Skip to Main Content


At the end of the chapter, the reader will be able to:


  1. Identify the nature of causation and association in pharmacoepidemiology studies

  2. Describe the key criteria to determine causation

  3. Identify the main types and sources of bias in pharmacoepidemiology studies

  4. Explain the concept of confounding

  5. Describe and discuss methods to deal with bias and confounding

  6. Explain the concept of risk adjustment

  7. Describe the methods for adjusting for risk in pharmacoepidemiology studies


One of the main objectives of the discipline of pharmacoepidemiology is to evaluate the use of and the effects of drugs in the postmarketing phase. In other words, pharmacoepidemiology is primarily concerned with the real-world usage and effects of drugs, as opposed to the use and effects in randomized controlled trials. In order to analyze pharmaceuticals in the postmarketing scenario, one must use large databases that are collected for either administrative claims processing or for the purposes of maintaining clinical records. These data are not collected and maintained for research purposes; therefore, they pose special challenges to researchers. Many of these challenges emerge because drugs are used by or prescribed to patients on the basis of a host of patient, provider and societal factors. In addition, drug exposure may be related to factors that may also be associated with its outcome. Furthermore, patient outcomes are generally a result of not only the drug exposure but also a variety of patient and nonpatient characteristics.


More often than not, the treatment and control groups are different from each other in clinical and nonclinical characteristics. These differences can be a range of patient characteristics or risk factors that can influence outcomes. In order to arrive at correct estimates of association between treatment and outcomes, it is important to remove or mitigate the impact of these risk factors. Risk-adjustment measures are used to evaluate the outcomes by statistically controlling for group differences when comparing dissimilar treatment groups.


Analyzing large databases to evaluate associations between treatment and outcomes and interpreting results obtained from such analyses requires understanding of certain key methodological issues in the fields of epidemiology and statistics. In the following sections, several important methodological issues that need to be taken into consideration in investigations of drug treatment and outcomes are discussed.


This chapter begins with a discussion of causation and the criteria that may be used to distinguish causal association from a noncausal association. The next section deals with the issues of bias and confounding commonly encountered in pharmacoepidemiology studies that use large databases. The final section introduces the topic of risk adjustment and outlines some of the key measures and methods of adjusting for risk.


In order to understand the concept of causation, it is important to distinguish it from the related concept of association. A scientific study of evaluation of the relationship between a treatment (i.e., intervention and exposure) and its outcome begins with a selection of participants who ...

Want remote access to your institution's subscription?

Sign in to your MyAccess profile while you are actively authenticated on this site via your institution (you will be able to verify this by looking at the top right corner of the screen - if you see your institution's name, you are authenticated). Once logged in to your MyAccess profile, you will be able to access your institution's subscription for 90 days from any location. You must be logged in while authenticated at least once every 90 days to maintain this remote access.


About MyAccess

If your institution subscribes to this resource, and you don't have a MyAccess profile, please contact your library's reference desk for information on how to gain access to this resource from off-campus.

Subscription Options

AccessPharmacy Full Site: One-Year Subscription

Connect to the full suite of AccessPharmacy content and resources including 30+ textbooks such as Pharmacotherapy: A Pathophysiologic Approach and Goodman & Gilman's The Pharmacological Basis of Therapeutics, high-quality videos, images, and animations, interactive board review, drug and herb/supplements databases, and more.

$595 USD
Buy Now

Pay Per View: Timed Access to all of AccessPharmacy

24 Hour Subscription $34.95

Buy Now

48 Hour Subscription $54.95

Buy Now

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.