Declared, A. Pastarnak: None Declared, J. Stonebraker: None Declared, A. Iorio: None Declared

View Poster: Early Retirement and Part-time Employment

Noone D, Chai-Adisaksopha C, Curtis R, Frick N, Nichol M, O’Mahony B, Page D, Pastarnak A, Stonebraker J, Iorio A, Skinner M. Predictors For Acute And Chronic Pain In Patients With Severe Haemophilia In The PROBE Cohort. Poster Presentations #P080. Haemophilia. 2019;25(S1):35-188. https://doi.org/10.1111/hae.13666

Introduction

For people with severe haemophilia, acute and chronic pain is often part of their daily reality. We looked at the extent to which this pain was influenced by annual bleed rate, presence of target joints or joints with reduced range of motion.

Methods

A binary regression analysis was performed to measure the association of acute and chronic pain with selected predictors from the PROBE Phase 2 data. The dependent variable (outcome) was the likelihood of reporting chronic and acute pain. The 5 predictor variables includedin the model were: age, reported annual bleeding rate (ABR), current treatment, presence of a target joint and range of motion (ROM) in a joint.

Results

There were 1287 respondents from 21 countries in total, 658 of whom had severe haemophilia and information for the predictor variables. For acute pain, the univariate logistic regression analysis showed a significant association for ABR (all bleeds) with patients reporting 2-3 bleeds/year being 2.9 times more likely to report acute pain compared to those with 0-1 bleeds/year, and those reporting more than 15 bleeds/year being 10.3 times more likely. Those reporting the presence of a target joint were 2.0 times more likely to report acute pain than thosewithout a target joint. In the full model (all 5 predictors) the impact of ABR is reduced but remains significant. Overall, the full model only predicts 13% of the variation in those who report acute pain. For chronic pain models, the univariate model predicts that those with 2-3 bleeds/year and >15 bleeds/year are 2.2 and 5.5 times more likely to report chronic pain compared to those with 0-1 bleeds/year, explaining 14% of the variance in chronic pain. In the full model however, the most responsible predictor was the presence of a joint with reduced ROM, withthose reporting a limitation being 5 times more likely to report chronic pain than those with full range of motion, which explains 23% of the variance.

Discussion/Conclusion

Our predictors were found to correlate with acute and chronic pain. While acute pain is primarily driven

by the frequency of bleeding and the presence of a target joint, chronic pain is primarily driven by the presence of a joint with reduced range of motion. Therefore, it would be worth exploring whether treatment regimens targeted to reduce annual bleeding rates or those aimed at improving the range of motion would be more effective in reducing chronic pain.

Disclosure of Interest

D. Noone Grant/Research support from: Baxalta, now part of Shire; Bayer; Bioverativ, a Sanofi Company; CSLBehring; Novo Nordisk, Roche and Sobi and the collaboration of the US National Hemophilia Foundation, Chai-Adisaksopha: None Declared, R. Curtis: None Declared, N. Frick: None Declared, M. Nichol: None Declared, B. O’Mahony: None Declared, D. Page: None Declared, A. Pastarnak: None Declared, J. Stonebraker: None Declared, A. Iorio: None Declared, M. Skinner: None Declared

View Poster: Predictors For Acute And Chronic Pain

Noone D, Chai-Adisaksopha C, Curtis R, Frick N, Nichol M, O’Mahony B, Page D, Pastarnak A, Stonebraker J, Iorio A, Skinner M. Impact of Acute and Chronic Pain on the EQ-5D: Insights From The PROBE Study. Poster Presentations #P079. Haemophilia. 2019;25(S1):35-188. https://doi.org/10.1111/hae.13666

Background

Acute and chronic pain as well as the potential access to medications, including haemophilia specific products, significantly impact the quality of life of people with haemophilia (PWH). Generic questionnaires such as the EQ-5D are used to measure the impact of the condition on life experience. EQ-5D in particular is designed to record the individual experience on the day of completion. There is little information on how the response to the pain domain in EQ-5D is driven by acute or chronic pain. The Patient Reported Outcomes, Burdens and Experiences (PROBE) is a questionnaire developed by patients to measure what matters to them in a way that allows comparison with people without bleeding disorders.

Aim and methods

We hypothesized that joint analysis of EQ-5D and PROBE measures would allow deeper understanding of the impact of acute and chronic pain on the respective scores. Descriptive and correlation analysis were performed.

Results

Of 1287 respondents, 686 have severe haemophilia and were examined in this article. We identified 4 subgroups based on responses to PROBE questions asking about acute and chronic pain: no pain (NP, 12.46%), acute pain (AP, 16.13%), chronic pain (CP, 16.23%) and both chronic and acute pain (A/CP, 55.13%). The mean (SD) ages for NP, AP, CP and A/CP were 27.5 (18.3), 24.8 (15.0), 39.2 (15.57) and 37.6 (16.0), respectively. There was a weak correlation (r =0.21, Pearson) between chronic and acute pain.

The mean (SD) EQ-5D utility values for NP, AP, CP and A/CP were 0.91 (0.12), 0.82 (0.21), 0.75 (0.17) and 0.65 (0.28), respectively. Standard t-tests indicated that all groups were statistically different from each other. A similar trend was seen in VAS score.

Conclusion

Acute pain has a significant impact on the quality of life of PWH.  This is further exacerbated by the presence of chronic pain and the combination of both leads to the greatest decrease in quality of life.   The EQ-5D does discern a difference between both types of pain. However, if chronic pain only is present at the time the EQ-5D is administered, the result may mask the full extent of the impact on the utility value unless the context and timing of using these generic tools is understood. It may lead to a misrepresentation of the true nature of pain within the severe haemophilia population.

View Poster: Impact of Acute and Chronic pain on the EQ-5D

Skinner M, Chai‐Adisaksopha C, O’Mahony B, Noone D, Curtis R, Frick N, Nichol M, Page D, Stonebraker J, Iorio A. Patient Reported Outcomes Burdens and Experiences Study Group. Validation of the Patient Reported Outcomes Burdens and Experiences (PROBE) Study Questionnaire. Abstract PB1412. Res Pract Thromb Haemost. 2019;3(S1):1-891. https://doi.org/10.1002/rth2.12229

Background

A substantial need exists to improve capacity to collect and interpret relevant patient-reported outcomes (PRO) data to support patient-centered research and optimal care in people with hemophilia (PWH).

Aims

Implement a structured data collection of PRO across countries to build a robust evidence base for comparative effectiveness research, evidence-based decision making, and advocacy. Three intermediate objectives were identified:

• develop a patient-led research network;
• develop a standardized questionnaire to gather PRO; and
• perform a feasibility study of implementing the PROBE questionnaire.

Additional aims were to explore the measurement properties of the PROBE questionnaire and demonstrate PROBEis valid to implement for assessing health status among PWH and participants without bleeding disorders acrossregions.

Methods

In data collection from April 2015 to February 2017, 2,101 surveys were collected through all studyphases; 1,541 met study criteria for analysis. Clinical Trial registration: NCT02439710.

Results

Outcomes of importance to PWH and metrics to consider for measurement were determined. The PROBEquestionnaire consists of four major sections (demographic data, general health problems, hemophilia-related healthproblems and health-related quality of life). PROBE questionnaire validation studies establish:

• Face validity, relevance, clarity and completeness
• Test-retest reliability (reproducibility)
• A core analytic framework (psychometric properties)
• Cross-cultural validation

Conclusions

The PROBE questionnaire is a valid and reliable tool for assessing health status among PWH and participants without bleeding disorders across regions. PROBE assesses patient-important PROs with ademonstrated short completion time. PROBE proved the feasibility to engage diverse patient communities instructured generation of real-world outcome data. The web‐based questionnaire and the paper‐based version maybe used interchangeably. The known group property of PROBE will allow its use in future clinical trials, longitudinalstudies, health technology assessment studies, routine clinical care or registries. Additional studies are planned totest responsiveness and sensitivity to change.

View Poster (English): Validation of PROBE’s Questionnaire

View Poster (Spanish): Validation of PROBE’s Questionnaire

O’Mahony B, Pastarnak A, Noone A, Skinner M. Patient Reported Outcome Data on Switch from Standard to Extended Half Life in Irish Adults with Haemophilia. Abstract OC 42.4. Res Pract Thromb Haemost. 2019;3(S1):1-228. https://doi.org/10.1002/rth2.12227

Background

From 2017 to the end of 2018, all people with Haemophilia B and the majority with Haemophilia A (PwH) in Ireland were switched to extended half-life FIX (rFIXFc) or FVIII (rFVIIIFc) concentrates.

Objectives

The Irish Haemophilia Society surveyed measurable impact on their health-related quality of life.

Methods

Utilising the Patient Reported Outcomes, Burdens and Experiences (PROBE) survey, the Society surveyed members of the organisation with Haemophilia A/B pre-change and a minimum of 10 months post product change.  There were 12 paired responses from people with Haemophilia B and 5 with haemophilia A.

Results

Three patients switched from episodic treatment to regular prophylaxis (2-HB, 1-HA).

Post-switch, there were reductions in PWH reporting the use of mobility aids (67% to 53%), acute pain (78% to 47%), frequency of use of pain medications, activities of daily living (ADL) being affected, reduced range of motion (83% v 65%) and chronic pain in a target joint (patient defined) (67% to 13%).

There was a significant reduction in reported bleeds.  Pre-switch 29% reported having greater than 8 bleeds/year and 41% having 1 or less bleed/year.  Post-switch there we no responses greater than 8 bleeds/year and 59% having 1 or less bleed/year.

Overall, VAS (68 v 73), EQ-5D (0.71 v 0.77) and PROBE (0.72 v 0.78) score improved post-switch, which equates to ~5-6% increase in utility in a year.  All dimensions of the EQ-5D showed improvement with the most significant changes seen in mobility, self-care and pain/discomfort. (Table 1).

Conclusions

From this initial data set, there is a demonstrated benefit to PWH switching to EHL products in reduced bleeding rates as well as in the physical and pain limitations that haemophilia imposes on daily life. Data collection and analysis are ongoing.

View Presentation: Data on switch from standard to extended half life in Irish adults with haemophilia

Chai-Adisaksopha C, Skinner MW, Page D, Stonebraker J, Noone D, Curtis R, Frick N, Nichol M, O’Mahony B, Iorio A, and Patient Reported Outcomes Burdens and Experiences Study Group. Health Status of People Living with Non- severe Hemophilia – Insights from the Patient Reported Outcomes, Burdens and Experiences (PROBE) Study. Abstract OC 32.4. Res Pract Thromb Haemost. 2019;3(S1):1-228. https://doi.org/10.1002/rth2/12227

Background

People living with non-severe hemophilia (PwNSH), FVIII/IX 2-40 IU/dL, generally receive factor concentrate episodically. In recent studies, life expectancy of PwNSH is comparable to the non-hemophilia male population. However, their health status has not been systematically investigated.

Aims

To evaluate the health status of PwNSH

Methods

PROBE data for PwNSH and participants without a bleeding disorder (controls) were analyzed. A match-paired analysis, using 1:1 ratio of PwNSH and controls was performed. Health status of the two groups were compared using parametric or non-parametric methods.

Results

366 participants were included in this analysis. Mean age was 44.7 (SD 17.4) years in PwNSH and 45.8 (SD 14.4) in controls. Table 1 demonstrates health status of participants. Acute pain and chronic pain were more commonly reported among PwNSH (72.4% and 68.1%) compared to controls (37.6% and 30.0%), P< 0.001. Pain medications were more commonly used among PwNSH as compared to controls (86.2% vs 68.0%, P< 0.001). Working full-time was more frequent among controls. PwNSH more frequently reported being on long-term sick or disability compared to controls. Mean sick days per year were significantly higher in PwNSH (3.7 days vs 44.9 days, P< 0.001). Self-evaluated health status using the visual analog scale (VAS) shows that PwNSH had a significantly lower VAS utility score compared to controls (72.8 vs 83.7, P< 0.001). Overall health status, which was evaluated by mean PROBE score, indicated that PwNSH had worse health status compared with controls (0.71 vs 0.89, P< 0.001).

Conclusions

PwNSH had more health-related problems, worse work/school life, and lower health-related quality of life when compared to controls. PROBE findings demonstrate non-severe hemophilia is not a benign disease. Traditional clinical outcomes, e.g., annualized bleeding rate or mortality, are less sensitive to detect health status in PwNSH. We encourage investigators and clinicians to evaluate PwNSH using a patient-reported outcome assessment tool.

View Presentation: Health Status of People Living with Non- severe Hemophilia

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

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 [Presentation]. ASH (2020), https://ash.confex.com/ash/2020/webprogram/Paper136397.html

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

O’Donovan M, Johnston K, Singleton E, Benson J, Ryan K, O’Connell N. Impact of Switching to Prophylaxis with Recombinant Factor IX Fc Fusion Protein Concentrate on Patient Reported Outcomes in People with Haemophilia B Using the PROBE Questionnaire [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/impact-of-switching-to-prophylaxis-with-recombinant-factor-ix-fc- fusion-protein-concentrate-on-patient-reported-outcomes-in-people-with-haemophilia-b-using-the- probe-questionnaire/. Accessed July 22, 2020.

Background

In 2017 all patients with severe Haemophilia B in Ireland switched to prophylaxis with recombinant factor IX Fc fusion protein (rFIXFc) concentrate from treatment with standard half-life (SHL) recombinant FIX. The Patient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire was developed to assess patient reported outcomes (PRO). Ithas four major sections; demographics, general health problems, haemophilia related health problems and health related quality of life.

Aims

To evaluate impact of switching to prophylaxis with rFIXFc from treatment with SHL FIX on PRO at two years after switchover.

Methods

Following ethical approval and informed consent, patients completed PROBE questionnaires pre switchover and at 24 months. Descriptive statistics were used for analysis.

Results

23 paired responses from 23 patients, median age 49 (31-72) years, with severe Haemophilia B were analysed. Acute pain, chronic pain and use of pain medication were reported at high rates at both 0 months (48%, 83% & 83%) and 24 months (64%, 74% & 95%). There was a reduction in chronic pain (83% to 74%) after 24 months of treatment with rFIXFc with a corresponding reduction in difficulties with activities of daily living (ADL). At 0 months, 61% reported :53difficulties with ADL. In comparison, at 24 months 68% reported :53 ADL difficulties, with greatest improvement seen with doing heavy domestic tasks (17%), bending down (13%), walking (13%) and going upstairs (13%). There was a reduction in reported number of bleeds; 50% :53 bleeds/annum in year prior to switchover, compared to 87% :53 bleeds/annum at 24months, with 35% reporting no bleeds.

Conclusions

From this initial data analysis there is a PRO benefit following a switch to rFIXFc prophylaxis with improvement in ADL, reduced chronic pain and bleeding rates. To further understand the patient experience post rFIXFc switch we plan to continue data analysis and perform qualitative interviews.

View Poster: Impact on switching to prophylaxis

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

Chai-Adisaksopha C, Curtis R, Frick N, Nichol M, Noone D, Germini F, O’Mahony B, Page D, Stonebraker J, Skinner M, Iorio A, PROBE . Non-Severe Hemophilia Is Not Benign? – Insights from the PROBE Study [abstract]. Res Pract Thromb Haemost. 2020;4(Suppl 1). https://abstracts.isth.org/abstract/non-sever-hemophilia-is-not-benign-insights-from-the-probe-study/. Accessed June 29, 2020.

Introduction

There are limited data on the impact of haemophilia on health status and health-related quality of life (HRQL) in people affected by non-severe haemophilia.

Aim

To evaluate the health status of people living with mild or moderate haemophilia.

Methods

A cross-sectional, multinational study was conducted as part of the Patient Reported Outcomes, Burdens and Experiences (PROBE) project. Respondents without bleeding disorder (NoBD) and those with mild or moderate hemophilia were included. Respondents were asked to complete the PROBE questionnaire, which contains haemophilia-related questions, general health questions and HRQL. Results were compared between unaffected individuals and people with mild or moderate hemophilia.

Results

A total of 862 respondents, of whom 143 with moderate haemophilia, 143 with mild haemophilia and 575 with NoBD were included. Median age (first-third quartile) was 33 (23-46),42 (25-55) and 43 (35-54), respectively.  In relation to bleeding in the previous 12 months, respondents with mild reported less bleeding frequency than those with moderate haemophilia, with similar patterns of bleeding frequency seen in both male and female cohorts. Reporting of acute pain is less in those with NoBD compared to the mild to moderate cohorts for both genders (male – 33%, 67%, 77%; female 38%,52%, 67%, respectively). Thirteen percent of those with NoBD reported an impact on activities of daily living compared with mild and moderate haemophilia who reported of 35% and 61%, respectively. The impact on quality of life due to mild haemophilia compared to those with NoBD was a reduction of 5.2%, 5.0% and 9.3% in VAS, EQ-5D-5L and PROBE Score respectively (p≤0.001).

Conclusion

People affected by mild or moderate hemophilia encountered a significant amount of haemophilia related sequalae. Future research is needed to identify the optimal management of moderate and mild hemophilia patients, with particular focus on early identification of patients with a severe clinical phenotype.

View Poster: Mild and moderate hemophilia

Kucher A, Noone D, Chai-Adisaksopha C, Curtis R, Frick N, Iorio A, Nichol M, O’Mahony B, Page D, Skinner M, Stonebraker J. Education in people with Hemophilia – Insights from the PROBE Study. Abstracts MTD-PP-045 (548). Haemophilia. 2020;26(S4):3-140. https://doi.org/10.1111/hae.13941

Introduction

Education is one of the key components relating to quality of life. The aim of this analysis was to examine the reported educational level of men with hemophilia in the PROBE study and compare it to the national average reported by the United Nations Development Programme (UNDP).

Methods

Annually, the UNDP Educational Index (EI), reports the highest degree of education an individual has completed. PROBE collects self-reported data on years of education. Data from all phases of PROBE were compiled on male PWH >25 years of age. To minimize the impact of patient duplication bias in the data set, for each pair of individuals from the same country, with the same hemophilia type and severity, born in the same year, and who reported the same number of years of education, one was excluded from the analysis. In total, 746 PWH from 17 countries, with a mean [SD] age of 45.4 [14.7] were analyzed. 80% had hemophilia A and 65% had severe hemophilia. Data was grouped by country and GNI category.

Results

The mean number of years of education reported was 15.5 [4.5] years with a range of 2-33 years with similar dispersion in both high (15.6 [4.3]) and upper middle-income countries (15.5 [4.7]). There was no significant difference in years of education reported between severe patients and mild/moderate patients by country or GNI category. In relation to EI, the mean UNDP data for high and upper middle-income countries whom participated in PROBE were 0.884 and 0.729 respectively; the mean EI data for the same countries were 0.951 and 0.853 for all PWH respectively and 0.936 and 0.859 for those with severe hemophilia (p<0.01).

Conclusions

EI calculated on PROBE data indicates that PWH aim to receive a higher education than those in the general population. This finding may be due to selection bias for the PROBE population or to PWH pursuing higher education in the face of career limitations imposed by hemophilia to increase their quality of life.  Further investigation is required to understand the finding.

View Poster: Education Level in Hemophilia Community

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

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

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

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.

Summary

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 Poster: Aging 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:

1. ≥50% item scores within a domian,
2. only one item score within a domain,
3. ≥50% item scores irrespective of any domain,
4. 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

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

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

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

Youttananukorn T, Coffin D, Diop S, Hermans C, Konkle B, Lambert C, Noone D, O’Hara J, Pierce G, W Skinner M, Iorio A. Incorporating Patient Reported Outcomes into Clinical Practice: A 360-degree Clinical Evaluation for Better Care and Treatment of People with Hemophilia through myWBDR and myPROBE [abstract]. Res Pract Thromb Haemost. 2021;5(Suppl 2). https://abstracts.isth.org/abstract/incorporating-patient-reported-outcomes-into-clinical-practice-a-360-degree-clinical-evaluation-for-better-care-and-treatment-of-people-with-hemophilia-through-mywbdr-and-myprobe/. Accessed March 12, 2022

Background

The World Federation of Hemophilia (WFH) World Bleeding Disorders Registry (WBDR) is designed to fill gaps in hemophilia care and knowledge that exist globally. The WBDR is a tool for clinicians to collect real world data on patient clinical care and quality of life, and a tool to empower people with hemophilia (PWH) to manage their own care and treatment.  The WFH will be introducing myWBDR – a mobile application for PWH participating in the WBDR through the participating hemophilia treatment centers.

Aims

To collect bleed and other patient-reported outcome (PRO) data in the WBDR.

Methods

myWBDR is designed to track bleeds, associated pain, treatments, and health status using EQ-5D-5L and the Patient Reported Outcomes, Burdens, and Experiences (PROBE) questionnaires (Table).  Initially, myWBDR will be available in English, French, Hindi, Spanish, and Vietnamese.

Results

myWBDR is undergoing field testing in non-WBDR PWH and will follow with a testing cohort of PWH within the WBDR.  Implementation will be regional, starting with 5 countries (2 regions) in Q2 2021. myWBDR is a simple tool, allowing users to record accurate bleeds and treatment in under 1 minute. The inclusion of the EQ-5D-5L and PROBE questionnaires, both available in a large number of languages, will allow users to track changes in their health status over time. Both myWBDR and myPROBE include an off-line feature so data can be entered at anytime and offer simple data visualization on bleeds (number, location), level of pain and health-status.

Conclusions

Integration of PRO via the myWBDR will allow PWH to play an active role in their care and treatment. With the 360-degree data, researchers can better understand hemophilia and work to improve quality of care and treatment for PWH around the world. A data dashboard for PWH to visualize and compare their personal data is in development.

View Poster: myWBDR and myPROBE

Jackson S, Sheridan B, Gue D, Lyons S, Waines R, Ireland T, Pete D, Iorio A, Walsh L, Skinner M, Germini F.
Feasibility of Integrating PROBE (Patient Reported Outcomes, Burdens and Experiences) into a Clinical Care Pathway to Facilitate Transformation to a Value-based Health Care Model in Hemophilia [abstract]. Res Pract Thromb Haemost. 2021;5(Suppl 2). https://abstracts.isth.org/abstract/feasibility-of-integrating-probe-patient-reported-outcomes-burdens-and-experiences-into-a-clinical-care-pathway-to-facilitate-transformation-to-a-value-based-health-care-model-in-hemophilia/ . Accessed July 2, 2021.

Introduction

The PROBE survey was developed by patients, hemophilia caregivers and methodological experts as a stand-alone cross-sectional instrument with multistep validation and control group data.  While not developed for use in clinics, it measures important value-based health outcomes including health status, mobility, independence, acute/chronic pain and overall quality of life.  We report initial results from a feasibility project using PROBE during routine care to enable patients to provide outcome measures to clinical teams and improve quality, value and experience of hemophilia care.

Methods

Three patients from the British Columbia Adult Bleeding Disorders Provincial Program were identified to guide the BC steering group and the McMaster PROBE database teams.  The steering group endorsed including 6 additional vocational survey items to the 30 question PROBE instrument. An anonymized link was sent 1-2 weeks pre-appointment and upon completion, patients were given the option to share survey results with the clinical team. All patients were sent an evaluation form post-visit.

Results

25 survey links were sent and 17 patients completed in full.  4 had technical issues sharing the survey and 13 independently completed and shared the survey. 7 patients completed a 10 question evaluation post-survey with 86% indicating PROBE covered all areas that they felt were important to address, 100% were willing to take it again, and 86 % felt the PROBE responses had a very beneficial or beneficial impact on the team members ability to have a meaningful discussion during the visit.

Conclusions

It is feasible to embed PROBE into routine care from a patient and clinician perspective for longitudinal single patient or population-based outcome tracking.  Next steps include enhancing the interface for clinician viewing, allowing patients to trend their results over time and allowing the option for patients to compare their results to selected peer groups within the National/Global PROBE system.

View Poster: Vancouver Study

López A, Uriarte X, Leytón I, Campos J, Aguilera S.
(2022), (Poster) Quality of life of people with hemophilia in Nicaragua: A case series with PROBE Survey, WFH Congress 2022.

View Poster: Calidad de Vida Nicaragua

Page D, Kucher A, Geremini F.
PP-72 (1160482) PROBE results show continued burden of disease in Canadians with severe haemophilia A and B. (2022), Abstracts. Haemophilia, 28: 5-97. https://doi.org/10.1111/hae.14537

Introduction

Prophylaxis with recombinant factor concentrates has been the standard of care for severe hemophilia A and B in Canada since the early 1990s and has resulted in significantly improved quality-of-life; however, the Patient Reported Outcomes, Burdens and Experiences (PROBE) study reports that burden of disease remains significant compared to the general population.

Methods

Patients reporting their home infusions through the patient portal of the Canadian Bleeding Disorders Registry are asked via email to complete the online PROBE questionnaire. 420 questionnaires have been completed by people with severe hemophilia A (PwSHA), 39.2% of the 1,069 severe patients identified in the Canadian Hemophilia Registry, and by 81 people with severe hemophilia B (PwSHB), 40.5% of the 200 severe patients. The survey was also completed by 198 controls with no bleeding disorder.

Results

88% of the PwSHA (369/420) and 89% (72/81) of PwSHB reported treating with regular prophylaxis. 28.1% of the PwSHA and 37% of the PwSHB reported using mobility aids or assistive devices in the last 12 months compared to 9% of the controls. 66% of the PwSHA and 75% of the PwSHB reported using pain medication in the last 12 months compared to 55% of the controls. 61% and 51% respectively of the PWSHA and PWSHB reported acute pain in the last 12 months compared to 34% of controls. 65% and 77% suffered from chronic pain, compared to 38% of controls. Rates of those with hemophilia acute pain decreased with age, except in those over 65. Chronic pain, however, increased with age, affecting 37% of severe patients aged 11-21 years, but 85% of those aged 45-64 years. 60% of PwSHA and 83% of PwSHB aged 22 to 64 years were employed either full-time or part-time compared to 78% of controls. In those same age groups, 13%, 7% and 5% of PwSHA, PwSHB and controls respectively reported being unemployed.

Conclusions

People with severe hemophilia of all ages, despite good access to prophylaxis, continue to experience a significantly higher burden of disease compared to the general population.

View Poster: PROBE Results Show Continued Burden of Disease

Kucher A, Gaitán C, Skinner M, Cruz M, Escobar A, Alfonso O, Iorio A, germini F, Parrish R, Sevestre M. LR-07.01 (1160466) Integration of the Mexican Registry of Coagulopathies (RMC) with PROBE. (2022), Abstracts. Haemophilia, 28: 5-97. https://doi.org/10.1111/hae.14537

Introduction

Registro Mexicano de Coagulopatías (RMC) is a national registry app connected to the Federation of Hemophilia of the Mexican Republic (FHRM) for people living with hemophilia (PWH) or other bleeding disorders or caregivers to report infusions and bleeds. Patient Reported Outcomes Burdens and Experiences Study (PROBE) is a validated global patient-reported quality of life questionnaire for PWH or individuals without a bleeding disorder available in app (myPROBE), web, or paper format. These two tools were linked such that the RMC login can be used to access PROBE using a single sign-on (SSO) authentication scheme.RMC users are followed longitudinally, receive yearly reminders to complete PROBE, and receive reports on changes to their PROBE score. This connectivity will make data collection more user-friendly, useful and efficient; provide personal health information feedback; and increase the number of people reporting without the need for dual reporting.

Methods

The Health Information Research Unit team at McMaster University and Design2Code Inc. developed an online survey using Windows.net and React Native technologies and implemented the OAuth 2 Client protocol in PROBE while FHRM implemented OAuth 2 Server in RMC. OAuth 2 is the authentication protocol that allows for SSO.

Results

In February 2020, RMC and PROBE developed a linkage between the two data sets for the online platform and mobile application (iOS and Android). In October 2020 the collaboration went live with a soft launch, allowing RMC users to take the PROBE survey using RMC. The applications have a WebView where the PROBE website is loaded and the users sign in with their RMC credentials. To date 32 PWH have initiated data collection.

Conclusions

The number of PWH reporting annually via PROBE will increase, revealing individual and population-level changes. With the demonstrated functionality and successful integration, plans are underway for wider rollout and promotion. The collaboration will provide the FHRM with valuable patient-reported outcome data on pain, education and employment, need for mobility aids, and impact of hemophilia on activities of daily living. These data in combination with data from the PROBE global data set may be used to support further access and improvements in clinical and patient outcomes.

View Presentation: Integration of the Mexican Registry

Gajewski B, Sumera A, Kaczmarek R, Kucher A, Noone D, Page D, Skinner M.
PP-75 (1160578) Changing community needs for those with a bleeding disorder in Poland. (2022), Abstracts. Haemophilia, 28: 5-97. https://doi.org/10.1111/hae.14537

Introduction

Treatment and care have improved for those with a bleeding disorder(BD) in Poland.  There is a generation who is ageing and a younger population with adequate care, each requiring different services.

Methods

In early 2020, a fully anonymised survey on access to haemophilia centre services was developed and fielded on-line through the Polish haemophilia society. The PROBE questionnaire was included.

Results

284 people with a bleeding disorder, parents or caregivers (PwBD) responded to the survey (Figure). The mean distance from the PwBD home to a haemophilia centre was 56 (±61) kms and a comprehensive care centre (CCC) was 258 (±147) km. The mean reported appointment waiting time nationally was 1.7 (±2.9) months. In PwBD reporting home treatment, 94% report access at home. Of these, 41% receive home delivery. The national mean of the EQ-5D utility and PROBE score for PwBD  was 0.748 (±0.219) and 0.730 (±0.135), respectively.  The mean for those without a bleeding disorder in Poland in the full PROBE dataset was 0.882 (±0.219) and 0.845 (±0.104), respectively. The majority of PwBD indicate they would like clinics, nursing facilities and physiotherapy to be available through telemedicine in the future. Excluding those currently attending a CCC, 30% would prefer telemedicine be delivered through the CCC rather than their local centre.

Summary

There is a still a clear gap in quality of life between those with and without a BD in Poland. There is an increasing and changing need for services and care nationally which needs to be addressed for overall improvement of quality of life for PwBD in Poland.

View Poster: Poland Study

Jackson S, Sheridan B, Due D, Lyons S, Waines R, Ireland T, Pete D, Iorio A, Walsh L, Skinner M, Germini F.
F. PP-60 (1160288) Feasibility of integrating PROBE (patient reported outcomes, burdens and experiences) into a clinical care pathway to facilitate transformation to a value-based health care model in haemophilia. (2022), Abstracts.Haemophilia, 28: 5-97. https://doi.org/10.1111/hae.14537

Introduction

The PROBE survey was developed by patients, hemophilia caregivers and methodological experts as a stand-alone cross-sectional instrument
with multistep validation and control group data. While not developed for use in clinics, it measures important value-based health outcomes
including health status, mobility, independence, acute/chronic pain and overall quality of life. We report initial results from a feasibility project
using PROBE during routine care to enable patients to provide outcome measures to clinical teams and improve quality, value and experience of
hemophilia care.

Methods

Three patients from the British Columbia Adult Bleeding Disorders Provincial Program were identified to guide the BC steering group and the
McMaster PROBE database teams. The steering group endorsed including 6 additional vocational survey items to the 30 question PROBE
instrument. An anonymized link was sent 1-2 weeks pre-appointment and upon completion, patients were given the option to share survey
results with the clinical team. All patients were sent an evaluation form post-visit.

Results

96 survey links were sent and 44 patients completed in full. 4 had technical issues sharing the survey and 44 independently completed and
shared the survey. 24 patients completed a 10 question evaluation post-survey with 96% indicating PROBE covered all areas that they felt were
important to address, 96% were willing to take it again, and 79% felt the PROBE responses had a very beneficial or beneficial impact on the team
members ability to have a meaningful discussion during the visit.

Conclusions

It is feasible to embed PROBE into routine care from a patient and clinician perspective for longitudinal single patient or population-based
outcome tracking. Next steps (in progress) include enhancing the interface for clinician viewing, allowing patients to trend their results over time
and allowing the option for patients to compare their results to selected peer groups within the National/Global PROBE system.

View Poster: Vancouver Study

Srivastava A, Brewer AK, Mauser-Bunschoten EP, Key NS, Kitchen S, Llinas A, Ludlam CA, Mahlangu JN, Mulder K, Poon MC, Street A and (2013). Guidelines for the management of hemophilia. Haemophilia. 19: e1-e47. https://doi.org/10.1111/j.1365-2516.2012.02909.x

Granados A, Mullin T, Moseley J, Meyer F, Avetisyan R, Wong-Rieger D, Kaatee M, Skinner M, Leyden S. Multi-stakeholder Approaches to Improve Evidence-Based Decisions in Rare Diseases: Engagement of Patients and Patient Organizations. Report of HTAi 2016 Panel Session. Health Technology Assessment International – Canada. (2016). Published at: http://www.htai.org 19 Sep 2016

O’Callaghan S, Jayaram P, Caris S. Getting older with a bleeding disorder: a needs assessment. Melbourne: HFA, 2020. Detailed PROBE findings are in Appendix 2

van Balen EC, O’Mahony B, Cnossen MH, Dolan G, Blanchette VS, Fischer K, Gue D, O’Hara J, Iorio A, Jackson S, Konkle BA, Nugent DJ, Coffin D,  Skinner MW,  Smit C, Srivastava A, van Eenennaam F, van der Bom JG, Gouw SC. Patient-relevant health outcomes for hemophilia care: development of an international standard outcomes set. Res Pract Thromb Haemost. 2021;5:e12488. https://doi.org/10.1002/rth2.12488

Bullinger M, Gardner D, Lewis H, Miesbach W, Nolte S, O’Hara J, O’Mahony B, Pollard D, Skinner M, Quinn J. The potential impact of gene therapy on health-related quality of life (HRQoL) domains in haemophilia. The Journal of Haemophilia Practice. 2021;8(1): 56-68. https://doi.org/10.17225/jhp00176

Germini F, Borg Debono V, Page D, Zuk V, Kucher A, Cotoi C, Hobson N, Sevestre M, Skinner MW, Iorio A, PROBE Investigators. User-Centered Development and Testing of the Online Patient-Reported Outcomes, Burdens, and Experiences (PROBE) Survey and the myPROBE App and Integration With the Canadian Bleeding Disorder Registry: Mixed Methods Study. JMIR Hum Factors. 2022;9(1):e30797. https://doi.org/10.2196/30797

Germini, F, Chai-Adisaksopha, C, Pete, D, Curtis, R, Frick, N, Nichol, M, Noone, D, O’Mahony, B, Page, D, Stonebraker, J, Thabane, L, Crowther, M, Skinner, M, Iorio, A.  Evaluation of the sexual health in people living with hemophilia. Haemophilia. 2021;27:993-1001. https://doi.org/10.1111/hae.14410

Chai‐Adisaksopha, C, Skinner, MW, Curtis, R, Frick N, Nichol MB, Noone D, O’Mahony B, Page D, Stonebraker J, Thabane L, Crowther MA, Iorio A. Exploring regional variations in the cross‐cultural, international implementation of the Patient Reported Outcomes Burdens and Experience (PROBE) study. Haemophilia. 2019;25:365–372. https://doi.org/10.1111/hae.13703

Chai‐Adisaksopha C, Skinner MW, Curtis R, Frick N, Nichol MB, Noone D, O’Mahony B, Page D, Stonebraker J, Thabane L, Crowther MA, Iorio A. Test‐retest properties of the Patient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire and its constituent domains. Haemophilia. 2019;25:75–83. https://doi.org/10.1111/hae.13649

Chai-Adisaksopha C, Skinner MW, Curtis R, Frick N, Nichol MB, Noone D, O’Mahony B, Page D, Stonebraker J, Thabane L, Crowther M, Iorio A. Psychometric properties of the Patient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire. BMJ Open. 2018;8:e021900. http://dx.doi.org/10.1136/bmjopen-2018-021900

Mark Skinner, President/CEO of the Institute for Policy Advancement, USA, and David Page, National Director of Health Policy at the Canadian Hemophilia Society, Canada, talk about the importance of data collection and patient-reported outcomes for enhancing the patient voice in healthcare decision-making. They discuss one data collection project in particular, called PROBE, and highlight how it can be used as an evidence-based tool by advocacy groups. https://shows.acast.com/amplify/episodes/episode-5

International Society on Thrombosis & Haemophilia (ISTH, SSC) 2020

Poster Abstract # PB 1012
Citation: 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. 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).

For Abstract Click HERE (PB 1012)

World Federation of Hemophilia Congress (2020)

Poster Abstract # MTD‐PP‐045 (548)
Citation: Kucher A, Noone D, Chai-Adisaksopha C, Curtis R, Frick N, Iorio A, Nichol M, O’Mahony B, Page D, Skinner M, Stonebraker J. Education in people with Hemophilia – Insights from the PROBE Study (2020), Abstracts. Haemophilia, 26: 3-140. doi:10.1111/hae.13941

For Abstract Click HERE (MTD‐MP‐045 (548))

World Federation of Hemophilia Congress (2020)

Poster Abstract # MTD‐PP‐025 (377)
Citation: Page D, 3 apps in 1: MyCBDR, myWAPPS and myPROBE. (2020), Abstracts. Haemophilia, 26: 3-140. doi:10.1111/hae.13941

For Abstract Click HERE (MTD‐MP‐025 (377))

Skinner, M. W., Chai-Adisaksopha, C., Curtis, R., Frick, N., Nichol M., Noone, D., O’Mahony, B., Page, P., Stonebraker, J. S. and Iorio, A. (2018). The Patient Reported Outcomes, Burdens and Experiences (PROBE) Project: development and evaluation of a questionnaire assessing patient reported outcomes in people with haemophilia. Pilot and Feasibility Studies, 2018 4:58. doi: 10.1186/s40814-018-0253-0

Chai-Adisaksopha C, Noone D, Curtis R, et al. Non-severe haemophilia: Is it benign? – Insights from the PROBE study. Haemophilia. 2020; 00:1-8. https://onlinelibrary.wiley.com/doi/epdf/10.1111/hae.14105