Hemophilia Guidelines for All A new ambition of the World Federation

Hemophilia Guidelines for All A new ambition of the World Federation of Hemophilia

WFH Guidelines for the Management of Hemophilia All recommendations are consensus based. Srivastava A et al. Haemophilia. 2020;26(Suppl 6):1–158.

Chapter 11: Outcome Assessment Pradeep M. Poonnoose MD Professor, Department of Orthopaedics Christian Medical College Vellore, India

Disclosures: Pradeep M. Poonnoose No competing interests to declare

Authors Pradeep M. Poonnoose Brian M. Feldman Piet de Kleijn Manuel A. Baarslag (PWH) Radoslaw Kaczmarek Johnny Mahlangu Margaret V. Ragni Glenn F. Pierce Alok Srivastava PWH, person with hemophilia.

Introduction Outcome refers to the condition of a patient that results from a disease or medical intervention, and is assessed by clinical evaluation, including the use of: Generic and disease-specific health related quality of life assessment instruments Patient-reported outcome measures Laboratory tests Imaging studies Outcome assessment instruments in hemophilia measure a variety of parameters including: Activities and participation Body structure and function Burden of disease Health status

Outcome assessment objectives The purposes of outcome assessment are to: Follow an individual's disease course Obtain information to guide routine clinical care Measure response to therapy Determine whether there is a need to modify therapy Quantify the health of a group of patients Measure quality of care Advocate for resources

Outcome assessment Two main aspects Disease-related outcomes effectiveness of hemostatic therapy Frequency of bleeding Pain Impact of bleeding on the musculoskeletal system Quality of life Therapy-related outcomes what needs to be monitored Inhibitor development Thrombosis Allergic/anaphylactic reactions

Outcome Frequency of bleeding Frequency of bleeding is the most important indicator of effectiveness of hemostatic therapy and the best surrogate predictor of long-term musculoskeletal outcomes Joint bleed An unusual sensation “aura” in the joint, in combination with any of the following increasing swelling or warmth of the skin over the joint; increasing pain; or progressive loss of range of motion or difficulty in using the limb as compared with baseline. An episode of bleeding into a muscle, determined clinically and/or by Muscle bleed imaging studies, generally associated with pain and/or swelling and loss of movement over baseline.

Outcome Frequency of bleeding Recommendation 11.2.1 For providers of care for people with hemophilia, the WFH recommends ensuring that the frequency of all bleeds is documented in real time by patients/caregivers and reviewed together at least annually, with particular reference to intra-articular, intramuscular, and central nervous system bleeds, including their recovery status. Standard criteria defined by the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis should be used.

Until two decades ago, severity of joint arthropathy was assessed by: Bleeding frequency Clinical Score – Gilbert’s score Radiological score – Pettersson (X-ray) Not standardized – no validity/reliability studies Insensitive to early change Do not consider normal childhood variants

Outcome assessment instruments ICF model Disease Hemophilia Body structure and function Environmental factors ICF, International Classification of Functioning, Disability and Health; QoL, Quality of Life. Activity Participation Personal factors L o Q

Outcome assessment instruments Body structure and function HJHS The HJHS assesses: Duration (swelling) Swelling Muscle Atrophy Crepitus on motion Flexion Loss Extension Loss Joint Pain Strength Joint Total Global Gait Score Total HJHS Score HJHS, Hemophilia Joint Health Score 2.1 – Summary Score Sheet. Available at: http://www1.wfh.org/docs/en/Publications/Assessment Tools/HJHS Summary Score.pdf

Outcome assessment instruments Body structure and function Pettersson score X-Ray

Recommended measures Body structure and function In hemophilia, body structure and function refers to, for example, the status of joints and specific muscle groups, assessed both clinically and radiologically HJHS X-Ray US MRI The Hemophilia Joint Health Score (HJHS) is the most commonly used tool for clinical assessment of joints; used in both children and adults. The radiological Pettersson score is the most widely used imaging measure of joint structure. It is however not sensitive to early change. Ultrasound (US) imaging can detect joint effusion, early joint disease, and subclinical joint disease, and promote medication adherence. Magnetic resonance imaging (MRI) is likely the most sensitive measure of joint structurebut is is expensive, time consuming, and difficult to perform in small children.

Outcome assessment instruments Body structure and function US MRI, magnetic resonance imaging; US, ultrasound. MRI

Outcome assessment instruments Activity and participation scales Disease Hemophilia HAL / PedHAL HJHS X-ray HAL / PedHAL FISH Body structure and function Activity COPM Participation SF-36 US PROBE MRI HAEMOQoL-A Environmental factors International Classification of Functioning and Health (ICF) model, with domain-related outcome assessment instruments Personal factors COPM, Canadian Occupational Performance Measure; FISH, Functional Independence Score in Hemophilia; HAEMO-QoL-A, hemophilia specific quality-of-life questionnaire for adults; HAL, Haemophilia Activities List; HJHS, Hemophilia Joint Health Score; ICF, International Classification of Functioning, Disability and Health; MRI, magnetic resonance imaging; PedHAL, Haemophilia Activities List for children; PROBE, Patient-Reported Outcomes, Burdens and Experiences; SF-36, 36-Item Short Form Survey Instrument; US, ultrasound.

Outcome assessment instruments Activity and participation scales In hemophilia, activity refers to instrumental activities of daily living (e.g., walking, climbing steps, brushing teeth, toileting) Participation refers to involvement in life situations in the context of social interactions HAL & PedHAL FISH PROBE COPM & MACTAR The Haemophilia Activities List (HAL) and PedHAL are diseasespecific, self reported measures of activities for adults and children, respectively. The Functional Independence Score in Hemophilia (FISH) is the best studied observed performance measure for people with hemophilia, used in many countries and age groups. The Patient-Reported Outcomes, Burdens and Experiences (PROBE) questionnaire includes metrics that assess activities and participation, such as school/education, employment, family life, and impact on activities of daily living. The Canadian Occupational Performance Measure (COPM) and the McMaster Toronto Patient Disability Questionnaire (MACTAR) are generic instruments used for dayto-day assessment of a person's perception of changes in their activities and participation.

Outcome assessment instruments Activity and participation scales HAL & PedHAL FISH, Functional Independence Score in Hemophilia; HAL, Haemophilia Activities List; PedHal, Haemophilia Activities List for children. FISH

Clinical Scenario:

ICF Model Environmental and personal factors Disease Hemophilia HAL / PedHAL HJHS X-ray HAL / PedHAL FISH Body structure and function Activity COPM Participation SF-36 US PROBE MRI HAEMOQoL-A Environmental factors International Classification of Functioning and Health (ICF) model, with domain-related outcome assessment instruments. Personal factors COPM, Canadian Occupational Performance Measure; FISH, Functional Independence Score in Hemophilia; HAEMO-QoL-A, hemophilia specific quality-of-life questionnaire for adults; HAL, Haemophilia Activities List; HJHS, Hemophilia Joint Health Score; ICF, International Classification of Functioning, Disability and Health; MRI, magnetic resonance imaging; PedHAL, Haemophilia Activities List for children; PROBE, Patient-Reported Outcomes, Burdens and Experiences; SF-36, 36-Item Short Form Survey Instrument; US, ultrasound.

Economic factors to consider Direct costs include the cost of medical treatments, health services, and surgical and medical supplies. CFCs account 90% of the treatment-related cost. Indirect costs arise from loss of work productivity of adult patients and of parents of pediatric patients due to the time they spend managing their child's hemophilia care. The costs that result from illness or seeking medical care are sometimes similar but often vary by country. CFCs, clotting factor concentrates.

Health-related quality of life HRQoL measurements are questionnaires that aim to quantify a patient's health in a global way, however it is best applied in combination with specific assessments of the ICF domains rather than in isolation The EQ-5D and SF-36 are widely used generic instruments for assessing QoL in hemophilia EQ-5D Instrument SF-36 Instrument EQ-5D, EuroQoL 5 Dimensions; HRQoL, health-related quality of life; ICF, International Classification of Functioning, Disability and Health; QoL, quality of life; SF-36, 36-Item Short Form Survey Instrument; VAS, visual analog scale.

Health-related quality of life The PROBE, CHO-KLOT, and HAEMO-QoL-A are disease specific instruments used to assess QoL in hemophilia PROBE Assesses QoL in addition to burden of disease in people with hemophilia. CHO-KLOT For children with hemophilia, the Canadian Hemophilia Outcomes-Kids Life Assessment Tool (CHO-KLAT) is widely used. PROBE, Patient-Reported Outcomes, Burdens and Experiences; QoL, quality of life. HAEMO-QoL-A For adults with hemophilia, the hemophilia-specific QoL questionnaire for adults (HAEMO-QoL-A) is widely used.

Patient-reported outcomes PROs provide a report of the status of a patient's health condition that comes directly from the patient It encompasses both single-dimensional and multi-dimensional measures of symptoms, HRQoL, health status, adherence to treatment, satisfaction with treatment, and other measures HRQoL, Health-Related Quality of Life; PRO, patient reported outcome.

Recommendations Recommendation 11.7.1 The WFH recommends assessing and documenting the musculoskeletal and overall health of each patient at least annually. This should include an assessment of body structure and function, activity levels, participation and health-related quality of life as per the World Health Organization's International Classification of Functioning, Disability and Health (WHO ICF), as much as possible, in the right clinical context. REMARK: Standard definitions and validated tools should be used as much as possible, including the following: For body structure and function, clinical assessment of joints is (most) commonly done using the Hemophilia Joint Health Score (HJHS) in both children and adolescents. Functional activity levels should be assessed using the most appropriate option available for that individual, including the Haemophilia Activities List (HAL), the Haemophilia Activities List for children (PedHAL), or the Functional Independence Score in Hemophilia (FISH). Under the same domain, early structural changes in joints are best assessed using ultrasound (US) or magnetic resonance imaging (MRI). Late osteochondral changes may be assessed on plain radiographs. HRQoL is an important aspect of outcome measurement that may be assessed using either generic or disease-specific tools, but only in combination with the other domains of the WHO ICF. HRQoL, Health-Related Quality of Life.

Core set of measures for use in the clinic or research setting To extract the potential of value-based health care, standardized outcome measures must be encouraged The WFH World Bleeding Disorders Registry (WBDR) provides a platform for hemophilia treatment centres to collect uniform and standardized patient data and outcomes globally to guide clinical practice http://www.wfh.org/en/our-work-research-data/world-bleeding-disorders-registry A selection of outcome assessment instruments can be accessed at the WFH Compendium of Assessment Tools webpage http://elearning.wfh.org/resource/compendium-of-assessment-tools/

Conclusions In order to optimize treatment and make economically sound clinical decisions, objective evidence of both short- and long-term outcomes of treatment regimens is required Both generic and hemophilia-specific assessment instruments make it possible to evaluate the nature of the physical impairments and functional limitations and their impacts on the lives of people with hemophilia and their families The increasing use of these instruments will standardize assessment and permit comparison of data between individuals and cohorts

Thank you to the Hemophilia Alliance for their support in developing this presentation