Authored By: OrthoEvidence
July 23, 2020
The OE team has recently published an OE original examining the differences between observational studies and randomized controlled trials (RCTs), including benefits and limitations to each study design (Read it here: Does the treatment of hip fractures with intramedullary nails kill patients?).
The Question: Does Early Surgery for Hip Fractures Decrease Major Complications?
In this OE original, we examine studies evaluating the timing of hip fracture surgery. Principally, two design options are compared. The first is a clinical trial in which patients are randomized to early (or accelerated) surgery or current usual practice. The second is a non-randomized study (observational) in which patients are allocated to earlier or standard times by a method other than randomization. Often, the allocations are based upon the surgeon’s (or health care team’s) preferences and sometimes on the patients’ preferences. Here, we provide a summary of the advantages and disadvantages of both study types, as well as the data of two studies examining the same research question.
A Multinational, Randomized Trial of 2970 Accelerated Hip Fracture Surgery: 6 hours vs 24 hours
A recent randomized controlled trial published in the Lancet examined the impact of accelerated surgery versus standard care in patients with hip fracture.1 The results of this study found that accelerated surgery did not lower the risk of 90-day mortality. However, subgroup analyses for the co-primary outcomes on the basis of whether patients had an increased troponin measurement before randomisation showed a statistically significant interaction (p=0·0076) for mortality. These analyses suggested patients with an increased troponin measurement at baseline had a lower risk of mortality with accelerated surgery than standard care (10% vs 24%; HR 0·38 [95% CI 0·21–0·66]). Patients in the accelerated surgery demonstrated significantly fewer strokes, less delirium, fewer infections and urinary tract infections. Rehabilitation was also significantly improved in the accelerated group.
A Large Meta-analysis of Observational studies (190,000 Patients): 12hrs vs 24 hrs
There were 35 independent studies, with 191,873 participants and 34,448 deaths. The majority considered a cut-off between 24 and 48 hours. Early hip surgery (less than 24 hours vs greater than 24 hours) was associated with a lower risk of death (pooled odds ratio (OR) 0.74, 95% confidence interval (CI) 0.67 to 0.81; P,0.000) and pressure sores (0.48, 95% CI 0.38 to 0.60). The cut-off of less than 12 hours vs greater than 12 hours failed to demonstrate a significant difference.
A single large RCT suggests benefits to accelerating hip fracture surgery to 6 hours. A very large review of non-RCTs argues that there is no benefit in accelerating to less than 12 hours, and recommends a 24-hour cut-off. Who’s right? There is one caveat: Maybe it’s a power issue. The large observational study arguably noted that evidence in the 12-hour cut-off was limited and the analysis (likely underpowered). But suppose, we took both datasets at face value? What would be your assessment of the optimal cut-off point?
One can argue that that clinical trials may not represent “real world” evidence; however, they are designed to limit the one critical challenge with non-RCTs—a true balance of groups with respect to prognosis (both known and unknown factors). This sets RCTs atop the hierarchy of evidence when evaluating a new treatment intervention.
While registry data present many opportunities for meaningful analysis, there are inherent challenges to making appropriate inferences. A principal concern with registries is that of making inferences without regard to the quality of data and the ability to address confounding. There is always the chance that unknown confounders will affect the interpretation of analyses derived from observational studies.
Resolution of the Scenario: Is 6 hr a better cut-off point than 24 hours?
Short answer: Yes. Evidence would suggest so.
Long answer: Maybe: To be absolutely definitive on the issue of “mortality”, another trial is needed to confirm or refute the subgroup finding in patients with elevated troponins.
Contextual answer: It Depends. For healthy adults with hip fractures, timing cut-offs of 24 hours may be just fine for mortality risk, but could still benefit major complications. For sicker patients with cardiac ischemic findings, early surgery may just save lives.
- HIP ATTACK Investigators. Accelerated surgery versus standard care in hip fracture (HIP ATTACK): an international, randomised, controlled trial. Lancet. 2020;395(10225):698-7083.
- Moja L, Piatti A, Pecoraro V, Ricci C, Virgili G, et al. (2012) Timing Matters in Hip Fracture Surgery: Patients Operated within 48 Hours Have Better Outcomes. A Meta-Analysis and Meta-Regression of over 190,000 Patients. PLoS ONE 7(10): e46175.