Regression discontinuity analysis for pharmacovigilance: statin example reflected trial findings showing little evidence of harm

Lauren J Scott; Maria Theresa Redaniel; Matthew J Booker; Rupert A Payne; Kate M Tilling

doi:10.1016/j.jclinepi.2021.10.003

Regression discontinuity analysis for pharmacovigilance: statin example reflected trial findings showing little evidence of harm

Lauren J Scott, Maria Theresa Redaniel^*, Matthew J Booker, Rupert A Payne, Kate M Tilling

^*Corresponding author for this work

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

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Abstract

Objective
The study aims to explore the use of regression discontinuity analysis (RDA) to examine effects of prescription of statins on total cholesterol and adverse outcomes (type 2 diabetes, rhabdomyolysis and myopathy, myalgia and myositis, liver disease, CVD and mortality).

Study Design and Setting
We conducted a prospective cohort study using the Clinical Practice Research Datalink including patients with QRISK scores of 10-30 in 2010-2013 who were last followed-up in October 2016. Comparing patients with QRISK>20 and QRISK<20, we explored RDA assumptions, provided proof of concept analyses (total cholesterol as outcome), and investigated the effect of statins prescription on adverse outcomes.

Results
RDA confirmed statin prescription reduced total cholesterol (Mean difference (MD) -1.33 mmol/l, 95%Confidence Interval (CI) -1.93 to -0.73). RDA provided little evidence for adverse effects on diabetes, myalgia and myositis, liver disease, CVD, or mortality. The RDA analysis findings are similar to RCT results. Findings from non-RDA analysis agree with published observational studies.

Conclusions
RDA can be used with large routine clinical datasets to provide evidence on effects of medications which are prescribed according to a threshold. Testable RDA assumptions were satisfied, but confidence intervals were wide, partly due to the low compliance with the prescribing threshold.

Original language	English
Pages (from-to)	121-131
Number of pages	11
Journal	Journal of Clinical Epidemiology
Volume	141
Early online date	12 Oct 2021
DOIs	https://doi.org/10.1016/j.jclinepi.2021.10.003
Publication status	E-pub ahead of print - 12 Oct 2021

Bibliographical note

Funding Information:
Funding statement: This research was funded by the National Institute for Health Research (NIHR) Applied Research Collaboration West (ARC West) at University Hospitals Bristol and Weston NHS Foundation Trust (core NIHR infrastructure funded: NIHR200181). KT works in the MRC Integrative Epidemiology Unit which receives funding from the UK Medical Research Council and the University of Bristol (MC_UU_00011/3). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.

Publisher Copyright:
© 2021 The Authors

Keywords

Regression discontinuity analysis
statins
cardiovascular disease
QRISK score
epidemiology
health service research

UN SDGs

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

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title = "Regression discontinuity analysis for pharmacovigilance: statin example reflected trial findings showing little evidence of harm",

abstract = "ObjectiveThe study aims to explore the use of regression discontinuity analysis (RDA) to examine effects of prescription of statins on total cholesterol and adverse outcomes (type 2 diabetes, rhabdomyolysis and myopathy, myalgia and myositis, liver disease, CVD and mortality).Study Design and SettingWe conducted a prospective cohort study using the Clinical Practice Research Datalink including patients with QRISK scores of 10-30 in 2010-2013 who were last followed-up in October 2016. Comparing patients with QRISK>20 and QRISK<20, we explored RDA assumptions, provided proof of concept analyses (total cholesterol as outcome), and investigated the effect of statins prescription on adverse outcomes.ResultsRDA confirmed statin prescription reduced total cholesterol (Mean difference (MD) -1.33 mmol/l, 95%Confidence Interval (CI) -1.93 to -0.73). RDA provided little evidence for adverse effects on diabetes, myalgia and myositis, liver disease, CVD, or mortality. The RDA analysis findings are similar to RCT results. Findings from non-RDA analysis agree with published observational studies.ConclusionsRDA can be used with large routine clinical datasets to provide evidence on effects of medications which are prescribed according to a threshold. Testable RDA assumptions were satisfied, but confidence intervals were wide, partly due to the low compliance with the prescribing threshold.",

keywords = "Regression discontinuity analysis, statins, cardiovascular disease, QRISK score, epidemiology, health service research",

author = "Scott, {Lauren J} and Redaniel, {Maria Theresa} and Booker, {Matthew J} and Payne, {Rupert A} and Tilling, {Kate M}",

note = "Funding Information: Funding statement: This research was funded by the National Institute for Health Research (NIHR) Applied Research Collaboration West (ARC West) at University Hospitals Bristol and Weston NHS Foundation Trust (core NIHR infrastructure funded: NIHR200181). KT works in the MRC Integrative Epidemiology Unit which receives funding from the UK Medical Research Council and the University of Bristol (MC_UU_00011/3). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2021",

month = oct,

day = "12",

doi = "10.1016/j.jclinepi.2021.10.003",

language = "English",

volume = "141",

pages = "121--131",

journal = "Journal of Clinical Epidemiology",

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TY - JOUR

T1 - Regression discontinuity analysis for pharmacovigilance

T2 - statin example reflected trial findings showing little evidence of harm

AU - Scott, Lauren J

AU - Redaniel, Maria Theresa

AU - Booker, Matthew J

AU - Payne, Rupert A

AU - Tilling, Kate M

N1 - Funding Information: Funding statement: This research was funded by the National Institute for Health Research (NIHR) Applied Research Collaboration West (ARC West) at University Hospitals Bristol and Weston NHS Foundation Trust (core NIHR infrastructure funded: NIHR200181). KT works in the MRC Integrative Epidemiology Unit which receives funding from the UK Medical Research Council and the University of Bristol (MC_UU_00011/3). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. Publisher Copyright: © 2021 The Authors

PY - 2021/10/12

Y1 - 2021/10/12

N2 - ObjectiveThe study aims to explore the use of regression discontinuity analysis (RDA) to examine effects of prescription of statins on total cholesterol and adverse outcomes (type 2 diabetes, rhabdomyolysis and myopathy, myalgia and myositis, liver disease, CVD and mortality).Study Design and SettingWe conducted a prospective cohort study using the Clinical Practice Research Datalink including patients with QRISK scores of 10-30 in 2010-2013 who were last followed-up in October 2016. Comparing patients with QRISK>20 and QRISK<20, we explored RDA assumptions, provided proof of concept analyses (total cholesterol as outcome), and investigated the effect of statins prescription on adverse outcomes.ResultsRDA confirmed statin prescription reduced total cholesterol (Mean difference (MD) -1.33 mmol/l, 95%Confidence Interval (CI) -1.93 to -0.73). RDA provided little evidence for adverse effects on diabetes, myalgia and myositis, liver disease, CVD, or mortality. The RDA analysis findings are similar to RCT results. Findings from non-RDA analysis agree with published observational studies.ConclusionsRDA can be used with large routine clinical datasets to provide evidence on effects of medications which are prescribed according to a threshold. Testable RDA assumptions were satisfied, but confidence intervals were wide, partly due to the low compliance with the prescribing threshold.

AB - ObjectiveThe study aims to explore the use of regression discontinuity analysis (RDA) to examine effects of prescription of statins on total cholesterol and adverse outcomes (type 2 diabetes, rhabdomyolysis and myopathy, myalgia and myositis, liver disease, CVD and mortality).Study Design and SettingWe conducted a prospective cohort study using the Clinical Practice Research Datalink including patients with QRISK scores of 10-30 in 2010-2013 who were last followed-up in October 2016. Comparing patients with QRISK>20 and QRISK<20, we explored RDA assumptions, provided proof of concept analyses (total cholesterol as outcome), and investigated the effect of statins prescription on adverse outcomes.ResultsRDA confirmed statin prescription reduced total cholesterol (Mean difference (MD) -1.33 mmol/l, 95%Confidence Interval (CI) -1.93 to -0.73). RDA provided little evidence for adverse effects on diabetes, myalgia and myositis, liver disease, CVD, or mortality. The RDA analysis findings are similar to RCT results. Findings from non-RDA analysis agree with published observational studies.ConclusionsRDA can be used with large routine clinical datasets to provide evidence on effects of medications which are prescribed according to a threshold. Testable RDA assumptions were satisfied, but confidence intervals were wide, partly due to the low compliance with the prescribing threshold.

KW - Regression discontinuity analysis

KW - statins

KW - cardiovascular disease

KW - QRISK score

KW - epidemiology

KW - health service research

U2 - 10.1016/j.jclinepi.2021.10.003

DO - 10.1016/j.jclinepi.2021.10.003

M3 - Article (Academic Journal)

C2 - 34648942

SN - 0895-4356

VL - 141

SP - 121

EP - 131

JO - Journal of Clinical Epidemiology

JF - Journal of Clinical Epidemiology

ER -

Regression discontinuity analysis for pharmacovigilance: statin example reflected trial findings showing little evidence of harm

Abstract

Bibliographical note

Keywords

UN SDGs

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