3 Pronged Approach to Reading a Clinical Study

There has been an interesting discussion on how to critically appraise a study on the Evidence-Based Health listserv over the last day. It is interesting to see different opinions on the role of critical appraisal.

One important thing to remember as pointed out by Ben Djulbegovic is that critical appraisal relies on the quality of reporting as these 2 studies showed: http://www.ncbi.nlm.nih.gov/pubmed/22424985  and http://www.ncbi.nlm.nih.gov/pmc/articles/PMC313900/ . The implications are important but difficult for the busy clinician to deal with.

There are 3 questions you should ask yourself as you read a clinical study:

  1. Are the findings TRUE?
  2. Are the findings FREE OF THE INFLUENCE OF BIAS?
  3. Are the findings IMPORTANT?

The most difficult question for a clinician to answer initially is if the findings are TRUE. This question gets at issues of fraud in a study. Thankfully major fraud(ie totally fabricated data) is a rare occurrence.  Totally fraudulent data usually gets exposed over time. Worry about fraudulent data when the findings seem too good to be true (ie not consistent with clinical experience). Usually other researchers in the area will try to replicate the findings and can’t. There are other elements of truth that are more subtle and occur more frequently. For example, did the authors go on a data dredging expedition to find something positive to report? This would most commonly occur with post hoc subgroup analyses. These should always be considered hypothesis generating and not definitive. Here’s a great example of a false subgroup finding:

The Second International Study of Infarct Survival (ISIS-2) investigators reported an apparent subgroup effect: patients presenting with myocardial infarction born under the zodiac signs of Gemini or Libra did not experience the same reduction in vascular mortality attributable to aspirin that patients with other zodiac signs had.

Classical critical appraisal, using tools like the Users’ Guides, is done to DETECT BIASES in the design and conduct of studies. If any are detected then you have to decide the degree of influence that the bias(es) has had on the study results. This is difficult, if not impossible, to determine with certainty but there are studies that estimate the influence of various biases (for example, lack of concealed allocation in a RCT) on study outcomes. Remember, most biases lead to overestimate of effects. There are 2 options if you detect biases in a study: 1) reduce the “benefit” seen in the study by the amounts demonstrated in the following table and then decide if the findings are still important enough to apply in patient care, or 2) discard the study and look for one that is not biased.

This table is synthesized from findings reported in the Cochrane Handbook (http://handbook.cochrane.org/chapter_8/8_assessing_risk_of_bias_in_included_studies.htm)

BIAS                                                                       EXAGGERATION  OF EFFECT OF BENEFIT

Lack of randomization                                                             25% (-2 to 45%)

Lack of allocation concealment                                              18% (5 to 29%)

Lack of blinding                                                                          9% (NR)

Finally, if you believe the findings are true and are free of significant bias,  you have to decide if they are CLINICALLY IMPORTANT. This requires clinical judgment and understanding the patient’s baseline risk of the bad outcome the intervention is trying to impact. Some people like to calculate NNTs to make this decision. Don’t just look at the relative risk reduction and be impressed because you can be misled by this measure as I discuss in this video: https://youtu.be/7K30MGvOs5s

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s