Dataset Information

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

ABSTRACT:

Objectives

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 to 30 in 2010 to 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.

Result

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.

Conclusion

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.

SUBMITTER: Scott L

PROVIDER: S-EPMC8982642 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Publications

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

Scott Lauren L Redaniel Maria Theresa MT Booker Matthew M Payne Rupert A RA Tilling Kate K

Journal of clinical epidemiology 20211012

<h4>Objectives</h4>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).<h4>Study design and setting</h4>We conducted a prospective cohort study using the Clinical Practice Research Datalink including patients with QRISK scores of 10 to 30 in 2010 to 2013 who were last followed-up in ...[more]

PMID: 34648942

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Project description:ImportanceRadiocontrast has long been thought of as nephrotoxic; however, a number of recent observational studies found no evidence of an association between intravenous contrast and kidney injury. Because these studies are at high risk of confounding and selection bias, alternative study designs are required to enable more robust evaluation of this association.ObjectiveTo determine whether intravenous radiocontrast exposure is associated with clinically significant long-term kidney impairment, using a study design that permits stronger causal interpretation than existing observational research.Design, setting, and participantsThis cohort study included all emergency department patients aged 18 years or older undergoing D-dimer testing between 2013 and 2018 in the Canadian province of Alberta. A fuzzy regression discontinuity design was used, exploiting the fact that individuals just either side of the eligibility cutoff for computed tomographic pulmonary angiogram (CTPA)-typically 500 ng/mL-have markedly different probabilities of contrast exposure, but should otherwise be similar with respect to potential confounders.ExposuresIntravenous contrast in the form of a CTPA.Main outcomes and measuresEstimated glomerular filtration rate (eGFR) up to 6 months following the index emergency department visit.ResultsDuring the study period 156 028 individuals received a D-dimer test. The mean age was 53 years, 68 206 (44%) were men and 87 822 (56%) were women, and the mean baseline eGFR level was 86 mL/min/1.73 m2. Patients just above and below the CTPA eligibility cutoff were similar in terms of measured confounders. There was no evidence for an association of contrast with eGFR up to 6 months later, with a mean change in eGFR of -0.4 mL/min/1.73 m2 (95% CI, -4.9 to 4.0) associated with CTPA exposure. There was similarly no evidence for an association with need for kidney replacement therapy (risk difference [RD], 0.07%; 95% CI, -0.47% to 0.61%), mortality (RD, 0.3%; 95% CI, -2.9% to 3.2%), and acute kidney injury (RD, 4.3%; 95% CI, -2.7% to 12.9%), though the latter analysis was limited by missing data. Subgroup analyses were potentially consistent with harm among patients with diabetes (mean eGFR change -6.4 mL/min/1.73 m2; 95% CI, -15.4 to 0.2), but not among those with other reported risk factors for contrast-induced nephropathy; these analyses, however, were relatively underpowered.Conclusions and relevanceUsing a cohort study design and analysis that permits stronger causal interpretation than existing observational research, we found no evidence for a harmful effect on kidney function of intravenous contrast administered for CTPA in an emergency setting.

Project description:BackgroundThe relationship between exposure to conflict violence during pregnancy and the risks of miscarriage, stillbirth, and perinatal mortality has not been studied empirically using rigorous methods and appropriate data. We investigated the association between reduced exposure to conflict violence during pregnancy and the risks of adverse pregnancy outcomes in Colombia.Methods and findingsWe adopted a regression discontinuity (RD) design using the July 20, 2015 cease-fire declared during the Colombian peace process as an exogenous discontinuous change in exposure to conflict events during pregnancy, comparing women with conception dates before and after the cease-fire date. We constructed the cohorts of all pregnant women in Colombia for each day between January 1, 2013 and December 31, 2017 using birth and death certificates. A total of 3,254,696 women were followed until the end of pregnancy. We measured conflict exposure as the total number of conflict events that occurred in the municipality where a pregnant woman lived during her pregnancy. We first assessed whether the cease-fire did induce a discontinuous fall in conflict exposure for women with conception dates after the cease-fire to then estimate the association of this reduced exposure with the risks of miscarriage, stillbirth, and perinatal mortality. We found that the July 20, 2015 cease-fire was associated with a reduction of the average number of conflict events (from 2.64 to 2.40) to which women were exposed during pregnancy in their municipalities of residence (mean differences -0.24; 95% confidence interval [CI] -0.35 to -0.13; p < 0.001). This association was greater in municipalities where Fuerzas Armadas Revolucionarias de Colombia (FARC) had a greater presence historically. The reduction in average exposure to conflict violence was, in turn, associated with a decrease of 9.53 stillbirths per 1,000 pregnancies (95% CI -16.13 to -2.93; p = 0.005) for municipalities with total number of FARC-related violent events above the 90th percentile of the distribution of FARC-related conflict events and a decrease of 7.57 stillbirths per 1,000 pregnancies (95% CI -13.14 to -2.00; p = 0.01) for municipalities with total number of FARC-related violent events above the 75th percentile of FARC-related events. For perinatal mortality, we found associated reductions of 10.69 (95% CI -18.32 to -3.05; p = 0.01) and 6.86 (95% CI -13.24 to -0.48; p = 0.04) deaths per 1,000 pregnancies for the 2 types of municipalities, respectively. We found no association with miscarriages. Formal tests support the validity of the key RD assumptions in our data, while a battery of sensitivity analyses and falsification tests confirm the robustness of our empirical results. The main limitations of the study are the retrospective nature of the information sources and the potential for conflict exposure misclassification.ConclusionsOur study offers evidence that reduced exposure to conflict violence during pregnancy is associated with important (previously unmeasured) benefits in terms of reducing the risk of stillbirth and perinatal deaths. The findings are consistent with such beneficial associations manifesting themselves mainly through reduced violence exposure during the early stages of pregnancy. Beyond the relevance of this evidence for other countries beset by chronic armed conflicts, our results suggest that the fledgling Colombian peace process may be already contributing to better population health.

Dataset Information

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

Objectives

Study design and setting

Result

Conclusion

Publications

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

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