QS Primer: Case-Crossover Design

August 21, 2012

We’ve already published this QS Show&Tell talk by Mark Drangsholt about using self-tracking to identify the triggers of his heart problems, lessen their frequency, and make good decisions about treatment. I’m re-posting it here to focus on attention on the interesting and powerful method Mark used, the case-crossover design, and invite you to think about whether this has promise for your own self-tracking projects.

Mark is a professor and chair of oral medicine at the University of Washington School of Dentistry. He’s a triathlete and long time self-tracker. He is in good physical condition, but suffers from heart ailments that are frightening and dangerous. For instance, he has tachycardia (sudden acceleration of heart rate). At times his heart goes from 60 to 220 beats per minute. It feels like his heart is going to jump out of his chest. He also has atrial fibrillation, with palpitations, a feeling of immanent doom, and a sense that he is choking.

“The first time it happened in 2003 I really thought I was dying,” Mark says in his talk. He had always assumed that if he ever had a heart attack he, of all people, would know to pick up the phone and call 911, but the opposite happened. He just thought to himself “this is it,” and slumped down in his chair. Fortunately, he survived, and when he recovered he asked himself whether he could identify the triggers of these unpleasant events and avoid them. He created a simple Excel table of all episodes for one year, on which he recorded information about his attacks.

Mark is an expert on evidence based medicine, so he was naturally curious about what kind of evidence his self-tracking data contained. In standard reference material on medical evidence, students learn about a hierarchy that goes something like this:

  1. 1 or more randomized controlled trials
  2. 1 or more cohort studies
  3. 1 or more case-control studies
  4. 1 or more case-series
  5. expert opinion without above evidence

Mark’s self-tracking data didn’t naturally fit with any of these approaches. To understand whether these triggers actually had an effect on his arrhythmias, he used a special technique originally proposed by the epidemiologists Murray Mittleman and K. Malcolm Maclure. A case-crossover design is a scientific way to answer the question: “Was the patient doing anything unusual just before the onset of the disease?” It is a design that compares the exposure to a certain agent during the interval when the event does not occur to the exposure during the interval when the event occurs.

Using this method, Mark discovered that events linked to his attacks included high intensity exercise, afternoon caffeine, public speaking to large groups, and inadequate sleep on the previous night. While these were not surprising discoveries, it was interesting to him to be able to rigorously analyze them, and see his intuition supported by evidence.
“A citizen scientist isn’t even on the conventional evidence pyramid,” Mark notes. “But you can structure a single subject design to raise the level of evidence and it will be more convincing.”

Please let us know if you use this method in your own projects. We’ll post more reports when we have them.


There are some tricks to doing a good case-crossover study on yourself. Mark’s video provides a basic introduction.  For technical details, this detailed introduction to case-crossover design by Yue-Fang Chang especially useful.

The seminal paper on case-crossover design is “The Case-Crossover Design: A Method for Studying Transient Effects on the Risk of Acute Events” by Malcom Maclure. (1991) [PDF] A search on Google Scholar for case-crossover design will get you deep into this literature. Unfortunately very little of it involves the kind of n-of-1 studies we’re usually interested in, but there are many technical details that may contain clues for dedicated experimenters.

One paper that will be of special interest is this one: “Should We Use a Case-Crossover Design?” by K. Malcolm Maclure and his collaborator Murray Mittleman. (2000) [PDF] In the midst of discussing technical details important for scientists proposing to use this method in studies funding by research grants whose reviewers may not be familiar with it, Maclure and Mittlemen describe using case-crossover analysis to retrospectively understand more about the death of Maclure’s father. I quote the relevant section below:

We did an n-of-1 case-crossover study of hypothesized triggers of repeated syncope experienced by Kenneth Maclure (MM’s father), who was diagnosed with sick sinus syndrome and died of fatal MI at age 73 during a morning swim, after several other potential triggers. The target person times wereKenneth’s 62nd–74th years (and subsequent years if he had lived longer). The study base comprised the years 1980–1981 and 1986, during which there were 33 instances of syncope. We restricted the study base to those years because his wife, Margaret, was willing to review only 3 years of her diaries because the memories rekindled her grief. We had no intention to generalize the findings to other individuals, only to other years. Our goal was to identify triggers to which Kenneth may have been susceptible and to test Margaret’s general hypothesis, “Perhaps I should have done more to help him avoid stress.” Hypothesized triggers included visitors to the home, trips out of town, eating out, unusual exertion, and so on. The 24-h period before an episode of syncope was classified as a case day. Each case day was matched with a control day, the same 24-h period 2 weeks before. Margaret was surprised by our null findings and relieved some lingering feelings of guilt.



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