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Quality of Life Research
Published in: Quality of Life Research 2/2019

Open Access 01-02-2019

Appraisal of patient-reported outcome measures in analogous diseases and recommendations for use in phase II and III clinical trials of pyruvate kinase deficiency

Published in: Quality of Life Research | Issue 2/2019

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Abstract

Purpose

Pyruvate kinase deficiency (PKD) is a rare disease and understanding of its epidemiology and associated burden remains limited. With no current curative therapy, clinical manifestations can be life threatening, clinically managed by maintaining adequate hemoglobin levels through transfusion and subsequent support, but with frequent complications. Treatment goals are to maintain/improve the patient’s quality of life. With new therapies, reliable, valid, and relevant patient-reported outcome (PRO) tools are required for use in clinical trials.

Methods

Systematic literature search identified no current PRO tools for capturing/measuring the impact of PKD and treatments in clinical trials. Therefore, the search strategy was revised to consider conditions analogous to PKD in terms of symptoms and impacts that might serve as parallels to the experience in PKD; this included sickle cell anemia, thalassemia, and hemolytic anemia. Psychometric properties, strengths, and weakness of selected appropriate PRO instruments were compared, and recommendations made for choice of PRO tools.

Results

In adult populations, EORTC QLQ C30 and SF-36v2 are recommended, the former being a basic minimum, covering generic HRQoL, and core symptoms such as fatigue. In pediatric populations, PedsQL Generic Core Scale to measure HRQoL and PedsQL MFS scale to measure fatigue are recommended.

Conclusions

Some symptoms/life impacts may be unique to PKD and not observable in analogous conditions. A ‘Physico-Psychosocial Model’ derived from the ‘Medical Model’ is proposed to form the basis for a hypothesized conceptual framework to address the development of PKD-specific PRO instruments.
Appendix
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Glossary
Allosteric activator
Binding of one ligand enhances the attraction between substrate molecules and other binding sites
Aplastic crises
Temporary cessation of red cell production
Autosomal recessive trait
Ways that a trait, disorder, or disease can be passed down through families whereby two copies of an abnormal gene must be present in order for the disease or trait to develop
β-Thalassemia
A genetic blood disorder that reduces the production of hemoglobin
Chelation Therapy
A form of complementary therapy involving circulating a chelating solution in the bloodstream to bind toxins
Chronic non-spherocytic hemolytic anemia
A group of rare, genetically transmitted blood disorders characterized by the premature destruction of red blood cells
Cytopenia
Reduction in the level of red blood cells
Desferoxamine
A medication that binds iron used to treat iron overload
Extramedullary hematopoiesis
Hematopoiesis (differentiation processes that lead to the formation of all blood cells from hematopoietic stem cells) occurring in organs outside of the bone marrow
Hematopoietic stem cell transplantation
Is the transplantation of multipotent hematopoietic stem cells
Hemolytic anemia
A form of anemia due to hemolysis, the abnormal breakdown of red blood cells
Myelodysplastic syndromes
A group of cancers in which immature blood cells in the bone marrow do not mature and therefore do not become healthy blood cells
Neonatal hemolysis
Hemolytic disease of the newborn
Neonatal jaundice
A yellowish discoloration of the white part of the eyes and skin in a newborn baby due to high bilirubin levels
Paroxysmal nocturnal hemoglobinuria
A rare blood condition where blood cells are prone to be attacked by part of the body’s immune system
Pathophysiology
Functional changes associated with or resulting from disease or injury
Post-splenectomy sepsis
Body’s response to infection causing injury to its own tissues and organs following removal of the spleen
Pulmonary hypertension
Increased blood pressure within the arteries of the lungs
Pyruvate kinase
The enzyme that catalyzes the final step of glycolysis
Structural equation modeling
A diverse set of mathematical models, computer algorithms, and statistical methods that fit networks of constructs to data and includes confirmatory factor analysis, path analysis, and partial least squares
Symptomatic hypersplenism
Exhibiting an overactive spleen, removing too many blood cells, including healthy ones
Path analysis
An extension of multiple regression used to provide estimates of the magnitude and significance of hypothesized causal connections between sets of variables and includes multiple regression analysis, factor analysis, and discriminant analysis
Vaso-occlusive crises
A common painful complication of sickle cell anemia where circulation of blood vessels is obstructed by sickled red blood cells, causing ischemic injuries
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Metadata
Title
Appraisal of patient-reported outcome measures in analogous diseases and recommendations for use in phase II and III clinical trials of pyruvate kinase deficiency
Publication date
01-02-2019
Published in
Quality of Life Research / Issue 2/2019
Print ISSN: 0962-9343
Electronic ISSN: 1573-2649
DOI
https://doi.org/10.1007/s11136-018-2025-y

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