Comparing the Burden of Illness of Hemophilia in the Developing and the Developed World

Comparing the Burden of Illness of Hemophilia in the Developing and the Developed World: The Sao Paulo - Toronto Hemophilia Study

Because of high cost, persons with hemophilia in many developing countries cannot afford adequate treatment. For example, many persons with hemophilia in India and China are only rarely treated with factor replacement in response to bleeds, and as a result many have developed significant arthropathy and disability. A pilot study in China estimated the mean Hemophilia Joint Health Score (HJHS) at 13.1 (SD 9.03) suggesting that these children had highly prevalent, severe joint disease. The lack of relationship between the HJHS and treatment history suggests overall inadequate therapy.

The proposed study will quantify the burden of arthropathy, physical disability, and quality of life (QoL) in boys with hemophilia in Brazil - where comprehensive treatment is just beginning to be widely available. This study will also provide an opportunity to compare these outcomes to those observed in Canada, where the dominant therapy has become life-long prophylaxis.

Study Overview

• Status: Completed
• Conditions: Hemophilia A; Hemophilia B

Detailed Description

In order to quantify the burden of illness in hemophilia, and to study the response to different treatments, it is necessary to have quantitative outcome measures of high validity and reliability. The International Prophylaxis Study Group (IPSG - chair Dr. Victor Blanchette) was established in 2001 with the stated purpose of developing and testing outcome tools for this purpose. The group has developed a magnetic resonance imaging (MRI) score for quantifying arthropathy (representing the domain of structure and function domain in the ICF framework), a quantitative physical examination score, and the Hemophilia Joint Health Score or HJHS, to replace the older and less sensitive World Federation of Hemophilia (WFH) score (representing the domain of structure and function in the ICF). In addition Canadian investigators have also developed a quality of life measure for boys with hemophilia, the Canadian Hemophilia Outcomes Kids' Life Assessment Tool or CHO-KLAT (representing the domain of participation in the ICF).

We will use these tools, and other validated measures, to begin to determine the burden of hemophilia in Brazil and compare it to the burden of disease in Canada. Additionally, we will use this study to demonstrate the validity of these tools in the Brazilian population.

• Study Type: Observational
• Enrollment (Actual): 100

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo, Brazil
    • Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
  • Sao Paulo, Brazil
    • Universidade Federal de São Paulo (UNIFESP)
  • Sao Paulo
    • Campinas, Sao Paulo, Brazil
      • Universidade Estadual de Campinas, Unicamp
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Probability Sample

Study Population

Participants will be a representative (random) sample of individuals from the comprehensive hemophilia treatment centres at HCFMUSP and SickKids. Boys between the ages of 7 and 18 years (inclusive) will be identified from the clinic ledgers at each of the centres. Using a computer generated random number list, proportionately stratified for Hemophilia A and B, and for moderate and severe disease (based on the baseline clinic proportions)

Description

Inclusion criteria

• Hemophilia A or B moderate or severe as determined by serum factor activity ≤ 5%
• Age 7 - 18 yrs. inclusive
• At least one parent or guardian fluent in written Portuguese or English and able to complete the study outcome questionnaires.

Exclusion criteria

• None (Children with inhibitors will be allowed into the study for 2 reasons: i) our study aims to document the health of persons with hemophilia in a generalizable way, ii) not all children will have had inhibitor testing done.)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Brazilian Subject's; Subject's will be recruited from the Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paolo (HCFMUSP); Universidade Estadual de Campinas (UNICAMP); Universidade Federal de São Paulo (UNIFESP)
Canadian Subject's; Recruited from The Hospital for Sick Children

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Burden of Illness	Burden of disability for Brazilian and Canadian children will be be determined by analysis of the following domains: Structure and Function Domain (HJHS score, Biometrics,Radiographs) Activity Domain (ASK and FISH scales) Participation Domain (CHO-KLAT and PedsQL Quality of Life Questionnaire) Health Condition Domain (bleeding frequency) Personal Factors Domain (Ethnicity, level of education of parent/guardian, habitual exercise) Environmental Domain (Household income of parent/guardian)	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Activity Scale for Kids (ASK)	Children's self-reported activities will be measured with the Activity Scales for Kids (ASK) as part of the Activity Domain	Day 1
Functional Independence Scale for Hemophilia (FISH)	Observed activity limitations will be measured with the FISH as part of the Activity Domain. The FISH has been validated for use in developing countries. It consists of observed activities of daily living that are scored for quality.	Day 1
Hemophilia Joint Health Score (HJHS)	The HJHS is a valid and reliable scored measure of joint structural limitations as applied to the index joints. This score will be a measure of the Structure and function domain.	Day 1
Radiographs	Radiographs will be taken of all 6 index joints. This will be done as part of the structure and function domain.	Day 1
Canadian Haemophilia Outcomes - Kids Life Assessment Tool (CHO-KLAT)	After the completion of the pre-study cultural validation of the Brazilian translation of the CHO-KLAT scale, we will use it as a Quality of Life tool to measure the Participation domain	Day 1
Bleeding Frequency	Families will be interviewed to determine bleeding frequency in the last 6 months. This factor will be incorporated into the Health condition domain.	Day 1
Biometrics	The height and weight will be compared to national nomograms.	Days 1
Personal Factors	Ethnicity, level of education of the parent-guardian will be self-reported.	Day 1
Environmental domain	Whether a subject lives in a rural or urban area and household income will be recorded.	Day 1

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Investigators: Principal Investigator: Brain M. Feldman, MD,MSc,FRCPC, The Hospital for Sick Children

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: October 6, 2010
• First Submitted That Met QC Criteria: October 7, 2010
• First Posted (Estimate): October 8, 2010

Study Record Updates

• Last Update Posted (Actual): June 6, 2018
• Last Update Submitted That Met QC Criteria: June 4, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Quality of Life; Pediatric; Participation; Disability; Hemophilia; Burden of Illness
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Blood Coagulation Disorders; Hemophilia A; Hemophilia B
• Other Study ID Numbers: 1000020214

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No