Phenotype Algorithms for the Identification and Characterization of Vaccine-Induced Thrombotic Thrombocytopenia in Real World Data: A Multinational Network Cohort Study

Azza Shoaibi; Gowtham A. Rao; Erica A. Voss; Anna Ostropolets; Miguel Angel Mayer; Juan Manuel Ramírez-Anguita; Filip Maljković; Biljana Carević; Scott Horban; Daniel R. Morales; Talita Duarte-Salles; Clement Fraboulet; Tanguy Le Carrour; Spiros Denaxas; Vaclav Papez; Luis H. John; Peter R. Rijneek; Evan Minty; Thamir M. Alshammari; Rupa Makadia; Clair Blacketer; Frank DeFalco; Anthony G. Sena; Marc A. Suchard; Daniel Prieto-Alhambra; Patrick B. Ryan

doi:10.1007/s40264-022-01187-y

Phenotype Algorithms for the Identification and Characterization of Vaccine-Induced Thrombotic Thrombocytopenia in Real World Data: A Multinational Network Cohort Study

Azza Shoaibi^*
, Gowtham A. Rao
, Erica A. Voss
, Anna Ostropolets
, Miguel Angel Mayer
, Juan Manuel Ramírez-Anguita
, Filip Maljković
, Biljana Carević
, Scott Horban
, Daniel R. Morales
, Talita Duarte-Salles
, Clement Fraboulet
, Tanguy Le Carrour
, Spiros Denaxas
, Vaclav Papez
, Luis H. John
, Peter R. Rijneek
, Evan Minty
, Thamir M. Alshammari
, Rupa Makadia

Clair Blacketer, Frank DeFalco, Anthony G. Sena, Marc A. Suchard, Daniel Prieto-Alhambra, Patrick B. Ryan

^*Corresponding author for this work

Medical Informatics

Janssen Research and Development, LLC
OHDSI Collaborators
Columbia University Irving Medical Center
Hospital del Mar Medical Research Institute (IMIM)
Heliant Ltd
Clinical Center of Serbia
University of Dundee
Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol)
University Hospital of Marseille
Easter-eggs
University College London
Erasmus University Rotterdam
Stanford University
Riyadh Elm University
David Geffen School of Medicine
Observational Health Data Sciences and Informatics (OHDSI)
University of California

Research output: Contribution to journal › Article › Academic › peer-review

9 Citations (Scopus)

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Abstract

Introduction: Vaccine-induced thrombotic thrombocytopenia (VITT) has been identified as a rare but serious adverse event associated with coronavirus disease 2019 (COVID-19) vaccines. Objectives: In this study, we explored the pre-pandemic co-occurrence of thrombosis with thrombocytopenia (TWT) using 17 observational health data sources across the world. We applied multiple TWT definitions, estimated the background rate of TWT, characterized TWT patients, and explored the makeup of thrombosis types among TWT patients. Methods: We conducted an international network retrospective cohort study using electronic health records and insurance claims data, estimating background rates of TWT amongst persons observed from 2017 to 2019. Following the principles of existing VITT clinical definitions, TWT was defined as patients with a diagnosis of embolic or thrombotic arterial or venous events and a diagnosis or measurement of thrombocytopenia within 7 days. Six TWT phenotypes were considered, which varied in the approach taken in defining thrombosis and thrombocytopenia in real world data. Results: Overall TWT incidence rates ranged from 1.62 to 150.65 per 100,000 person-years. Substantial heterogeneity exists across data sources and by age, sex, and alternative TWT phenotypes. TWT patients were likely to be men of older age with various comorbidities. Among the thrombosis types, arterial thrombotic events were the most common. Conclusion: Our findings suggest that identifying VITT in observational data presents a substantial challenge, as implementing VITT case definitions based on the co-occurrence of TWT results in large and heterogeneous incidence rate and in a cohort of patints with baseline characteristics that are inconsistent with the VITT cases reported to date.

Original language	English
Pages (from-to)	685-698
Number of pages	14
Journal	Drug Safety
Volume	45
Issue number	6
DOIs	https://doi.org/10.1007/s40264-022-01187-y
Publication status	Published - 2 Jun 2022

Bibliographical note

Funding Information:
AS, GR, EAV, RM, AGS, CB, FD, and PBR are employees of Janssen Biotech Inc., a Janssen Pharmaceutical Company of Johnson & Johnson and shareholder of Johnson & Johnson, the product manufacturer of Janssen COVID-19 Vaccine. PRR is an employee of an institution that receives/received research grants from Janssen Research and Development LLC. DPA’s research group has received research grants from the European Medicines Agency, from the Innovative Medicines Initiative, and from Amgen, Chiesi, and UCB Biopharma; and consultancy or speaker fees from Astellas, Amgen, and UCB Biopharma. AO has received funding from the US National Institutes of Health and the US Food and Drug Administration. MAS receives grants and contracts from the US Food and Drug Administration and the US Department of Veterans Affairs within the scope of this research, and grants and contracts from the US National Institutes of Health, IQVIA, and Private Health Management outside the scope of this research. MAM, JMRA, FM, BC, SH, DRM, TDS, CF, TC, SD, VP, LHJ, EM, and TMA have no conflicts of interest to declare that are directly relevant to the contents of this study.

Funding Information:
This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 806968. The JU receives support from the European Union’s Horizon 2020 research and innovation program and EFPIA. Funders had no role in the conceptualization, design, data collection, analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
© 2022, The Author(s).

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Cite this

Shoaibi, A., Rao, G. A., Voss, E. A., Ostropolets, A., Mayer, M. A., Ramírez-Anguita, J. M., Maljković, F., Carević, B., Horban, S., Morales, D. R., Duarte-Salles, T., Fraboulet, C., Le Carrour, T., Denaxas, S., Papez, V., John, L. H., Rijneek, P. R., Minty, E., Alshammari, T. M., ... Ryan, P. B. (2022). Phenotype Algorithms for the Identification and Characterization of Vaccine-Induced Thrombotic Thrombocytopenia in Real World Data: A Multinational Network Cohort Study. Drug Safety, 45(6), 685-698. https://doi.org/10.1007/s40264-022-01187-y

@article{25d80fd30afe43bda2624e84ece65d67,

title = "Phenotype Algorithms for the Identification and Characterization of Vaccine-Induced Thrombotic Thrombocytopenia in Real World Data: A Multinational Network Cohort Study",

abstract = "Introduction: Vaccine-induced thrombotic thrombocytopenia (VITT) has been identified as a rare but serious adverse event associated with coronavirus disease 2019 (COVID-19) vaccines. Objectives: In this study, we explored the pre-pandemic co-occurrence of thrombosis with thrombocytopenia (TWT) using 17 observational health data sources across the world. We applied multiple TWT definitions, estimated the background rate of TWT, characterized TWT patients, and explored the makeup of thrombosis types among TWT patients. Methods: We conducted an international network retrospective cohort study using electronic health records and insurance claims data, estimating background rates of TWT amongst persons observed from 2017 to 2019. Following the principles of existing VITT clinical definitions, TWT was defined as patients with a diagnosis of embolic or thrombotic arterial or venous events and a diagnosis or measurement of thrombocytopenia within 7 days. Six TWT phenotypes were considered, which varied in the approach taken in defining thrombosis and thrombocytopenia in real world data. Results: Overall TWT incidence rates ranged from 1.62 to 150.65 per 100,000 person-years. Substantial heterogeneity exists across data sources and by age, sex, and alternative TWT phenotypes. TWT patients were likely to be men of older age with various comorbidities. Among the thrombosis types, arterial thrombotic events were the most common. Conclusion: Our findings suggest that identifying VITT in observational data presents a substantial challenge, as implementing VITT case definitions based on the co-occurrence of TWT results in large and heterogeneous incidence rate and in a cohort of patints with baseline characteristics that are inconsistent with the VITT cases reported to date.",

author = "Azza Shoaibi and Rao, \{Gowtham A.\} and Voss, \{Erica A.\} and Anna Ostropolets and Mayer, \{Miguel Angel\} and Ram{\'i}rez-Anguita, \{Juan Manuel\} and Filip Maljkovi{\'c} and Biljana Carevi{\'c} and Scott Horban and Morales, \{Daniel R.\} and Talita Duarte-Salles and Clement Fraboulet and \{Le Carrour\}, Tanguy and Spiros Denaxas and Vaclav Papez and John, \{Luis H.\} and Rijneek, \{Peter R.\} and Evan Minty and Alshammari, \{Thamir M.\} and Rupa Makadia and Clair Blacketer and Frank DeFalco and Sena, \{Anthony G.\} and Suchard, \{Marc A.\} and Daniel Prieto-Alhambra and Ryan, \{Patrick B.\}",

note = "Funding Information: AS, GR, EAV, RM, AGS, CB, FD, and PBR are employees of Janssen Biotech Inc., a Janssen Pharmaceutical Company of Johnson \& Johnson and shareholder of Johnson \& Johnson, the product manufacturer of Janssen COVID-19 Vaccine. PRR is an employee of an institution that receives/received research grants from Janssen Research and Development LLC. DPA{\textquoteright}s research group has received research grants from the European Medicines Agency, from the Innovative Medicines Initiative, and from Amgen, Chiesi, and UCB Biopharma; and consultancy or speaker fees from Astellas, Amgen, and UCB Biopharma. AO has received funding from the US National Institutes of Health and the US Food and Drug Administration. MAS receives grants and contracts from the US Food and Drug Administration and the US Department of Veterans Affairs within the scope of this research, and grants and contracts from the US National Institutes of Health, IQVIA, and Private Health Management outside the scope of this research. MAM, JMRA, FM, BC, SH, DRM, TDS, CF, TC, SD, VP, LHJ, EM, and TMA have no conflicts of interest to declare that are directly relevant to the contents of this study. Funding Information: This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 806968. The JU receives support from the European Union{\textquoteright}s Horizon 2020 research and innovation program and EFPIA. Funders had no role in the conceptualization, design, data collection, analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = jun,

day = "2",

doi = "10.1007/s40264-022-01187-y",

language = "English",

volume = "45",

pages = "685--698",

journal = "Drug Safety",

issn = "0114-5916",

publisher = "Adis",

number = "6",

}

Shoaibi, A, Rao, GA, Voss, EA, Ostropolets, A, Mayer, MA, Ramírez-Anguita, JM, Maljković, F, Carević, B, Horban, S, Morales, DR, Duarte-Salles, T, Fraboulet, C, Le Carrour, T, Denaxas, S, Papez, V, John, LH, Rijneek, PR, Minty, E, Alshammari, TM, Makadia, R, Blacketer, C, DeFalco, F, Sena, AG, Suchard, MA, Prieto-Alhambra, D & Ryan, PB 2022, 'Phenotype Algorithms for the Identification and Characterization of Vaccine-Induced Thrombotic Thrombocytopenia in Real World Data: A Multinational Network Cohort Study', Drug Safety, vol. 45, no. 6, pp. 685-698. https://doi.org/10.1007/s40264-022-01187-y

TY - JOUR

T1 - Phenotype Algorithms for the Identification and Characterization of Vaccine-Induced Thrombotic Thrombocytopenia in Real World Data

T2 - A Multinational Network Cohort Study

AU - Shoaibi, Azza

AU - Rao, Gowtham A.

AU - Voss, Erica A.

AU - Ostropolets, Anna

AU - Mayer, Miguel Angel

AU - Ramírez-Anguita, Juan Manuel

AU - Maljković, Filip

AU - Carević, Biljana

AU - Horban, Scott

AU - Morales, Daniel R.

AU - Duarte-Salles, Talita

AU - Fraboulet, Clement

AU - Le Carrour, Tanguy

AU - Denaxas, Spiros

AU - Papez, Vaclav

AU - John, Luis H.

AU - Rijneek, Peter R.

AU - Minty, Evan

AU - Alshammari, Thamir M.

AU - Makadia, Rupa

AU - Blacketer, Clair

AU - DeFalco, Frank

AU - Sena, Anthony G.

AU - Suchard, Marc A.

AU - Prieto-Alhambra, Daniel

AU - Ryan, Patrick B.

N1 - Funding Information: AS, GR, EAV, RM, AGS, CB, FD, and PBR are employees of Janssen Biotech Inc., a Janssen Pharmaceutical Company of Johnson & Johnson and shareholder of Johnson & Johnson, the product manufacturer of Janssen COVID-19 Vaccine. PRR is an employee of an institution that receives/received research grants from Janssen Research and Development LLC. DPA’s research group has received research grants from the European Medicines Agency, from the Innovative Medicines Initiative, and from Amgen, Chiesi, and UCB Biopharma; and consultancy or speaker fees from Astellas, Amgen, and UCB Biopharma. AO has received funding from the US National Institutes of Health and the US Food and Drug Administration. MAS receives grants and contracts from the US Food and Drug Administration and the US Department of Veterans Affairs within the scope of this research, and grants and contracts from the US National Institutes of Health, IQVIA, and Private Health Management outside the scope of this research. MAM, JMRA, FM, BC, SH, DRM, TDS, CF, TC, SD, VP, LHJ, EM, and TMA have no conflicts of interest to declare that are directly relevant to the contents of this study. Funding Information: This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 806968. The JU receives support from the European Union’s Horizon 2020 research and innovation program and EFPIA. Funders had no role in the conceptualization, design, data collection, analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2022, The Author(s).

PY - 2022/6/2

Y1 - 2022/6/2

N2 - Introduction: Vaccine-induced thrombotic thrombocytopenia (VITT) has been identified as a rare but serious adverse event associated with coronavirus disease 2019 (COVID-19) vaccines. Objectives: In this study, we explored the pre-pandemic co-occurrence of thrombosis with thrombocytopenia (TWT) using 17 observational health data sources across the world. We applied multiple TWT definitions, estimated the background rate of TWT, characterized TWT patients, and explored the makeup of thrombosis types among TWT patients. Methods: We conducted an international network retrospective cohort study using electronic health records and insurance claims data, estimating background rates of TWT amongst persons observed from 2017 to 2019. Following the principles of existing VITT clinical definitions, TWT was defined as patients with a diagnosis of embolic or thrombotic arterial or venous events and a diagnosis or measurement of thrombocytopenia within 7 days. Six TWT phenotypes were considered, which varied in the approach taken in defining thrombosis and thrombocytopenia in real world data. Results: Overall TWT incidence rates ranged from 1.62 to 150.65 per 100,000 person-years. Substantial heterogeneity exists across data sources and by age, sex, and alternative TWT phenotypes. TWT patients were likely to be men of older age with various comorbidities. Among the thrombosis types, arterial thrombotic events were the most common. Conclusion: Our findings suggest that identifying VITT in observational data presents a substantial challenge, as implementing VITT case definitions based on the co-occurrence of TWT results in large and heterogeneous incidence rate and in a cohort of patints with baseline characteristics that are inconsistent with the VITT cases reported to date.

AB - Introduction: Vaccine-induced thrombotic thrombocytopenia (VITT) has been identified as a rare but serious adverse event associated with coronavirus disease 2019 (COVID-19) vaccines. Objectives: In this study, we explored the pre-pandemic co-occurrence of thrombosis with thrombocytopenia (TWT) using 17 observational health data sources across the world. We applied multiple TWT definitions, estimated the background rate of TWT, characterized TWT patients, and explored the makeup of thrombosis types among TWT patients. Methods: We conducted an international network retrospective cohort study using electronic health records and insurance claims data, estimating background rates of TWT amongst persons observed from 2017 to 2019. Following the principles of existing VITT clinical definitions, TWT was defined as patients with a diagnosis of embolic or thrombotic arterial or venous events and a diagnosis or measurement of thrombocytopenia within 7 days. Six TWT phenotypes were considered, which varied in the approach taken in defining thrombosis and thrombocytopenia in real world data. Results: Overall TWT incidence rates ranged from 1.62 to 150.65 per 100,000 person-years. Substantial heterogeneity exists across data sources and by age, sex, and alternative TWT phenotypes. TWT patients were likely to be men of older age with various comorbidities. Among the thrombosis types, arterial thrombotic events were the most common. Conclusion: Our findings suggest that identifying VITT in observational data presents a substantial challenge, as implementing VITT case definitions based on the co-occurrence of TWT results in large and heterogeneous incidence rate and in a cohort of patints with baseline characteristics that are inconsistent with the VITT cases reported to date.

UR - https://www.scopus.com/pages/publications/85131308910

U2 - 10.1007/s40264-022-01187-y

DO - 10.1007/s40264-022-01187-y

M3 - Article

C2 - 35653017

AN - SCOPUS:85131308910

SN - 0114-5916

VL - 45

SP - 685

EP - 698

JO - Drug Safety

JF - Drug Safety

IS - 6

ER -

Phenotype Algorithms for the Identification and Characterization of Vaccine-Induced Thrombotic Thrombocytopenia in Real World Data: A Multinational Network Cohort Study

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