Pharmacoepidemiological Evaluation in Prostate Cancer—Common Pitfalls and How to Avoid Them

Abstract

Pharmacoepidemiologic research provides opportunities to evaluate how commonly used drug groups, such as cholesterol-lowering or antidiabetic drugs, may affect the prostate cancer risk or mortality. This type of research is valuable in estimating real-life drug effects. Nonetheless, pharmacoepidemiological studies are prone to multiple sources of bias that mainly arise from systematic differences between medication users and non-users. If these are not appreciated and properly controlled for, there is a risk of obtaining biased results and reaching erroneous conclusions. Therefore, in order to improve the quality of future research, we describe common biases in pharmacoepidemiological studies, particularly in the context of prostate cancer research. We also list common ways to mitigate these biases and to estimate causality between medication use and cancer outcomes.

Antihypertensive Drug Use and the Risk of Ovarian Cancer Death among Finnish Ovarian Cancer Patients—A Nationwide Cohort Study

“…All calendar years with any amount of use were recorded as usage years. After anti-HT drug use had been discontinued, participants remained in the user category to avoid bias caused by selective discontinuation of drugs, for example anti-HT drugs are not used in the palliative care of advanced cancer or heart failure [ 26 ].…”

“…Long time associations and the possible role of a protopathic bias were evaluated by lagging the exposure of anti-HT drug use forward for one, three and five years. This means that we estimated the association between the risk of OC death and anti-HT drug use that had occurred for one, three or five years earlier [ 26 ]. The data were analysed using the SPSS statistics v. 25 program (IBM, New York, NY, USA).…”

Prostate Cancer–specific Survival After Radical Prostatectomy Is Improved Among Metformin Users but Not Among Other Antidiabetic Drug Users

“…In order to minimize protopathic bias, we employed lag-time analysis [14] . The risk association was reanalyzed with a time lag of 1, 3, or 5 yr. For example, in the 3-yr lag-time analysis, the risks of PCa death and ADT initiation in 2003 were analyzed by AD use occurring in 2000.…”

“…Prediagnostic AD use was analyzed as a time-fixed variable. Postdiagnostic use of ADs was analyzed as a time-dependent variable, where the user status was updated for each follow-up year according to purchases, to minimize immortal time bias [14] . All participants with no baseline medication usage remained as nonusers until the year of first AD purchase.…”

Pharmacological Efficacy of Repurposing Drugs in the Treatment of Prostate Cancer

“…Thus, patients with PC generally have high cholesterol production because PC cells depend more on the endogenous production of cholesterol than dietary cholesterol. For that reason, men with high levels of serum cholesterol are at greater risk of developing PC, and it is known that cholesterol also plays an important role in the growth, proliferation, migration and invasion of cancer cells [ 10 ].…”