Quantifying and Adjusting for Confounding From Health-Seeking Behavior and Health Care Access in Observational Research

Sophie Graham; Jemma L. Walker; Nick Andrews; William J. Hulme; Dorothea Nitsch; Edward P. K. Parker; Helen I. McDonald

doi:10.1093/ofid/ofae598

Quantifying and Adjusting for Confounding From Health-Seeking Behavior and Health Care Access in Observational Research

Sophie Graham, Jemma L. Walker, Nick Andrews, William J. Hulme, Dorothea Nitsch, Edward P. K. Parker, Helen I. McDonald

Department of Life Sciences

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

Abstract

BACKGROUND: Health-seeking behavior and health care access (HSB/HCA) are recognized confounders in many observational studies but are not directly measurable in electronic health records. We used proxy markers of HSB/HCA to quantify and adjust for confounding in observational studies of influenza and COVID-19 vaccine effectiveness (VE).

METHODS: This cohort study used primary care data prelinked to secondary care and death data in England. We included individuals aged ≥66 years on 1 September 2019 and assessed influenza VE in the 2019-2020 season and early COVID-19 VE (December 2020-March 2021). VE was estimated with sequential adjustment for demographics, comorbidities, and 14 markers of HSB/HCA. Influenza vaccination in the 2019-2020 season was also considered a negative control exposure against COVID-19 before COVID-19 vaccine rollout.

RESULTS: We included 1 991 284, 1 796 667, and 1 946 943 individuals in the influenza, COVID-19, and negative control exposure populations, respectively. Markers of HSB/HCA were positively correlated with influenza and COVID-19 vaccine uptake. For influenza, adjusting for HSB/HCA markers in addition to demographics and comorbidities increased VE against influenza-like illness from -1.5% (95% CI, -3.2% to .1%) to 7.1% (95% CI, 5.4%-8.7%) with a less apparent trend for more severe outcomes. For COVID-19, adjusting for HSB/HCA markers did not change VE estimates against infection or severe disease (eg, 2 doses of BNT162b2 against infection: 82.8% [95% CI, 78.4%-86.3%] to 83.1% [95% CI, 78.7%-86.5%]). Adjusting for HSB/HCA markers removed bias in the negative control exposure analysis (-7.5% [95% CI, -10.6% to -4.5%] vs -2.1% [95% CI, -6.0% to 1.7%] before vs after adjusting for HSB/HCA markers).

CONCLUSIONS: Markers of HSB/HCA can be used to quantify and account for confounding in observational vaccine studies.

Original language	English
Article number	ofae598
Journal	Open Forum Infectious Diseases
Volume	11
Issue number	10
Early online date	23 Oct 2024
DOIs	https://doi.org/10.1093/ofid/ofae598
Publication status	Published - 31 Oct 2024

Data Availability Statement

These data were obtained from the CPRD, provided by the UK Medicines and Healthcare products Regulatory Agency. The authors' licence for using these data does not allow sharing of raw data with third parties. Information about access to CPRD data is available here: https://www.cprd.com/research-applications.

Acknowledgements

This work uses data provided by patients and collected by the NHS as part of their care and support (usemydata.org).

Funding

This work uses data provided by patients and collected by the NHS as part of their care and support (usemydata.org). Data availability statement. These data were obtained from the CPRD, provided by the UK Medicines and Healthcare products Regulatory Agency. The authors' licence for using these data does not allow sharing of raw data with third parties. Information about access to CPRD data is available here: https://www.cprd.com/research-applications. This work was supported by the National Institute of Health and Care Research's Health Protection Research Unit in Vaccines and Immunisation (grant NIHR200929 to S. G., E. P. K. P., N. A., J. L. W., and H. I. M.), a partnership between the UK Health Security Agency and London School of Hygiene and Tropical Medicine. Financial support. This work was supported by the National Institute of Health and Care Research\u2019s Health Protection Research Unit in Vaccines and Immunisation (grant NIHR200929 to S. G., E. P. K. P., N. A., J. L. W., and H. I. M.), a partnership between the UK Health Security Agency and London School of Hygiene and Tropical Medicine.

Funders	Funder number
UK Medicines and Healthcare Products Regulatory Agency
Health Security Agency and London School of Hygiene and Tropical Medicine
National Institute of Health and Care Research's Health Protection Research Unit in Vaccines and Immunisation
Center for Participatory Research and Development
National Institute of Health and Care Research’s Health Protection Research Unit in Vaccines and Immunisation	NIHR200929

Keywords

COVID-19
confounding from health-seeking behavior and health care access
influenza
vaccine effectiveness
vaccines

ASJC Scopus subject areas

Oncology
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1093/ofid/ofae598Licence: CC BY

Cite this

@article{b731735164f64db586f8fa9b3ced7cba,

title = "Quantifying and Adjusting for Confounding From Health-Seeking Behavior and Health Care Access in Observational Research",

abstract = "BACKGROUND: Health-seeking behavior and health care access (HSB/HCA) are recognized confounders in many observational studies but are not directly measurable in electronic health records. We used proxy markers of HSB/HCA to quantify and adjust for confounding in observational studies of influenza and COVID-19 vaccine effectiveness (VE).METHODS: This cohort study used primary care data prelinked to secondary care and death data in England. We included individuals aged ≥66 years on 1 September 2019 and assessed influenza VE in the 2019-2020 season and early COVID-19 VE (December 2020-March 2021). VE was estimated with sequential adjustment for demographics, comorbidities, and 14 markers of HSB/HCA. Influenza vaccination in the 2019-2020 season was also considered a negative control exposure against COVID-19 before COVID-19 vaccine rollout.RESULTS: We included 1 991 284, 1 796 667, and 1 946 943 individuals in the influenza, COVID-19, and negative control exposure populations, respectively. Markers of HSB/HCA were positively correlated with influenza and COVID-19 vaccine uptake. For influenza, adjusting for HSB/HCA markers in addition to demographics and comorbidities increased VE against influenza-like illness from -1.5% (95% CI, -3.2% to .1%) to 7.1% (95% CI, 5.4%-8.7%) with a less apparent trend for more severe outcomes. For COVID-19, adjusting for HSB/HCA markers did not change VE estimates against infection or severe disease (eg, 2 doses of BNT162b2 against infection: 82.8% [95% CI, 78.4%-86.3%] to 83.1% [95% CI, 78.7%-86.5%]). Adjusting for HSB/HCA markers removed bias in the negative control exposure analysis (-7.5% [95% CI, -10.6% to -4.5%] vs -2.1% [95% CI, -6.0% to 1.7%] before vs after adjusting for HSB/HCA markers).CONCLUSIONS: Markers of HSB/HCA can be used to quantify and account for confounding in observational vaccine studies.",

keywords = "COVID-19, confounding from health-seeking behavior and health care access, influenza, vaccine effectiveness, vaccines",

author = "Sophie Graham and Walker, {Jemma L.} and Nick Andrews and Hulme, {William J.} and Dorothea Nitsch and Parker, {Edward P. K.} and McDonald, {Helen I.}",

year = "2024",

month = oct,

day = "31",

doi = "10.1093/ofid/ofae598",

language = "English",

volume = "11",

journal = "Open Forum Infectious Diseases",

issn = "2328-8957",

publisher = "Oxford University Press",

number = "10",

}

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T1 - Quantifying and Adjusting for Confounding From Health-Seeking Behavior and Health Care Access in Observational Research

AU - Graham, Sophie

AU - Walker, Jemma L.

AU - Andrews, Nick

AU - Hulme, William J.

AU - Nitsch, Dorothea

AU - Parker, Edward P. K.

AU - McDonald, Helen I.

PY - 2024/10/31

Y1 - 2024/10/31

N2 - BACKGROUND: Health-seeking behavior and health care access (HSB/HCA) are recognized confounders in many observational studies but are not directly measurable in electronic health records. We used proxy markers of HSB/HCA to quantify and adjust for confounding in observational studies of influenza and COVID-19 vaccine effectiveness (VE).METHODS: This cohort study used primary care data prelinked to secondary care and death data in England. We included individuals aged ≥66 years on 1 September 2019 and assessed influenza VE in the 2019-2020 season and early COVID-19 VE (December 2020-March 2021). VE was estimated with sequential adjustment for demographics, comorbidities, and 14 markers of HSB/HCA. Influenza vaccination in the 2019-2020 season was also considered a negative control exposure against COVID-19 before COVID-19 vaccine rollout.RESULTS: We included 1 991 284, 1 796 667, and 1 946 943 individuals in the influenza, COVID-19, and negative control exposure populations, respectively. Markers of HSB/HCA were positively correlated with influenza and COVID-19 vaccine uptake. For influenza, adjusting for HSB/HCA markers in addition to demographics and comorbidities increased VE against influenza-like illness from -1.5% (95% CI, -3.2% to .1%) to 7.1% (95% CI, 5.4%-8.7%) with a less apparent trend for more severe outcomes. For COVID-19, adjusting for HSB/HCA markers did not change VE estimates against infection or severe disease (eg, 2 doses of BNT162b2 against infection: 82.8% [95% CI, 78.4%-86.3%] to 83.1% [95% CI, 78.7%-86.5%]). Adjusting for HSB/HCA markers removed bias in the negative control exposure analysis (-7.5% [95% CI, -10.6% to -4.5%] vs -2.1% [95% CI, -6.0% to 1.7%] before vs after adjusting for HSB/HCA markers).CONCLUSIONS: Markers of HSB/HCA can be used to quantify and account for confounding in observational vaccine studies.

AB - BACKGROUND: Health-seeking behavior and health care access (HSB/HCA) are recognized confounders in many observational studies but are not directly measurable in electronic health records. We used proxy markers of HSB/HCA to quantify and adjust for confounding in observational studies of influenza and COVID-19 vaccine effectiveness (VE).METHODS: This cohort study used primary care data prelinked to secondary care and death data in England. We included individuals aged ≥66 years on 1 September 2019 and assessed influenza VE in the 2019-2020 season and early COVID-19 VE (December 2020-March 2021). VE was estimated with sequential adjustment for demographics, comorbidities, and 14 markers of HSB/HCA. Influenza vaccination in the 2019-2020 season was also considered a negative control exposure against COVID-19 before COVID-19 vaccine rollout.RESULTS: We included 1 991 284, 1 796 667, and 1 946 943 individuals in the influenza, COVID-19, and negative control exposure populations, respectively. Markers of HSB/HCA were positively correlated with influenza and COVID-19 vaccine uptake. For influenza, adjusting for HSB/HCA markers in addition to demographics and comorbidities increased VE against influenza-like illness from -1.5% (95% CI, -3.2% to .1%) to 7.1% (95% CI, 5.4%-8.7%) with a less apparent trend for more severe outcomes. For COVID-19, adjusting for HSB/HCA markers did not change VE estimates against infection or severe disease (eg, 2 doses of BNT162b2 against infection: 82.8% [95% CI, 78.4%-86.3%] to 83.1% [95% CI, 78.7%-86.5%]). Adjusting for HSB/HCA markers removed bias in the negative control exposure analysis (-7.5% [95% CI, -10.6% to -4.5%] vs -2.1% [95% CI, -6.0% to 1.7%] before vs after adjusting for HSB/HCA markers).CONCLUSIONS: Markers of HSB/HCA can be used to quantify and account for confounding in observational vaccine studies.

KW - COVID-19

KW - confounding from health-seeking behavior and health care access

KW - influenza

KW - vaccine effectiveness

KW - vaccines

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Quantifying and Adjusting for Confounding From Health-Seeking Behavior and Health Care Access in Observational Research

Abstract

Data Availability Statement

Acknowledgements

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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