Considerations for Pharmacoepidemiological Studies of Drug-Cancer Associations

Basic Clin Pharmacol Toxicol. 2018 May;122(5):451-459. doi: 10.1111/bcpt.12946. Epub 2018 Jan 15.


In this MiniReview, we provide general considerations for the planning and conduct of pharmacoepidemiological studies of associations between drug use and cancer development. We address data sources, study design, assessment of drug exposure, ascertainment of cancer outcomes, confounder adjustment and future perspectives. Aspects of data sources include assessment of complete history of drug use and data on dose and duration of drug use, allowing estimates of cumulative exposure. Outcome data from formal cancer registries are preferable, but cancer data from other sources, for example, patient or pathology registries, medical records or claims are also suitable. The two principal designs for observational studies evaluating drug-cancer associations are the cohort and case-control designs. A key challenge in studies of drug-cancer associations is the exposure assessment due to the typically long period of cancer development. We present methods to examine early and late effects of drug use on cancer development and discuss the need for employing 'lag-time' in order to avoid reverse causation. We emphasize that a new-user study design should always be considered. We also underline the need for 'dose-response' analyses, as drug-cancer associations are likely to be dose-dependent. Generally, studies of drug-cancer associations should explore risk of site-specific cancer, rather than cancer overall. Additional differentiation may also be crucial for organ-specific cancer with various distinct histological subtypes (e.g., lung or ovary cancer). We also highlight the influence of confounding factors and discuss various methods to address confounding, while emphasizing that the choices of methods depend on the design and specific objectives of the individual study. In some studies, use of active comparator(s) may be preferable. Pharmacoepidemiological studies of drug-cancer associations are expected to evolve considerably in the coming years, due to the increasing availability of long-term data on drug exposures and cancer outcomes, the increasing conduct of multinational studies, allowing studies of rare cancers and subtypes of cancer, and methodological improvements specifically addressing cancer and other long-term outcomes.

Publication types

  • Review

MeSH terms

  • Confounding Factors, Epidemiologic
  • Drug-Related Side Effects and Adverse Reactions / diagnosis
  • Drug-Related Side Effects and Adverse Reactions / epidemiology*
  • Epidemiologic Research Design*
  • Humans
  • Neoplasms / chemically induced*
  • Neoplasms / diagnosis
  • Neoplasms / epidemiology*
  • Observational Studies as Topic
  • Pharmacoepidemiology / methods*
  • Prognosis
  • Risk Assessment
  • Risk Factors
  • Time Factors