A significant difference in follow-up rates in two arms of a comparative study could have an impact on randomization and equality between the two treatments.
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Published 2/1/2012
Daniel J. Stinner, MD; David J. Tennent, BS

Losses to Follow-up Presenta Risk to Study Validity

Differential attrition can be a shortcoming in clinical research

In 1996, evidence-based medicine was described as the “conscientious, explicit, and judicious use of current best evidence about the care of individual patients.” Today, the AAOS defines evidence-based medicine as “the integration of best research evidence with clinical expertise and patient values.” Both definitions rely on the results of research.

To build an evidence base, researchers must perform studies that lead to valid conclusions based on the data collected. At first glance, this may seem like a straightforward task. However, preserving the validity of a clinical trial with a number of patient-specific variables is a complex endeavor and often difficult to achieve.

Well-constructed randomized trials rely heavily on the participants’ willingness and ability to follow up at regular intervals. One risk to study validity that has garnered attention in the orthopaedic literature recently is differential attrition. Within a comparative study, differential attrition refers to the number of patients lost to follow-up in one group versus another group.

The 20 percent rule
It is generally believed that attrition rates of up to 20 percent are acceptable. A loss to follow-up of more than 20 percent typically downgrades an otherwise Level 1 study to a Level 2 study. However, literature reports on prospective clinical trials often do not include attrition rates.

Loss to follow-up can affect the validity and overall outcome of a study when one arm of the study has a much higher attrition rate than the other arm. This differential attrition is so influential due to the possibility that randomization and equality are lost between separate treatment arms.

For example, studies comparing surgical and nonsurgical treatments often have high rates of differential attrition. A study conducted by the Canadian Orthopaedic Trauma Society compared surgical to nonsurgical treatment of clavicle fractures. The authors reported that at one-year follow-up, the attrition rate in the nonsurgical treatment group was 25 percent, while in the surgical group it was just 6 percent.

It is possible that the high attrition rate among patients who received nonsurgical treatment occurred because the patients were unhappy with their treatment outcomes and sought care from different providers. But it is also possible that the high attrition rate was due to the success of the nonsurgical treatment, so that patients thought they no longer needed to see a physician.

The impact of attrition
At the 2011 Orthopaedic Trauma Association annual meeting, Boris A. Zelle, MD, presented a paper that addressed the degree to which loss to follow-up affects the statistical significance of orthopedic outcome studies. His study used an existing database from a previous study that found a statistically significant difference in the outcomes measured. Using a computer-based random number generator to determine who was “lost to follow-up,” researchers systematically increased the percentage of patients lost until the significance changed.

Depending on which patients were randomly allocated to being lost to follow-up, the turning point occurred at a loss to follow-up of between 15 percent and 75 percent. In more than a quarter of the scenarios studied, the results changed from significant to not signficant with a loss to follow-up of 20 percent or less. As a result, the researchers recommended that protocols to minimize loss of follow-up be established during the planning phase of clinical studies, and that the actual loss of follow-up be clearly stated in manuscript publications.

Implications for care
If clinicians are to optimize the care they deliver to patients, they need research that accurately measures the impact of various treatments. Investigators must report all aspects of a clinical trial, including loss to follow-up, to increase the “completeness and transparency” of clinical research. And, perhaps more importantly, readers must be aware of the shortcomings associated with loss to follow-up when critically analyzing journal articles.

Daniel J. Stinner, MD, (no conflicts) is a chief resident at the San Antonio Military Medical Center, San Antonio, Texas; David J. Tennent, BS (no conflicts) is a 4th year medical student at the University of Texas Medical School in Houston.


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