Study designSystematic Review.ObjectivesCervical total disc arthroplasty (CTDA) remains an alternative to anterior cervical discectomy and fusion (ACDF) in select patients with cervical radiculopathy or myelopathy secondary to degenerative disc disease. Studies comparing CTDA to ACDF often have conflicting conclusions and varying quality. The purpose of this study was to utilize the fragility index (FI) to assess the robustness of randomized controlled trials (RCT) comparing CTDA to ACDF.MethodsA systematic review was performed by searching PubMed, Ovid MEDLINE, Web of Science, and Embase for RCTs with 2 parallel study arms and 1:1 allocation of subjects investigating CTDA vs ACDF with at least 1 statistically significant, dichotomous outcome. The FI was calculated by individually shifting 1 patient from the event group to the non-event group with re-calculation of Fisher's Exact test until the reported P value was no longer statistically significant (P > 0.05).ResultsThe search identified 934 abstracts with 19 RCTs meeting inclusion criteria. The mean patient sample size was 276.4 (median 209, range 30-541). The number of patients lost to follow-up ranged from 0-229 (mean 69.7, median 45). The mean FI was 4.6 (range 0-30, median 2) with 3 (13.6%) of the studies having an associated FI of 0. Loss to follow up exceeded the fragility index in all but 2 studies.ConclusionRCTs comparing ACDF to CTDA are often fragile with only 1-2 patients experiencing an alternative outcome or lost to follow-up to change the studied outcome.

To (1) analyze trends in the publishing of statistical fragility index (FI)-based systematic reviews in the orthopaedic literature, including the prevalence of misleading or inaccurate statements related to the statistical fragility of randomized controlled trials (RCTs) and patients lost to follow-up (LTF), and (2) determine whether RCTs with relatively "low" FIs are truly as sensitive to patients LTF as previously portrayed in the literature.

All FI-based studies published in the orthopaedic literature were identified using the Cochrane Database of Systematic Reviews, Web of Science Core Collection, PubMed, and MEDLINE databases. All articles involving application of the FI or reverse FI to study the statistical fragility of studies in orthopaedics were eligible for inclusion in the study. Study characteristics, median FIs and sample sizes, and misleading or inaccurate statements related to the FI and patients LTF were recorded. Misleading or inaccurate statements-defined as those basing conclusions of trial fragility on the false assumption that adding patients LTF back to a trial has the same statistical effect as existing patients in a trial experiencing the opposite outcome-were determined by 2 authors. A theoretical RCT with a sample size of 100, P = .006, and FI of 4 was used to evaluate the difference in effect on statistical significance between flipping outcome events of patients already included in the trial (FI) and adding patients LTF back to the trial to show the true sensitivity of RCTs to patients LTF.

Of the 39 FI-based studies, 37 (95%) directly compared the FI with the number of patients LTF. Of these 37 studies, 22 (59%) included a statement regarding the FI and patients LTF that was determined to be inaccurate or misleading. In the theoretical RCT, a reversal of significance was not observed until 7 patients LTF (nearly twice the FI) were added to the trial in the distribution of maximal significance reversal.

The claim that any RCT in which the number of patients LTF exceeds the FI could potentially have its significance reversed simply by maintaining study follow-ups is commonly inaccurate and prevalent in orthopaedic studies applying the FI. Patients LTF and the FI are not equivalent. The minimum number of patients LTF required to flip the significance of a typical RCT was shown to be greater than the FI, suggesting that RCTs with relatively low FIs may not be as sensitive to patients LTF as previously portrayed in the literature; however, only a holistic approach that considers the context in which the trial was conducted, potential biases, and study results can determine the merits of any particular RCT.

Surgeons may benefit from re-examining their interpretation of prior FI reviews that have made claims of substantial RCT fragility based on comparisons between the FI and patients LTF; it is possible the results are more robust than previously believed.

Today, well-designed randomized clinical trials (RCTs) are considered the pinnacle of clinical research, and they inform many practices in orthopaedics. When designing these studies, researchers conduct a power analysis, which allows researchers to strike a balance between (1) enrolling enough patients to detect a clinically important treatment effect (i.e., researchers can be confident that the effect is unlikely due to chance) and (2) cost, time, and risk to patients, which come with enrolling an excessive number of patients. Because researchers will have a desire to conduct resource-efficient RCTs and protect patients from harm, many studies report a p value that is close to the threshold for significance. The concept of the fragility index (FI) was introduced as a simple way to interpret RCT findings, but it does not account for RCT design. The adoption of the FI conflicts with researchers' goals of designing efficient RCTs that conserve resources and limit ineffective or harmful treatments to patients. The use of the FI may reflect many clinicians' lack of familiarity with interpreting p values beyond "significant" or "nonsignificant." Instead of inventing new metrics to convey the same information provided by the p value, greater emphasis should be placed on educating clinicians on how to interpret p values and, more broadly, statistics, when reading scientific studies.

The fragility index represents the minimum number of patients required to convert an outcome from statistically significant to insignificant. This report assesses the fragility index of head and neck cancer randomised, controlled trials.

Studies were extracted from PubMed/Medline, Scopus, Embase and Cochrane databases.

Overall, 123 randomised, controlled trials were included. The sample size and fragility index medians (interquartile ranges) were 103 (56-213) and 2 (0-5), respectively. The fragility index exceeded the number of patients lost to follow up in 42.3 per cent (n = 52) of studies. A higher fragility index correlated with higher sample size (r = 0.514, p < 0.001), number of events (r = 0.449, p < 0.001) and statistical significance via p-value (r = -0.367, p < 0.001).

Head and neck cancer randomised, controlled trials demonstrated low fragility index values, in which statistically significant results could be nullified by altering the outcomes of just two patients, on average. Future head and neck oncology randomised, controlled trials should report the fragility index in order to provide insight into statistical robustness.

The Fragility Index (FI) provides the number of patients whose outcome would need to have changed for the results of a clinical trial to no longer be statistically significant. Although it's a well-intended and easily interpreted metric, its calculation is based on reversing a significant finding and therefore its interpretation is only relevant in the domain of statistical significance. Its interpretation is only relevant in the domain of statistical significance. A well-designed clinical trial includes an a priori sample size calculation that aims to find the bare minimum of patients needed to obtain statistical significance. Such trials are fragile by design! Examining the robustness of clinical trials requires an estimation of uncertainty, rather than a misconstrued, dichotomous focus on statistical significance. Confidence intervals (CIs) provide a range of values that are compatible with a study's data and help determine the precision of results and the compatibility of the data with different hypotheses. The width of the CI speaks to the precision of the results, and the extent to which the values contained within have potential to be clinically important. Finally, one should not assume that a large FI indicates robust findings. Poorly executed trials are prone to bias, leading to large effects, and therefore, small P values, and a large FI. Let's move our future focus from the FI toward the CI.

P values were frequently misused and misinterpreted, the fragility index (FI) has been utilized to evaluate the robustness of randomized controlled trials (RCTs) as a complement to p-values. This study aimed to assess the statistical robustness of RCTs for femoral neck fractures through the utilization of the FI.

We systematically reviewed PubMed, Cochrane Library, and Embase database to identify RCTs pertaining to femoral neck fractures published in the top 25 highest-impact orthopaedic journals and 4 high-impact general medical journals from January 1, 2000, to December 31, 2022. The FI was calculated for the dichotomous, categorical study outcomes in the identified RCTs using the Fisher exact test, with previously published methods. Spearman correlation analyses were used to evaluate potential associated factors associated with the FI.

We identified 10 eligible RCTs with a median total sample size of 101 (IQR, 79.5 to 174.75) and a number of patients lost to follow-up of 19.5 (IQR, 4.5 to 28). The median FI was 3.5 (IQR, 1 to 14.25), implying that reversal of outcome in only 4 patients was sufficient to alter trial significance. The FI was less than the number of patients lost to follow-up in seven (70%) RCTs. P values were negatively associated with the FI, while the number of patients lost to follow-up and patients enroled were not statistically significantly associated with the FI.

The RCTs pertaining to femoral neck fractures were not as statistically robust as previously thought and should be interpreted with caution. We recommend that the orthopaedic RCT report FI as a supplement for the P values to help readers draw reliable conclusions based on the fragility of the outcomes.

Fragility index (FI) is a metric used to interpret the results of randomized controlled trials (RCTs), and describes the number of subjects that would need to be switched from event to non-event for a result to no longer be significant. Studies that analyze FI of RCTs in various orthopedic subspecialties have shown the RCTs to be largely underpowered and highly fragile. However, FI has not been assessed in foot and ankle RCTs. The MEDLINE and Embase online databases were searched from 1/1/2011 through 11/19/2021 for RCTs involving foot and ankle conditions. FI, fragility quotient (FQ), and difference between the FI and number of subjects lost to follow-up was calculated. Spearman correlation was performed to determine the relationship between sample size and FI. Overall, 1262 studies were identified of which 18 were included in the final analysis. The median sample size was 65 (interquartile range [IQR] 57-95.5), the median FI was 2 (IQR 1-2.5), and the median FQ was 0.026 (IQR 0.012-0.033). Ten of 15 (67%) studies with non-zero FI values had FI values less than the number of subjects lost to follow-up. There was linear association between FI and sample size (R² = 0.495, p-value: .031). This study demonstrates that RCTs in the field of foot and ankle surgery are highly fragile, similar to other orthopedic subspecialties.

The statistical significance of randomized controlled trials (RCTs) and comparative studies is often conveyed utilizing the P value. However, P values are an imperfect measure and may be vulnerable to a small number of outcome reversals to alter statistical significance. The interpretation of the statistical strength of these studies may be aided by the inclusion of a Fragility Index (FI) and Fragility Quotient (FQ). This study examines the statistical stability of studies comparing operative vs nonoperative management for Achilles tendon rupture.

A systematic search was performed of 10 orthopaedic journals between 2000 and 2021 for comparative studies focusing on management of Achilles tendon rupture reporting dichotomous outcome measures. FI for each outcome was determined by the number of event reversals necessary to alter significance (P < .05). FQ was calculated by dividing the FI by the respective sample size. Additional subgroup analyses were performed.

Of 8020 studies screened, 1062 met initial search criteria with 17 comparative studies ultimately included for analysis, 10 of which were RCTs. A total of 40 outcomes were examined. Overall, the median FI was 2.5 (interquartile range [IQR] 2-4), the mean FI was 2.90 (±1.58), the median FQ was 0.032 (IQR 0.012-0.069), and the mean FQ was 0.049 (±0.062). The FI was less than the number of patients lost to follow-up for 78% of outcomes.

Studies examining the efficacy of operative vs nonoperative management of Achilles tendon rupture may not be as statistically stable as previously thought. The average number of outcome reversals needed to alter the significance of a given study was 2.90. Future analyses may benefit from the inclusion of a fragility index and a fragility quotient in their statistical analyses.

Probability analysis with reporting of P values is often used to determine the statistical significance of study findings in the orthopedic literature. The fragility index (FI) has been used to evaluate the robustness of a significant result. The purpose of this study was to determine the utility of applying a fragility analysis to randomized controlled trials (RCTs) evaluating distal radius fractures (DRFs).

We identified all dichotomous outcome data for randomized controlled trials of distal radius fractures (DRFs) published in 13 orthopedic journals from 2000 to 2020. The fragility index (FI) was determined by the number of event reversals required to change a P value from less than 0.05 to greater than 0.05, or vice-versa. The associated fragility quotient (FQ) was determined by dividing the FI by the sample size. The interquartile ranges (IQR) for the FI and FQ were calculated as the difference between the 25th and 75th percentiles for the overall study.

Of the 7352 studies screened, 221 met the search criteria, with 34 randomized controlled trials evaluating distal radius fractures and 151 total outcome events included for analysis. The overall FI was 9 (IQR 6.5-11) with an associated fragility quotient of 0.097 (IQR 0.060-0.140). However, a majority of outcomes (78.8%) were not significant. Fragility analysis of statistically significant outcomes had an FI of 4 (IQR 1-10). All of the studies reported lost to follow-up (LTF) data where 20.6% reported lost to follow-up of greater or equal to 9.

The RCTs in distal radius fracture outcomes have comparable statistical robustness to literature in other orthopedic surgical specialties, are not as statistically stable as previously thought and should be interpreted with caution. We recommend that orthopedic literature report the FI and FQ along with the P values to help the reader draw reliable conclusions based on the fragility of outcome measures.

Level I.

Proximal humeral fracture represents an increasingly common pathology with evaluation and treatment often guided by evidence from randomized controlled trials (RCTs), but the strength of an RCT must be considered in this process. The purpose of this study was to evaluate the strength of outcomes in RCTs on the management of proximal humeral fractures using the fragility index (FI), a method used with statistically significant dichotomous outcomes to assess the number of patients that would change an outcome measure from significant (P ≤ .05) to nonsignificant if the patient outcome changed. We also aimed to correlate the FI with other measures of study strength.

A systematic review was performed using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines to evaluate RCTs on the management of proximal humeral fractures. The PubMed, Ovid MEDLINE, Web of Science, and Embase databases were searched from database inception to May 2021. RCTs with at least 1 statistically significant (P ≤ .05) dichotomous outcome were included. The FI was calculated for each included trial using the Fisher exact test. The FI was correlated with the study sample size and journal impact factor.

Ten RCTs reporting on 656 patients and published between 2011 and 2020 were included. The median patient sample size was 67 (mean, 65.6; range, 40-86). Complications were the most commonly reported dichotomous statistically significant outcome. The median FI was 1 (mean, 2.6; range, 0-18), with 4 studies having an FI of 0. A median FI of 1 indicates that 1 patient experiencing an alternative outcome or having not been lost to follow-up could have changed the pertinent conclusions of the trial for a given outcome. The median number of patients lost to follow-up was 3 (mean, 4.9; range, 0-16) and exceeded the FI in 50% of studies. There was no correlation between the FI and sample size (Spearman coefficient = 0.0592, P = .865) or between the FI and journal impact factor (Spearman coefficient = -0.0229, P = .522).

In most studies of proximal humeral fractures, only 1 or 2 patients experiencing an alternative outcome or lost to follow-up would change the conclusions for the dichotomous outcome studied. Although the FI cannot be used to assess continuous variables, which are often the primary outcome variables of RCTs, it does offer an additional unique measure of study strength that surgeons should consider when evaluating RCTs.

Randomized controlled trials (RCTs) are considered the gold standard for evidence-based medicine, and although a well-designed and executed RCT can be extremely powerful, many RCTs have significant flaws that may significantly impact the strength of their conclusions. The fragility index is a metric that objectifies the strength of results from RCTs and is one such metric that should be considered when critically evaluating individual studies. Although the RCTs pertaining to hip arthroscopy have a median value of 4, which is slightly greater than other orthopaedic subspecialties investigated thus far, this is far from a robust result, which mostly highlights the difficulty in performing an RCT in the surgical realm. Some topics of investigation may be better suited for well performed case-control, matched cohort, and meta-analysis studies (among other investigation types), which may provide better and more robust conclusions than a poorly performed RCT. In essence, don't be enamored by level of evidence alone.