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

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

Summary data from the first collaboration of PROBE and Drustvo Hemofilikov Slovenije (DHS) – an ongoing quality of life study

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

National Member Organization’s PROBE Data Dashboard Update – Adding A Pain Dashboard Page for Better Understanding of the Pain Impact in People with Hemophilia

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

Test-Retest Reliability Analysis of the Patient Reported Outcomes Burdens and Experiences (PROBE) Study

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

Test-Retest Reliability Analysis of the Patient Reported Outcomes Burdens and Experiences (PROBE) Study

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

Impact on Pain and Activities of Daily Living after Switching to Emicizumab: Insight from PROBE

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.

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Exploring Regional Variations in the Cross‐cultural, International Implementation of the Patient Reported Outcomes Burdens and Experience (PROBE) Study

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.

Validation of the Patient Reported Outcomes Burdens and Experiences (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. Validation of the Patient Reported Outcomes Burdens and Experiences (PROBE) Study Questionnaire (Abstract). HAAB (2019).

Introduction

The interest of health care agencies, private payers and policy makers for patient-reported outcomes (PRO) is continuously increasing. There has been a substantial need to improve capacity to collect and interpret relevant PRO data to support implementation of patient-centered research and optimal care in hemophilia.

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:

Data collection was initiated 8 April 2015 and completed on 23 February 2017. In total, 2,101 surveys were collected through all phases of the study.   Of these, 1,541 met study criteria for the relevant phases of research and were suitable for analysis.

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

i.Skinner M, Chai-Adisaksopha C, Curtis R, Frick N, Nichol M, Noone D, et al. 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(1):58.
ii.Chai-Adisaksopha C, Skinner MW, Curtis R, Frick N, Nichol MB, Noone D, et al. Test-retest properties of the Patient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire and its constituent domains. Haemophilia.0(0).
iii.Chai-Adisaksopha C, Skinner MW, Curtis R, Frick N, Nichol MB, Noone D, et al. Psychometric properties of the Patient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire. BmjOpen. 2018;8(8):10.
iv.Chai-Adisaksopha C, Noone D, Curtis R, Frick N, Nichol M, O’Mahony B, et al. Exploring regional variations in the cross-cultural, international implementation of the patient reported outcomes burdens and experience (PROBE) study. Research and Practice in Thrombosis and Haemostasis. 2018;2(S1):92.

View Poster: Validation of the PROBE Study Questionnaire

Comparison of the Measurement Properties of the PROBE and EQ5D on Pain

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

Part-Time Employment and Early Retirement In People With Severe Haemophilia: Insights From The PROBE Study

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