Clinical Validation of a Dried Blood Spot Method for Analysis of Immunosuppressives and Antifungals in Pediatrics
Condition: Hematologic Diseases; Oncology Problem; Kidney Diseases; Transplantation Infection
MeSH terms: Kidney Diseases; Hematologic Diseases
Study type: Observational

Summary: 
      This is a clincial validation study of a dried blood spot (DBS) method for the analysis of
      immunosuppressive and antifungal agents currently subject of therapeutic drug monitoring
      (TDM) in a pediatric population.

      The primary goal is to clinically validate a finger prick DBS method compared to conventional
      venous sampling for the analysis of 5 immunosuppressive and 4 azole antifungal drugs in the
      pediatric population. Secondairy goals include feasibility of the finger prick DBS method in
      the target population, to design an inventory of costs that will be incurred in future
      health-economic analyses and to construct a population PK model based on the available data
      collected for the primariy goal.
    

Detailed description: 
      Therapeutic drug monitoring (TDM) offers the possibility to individualize and improve a
      patient's pharmacological treatment, based on the measurement of drug concentrations in
      biological samples. Conventionally, TDM is performed with blood or plasma obtained by venous
      blood sampling. This method is associated with several challenges such as i) the need for the
      patient to travel to the hospital or health center; ii) special conditions for sample
      transport to guarantee stability of the analyte and to decrease the biohazard risk; iii)
      sampling times not always representing the preferable peak or trough concentrations; iv) the
      method being invasive and v) delay of the outcome of the analyses with regard to the
      outpatient visit.

      The Dried Blood Spot (DBS) may offer a solution for all these challenges. DBS is thought to
      offer benefits over plasma venous sampling for TDM. The main purpose of the PROTECT
      (Personalized treatment of immunosuppressive and antifungal drugs through continuous home
      based monitoring with Dried Blood Spot sampling techniques in pediatric patients) study is to
      improve therapeutic management and patient participation in pediatric patients treated with
      antifungal and immunosuppressive agents. PROTECT is mainly financed by a ZonMW grant 'Goed
      Gebruik Geneesmiddelen'.

      Four patient organizations are actively involved in the PROTECT study.

      Objective of the study:

      Primairy To clinically validate a finger prick DBS method compared to conventional venous
      sampling for the analysis of 5 immunosuppressive and 4 azole antifungal drugs in the
      pediatric population. Secondairy

        -  Feasibility of the novel finger prick DBS method in the pediatric population will be
           assessed. This includes scoring of relevant characteristics (attributes) of blood
           drawing methods for TDM, evaluation of the experience and attitude of both patients and
           parents regarding finger prick DBS sampling and evaluation of the understanding of the
           written instructions provided for performing the finger prick at home. The data obtained
           in this validation study will be used for the implementation of the DBS in therapeutic
           drug monitoring (TDM) being a less invasive procedure, and as a base for a discrete
           choice-experiment as part of the HTA.

        -  To design an inventory of types of costs that will be incurred in the process of
           DBS-based and conventional TDM as a preparation step for later health economic analysis.

        -  Data from this study will be used to construct a population pharmacokinetic model to
           optimize dosing and design new guidelines.

      This is an observational mono-centre study in which DBS sampling is compared with
      conventional sampling for TDM in a steady state situation.

      Clearly, information on feasibility of DBS sampling in children and on costs relevant to DBS
      sampling in children can only be obtained through actual sampling in children.
    

Intervention name(s): blood drawing
Intervention type(s): Procedure
Intervention description(s): The association between conventional venous sampling and finger prick dried blood spot (DBS) will be associated by drawing blood in both ways.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Pediatric hemato-oncology and primariy immunodeficient patients and pediatric renal
        transplantation patients.
      
Biospecimen description: 
      Plasma without DNA, blood with DNA and dried blood spot (with DNA)
    
Keywords: TDM; dried blood spot; immunosuppressive; antifungal