Dataset Information

Emulating a target trial of statin use and risk of dementia using cohort data.

ABSTRACT:

Objective

Observational data can be used to attempt to emulate a target trial of statin use and estimate analogues of intention-to-treat and per protocol effects on dementia risk.

Methods

Using data from a prospective cohort study in the Netherlands, we conceptualized a sequence of "trials" in which eligible individuals ages 55-80 years were classified as statin initiators or noninitiators for every consecutive month between 1993 and 2007 and were followed until diagnosis of dementia, death, loss to follow-up, or the end of follow-up. We estimated 2 types of effects of statin use on dementia and a combined endpoint of dementia or death: the effect of initiation vs no initiation and the effect of sustained use vs no use. We estimated risk by statin treatment strategy over time via pooled logistic regression. We used inverse-probability weighting to account for treatment-confounder feedback in estimation of per-protocol effects.

Results

Of 233,526 eligible person-trials (6,373 individuals), there were 622 initiators and 232,904 noninitiators. Comparing statin initiation with no initiation, the 10-year risk differences (95% confidence interval) were -0.1% (-2.3% to 1.8%) for dementia and 0.3% (-2.7% to 3.3%) for dementia or death. Comparing sustained statin use vs no use, the 10-year risk differences were -2.2% (-5.2% to 1.6%) for dementia and -5.1% (-10.5% to -1.1%) for dementia or death.

Conclusions

Individuals with sustained statin use, but not statin initiation alone, had reduced 10-year risks of dementia and dementia or death. Our results should be interpreted with caution due to the small number of initiators and events and potential for residual confounding.

SUBMITTER: Caniglia EC

PROVIDER: S-EPMC7538212 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Rationale: "Target trial emulation" has been proposed as an observational method to answer comparative effectiveness questions, but it has rarely been attempted concurrently with a randomized clinical trial (RCT).Objectives: We tested the hypothesis that blinded analysts applying target trial emulation to existing observational data could predict the results of an RCT.Methods: PreVent (Preventing Hypoxemia with Manual Ventilation during Endotracheal Intubation) was a multicenter RCT examining the effects of positive-pressure ventilation during tracheal intubation on oxygen saturation and severe hypoxemia. Analysts unaware of PreVent's results used patient-level data from three previous trials evaluating airway management interventions to emulate PreVent's eligibility criteria, randomization procedure, and statistical analysis. After PreVent's release, results of this blinded observational analysis were compared with those of the RCT. Difference-in-differences estimates for comparison of treatment effects between the observational analysis and the PreVent trial are reported on the absolute scale.Results: Using observational data, we were able to emulate PreVent's randomization procedure to produce balanced groups for comparison. The lowest oxygen saturation during intubation was higher in the positive-pressure ventilation group than the no positive-pressure ventilation group in the observational analysis (n = 360; mean difference = 1.8%; 95% confidence interval [CI] = -1.0 to 4.6) and in the PreVent trial (n = 401; mean difference = 3.9%; 95% CI = 1.4 to 6.4), though the observational analysis could not exclude no difference. Difference-in-differences estimates comparing treatment effects showed reasonable agreement for lowest oxygen saturation between the observational analysis and the PreVent trial (mean difference = -2.1%; 95% CI = -5.9 to 1.7). Positive-pressure ventilation resulted in lower rates of severe hypoxemia in both the observational analysis (risk ratio = 0.60; 95% CI = 0.38 to 0.93) and in the PreVent trial (risk ratio = 0.48; 95% CI = 0.30 to 0.77). The absolute reduction in the incidence of severe hypoxemia with positive-pressure ventilation was similar in the observational analysis (9.4%) and the PreVent trial (12.0%), though the difference between these estimates had wide CIs (mean difference = 2.5%; 95% CI = -8.0 to 13.6%).Conclusions: Applying target trial emulation methods to existing observational data for the evaluation of a novel intervention produced results similar to those of a randomized trial. These findings support the use of target trial emulation for comparative effectiveness research.