The study aims of the feasibility is to determine the number of patients with a diagnosis of Pyruvate kinase deficiency (PKD) and their date of diagnosis in CPRD Gold and Aurum database linked with Hospital episode statistics (HES) database. The availability of information on healthcare resources involved with PKD such as hospital visits and treatment received will be accessed. Clinical characteristics will also be accessed such as age, sex and other factors that are associated with PKD such as history of splenectomy and blood transfusions.
All CPRD Gold/Aurum-HES linked patients with a diagnosis of PKD in their case records will be included and possible patients will be further added following a questionnaire to GPs in a later stage of the study. The feasibility will be used to determine the level of recording of the factors such as those mentioned above in the data source to help better define the point a patient is diagnosed with PKD.
PKD is a rare disease and its true prevalence in the UK is unknown, likely due to misdiagnosis of mildly affected patients. By describing Healthcare resource utilization (HCRU) and patient characteristics of these patients this study may help to better define patients and to understand HCRU associated with PKD to better inform treatment areas.
This is a retrospective, observational cohort study of a population of patients with pyruvate kinase deficiency (PKD) identified from CPRD GOLD and Aurum and matched with non-PKD patients in England. This study aims to describe the sociodemographic and clinical characteristics of PKD patients; the health care resource utilization (HCRU) and overall survival of PKD patients and matched non-PKD patients; estimate the disease burden of gallstones, and iron overload in PKD patients.
All patients with a record of definite PKD diagnosis will be identified in CPRD GOLD and Aurum database and followed-up from the earliest available record until censoring, death or end of the study time period. A suitably matched non-PKD cohort (matched on birth year, sex, GP practice, data source (CPRD GOLD vs Aurum) and year of PKD diagnosis (in non-PKD patients, this would be a medical visit in the same year of matched PKD case)) will be obtained using exact matching and a ratio of 1 PKD patient:5 matched non-PKD controls. Descriptive summary statistics will be used to describe the demographic and clinical characteristics of PKD patients and matched non-PKD patients; HCRU will be presented as annualized rates, and the summary statistics will be calculated per patient using summary statistics and compared between PKD patients and non-matched PKD patients using Poisson regression analysis. Overall survival will be investigated using time to death analysis and depicted in Kaplan-Meier curves with a log rank test used to compare the overall survival between the PKD population and the matched non-PKD population.
Sensitivity analyses will be also conducted on study objectives including all patients with a possible PKD record in CPRD GOLD and Aurum and their matched non-PKD controls first evaluating HRCU, demographic summary statistics and overall survival, and then combining the definite and possible PKD populations to reperform all study objectives.
Primary outcomes: Hospitalizations (all cause hospitalizations, duration of all cause hospitalizations in days (inpatients visits), number of all cause inpatient visits, number of outpatient visits by specialty - hematology, genetics, pediatrics, number of A&E visits); Procedures (RBC transfusions); Laboratory blood tests (full blood count, reticulocyte count, platelet count, red blood cell count, white blood cell count, liver function test, bilirubin test, lactate dehydrogenase levels, iron levels); Prescriptions (prescriptions of interest in the primary care setting - antibiotics, antidepressants, antianxiety, folic acid products, hematopoietic agents, antithrombotic therapies)
Secondary outcomes: Sociodemographic and Clinical Characteristics (age, sex, socioeconomic status, region, race, comorbidities- depression, anxiety, cirrhosis, number of patients with iron overload, iron chelation use and gallstones; Disease Burden of Gallstone (annualized and overall rates of gallstones, time to cholecystectomy in patients with gallstones); Burden of Iron Overload (overall rate of iron overload stratified by red blood cell transfusion history, incidence of iron chelation).
Exploratory variables: Outcomes in primary objective stratified by age during follow up (<18 years vs ≥ 18 years of age), Antibiotic use stratified by splenectomy; Overall Survival; Burden of Iron Overload (using ferritin levels stratified by red blood cell transfusion history), outcomes in primary objective stratified by iron chelation therapy and calculated for patients with at least one RBC transfusion), possible iron chelation (using ferritin levels and MRI scan)
Paul Berg - Chief Investigator - IQVIA Ltd ( UK )
Archie Farrer - Corresponding Applicant - IQVIA Ltd ( UK )
Alessandra Venerus - Collaborator - IQVIA Solutions Italy S.r.l
Catrina Richards - Collaborator - IQVIA Ltd ( UK )
Eleni Demas - Collaborator - IQVIA Hellas Technology Solutions S.A.
Eleonora Iob - Collaborator - IQVIA Ltd ( UK )
Karabo Keapoletswe - Collaborator - IQVIA Ltd ( UK )
Lorena Cirneanu - Collaborator - IQVIA Ltd ( UK )
Louise Raiteri - Collaborator - IQVIA Ltd ( UK )
Sarah Lay-Flurrie - Collaborator - IQVIA Ltd ( UK )
Saskia Hagenaars - Collaborator - IQVIA Ltd ( UK )
Alessandra Venerus - Collaborator - IQVIA Solutions Italy S.r.l
alessandra venerus - Collaborator - IQVIA Ltd ( UK )
Eileen Dareng - Collaborator - IQVIA Ltd ( UK )
Eleni Demas - Collaborator - IQVIA Hellas Technology Solutions S.A.
Quratul Ann - Collaborator - IQVIA Ltd ( UK )
HES Accident and Emergency;HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation