Randomized Controlled Trials Evaluating LET and ALL for Anterolateral Rotatory Instability in ACLR Are Fragile: A Systematic Review

Abstract

Context:

Lateral extra-articular tenodesis (LET) and anterolateral ligament (ALL) reconstruction have been adopted by some surgeons as augmentations during anterior cruciate ligament reconstruction (ACLR) to improve anterolateral rotatory instability.

Objective:

The objective of this study was to assess the statistical robustness of outcomes reported in randomized controlled trials (RCTs) assessing the clinical significance of LET and ALL reconstruction in ACLR.

Methods:

PubMed, Embase, and MEDLINE were systematically searched. RCTs published January 1, 2010 to December 31, 2024 assessing LET and ALL reconstruction during ACLR were included. Fragility index (FI) or reverse FI (rFI) was calculated for each outcome, representing the number of event reversals required to alter statistical significance for significant and nonsignificant outcomes, respectively. The fragility quotient (FQ) was determined by dividing the FI or rFI by sample size.

Level of Evidence:

Level 1.

Results:

Of 112 RCTs screened for inclusion, 17 were included for analysis, resulting in 51 total outcomes. The median FI across the 51 outcomes was 4 [interquartile range (IQR), 2-7] with an associated median FQ of 0.031 (IQR, 0.014-0.049). Statistically significant outcomes were more fragile (median FI, 3.5; median FQ, 0.015) than statistically nonsignificant outcomes (median rFI, 5; median FQ, 0.038). In 60.8% of all outcomes (31 of 51), the number of patients lost to follow-up was greater than the outcome’s respective FI or rFI. In the 7 RCTs assessing LET, the median FQ was 0.015 (IQR, 0.012-0.042) across 23 outcomes. In the 10 RCTs assessing ALL, the median FQ was 0.035 (IQR, 0.019-0.051) across 28 outcomes. Graft failure, pivot shift, and Lachman/anterior laxity were the most common outcome categories reported, with median FQs of 0.017, 0.035, and 0.048, respectively.

Conclusion:

Outcomes reported in RCTs for LET and ALL reconstruction as augments of ACLR are statistically fragile, emphasizing the need for additional robust and adequately powered RCTs to better understand the impact of anterolateral augmentation on ACLR outcomes.

Keywords

anterior cruciate ligament reconstruction anterolateral ligament reconstruction lateral extra-articular tenodesis statistical fragility

Although anterior cruciate ligament reconstruction (ACLR) is increasingly being performed,³¹ graft failure rates remain a major concern, occurring in up to 20% of patients.^20,30 In recent years, there has been a heightened focus on rotational instability, with anterolateral rotatory laxity emerging as a potential contributing factor in up to 25% of ACLR failures.^21,30,38 To address this, some surgeons have adopted lateral extra-articular tenodesis (LET) and anterolateral ligament (ALL) reconstruction as augments to ACLR to provide rotatory stability to the anterolateral complex.^19,21,43 In a recent systematic review of randomized controlled trials (RCTs) by D’Ambrosi et al,⁸ ACLR + ALL and ACLR + LET were both independently found to decrease graft failure rates significantly compared with ACLR alone without increasing complication rate. A systematic review by Bosco et al² similarly reported that ALL or LET procedures are independently associated with significantly improved pivot-shift tests, patient-reported outcome measures, and graft failure rates. In contrast, however, RCTs by Sonnery-Cottet et al³⁷ and Mogos et al²⁸ reported no significant difference in graft failure rates for ACLR + ALL compared with ACLR alone. Furthermore, RCTs by El-Azab et al,¹⁰ Hamido et al,¹⁵ and Rezansoff et al³⁴ report no significant differences in pivot shift for ACLR alone compared with ACLR with an anterolateral augment procedure. While recent RCTs have assessed the clinical significance of LET and ALL reconstruction in providing rotatory stability for ACLR,^16,23,28,34 the conflicting findings in the literature highlight the uncertainty surrounding the clinical benefit of anterolateral augment procedures.

RCTs represent the highest level of evidence in guiding surgical decision-making for ACLR.²⁴ ACLR RCTs evaluating LET and ALL reconstruction ubiquitously utilize P values to convey the statistical significance of their results with considerable clinical implications. However, P values have received criticism as they do not convey effect size, indicate clinical significance, or take into account important study design elements such as attrition rate.^1,24,41 Recent studies in the orthopaedic literature have highlighted a lack of statistical robustness in RCTs by delineating that statistically significant study outcomes can be reversed by altering just a few outcome events.^{4,5,7,22,26,27,32,44
-47} These analyses have utilized the fragility index (FI), which is a concept that was first introduced by Feinstein et al¹² in 1990 to supplement the P value’s limitations. The FI represents the “fragility” of an outcome and is calculated as the number of outcome event reversals required to reverse statistical significance.¹² The reverse fragility index (rFI) was similarly defined as the number of outcome event reversals required for a nonsignificant outcome to obtain statistical significance.^3,18,25,35 The fragility quotient (FQ) takes sample size into consideration and is calculated as the FI divided by the sample size.^14,33,42

The purpose of this study was to evaluate the statistical fragility of RCTs reporting on LET and ALL reconstruction as augments for ACLR. We hypothesized that statistical outcomes in RCTs assessing LET and ALL reconstruction for rotational stability would be fragile. We further hypothesized that statistically significant outcomes would demonstrate greater fragility than nonsignificant outcomes and that fragility would be identified for outcomes relating to graft failure, pivot shift testing, and anterior laxity.

Methods

Literature Review

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were utilized for this systematic review (Figure 1). PubMed, Embase, and MEDLINE were queried for RCTs published from January 1, 2010, to December 31, 2024, using the following search terms: ((lateral extra-articular tenodesis OR LET) OR (anterolateral ligament OR ALL)) AND (anterior cruciate ligament OR ACL). RCTs written in English that reported dichotomous, categorical outcomes related to LET and ALL reconstruction in ACLR were included. Meta-analyses, case reports, papers without full-text availability, proposals, in vitro studies, and animal studies were excluded. Duplicates were removed after the initial review. Abstract screening and full-text review were performed by 2 independent authors (N.H.K. and A.R.L.) in parallel. Any disagreements or conflicts between the 2 primary screeners were resolved by a third, independent author (A.Y.) for ultimate inclusion or exclusion. Interrater reliability was assessed using Cohen’s kappa statistic. Bias assessment was conducted using the revised Cochrane Risk of Bias tool for evaluating bias in randomized trials by A.C.⁴⁰ A second independent author (A.Y.) subsequently performed bias assessment of all included RCTs using the revised Cochrane Risk of Bias tool blinded to the primary author’s assessment. A third independent author (C.G.) consolidated the risk of bias assessments from the 2 authors (A.Y. and A.C.) for all RCTs and resolved any discrepancies.

Figure 1.

PRISMA flow diagram showing identification, screening, and inclusion, of eligible articles from PubMed, Embase, and Medline.

Data Extraction

Author name, publication year, study title, journal of publication, and intervention studied were extracted and included in Table 1. Study interventions, outcomes measured, number of patients per intervention with each outcome, number lost to follow-up, and reported P values were also extracted from each article. This study focused on the statistical significance of outcomes rather than evaluating the efficacy of interventions and, thus, did not qualify for PROSPERO international registration.

Table 1.

Characteristics of Included Studies^a

Author(s)	Year	Study title	Journal of publication	Augment assessed	Sample size	Patients lost to follow-up
Abdelrazek et al	2019	Rotational stability after ACL reconstruction using anatomic double bundle technique versus anatomic single bundle technique plus anterolateral ligament augmentation	Journal of Arthroscopy and Joint Surgery	ALL	40	0
Castoldi et al	2020	A Randomized Controlled Trial of Bone-Patellar Tendon-Bone Anterior Cruciate Ligament Reconstruction With and Without Lateral Extra-articular Tenodesis: 19-Year Clinical and Radiological Follow-up	The American Journal of Sports Medicine	LET	80	40
Chen et al	2021	Reconstruction for Chronic ACL Tears with or without Anterolateral Structure Augmentation in Patients at High Risk for Clinical Failure: A Randomized Clinical Trial	The Journal of Bone and Joint Surgery	ALL	114	0
El-Azab et al	2023	A comparison of the outcomes of anterior cruciate ligament reconstruction with large-size graft versus reconstruction with average-size graft combined with extraarticular tenodesis	Injury	LET	95	5
Erden et al	2021	Comparison of the outcomes of isolated anterior cruciate ligament reconstruction and combined anterolateral ligament suture tape augmentation and anterior cruciate ligament reconstruction	Joint Diseases and Related Surgery	ALL	63	0
Getgood et al	2020	Lateral Extra-articular Tenodesis Reduces Failure of Hamstring Tendon Autograft Anterior Cruciate Ligament Reconstruction: 2-Year Outcomes From the STABILITY Study Randomized Clinical Trial	The American Journal of Sports Medicine	LET	589	18
Getgood et al	2020	No Difference in Functional Outcomes When Lateral Extra-Articular Tenodesis Is Added to Anterior Cruciate Ligament Reconstruction in Young Active Patients: The Stability Study	The Journal of Arthroscopy and Related Surgery	LET	300	56
Hamido et al	2020	Anterolateral ligament reconstruction improves the clinical and functional outcomes of anterior cruciate ligament reconstruction in athletes	Knee Surgery, Sports Traumatology, Arthroscopy	ALL	102	5
Heard et al	2023	No increase in adverse events with lateral extra-articular tenodesis augmentation of anterior cruciate ligament reconstruction - Results from the stability randomized trial	Journal Isakos	LET	618	18
Ibrahim et al	2017	Anatomic Reconstruction of the Anterior Cruciate Ligament of the Knee With or Without Reconstruction of the Anterolateral Ligament: A Randomized Clinical Trial	The American Journal of Sports Medicine	ALL	103	7
Lee et al	2023	Single Bundle Anterior Cruciate Ligament With Anterolateral Ligament Reconstruction Yields Similar Clinical and Radiographic Results at Minimum 2-Year Follow-Up Versus Double Bundle Anterior Cruciate Ligament Reconstruction: A Prospective Randomized Controlled Trial	The Journal of Arthroscopy and Related Surgery	ALL	74	10
Mogos et al	2023	Combined Anterior Cruciate Ligament and Anterolateral Ligament Reconstruction Results in Superior Rotational Stability Compared with Isolated Anterior Cruciate Ligament Reconstruction in High Grade Pivoting Sport Patients: A Prospective Randomized Clinical Trial	The Journal of Knee Surgery	ALL	57	3
Mogos et al	2023	Superior rotational stability and lower re-ruptures rate after combined anterolateral and anterior cruciate ligament reconstruction compared to isolated anterior cruciate ligament reconstruction: a 2-year prospective randomized clinical trial	The Physician and Sports Medicine	ALL	58	0
Porter et al	2022	Modified iliotibial band tenodesis versus lateral extracapsular tenodesis, to augment anterior cruciate ligament reconstruction: a 2-year randomized controlled trial	ANZ Journal of Surgery	LET	160	4
Rezansoff et al	2023	Anterior Cruciate Ligament Reconstruction Plus Lateral Extra-articular Tenodesis Has a Similar Return-to-Sport Rate to Anterior Cruciate Ligament Reconstruction Alone but a Lower Failure Rate	The Journal of Arthroscopic and Related Surgery	LET	553	7
Sonnery-Cottet et al	2020	Combined ACL and Anterolateral Reconstruction Is Not Associated With a Higher Risk of Adverse Outcomes: Preliminary Results From the SANTI Randomized Controlled Trial	Orthopaedic Journal of Sports Medicine	ALL	224	0
Sorensen et al	2023	Combined anterior cruciate ligament revision with reconstruction of the antero-lateral ligament does not improve outcome at 2-year follow-up compared to isolated ACL revision; a randomized controlled trial	Knee Surgery, Sports Traumatology, Arthroscopy	ALL	100	0

Includes first author, journal/year of publication, study title, augment assessed for rotational laxity, sample size, and number of patients lost to follow-up. ALL, anterolateral ligament reconstruction. LET, lateral extra-articular tenodesis.

Statistical Analysis

Reported P values for all included outcomes were verified using the 2-tailed Fisher exact test, and values less than 0.05 were considered significant. A 2 × 2 chi-square table was then generated for each included outcome. Iterative outcome event manipulations were performed until outcome significance was altered, either from significant to nonsignificant (FI), or from nonsignificant to significant (rFI). Figure 2 outlines the methodology utilized for significance reversal. The FQ was determined by dividing the FI or rFI by the respective sample size. Summary statistics are reported as median (IQR [interquartile range]). All outcomes were pooled to report the summary median and IQR for FI and FQ across all RCTs. Summary statistics were subsequently calculated for significant outcomes (FI/FQ) and nonsignificant outcomes (rFI/FQ). Pooled (significant and nonsignificant outcomes) fragility assessment was also performed, stratifying ALL and LET RCTs. Outcomes were then assigned to and analyzed in 6 subgroups: graft failure, positive pivot shift test, positive Lachman/anterior laxity, return to sport, progression to osteoarthritis, and other. The “other” subgroup included outcomes such as International Knee Documentation Committee (IKDC) improvement, surgical complications, contralateral rupture, and postoperative pain. The subgroup analysis by outcome type was performed by pooling significant and nonsignificant outcomes for the respective subgroup and analyzing them collectively.

Figure 2.

Demonstration of statistical significance reversal using a 2 × 2 contingency table with a resulting fragility index (FI) = 1.

Results

Of 116 RCTs screened for inclusion, 17 were ultimately included for analysis, comprising a total of 3330 patients. The interrater agreement for title and abstract screening was 89.5%. The interrater agreement for full-text review was 79.5%. In 7 of the included RCTs, LET was assessed as an augment for ACLR and, in 10 included RCTs, ALL reconstruction was assessed (Table 1).

The median FI across all 51 total outcomes was 4 (IQR 2-7), indicating that a median of 4 outcome event reversals may alter the significance of the RCTs assessing LET and ALL reconstruction as augments for ACLR (Table 2). The median FQ across all outcomes was 0.031 (IQR 0.014-0.049). Thus, an outcome event reversal in just 3.1% of patients may be sufficient to alter outcome significance across the 17 RCTs. For 14 outcomes denoted in the RCTs as primary outcomes, the median FI was 4.5 (IQR 2.25-6.75) with an associated FQ of 0.018 (IQR 0.015-0.035). In 60.8% of all outcomes (31/51), the number of patients lost to follow-up was greater than the respective outcome’s FI.

Table 2.

Fragility Data Based on Trial and Outcome Characteristics

	Number of Outcomes	FI, median (IQR)	FQ, median (IQR)
All RCT outcomes	51	4 (2-7)	0.031 (0.014-0.049)
Significant outcomes (P < 0.05)	14	3.5 (2-5.75)	0.015 (0.011-0.024)
Nonsignificant outcomes (P ≥ 0.05)	37	5 (3-7)	0.038 (0.017-0.058)

FI, fragility index; FQ, fragility quotient; IQR, interquartile range; RCT, randomized controlled trial.

Statistically significant outcomes demonstrated greater fragility than nonsignificant outcomes. The median FI for statistically significant outcomes was 3.5 (IQR 2-5.75) and the associated median FQ was 0.015 (IQR 0.011-0.024). Thus, an outcome event reversal in just 1.5% of patients may lead to a reversal of the significance of outcomes. There were 9 statistically significant outcomes in favor of an ACLR + an anterolateral augment compared with ACLR alone, with a median FQ of 0.17, suggesting that these outcomes may be reversed by changes in the outcomes of less than 2% of patients. There were 3 significant outcomes which favored ACLR alone compared with ACLR + LET, with 2 being related to surgical complications and 1 assessing osteoarthritis. These outcomes were particularly fragile, however, with a median FQ of 0.006. The median rFI for outcomes that were not statistically significant was 5 (IQR 3-7) with an associated median FQ of 0.038 (IQR 0.017-0.058).

In the 7 RCTs assessing LET as an augment for ACLR, the median FI was 6 (IQR 3.5-8.5) across 23 outcomes (Table 3). The associated median FQ was 0.015 (IQR 0.012-0.042). For the 10 RCTs assessing ALL reconstruction as an augment for ACLR, the median FI was 3.5 (IQR 2-5) across 28 outcomes. The associated median FQ was 0.035 (IQR 0.019-0.051). These findings indicate that an outcome event reversal in 1.5% of patients in the LET RCTs and in 3.5% of patients in the ALL reconstruction RCTs for augmenting ACLR may be sufficient to alter outcome significance.

Table 3.

Subgroup Analysis Based on Rotational Laxity Augment Type for Anterior Cruciate Ligament Reconstruction

	Number of Studies	Number of Outcomes	FI, median (IQR)	FQ, median (IQR)
LET RCTs	7	23	6 (3.5-8.5)	0.015 (0.012-0.042)
ALL RCTs	10	28	3.5 (2-5)	0.035 (0.019-0.051)

ALL, anterolateral ligament reconstruction; FI, fragility index; FQ, fragility quotient; IQR, interquartile range; LET, lateral extra-articular tenodesis.

Across 11 graft failure outcomes, the median FI was 4 (IQR 2-6.5) with an associated FQ of 0.017 (IQR 0.013-0.029) (Table 4). For the 11 pivot shift outcomes, the median FI was 3 (IQR 2-4) with an associated FQ of 0.035 (IQR 0.019-0.048). In 9 outcomes relating to anterior laxity, the median FI was 4 (IQR 3-5) with an associated FQ of 0.048 (IQR 0.013-0.033). For 4 outcomes relating to return to sport and 3 outcomes relating to progression to osteoarthritis, the median FI’s were 7.5 and 6, respectively.

Table 4.

Subgroup Analysis Based on Outcome Category

	Number of Outcomes	FI, median (IQR)	FQ, median (IQR)
Graft failure	11	4 (2-6.5)	0.017 (0.013-0.029)
Positive pivot shift test	11	3 (2-4)	0.035 (0.019-0.048)
Positive Lachman/anterior laxity	9	4 (3-5)	0.048 (0.039-0.070)
Return to sport	4	7.5 (7-8.25)	0.014 (0.013-0.033)
Progression to osteoarthritis	3	6 (5.5-8)	0.075 (0.069-0.10)
Other	13	5 (2-8)	0.018 (0.011-0.036)

FI, fragility index; FQ, fragility quotient; IQR, interquartile range.

Bias assessment of the RCTs performed with the revised Cochrane risk-of-bias tool revealed that only 3 of 17 included studies demonstrated “some concerns” for bias. The remainder of the studies were found to have low risk of bias (Table 5). Bias was most frequently identified in domains concerning missing outcome data.

Table 5.

Cochrane Risk of Bias Assessment for Evaluating Randomized Controlled Trials

First Author	Domain 1: Risk of Bias Arising from Randomization Process	Domain 2: Risk of Bias Due to Deviations From the Intended Interventions	Domain 3: Risk of Bias Due to Missing Outcome Data	Domain 4: Risk of Bias in Measurement of the Outcome	Domain 5: Risk of Bias in Selection of the Reported Result	Overall Risk of Bias
Abdelrazek	Low Risk	Low Risk	Low Risk	Low Risk	Low Risk	Low Risk
Castoldi	Low Risk	Low Risk	Some concerns	Low Risk	Low Risk	Some concerns
Chen	Low Risk	Low Risk	Low Risk	Low Risk	Low Risk	Low Risk
El-Azab	Low Risk	Low Risk	Low Risk	Low Risk	Low Risk	Low Risk
Erden	Low Risk	Low Risk	Low Risk	Low Risk	Low Risk	Low Risk
Getgood	Low Risk	Low Risk	Low Risk	Low Risk	Low Risk	Low Risk
Getgood	Low Risk	Low Risk	Some concerns	Low Risk	Low Risk	Some concerns
Hamido	Low Risk	Low Risk	Low Risk	Low Risk	Low Risk	Low Risk
Heard	Low Risk	Low Risk	Low Risk	Low Risk	Low Risk	Low Risk
Ibrahim	Low Risk	Low Risk	Low Risk	Low Risk	Low Risk	Low Risk
Lee	Low Risk	Low Risk	Low Risk	Low Risk	Low Risk	Low Risk
Mogos	Low Risk	Low Risk	Low Risk	Low Risk	Low Risk	Low Risk
Mogos	Low Risk	Low Risk	Low Risk	Low Risk	Low Risk	Low Risk
Porter	Low Risk	Low Risk	Low Risk	Low Risk	Low Risk	Low Risk
Rezansoff	Low Risk	Low Risk	Some concerns	Low Risk	Low Risk	Some concerns
Sonnery-Cottet	Low Risk	Low Risk	Some concerns	Low Risk	Low Risk	Some concerns
Sorensen	Low Risk	Low Risk	Low Risk	Low Risk	Low Risk	Low Risk

Green shading, low risk of bias; yellow shading, some concerns for risk of bias; red shading, high risk of bias.

Discussion

This study utilized the FI, rFI, and FQ metrics to assess the robustness of outcomes reported in RCTs evaluating LET and ALL reconstruction as augments for rotatory instability in ACLR. We systematically reviewed the PubMed, Embase, and Medline databases and identified 17 RCTs for inclusion that reported 51 total outcomes. The median FI for 14 significant outcomes was just 3.5 and the median rFI for 37 nonsignificant outcomes was 5. Furthermore, we found that event reversals in just 1.5% of patients could reverse the statistical significance of outcomes studied in RCTs assessing LET for ACLR. Similarly, event reversals in 3.5% of patients could reverse the statistical significance of outcomes from RCTs investigating ALL reconstruction. Finally, in 60.8% of all outcomes studied, the number of patients lost to follow-up exceeded the respective outcome’s FI or rFI.

Trials investigating LET and ALL in ACLR have led to an increase in their popularity over the last several years. However, our assessment of RCTs that investigate LET and ALL reconstruction as augments for ACLR indicates that the significance of outcomes studied may be lost if there are outcome reversals in less than 4% of patient outcome events. This highlights the potential for type-1 alpha errors in these studies, wherein the null hypothesis is wrongfully rejected with 1 treatment arm falsely being touted as clinically superior. The studies included in this systematic review reported several significant outcomes in favor of anterolateral augments in ACLR. In particular, improvements in graft failure rate and pivot shift testing were frequently reported. For example, Chen et al⁶ reported a failure rate of 20.4% in the ACLR alone group compared with 3.3% in the ACLR and ALL reconstruction group. However, this outcome hinges on just 3 patient outcome events and would be reversed by outcome event reversals in less than 3% of RCT patients (FQ = 0.26). Furthermore, Mogos et al²⁹ evaluated ACLR and ALL reconstruction versus ACLR alone and reported a significant difference in positive pivot shift tests at 1 year postoperative follow-up in favor of ACLR+ALL (2/32 for ACLR + ALL versus 9/25 for ACLR alone). However, this finding had an FI of 2, which was found to be less than the number of patients lost to follow-up in the RCT. Considering that the median FQ across the 14 statistically significant findings was 0.015, these significant findings should be interpreted with caution, as outcome event reversals in just 1.5% of patients could reverse statistical significance.

The included studies reported 37 outcomes as not statistically significant. As Khan et al¹⁸ highlight, a lack in statistical significance in the form of P values may not correlate with the real treatment effects of interventions. Furthermore, the group recommends that P values of study outcomes that are between 0.05 and 0.10 should be assessed thoroughly to ensure that potentially significant differences between interventions are not missed.¹⁸ This allows for P values to be viewed in less of a dichotomous manner and for all aspects of a reported outcome to be taken into consideration when guiding clinical decision-making. Recent fragility analyses have employed the rFI to evaluate outcomes lacking statistical significance in orthopaedic RCTs. In a 2024 study, Mazzucco et al²⁵ employed the rFI to assess mortality endpoints for hemiarthroplasty for hip fractures and found median rFIs of 3, 6, and 7 at the 30-day, 90-day, and latest follow-up points. Furthermore, Shi et al³⁶ used the rFI to assess survivorship of computer-navigated versus conventional total knee arthroplasty and found a median rFI of 4. Importantly, the group recommends that when interpreting results lacking statistical significance, several factors should be considered beyond just the reported P value, including the rFI, study power, and the effect size.

Recent systematic reviews by D’Ambrosi et al⁸ and Bosco et al² have demonstrated significantly improved graft failure rates,^2,8 pivot shift tests,² and patient-reported outcomes measures² favoring anterolateral augments for ACLR. However, several RCTs have also demonstrated no significant differences between ACLR alone and ACLR with an anterolateral augment. El-Azab et al,¹⁰ for example, found no significant difference in graft failure with LET. Similarly, Erden et al,¹¹ Ibrahim et al,¹⁷ and Sorensen et al³⁹ showed no significant differences in pivot shift for ALL augment to ACLR. In addition, no significant differences in Lachman tests were identified by Mogos et al,²⁸ Lee et al,²³ Hamido et al,¹⁵ and Erden et al¹¹ for ALL + ACLR compared with ACLR. In our study, we identified an rFI of 5 for these nonsignificant outcomes relating to ACLR alone compared with ACLR with an anterolateral complex augment. This statistical fragility identified for nonsignificant outcomes suggests the possibility of type 2 errors in which a lack of power or an inadequate sample size may lead to statistically significant differences being missed. Thus, appropriately powered comparative trials that perform pre hoc power analysis are needed in order to reliably assess the clinical efficacy of LET and ALL reconstruction anterolateral augments for ACLR.

Outcomes in studies evaluating LET were found to hinge on outcome events in just 1.5% of trial patients, whereas outcomes from studies evaluating ALL reconstruction hinge on 3.5% of trial patients. The FQ metric serves as a valuable tool for comparing statistical fragility across RCTs with different sample sizes. The FQs identified in this study highlight the alarming level of statistical fragility in LET and ALL reconstruction RCTs. Outcome event reversals in less than 4% of patients may be sufficient to alter the statistical significance of reported outcomes, which undoubtedly raises concern over their robustness. These findings also highlight the value in standardized reporting of the FQ metric along with the FI and rFI to ensure statistical fragility of endpoints from RCTs with different sample sizes may be compared effectively.

Statistical fragility by outcome type revealed that outcomes related to return to sport, graft failure, and pivot shift testing were the most fragile (FQ = 0.014, 0.017, and 0.035, respectively). In a systematic review, Feng et al¹³ reported that ACLR and LET results in a significant reduction in pivot shift and graft failure rates. In a systematic review by Lai et al,²¹ patients who underwent ACLR and ALL had significantly better knee stability based on pivot shift testing as well as reduced anterior laxity and a lower incidence of graft failure. However, given that these systematic reviews are based on fragile findings from RCTs, their conclusions may be called into question.

Recent fragility analyses in the orthopaedic surgery literature have assessed the statistical fragility of outcomes relating to ACLR. Lawrence et al²² reported a median FQ of 0.082 across 55 total outcomes in RCTs comparing bone-patellar tendon-bone versus hamstring autografts. In an analysis of RCTs comparing autograft versus allograft for ACLR, Megafu et al²⁶ identified a median FQ of 0.041 for statistically significant outcomes. Furthermore, Ehlers et al⁹ reported a mean FQ of 0.050 for outcomes in comparative studies on single-bundle versus double-bundle autografts for ACLR. Ruelos et al utilized the reverse FQ to evaluate differences lacking statistical significance in failure rates for hamstring and bone-patellar tendon-bone autografts and found a median reverse FQ of 0.04.³⁵ The FQs of 0.31 across our outcomes and 0.15 for significant outcomes and the reverse FQ of 0.038 for nonsignificant outcomes in our study highlight that LET and ALL reconstruction augments for ACLR are particularly fragile compared with the broader ACLR fragility literature. Thus, additional adequately powered RCTs with power analysis may be required to further elucidate whether ALLs have a clinically meaningful benefit for patients undergoing ACLR.

Limitations

There are important limitations to consider with the present study. First, the FI and FQ are only able to be calculated for categorical, dichotomous outcomes. Some RCTs screened in this systematic review could not be ultimately included due to their failure to meet these criteria. The continuous FI has recently emerged as a potential metric that may be used to assess the statistical fragility of continuous outcomes. However, it is important to consider that the continuous FI also has limitations as it was only recently introduced, and the metric relies on the reported outcome having a mean and standard deviation reported for both intervention arms. Future studies may consider incorporating continuous fragility analyses as the metric undergoes further validation. Second, LET and ALL reconstruction augments for ACLR is a narrow topic of investigation which limited the number of RCT outcomes able to be analyzed. Finally, it is important to note that there have not been any threshold values for the FI, rFI, or FQ established for ACLR RCTs to accurately assess the reliability of the data. Threshold FI, rFI, or FQ values would serve as a benchmark for clinicians to effectively interpret the robustness of reported study findings in orthopaedic comparative trials. In addition to statistical fragility metrics, consistent reporting of clinically significant threshold measures such as the minimal clinically important difference, substantial clinical benefit, and patient acceptable symptom state may allow for study findings to be better correlated with clinically meaningful differences in reported outcome measures.⁴⁴

Conclusion

Outcomes reported in RCTs evaluating LET and ALL reconstruction as augments for rotatory instability in ACLR are statistically fragile. These findings highlight the need for additional adequately powered RCTs to better understand the effect of anterolateral augmentation on ACLR outcomes. We recommend combined reporting of P values with the FI, rFI, and FQ to aid in interpreting clinical findings of ACLR RCTs.

Footnotes

The following authors declared potential conflicts of interest: R.L.P. has received educational support from Gotham Surgical Solutions and Devices. M.J.A. has received consulting fees from DePuy Synthes, educational support from SUVON SURGICAL, and hospitality from Bodycad USA Corp. B.R.W. has received educational support from Arthrex, Vericel, and Peerless Surgical, and consulting fees from Vericel, Medical Device Business Services, and DePuy Synthes. X.L. has received consulting fees from FH Orthopedics.

ORCID iDs

Avanish Yendluri

Auston R. Locke

References

Andrade

The P value and statistical significance: misunderstandings, explanations, challenges, and alternatives. Indian J Psychol Med. 2019;41:210-215. PMID: 31142921

Bosco

Giustra

Masoni

, et al. Combining an anterolateral complex procedure with anterior cruciate ligament reconstruction reduces the graft reinjury rate and improves clinical outcomes: A systematic review and meta-analysis of randomized controlled trials. Am J Sports Med. 2024;52:2129-2147. PMID: 38353002

Bragg

Ruelos

VCB

McIntyre

, et al. Reverse fragility index comparing rates of rerupture after open achilles tendon repair versus early functional rehabilitation: A systematic review of randomized controlled trials. Am J Sports Med. [Epub ahead of print] June 12, 2023:3635465231178831. PMID: 37306060

Brown

Yendluri

Lawrence

, et al. The statistical fragility of tranexamic acid use in the orthopaedic surgery literature: A systematic review of randomized controlled trials. J Am Acad Orthop Surg. [Epub ahead of print] April 3, 2024. PMID: 38574390

Chan

Vrla

Thompson

, et al. Statistical fragility of randomized controlled trials evaluating platelet-rich plasma use for knee osteoarthritis: A systematic review. Orthop J Sports Med. 2023;11:23259671231187894. PMID: 37655254

Chen

Cho

Huangfu

Zhao

Reconstruction for chronic ACL tears with or without anterolateral structure augmentation in patients at high risk for clinical failure: A randomized clinical trial. J Bone Joint Surg Am. 2021;103:1482-1490. PMID: 34138788

Cordero

Lawrence

Brown

Hayden

Parisien

RL.

The fragility of tourniquet use in total knee arthroplasty: A systematic review of randomized controlled trials. J Arthroplasty. 2023;38:1177-1183. PMID: 36566999

D’Ambrosi

Corona

Cerciello

, et al. Combining an anterolateral complex procedure with anterior cruciate ligament reconstruction reduces graft reinjury without increasing the rate of complications: A systematic review and meta-analysis of randomized controlled trials. Am J Sports Med. [Epub ahead of print] January 12, 2025:3635465241285887. PMID: 39799408

Ehlers

Curley

Fackler

, et al. The statistical fragility of single-bundle vs double-bundle autografts for ACL reconstruction: A systematic review of comparative studies. Orthop J Sports Med. 2021;9:23259671211064626. PMID: 34988239

10.

El-Azab

Moursy

Mohamed

Elsayed

A comparison of the outcomes of anterior cruciate ligament reconstruction with large-size graft versus reconstruction with average-size graft combined with extraarticular tenodesis. Injury. 2023;54:976-982. PMID: 36720663

11.

Erden

Toker

Toprak

Taşer

Ö.

Comparison of the outcomes of isolated anterior cruciate ligament reconstruction and combined anterolateral ligament suture tape augmentation and anterior cruciate ligament reconstruction. Jt Dis Relat Surg. 2021;32:129-136. PMID: 33463428

12.

Feinstein

AR.

The unit fragility index: an additional appraisal of “statistical significance” for a contrast of two proportions. J Clin Epidemiol. 1990;43:201-209. PMID: 2303850

13.

Feng

Cao

Tan

, et al. Anterior cruciate ligament reconstruction with lateral extra-articular tenodesis reduces knee rotation laxity and graft failure rate: A systematic review and meta-analysis. J Orthop Surg. 2022;30:10225536221095969. PMID: 35465765

14.

Garcia

MVF

Ferreira

Caruso

. Fragility index and fragility quotient in randomized clinical trials. J Bras Pneumol. 2023;49:e20230034. PMID: 36946820

15.

Hamido

Habiba

Marwan

, et al. Anterolateral ligament reconstruction improves the clinical and functional outcomes of anterior cruciate ligament reconstruction in athletes. Knee Surg Sports Traumatol Arthrosc. 2021;29:1173-1180. PMID: 32617609

16.

Heard

Marmura

Bryant

, et al. No increase in adverse events with lateral extra-articular tenodesis augmentation of anterior cruciate ligament reconstruction - Results from the stability randomized trial. J ISAKOS. 2023;8:246-254. PMID: 36646169

17.

Ibrahim

Shohdy

Marwan

, et al. Anatomic reconstruction of the anterior cruciate ligament of the knee with or without reconstruction of the anterolateral ligament: A randomized clinical trial. Am J Sports Med. 2017;45:1558-1566. PMID: 28293966

18.

Khan

Fonarow

Friede

, et al. Application of the reverse fragility index to statistically nonsignificant randomized clinical trial results. JAMA Netw Open. 2020;3:e2012469. PMID: 32756927

19.

Kittl

El-Daou

Athwal

, et al. The role of the anterolateral structures and the ACL in controlling laxity of the intact and ACL-deficient knee. Am J Sports Med. 2016;44:345-354. PMID: 26657572

20.

Laboudie

Douiri

Bouguennec

Biset

Graveleau

Combined ACL and ALL reconstruction reduces the rate of reoperation for graft failure or secondary meniscal lesions in young athletes. Knee Surg Sports Traumatol Arthrosc. 2022;30:3488-3498. PMID: 35364738

21.

Lai

Zhang

W-L.

Comparison of anterior cruciate ligament reconstruction with versus without anterolateral augmentation: A systematic review and meta-analysis of randomized controlled trials. Orthop J Sports Med. 2023;11:23259671221149403. PMID: 37025126

22.

Lawrence

Okewunmi

Chakrani

Cordero

Parisien

RL.

Randomized controlled trials comparing bone-patellar tendon-bone versus hamstring tendon autografts in anterior cruciate ligament reconstruction surgery are statistically fragile: A systematic review. Arthroscopy. 2024;40:998-1005. PMID: 37543146

23.

Lee

S-S

Kwon

Lee

Ryu

Jang

Wang

JH.

Single bundle anterior cruciate ligament with anterolateral ligament reconstruction yields similar clinical and radiographic results at minimum 2-year follow-up versus double bundle anterior cruciate ligament reconstruction: A prospective randomized controlled trial. Arthroscopy. 2023;39:2502-2512. PMID: 37207917

24.

Leopold

Porcher

Editorial: Threshold P values in orthopaedic research-we know the problem. What is the solution?

Clin Orthop Relat Res. 2018;476:1689-1691. PMID: 30024469

25.

Mazzucco

Bhandari

Piuzzi

Kunze

KN.

The reverse fragility index for mortality end points in randomized trials comparing uncemented and cemented hemiarthroplasty for intracapsular hip fractures. J Arthroplasty. 2024;39:701-707. PMID: 37793507

26.

Megafu

Mian

, et al. Fragile statistical findings in randomized controlled trials evaluating autograft versus allograft use in anterior cruciate ligament reconstruction: A systematic review. Arthroscopy. 2024;40:1009-1018. PMID: 37579956

27.

Megafu

Mian

Hassan

Parsons

Parisien

RL.

The fragility of statistical findings in distal biceps tendon repairs: a systematic review of randomized controlled trials. J Shoulder Elbow Surg. 2023;32:e379-e386. PMID: 37075937

28.

Mogoş

Antonescu

Stoica

I-C

D’Ambrosi

. Superior rotational stability and lower re-ruptures rate after combined anterolateral and anterior cruciate ligament reconstruction compared to isolated anterior cruciate ligament reconstruction: A 2-year prospective randomized clinical trial. Phys Sportsmed. 2023;51:371-378. PMID: 35968574

29.

Mogoş

D’Ambrosi

Antonescu

Stoica

I-C

. Combined anterior cruciate ligament and anterolateral ligament reconstruction results in superior rotational stability compared with isolated anterior cruciate ligament reconstruction in high grade pivoting sport patients: A prospective randomized clinical trial. J Knee Surg. 2023;36:54-61. PMID: 33932949

30.

Nazzal

Keeling

Ryan

Herman

Hughes

JD.

The role of lateral extra-articular tenodesis in anterior cruciate ligament reconstruction and treatment of rotatory knee instability: A scoping review. Curr Rev Musculoskelet Med. 2023;16:235-245. PMID: 36995532

31.

Paudel

Sommerfeldt

Voaklander

Increasing incidence of anterior cruciate ligament reconstruction: a 17-year population-based study. Knee Surg Sports Traumatol Arthrosc. 2023;31:248-255. PMID: 35948850

32.

Pearsall

Constant

Saltzman

Parisien

Levine

Trofa

The fragility of statistical significance in sham orthopaedic surgery: A systematic review of randomized controlled trials. J Am Acad Orthop Surg. 2023;31:e994-e1002. PMID: 37678845

33.

Placer-Galán

Arocena

EB.

Fragility index, reverse fragility index, fragility quotients, and susceptibility index. Novel tools for assessing of randomized clinical trials. Cir Esp. 2024;102:41-43. PMID: 37949365

34.

Rezansoff

Firth

Bryant

, et al. Anterior cruciate ligament reconstruction plus lateral extra-articular tenodesis has a similar return-to-sport rate to anterior cruciate ligament reconstruction alone but a lower failure rate. Arthroscopy. 2024;40:384-396.e1. PMID: 37270112

35.

Ruelos

VCB

Masood

Puzzitiello

, et al. The reverse fragility index: RCTs reporting non-significant differences in failure rates between hamstring and bone-patellar tendon-bone autografts have fragile results. Knee Surg Sports Traumatol Arthrosc. 2023;31:3412-3419. PMID: 37093236

36.

Shi

Mojica

Moverman

, et al. The reverse fragility index: interpreting the current literature on long-term survivorship of computer-navigated versus conventional TKA: A systematic review and cross-sectional study of randomized controlled trials. J Bone Joint Surg Am. 2023;105:157-163. PMID: 36651891

37.

Sonnery-Cottet

Pioger

Vieira

, et al. Combined ACL and anterolateral reconstruction is not associated with a higher risk of adverse outcomes: Preliminary results from the SANTI randomized controlled trial. Orthop J Sports Med. 2020;8:2325967120918490. PMID: 32490026

38.

Sonnery-Cottet

Thaunat

Freychet

Pupim

BHB

Murphy

Claes

Outcome of a combined anterior cruciate ligament and anterolateral ligament reconstruction technique with a minimum 2-year follow-up. Am J Sports Med. 2015;43:1598-1605. PMID: 25740835

39.

Sørensen

Faunø

Konradsen

, et al. Combined anterior cruciate ligament revision with reconstruction of the antero-lateral ligament does not improve outcome at 2-year follow-up compared to isolated ACL revision; A randomized controlled trial. Knee Surg Sports Traumatol Arthrosc. 2023;31:5077-5086. PMID: 37733288

40.

Sterne

JAC

Savović

Page

, et al. RoB 2: A revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898. PMID: 31462531

41.

Sterne

JAC

Smith

GD.

Sifting the evidence—what’s wrong with significance tests?

Phys Ther. 2001;81:1464-1469.

42.

Tignanelli

Napolitano

LM.

The fragility index in randomized clinical trials as a means of optimizing patient care. JAMA Surg. 2019;154:74-79. PMID: 30422256

43.

Willinger

Athwal

Holthof

Imhoff

Williams

Amis

AA.

Role of the anterior cruciate ligament, anterolateral complex, and lateral meniscus posterior root in anterolateral rotatory knee instability: A biomechanical study. Am J Sports Med. 2023;51:1136-1145. PMID: 36917838

44.

Yendluri

Alexanian

Chari

, et al. The statistical fragility of marrow stimulation for cartilage defects of the knee: A systematic review of randomized controlled trials. Cartilage. [Epub ahead of print] February 25, 2024:19476035241233441. PMID: 38403983

45.

Yendluri

Chiang

Linden

, et al. The fragility of statistical findings in the reverse total shoulder arthroplasty literature: A systematic review of randomized controlled trials. J Shoulder Elbow Surg. [Epub ahead of print] January 26, 2024. PMID: 38281679

46.

Yendluri

Gonzalez

Cordero

Hayden

Moucha

Parisien

. Statistical outcomes guiding periprosthetic joint infection prevention and revision are fragile: A systematic review of randomized controlled trials. J Arthroplasty. [Epub ahead of print] February 6, 2024. PMID: 38331358

47.

Yendluri

Megafu

Wang

, et al. The fragility of statistical findings in the femoral neck fracture literature: A systematic review of randomized controlled trials. J Orthop Trauma. [Epub ahead of print] March 4, 2024. PMID: 38442195