If you're criticizing methods, your methods better be strong

This morning I innocently set out to review a new study in ARIC that looks at methodological issues in C. difficile outcomes studies assessing the association between infection and excess hospital stay.  The authors make a very important point in the paper: "The studies did not collect data concerning the time of onset of CDI; therefore, it is not possible to exclude the possibility of reverse causality, in which longer lengths of hospitalisation may have increased the risk of CDI." They then go on to discuss time-dependent bias and recommend the use of multi-state models...we've made this point before.

What caused me the emotional anguish was their Table 1 that lists the 16 studies included in the review. In column two, three of the studies are listed as retrospective case-control studies...what??!!  How can you do a case-control study with an outcome being hospital length of stay?  I'm pretty sure you can't, at least not easily.

You see, a case-control study requires identifying an outcome and looking back for risk-factors associated with the outcome. For example, you could look at 50 people that died (and 100 that didn't die) and see how many had CDI, to determine if CDI was a risk-factor for death.  For length of stay, I can't even make up a good way to do a case-control study.  Would you find patients who stay >14 days and compare them to patients that stay <14 days? The three studies listed MUST have been cohort studies, so why did the authors of the ARIC paper seeking to teach us about proper methods for outcomes studies list them as case-control studies? Perhaps they pasted them from the individual studies' methods sections?

Just to confirm this, I looked at all three papers: (Ananthakrishnan (2008), Bajaj (2010), Pepin 2005).

Pepin: from the Methods  - "We compared mortality and total length of hospital stay among inpatients in whom nosocomial CDAD developed and among control subjects without CDAD."  This is a cohort study - exposed and unexposed to CDAD, looking forward to outcomes.  Just because they incorrectly use the word control, doesn't make this a case-control study. (Strike 1)

Ananthakrishnan: "Our primary case group (C difficile–IBD group) included patients who had a primary diagnosis of C difficile colitis and a secondary diagnosis of either Chrohn's Disease (CD) or Ulcerative Colitis (UC). Patients admitted to hospital with a primary diagnosis of CD or UC without a diagnosis of C. difficile colitis formed one of our comparison groups (IBD group)." Another cohort study - defined by the exposure to C. difficile and not by the outcome. (Strike 2)

Bajaj: "Among the cohort of hospitalized patients with any diagnosis of cirrhosis, co-existing diagnosis of C. difficile was associated with significantly greater in-hospital mortality."(Strike 3)

The error of incorrectly describing cohort studies as case-control studies is very common - enough to be a pandemic.  The journal CID is one of the worst offenders. One of my favorite examples is this recent VAP treatment cohort study described as a case-control study in the title!  When I've mentioned the problem to CID editors, they suggest I write a letter.  You can't write letters for each issue.

OK: Cohort - exposed/unexposed look forward in time to the outcome. Case-control - find outcomes and look back for exposures. Got it?  EOR


  1. Please, please write a letter to CID. I will plaster it all over my office. I had a long, painful conversation this morning with a colleague who insisted that the paper he was working on was a case-control study (it's clearly a cohort study, subjects grouped according to receipt of specific drug therapy, data collected forward in time to compare LOS and duration of bacteremia). And he cited a handful of mischaracterized CID papers to support his study design. It's embarrassing!

  2. The authors need to take EpiI from Dr. Lynch and Design/Analysis with Dr. Torner here at the UICPH. That's a really elementary mistake to make in study design and analysis.

    1. Hmmm, that ought to be "Epi ONE", not "Epil". Silly font changes.

  3. Dear IDPharmProf; if you could send along the CID papers, I will review...maybe I should reconsider.

    Dear Melissa, we like silly font changes, like autocorrect on phones. always a good laugh.


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