Indeed, patients may remain at risk for an extended period of time long after discontinuation of treatment. This article focused specifically on time-related biases, where metformin was associated with strong risk reductions, ranging from relative risks of 0.
Patients with diabetes mellitus, who are at higher risks for both cancer and atherosclerosis, are usually indicated for statin use. The patient characteristics are described in detail elsewhere.
Materials and methods Data sources Our department has access to regional health information systems that contain mortality, hospital admission and drug claims data. Time-related biases include immortal time bias, a bias introduced with time-fixed cohort analyses that misclassify unexposed time as exposed; time-window bias, a bias introduced because of differential exposure opportunity time windows between subjects; and time-lag bias, a bias introduced by comparing treatments given at different stages of the disease 12.
We included individuals with a new diagnosis of colorectal, breast, prostate, or bladder cancer who had not been prescribed statins for at least 6 months before the cancer diagnosis.
The first study used the U.
The second study used the Kaiser Permanente database and found no effect of metformin on the incidence of the 10 different cancers studied, with HRs ranging between 0.
Index date was defined as date of first reporting of OAC diagnosis during follow-up. This article has been cited by other articles in PMC. All cases of reinfarction were included in the analyses.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. Food and Drug Administration arrived at similar conclusions 51 — Although it is possible that the in vitro science is strong and metformin may lead to positive results, we have shown that the pharmacoepidemiological evidence from observational studies is weak at best.
There was no association between statin use and adenocarcinoma HR, 0. Diabetes Care ;35 Immortal time bias is introduced in this study from its definition of exposure and related analysis. However, the use of a non-experimental setting to analyse the associations between drug exposures and health outcomes carries the risk of specific biases that may lead to erroneous results, especially when drug treatments and outcomes are both measured in the same time window.
Although this is a useful instrument for comparing the results from different studies, misclassification of drug utilisation may have occurred. This article has been cited by other articles in PMC.
Metformin and the risk of cancer: Immortal time bias Immortal time bias in Pharmacoepidemiology refers to a period of cohort follow-up time during which death or an outcome that determines end of follow-up cannot occur.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. However, this strong inverse association was likely due to immortal time bias because exposure to metformin was assessed at any time during follow-up and thus included person-time during which patients were not yet exposed to this therapy Table 1.
Generalisation and extrapolation of results from the latter studies to the general population is, however, difficult as both studies were performed in US veterans. Samy Suissa described the effect of the time-window bias in case—control studies.
Our pharmaceutical database does not contain information on the prescribed daily doses, and adherence to drug treatment was estimated on the basis of the defined daily doses. Our goals were to estimate the association between adherence to drug therapies after myocardial infarction MI and the incidence of a new MI, and to quantify the error that would have been produced by a time-window bias.
The end of the observation period was defined as either the end of the study period 31 Decemberthe time of death not related to MI, or the date of an outcome, whichever occurred first. However, there was no matching on time since diabetes diagnosis or since the first prescription for an oral hypoglycemic agent.
Acknowledgments No potential conflicts of interest relevant to this article were reported. No studies have measured the impact of this bias on the assessment of the effect of medication adherence on health outcomes.
Second, the a priori risk factors were further selected using a bootstrap stepwise procedure to determine which factors were actually associated with the outcomes of interest. Although these studies were designed and analyzed with no obvious time-related biases, it is of course possible that other epidemiological biases such as selection, information, or confounding could have affected them.
Other forms of time-related bias Time-window Bias in Case-control Studies.Importance Patients with cancer who use statins appear to have a substantially better survival than nonusers in observational studies.
However, this inverse association between statin use and mortality may be due to selection bias and immortal-time bias. Objective To emulate a randomized trial of statin therapy initiation that is free of. It does not guarantee the same duration of treated diabetes in cases and controls that would avoid time-window bias.
Suissa S, Dell’aniello S, Vahey S, Renoux C. Time-window bias in case-control studies: statins and.
The publications were classified according to the potential bias induced by the study design, including immortal time bias, immeasurable time bias, selection bias, and confounding (all described in the following text in the context of selected studies).
NSAIDs, statins, low-dose aspirin and PPIs, and the risk of oesophageal adenocarcinoma among patients with Barrett's oesophagus: a population-based case–control study Gwen M C Masclee, 1, 2 Preciosa M Coloma, 1 Manon C W Spaander, 2 Ernst J Kuipers, 2 and Miriam C J M Sturkenboom 1, 3.
A retrospective case-control study demonstrated that statin use was associated with a risk reduction of lung cancer of 55%. 7 It has been argued that the beneficial effect might result from “time-window bias” because different time lengths between cases and controls are used to define time-dependent exposures.
A case-control approach that properly accounts for time produces a rate ratio of (–)—suggesting no benefit of statins on lung cancer risk. We show analytically that the magnitude of the bias is proportional to .Download