More than 1100 articles now appear annually investigating “independent risk factors” or “independent predictors” for various clinical outcomes. In medical research, independence is generally defined in a statistical sense: a variable is called an independent risk factor if it has a significant contribution to an outcome in a statistical model that includes established risk factors. As such, independence is based on a specific statistical model and depends on the set of established risk factors included in that model. Even when strong statistical evidence indicates that a variable is an independent risk factor for an outcome, this does not necessarily indicate that the risk factor causally contributes to the outcome. The opposite is also true: risk factors that have causal relationships with the outcome will not necessarily prove to be independent risk factors. These are basic statistical principles that are too often given short shrift in medical research. Herein, we discuss the clinical implications conferred by the above definition of independence, primarily using examples from recent cardiovascular literature. A glossary and schema are provided to help clinicians and researchers understand and discuss these matters effectively.
Increase in the number of articles per year that contain the terms independent risk factor or independent predictor in their title or abstract.
Arrows denote causation in this idealized example to illustrate the distinctions between 3 types of risk factors. Bidirectional arrows, which may exist in real life, are not included, and this example does not include all possible relationships. In medical research, it may be impossible to discern whether a particular risk factor is a direct causal risk factor, a noncausal risk factor, or an indirect causal risk factor or if it falls into more than 1 category.
Hypothetical model with 2 uncorrelated direct causal factors, 3 noncausal risk factors, and an outcome. All variables are binary. Odds ratios (ORs) define relationships between the variables. Percentages define prevalence rates for the risk factors and the incidence rate for the outcome. For simplicity, bidirectional arrows and interaction terms are not included in this idealized example. Table 3 lists power probabilities for various statistical models applied to this scenario.
Hypothetical model in which a therapy affects a noncausal risk factor and a causal factor. When multiple clinical variables are favorably affected by an efficacious therapy, it may be impossible to discern which of these variables are causal for the outcome.
Thank you for submitting a comment on this article. It will be reviewed by JAMA Internal Medicine editors. You will be notified when your comment has been published. Comments should not exceed 500 words of text and 10 references.
Do not submit personal medical questions or information that could identify a specific patient, questions about a particular case, or general inquiries to an author. Only content that has not been published, posted, or submitted elsewhere should be submitted. By submitting this Comment, you and any coauthors transfer copyright to the journal if your Comment is posted.
* = Required Field
Disclosure of Any Conflicts of Interest*
Indicate all relevant conflicts of interest of each author below, including all relevant financial interests, activities, and relationships within the past 3 years including, but not limited to, employment, affiliation, grants or funding, consultancies, honoraria or payment, speakers’ bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued. If all authors have none, check "No potential conflicts or relevant financial interests" in the box below. Please also indicate any funding received in support of this work. The information will be posted with your response.
Some tools below are only available to our subscribers or users with an online account.
Download citation file:
Web of Science® Times Cited: 56
Customize your page view by dragging & repositioning the boxes below.
More Listings atJAMACareerCenter.com >
The Rational Clinical Examination EDUCATION GUIDESAbdominal Aortic Aneurysm
All results at
Enter your username and email address. We'll send you a link to reset your password.
Enter your username and email address. We'll send instructions on how to reset your password to the email address we have on record.
Athens and Shibboleth are access management services that provide single sign-on to protected resources. They replace the multiple user names and passwords necessary to access subscription-based content with a single user name and password that can be entered once per session. It operates independently of a user's location or IP address. If your institution uses Athens or Shibboleth authentication, please contact your site administrator to receive your user name and password.