Evidence map›Paper›PMID 29298994›Full record

ArticleThe pharmacogenomics journal2019

Cost-effectiveness of HLA-DQB1/HLA-B pharmacogenetic-guided treatment and blood monitoring in US patients taking clozapine.

François R Girardin, Antoine Poncet, Arnaud Perrier, Nathalie Vernaz, Mark Pletscher, Caroline F Samer, Jeffrey A Lieberman, Jean Villard

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The pharmacogenomics journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 5 pooled it
4.3field-weighted citation impact, top 5% of its field
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

21 citing papers in PubMed, 5 syntheses or guidelines pooled it, 42 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Trial
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Review
  20. Review
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

8 authors at 3 institutions in 2 countries.

François R GirardinDivision of Clinical Pharmacology and Toxicology, Department of Anesthesiology, Intensive Care, and Clinical Pharmacology, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland. francois.girardin@hcuge.ch.ORCID http://orcid.org/0000-0002-0842-927X
Antoine PoncetThe Clinical Research Centre, Division of Clinical Epidemiology, Department of Health and Community Medicine, University of Geneva and University Hospitals of Geneva, Geneva, Switzerland.
Arnaud PerrierMedical Direction, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland.
Nathalie VernazMedical Direction, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland.
Mark PletscherWinterthur Institute of Health Economics, Zurich University of Applied Sciences, Winterthur, Switzerland.
Caroline F SamerDivision of Clinical Pharmacology and Toxicology, Department of Anesthesiology, Intensive Care, and Clinical Pharmacology, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland.
Jeffrey A LiebermanDepartment of Psychiatry, Columbia University and New York State Psychiatric Institute, New York, NY, 10032, USA.
Jean VillardDivision of Nephrology, University Hospitals of Geneva and University of Geneva, Geneva, Switzerland.
University of Geneva · CHNew York Psychoanalytic Society and Institute · USZHAW Zurich University of Applied Sciences · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Less than 1% of adult patients with schizophrenia taking clozapine develop agranulocytosis, and most of these cases occur within the first weeks of treatment. The human leukocyte antigen (HLA) region has been associated with genetic susceptibility to clozapine-induced agranulocytosis (single amino acid changes in HLA-DQB1 (126Q) and HLA-B (158T)). The current study aimed to evaluate the cost-effectiveness, from a healthcare provider's perspective, of an HLA genotype-guided approach in patients with treatment-resistant schizophrenia who were taking clozapine and to compare the results with the current absolute neutrophil count monitoring (ANCM) schemes used in the USA. A semi-Markovian model was developed to simulate the progress of a cohort of adult men and women who received clozapine as a third-line antipsychotic medication. We compared current practices using two genotype-guided strategies: (1) HLA genotyping followed by clozapine, with ANCM only for patients who tested positive for one or both alleles (genotype-guided blood sampling); (2) HLA genotyping followed by clozapine for low-risk patients and alternative antipsychotics for patients who tested positive (clozapine substitution scheme). Up to a decision threshold of $3.9 million per quality-adjusted life-year (90-fold the US gross domestic product per capita), the base-case results indicate that compared with current ANCM, genotype-guided blood sampling prior to clozapine initiation appeared cost-effective for targeted blood monitoring only in patients with HLA susceptibility alleles. Sensitivity analysis demonstrated that at a cost of genotype testing of up to USD700, HLA genotype-guided blood monitoring remained a cost-effective strategy compared with either current ANCM or clozapine substitution.

Indexed as

AdultAgranulocytosisAllelesClozapineCohort StudiesCost-Benefit AnalysisFemaleGenetic Predisposition to DiseaseGenotypeHLA-B AntigensHLA-DQ beta-ChainsHumansMaleMiddle AgedPharmacogenomic TestingSchizophreniaClozapineHLA-B AntigensHLA-DQB1 antigenHLA-DQ beta-Chains

Identifiers

PMID29298994
PMCPMC6462824
OpenAlexW2781558796

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.