Evidence map›Paper›PMID 31435896›Full record

ArticleClinical pharmacokinetics2020

Development and Validation of a Population-Pharmacokinetic Model for Rurioctacog Alfa Pegol (Adynovate

Pierre Chelle, Cindy H T Yeung, Stacy E Croteau, Jennifer Lissick, Vinod Balasa, Christina Ashburner, Young Shil Park, Santiago Bonanad, Juan Eduardo Megías-Vericat, Azusa Nagao and 8 more

Abstract readComparative Study
PubMed Publisher
In one paragraph

Article in Clinical pharmacokinetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Pierre ChelleSchool of Pharmacy, University of Waterloo, Waterloo, ON, Canada.
Cindy H T YeungDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main Street West, Hamilton, ON, L8S 4K1, Canada.
Stacy E CroteauBoston Children's Hospital/Harvard Medical School, Boston, MA, USA.
Jennifer LissickChildren's Minnesota, Minneapolis, MN, USA.
Vinod BalasaValley Children's Healthcare, Madera, CA, USA.
Christina AshburnerValley Children's Healthcare, Madera, CA, USA.
Young Shil ParkKyung Hee University Hospital at Gangdong, Seoul, Republic of Korea.
Santiago BonanadHospital Universitari i Politècnic La Fe, Valencia, Spain.
Juan Eduardo Megías-VericatHospital Universitari i Politècnic La Fe, Valencia, Spain.
Azusa NagaoOgikubo Hospital, Tokyo, Japan.
Tung WynnUniversity of Florida, Gainesville, FL, USA.
Fernando Corrales-MedinaUniversity of Miami Hemophilia Treatment Center, Miami, FL, USA.
Huyen TranRonald Sawers Haemophilia Treatment Centre, Melbourne, VIC, Australia.
Anjali SharathkumarUniversity of Iowa Carver College of Medicine, Stead Family Department of Pediatrics, University of Iowa Children's Hospital, Iowa City, IA, USA.
Meera ChitlurChildren's Hospital of Michigan, Detroit, MI, USA.
Samuel SarmientoIntegral Solutions SD S.A.S, Bogotá, Colombia.
Andrea EdgintonSchool of Pharmacy, University of Waterloo, Waterloo, ON, Canada.
Alfonso IorioDepartment of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main Street West, Hamilton, ON, L8S 4K1, Canada. iorioa@mcmaster.ca.ORCID http://orcid.org/0000-0002-3331-8766

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectiveRurioctacog alfa pegol (Adynovate) is a modified recombinant factor VIII concentrate used for treating hemophilia A. Aiming to improve treatment tailoring on the Web-Accessible Population Pharmacokinetic Service-Hemophilia (WAPPS-Hemo) platform for patients of all ages treated with Adynovate, we have developed and evaluated a population pharmacokinetic (PopPK) model. On the platform, PopPK models are used as priors for Bayesian forecasting that derive individual PK of hemophilia patients and are subsequently used for personalized dose regimen design.

methodsFactor activity measurements and demographic covariate data from patients infused with Adynovate were extracted from the WAPPS-Hemo database. Evaluations testing the appropriateness of Bayesian forecasting included 10-fold cross validation, a limited sampling analysis (LSA), and an external evaluation using additional independent data extracted from the WAPPS-Hemo database at a later date.

resultsThe model was constructed using 650 plasma factor activity observations (555 one stage assay and 95 chromogenic assay - 4.6% below limit of quantification) measured in 154 patients from 36 hemophilia centres. A two-compartment model including between subject variability on clearance and central volume was selected as the base model. Covariates were fat free mass on clearance and central volume, age on clearance and assay type on activity. The final model was well-suited to predict PK parameters of new individuals (n = 26) from sparse observations.

conclusionsThe development of a PopPK model for Adynovate using real-world data increases the covariate space (e.g. age) beyond what is possible from clinical trial data. This model is available on the WAPPS-Hemo platform for tailoring treatment in hemophilia A patients.

Indexed as

AdolescentAdultBayes TheoremBody Mass IndexChildDatabases, FactualFactor VIIIHemophilia AHumansInfusions, IntravenousInternet-Based InterventionModels, TheoreticalRecombinant ProteinsYoung AdultBAX 855Factor VIIIRecombinant Proteins

Identifiers

PMID31435896

What OpenQuestion holds

Textmetadata
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.