Multicenter randomized controlled trials (RCTs) are considered the gold standard in clinical research. Such trials, although difficult and labor-intensive, are being conducted with increasing frequency in orthopaedic trauma and are providing important answers to key clinical questions1,2. Even the best-designed RCT, however, suffers when patients are lost to follow-up. It has been suggested by many researchers that a loss to follow-up of <5% probably leads to little bias whereas a loss of >20% poses serious threats to the validity of the investigation. Statements such as that led to the general acceptance, in the past, of up to 20% loss to follow-up in orthopaedic trauma trials.
Recent literature indicates that rates of loss to follow-up in orthopaedic trauma trials are decreasing, and a 20% rate is no longer considered acceptable. An analysis of trials of tibial nailing published from 1996 to 2000 revealed rates as high as 28%3. A 2016 systematic review of orthopaedic trials published from 2008 to 2011 indicated a mean loss to follow-up of 10.4% overall and 10.5% in 61 trauma trials reviewed4.
In the present study, Madden et al., on the behalf of the FLOW trial group, reported a loss to follow-up of 6.7%, an excellent achievement in a patient population of >2,300, which is one of the largest orthopaedic trauma trials reported to date. Male sex, current smoking, high-risk alcohol consumption, an age of <30 years, and treatment in the United States significantly increased the likelihood of a patient being lost to follow-up; each of these associations had been previously reported but in trials with smaller samples. In the FLOW trial, patients who sustained polytrauma were less likely to be lost to follow-up than those with an isolated injury; this finding had also been reported previously.
One key concept that can be said to underlie the current investigation deserves additional discussion as a generalizable tactic to decrease loss to follow-up in trauma trials. This is the concept of “contractability,”5 which means that, in choosing strategies to minimize attrition among hard-to-reach populations, one should give strong consideration to employing mechanisms that maintain, foster, and maximize engagement before follow-up begins. By receiving frequent communications from the investigators, regardless of the mechanisms, the subject remains more amenable to following through on the study contract into which he or she entered—the subject is more “contractable.” Contractability could be one explanation for why those with polytrauma in orthopaedic trials are less likely to be lost to follow-up than those with an isolated injury. Because a patient with polytrauma has numerous active medical issues, has larger barriers to returning to the functions of daily life, and has a greater need for health-care services and physician follow-up, he or she is more contractable and thus could be expected to be more likely to participate in follow-up.
The FLOW trial group employed several design features and techniques that may have optimized contractability and can be generalized to other orthopaedic trials. First, the nature of the primary outcome measure in the trial (reoperation) did not necessitate in-person follow-up; it could be monitored and assessed remotely. The ability to successfully participate in the trial without frequent in-person follow-up visits made participation easier and may have helped decrease loss to follow-up. Second, the patients’ ability to complete follow-up forms and assessments by telephone not only was easier for them, but also provided the FLOW sites the opportunity to frequently contact patients in a conversational manner, engaging them in more robust and effective ways than were possible via mailed or electronic outcome surveys. Finally, as is advisable for all clinical trials, the FLOW trial investigators collected numerous forms of contact information for each patient (mailing and e-mail addresses, telephone numbers, etc.) and then employed all methods repeatedly when they had difficulty reaching a patient. Repeated contact attempts are yet another method for increasing contractability, with the investigators in at least 1 study employing daily telephone calls until the patient engaged and the follow-up information was obtained5.
The FLOW trial is an outstanding example of a well-designed, well-conducted RCT in orthopaedic trauma that answered a very important clinical question. It is also an excellent example of how the study design and techniques for obtaining study follow-up can be used as tools to enhance the contractability of study patients and result in a low loss to follow-up. Authors of future orthopaedic trials should consider emulating, wherever possible, the features and techniques employed in the FLOW trial to optimize study success.
1. Bhandari M, Jeray KJ, Petrisor BA, Devereaux PJ, Heels-Ansdell D, Schemitsch EH, Anglen J, Della Rocca GJ, Jones C, Kreder H, Liew S, McKay P, Papp S, Sancheti P, Sprague S, Stone TB, Sun X, Tanner SL, Tornetta P 3rd, Tufescu T, Walter S, Guyatt GH; FLOW Investigators. A trial of wound irrigation in the initial management of open fracture wounds. N Engl J Med. 2015 Dec 31;373(27):2629-41. Epub 2015 Oct 8.
2. Bhandari M, Guyatt G, Tornetta P 3rd, Schemitsch EH, Swiontkowski M, Sanders D, Walter SD; Study to Prospectively Evaluate Reamed Intramedullary Nails in Patients with Tibial Fractures Investigators. Randomized trial of reamed and unreamed intramedullary nailing of tibial shaft fractures. J Bone Joint Surg Am. 2008 Dec;90(12):2567-78.
3. Sprague S, Leece P, Bhandari M, Tornetta P 3rd, Schemitsch E, Swiontkowski MF; S.P.R.I.N.T. Investigators. Limiting loss to follow-up in a multicenter randomized trial in orthopedic surgery. Control Clin Trials. 2003 Dec;24(6):719-25.
4. Somerson JS, Bartush KC, Shroff JB, Bhandari M, Zelle BA. Loss to follow-up in orthopaedic clinical trials: a systematic review. Int Orthop. 2016 Nov;40(11):2213-9. Epub 2016 May 3.
5. David MC, Alati R, Ware RS, Kinner SA. Attrition in a longitudinal study with hard-to-reach participants was reduced by ongoing contact. J Clin Epidemiol. 2013 May;66(5):575-81. Epub 2013 Feb 4.