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

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

Objective

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

Methods

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

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

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

Background

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

Objective

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

  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

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

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

Introduction

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

Methods

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

Results

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

Discussion/Conclusion

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

Disclosure of Interest

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

View Presentation: EAHAD21-ABS-1393

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

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

Introduction

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

Methods

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

Results

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

Discussion/Conclusion

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

Disclosure of Interest

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

View Presentation: EAHAD21-ABS-1390

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

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

Introduction

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

Methods

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

Results

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

Discussion

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

Conclusion

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

View Poster: Kyrgyz Republic NMO

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

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

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

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

Quality of life of people with hemophilia in Nicaragua: A case series with PROBE Survey

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

 

PROBE Results Show Continued Burden of Disease in Canadians with Hemophilia A and B

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

Integration of the Mexican Registry of Coagulopathies (RMC) with PROBE

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