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Background: Fragility Index (FI) is increasingly used to assess robustness of statistically significant p-values reported in randomized controlled trials (RCTs). FI represents the lowest number of non-events changed to events that would make study findings non-significant. This methodological survey was designed to assess the fragility of the evidence for extended VTEp following major abdominopelvic surgery., Methods: MEDLINE, Embase, and CENTRAL were searched from inception to November 2023. RCTs with parallel, double-armed, superiority design comparing extended VTEp for patients undergoing major abdominopelvic surgery to controls with at least one statistically significant dichotomous outcome were included. Walsh et al.'s method of calculating FI was utilized., Results: After review of 611 citations, 6 RCTs were identified with 12 statistically significant outcomes between groups. The mean number of patients randomized per RCT was 419 (SD 176). The median FI was 1.5 (range: 1-4). The number of patients lost to follow-up was greater than the FI for 10/12 (83.3 ​%) outcomes., Conclusions: Statistically significant differences reported in RCTs evaluating extended VTEp following major abdominopelvic surgery are not robust., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Symptomatic rotator cuff tears often undergo surgical repair, which may be paired with various augmentation strategies to enhance structural healing rates. While many randomized controlled trials (RCTs) evaluate augmentation techniques, the statistical robustness of many findings in these studies is unknown. This systematic review aims to evaluate the continuous fragility index (CFI) of RCTs on augmentation techniques for rotator cuff repairs., Methods: MEDLINE, Embase, and CENTRAL databases were comprehensively searched from inception to September 2023 for RCTs assessing the efficacy of at least one augmentation strategy during rotator cuff repair. Eligible studies reported at least one statistically significant finding for a continuous outcome. The CFI for eligible outcomes was calculated, with median CFI presented by type of augmentation and outcome. Multivariable regression was performed to identify associations between CFI and other outcome variables., Results: Nineteen RCTs (1417 patients) were included in the final analysis. The median CFI for the 86 outcomes analyzed was 5.85 (IQR 2.3 - 14.4). Augmentation-specific analysis demonstrated variability in CFIs, with the most robust outcomes found in platelet-rich plasma studies (median 10.95, IQR 3.3 - 19.0) and suture-spanning augmentation studies (median 11.90, IQR 11.45 - 14.35). Outcome-specific analysis demonstrated range of motion outcomes as most robust (median 9.85, IQR 7.58 - 14.0) and strength-related outcomes as most fragile (median 2.00, IQR 1.0 - 16.3). Multivariable regression identified larger sample size as a statistically significant predictor of greater CFI. Notably, loss to follow-up exceeded the CFI in 31.4% of outcomes., Conclusion: The observed median CFI of 5.85 in augmentation trials is consistent with the CFI reported in orthopedic and sports medicine literature. However, almost a third of outcomes had a loss to follow-up exceeding their CFI, risking the reversal of study findings with more robust follow-up and outcomes. Clinicians and researchers should consider fragility in addition to p-values when assessing study results, especially in the context of high loss to follow-up. Future trials should report the fragility of their findings., Level of Evidence: Systematic Review; Research Methodology Study., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: To determine the robustness of randomized controlled trials (RCTs) supporting the current rhinosinusitis guideline; International Consensus Statement on Allergy and Rhinology: rhinosinusitis (ICAR-RS)., Materials & Methods: RCTs referenced by ICAR-RS with primary dichotomous outcomes were analyzed. The Fragility Index (FI) was calculated for trials with statistically significant findings. Trial characteristics, the FI, and FI minus number lost to follow-up (LTF) were assessed for associations., Results: A total of 317 RCTs were identified, with 38 trials possessing a primary dichotomous outcome. Thirty-one percent evaluated surgical interventions and 24 % were industry-sponsored. The mean sample size was 116 with 9 patients, on average, LTF. Sixty-three percent were eligible for FI calculation and had a median FI of 2.5 (IQR 1, 4.25). Sixty-seven percent of trials had an FI ≤ 3, indicating low robustness. No difference in FI was observed between trials with and without industry support (p = 0.577). The FI was less than or equal to the number of patients LTF in 33 % of trials (n = 8). Higher FI was strongly correlated with higher sample size, total number of events, p-value, and grade of recommendation (p < 0.001). After adjusting for covariates, higher sample size and total number of events were associated with higher FI., Conclusion: The RCTs used to support the ICAR-RS have an overall low robustness and future rhinosinusitis trials should report FI measures to provide improved context of their results., Competing Interests: Declaration of competing interest Masayoshi Takashima is a consultant for Neurent Medical and Medtronic ENT. Edward D. McCoul is a consultant for 3D Matrix, Advanced Rx, Optinose, Sanofi, Stryker and Zsquare. Omar G. Ahmed is a consultant for Aerin Medical and Medtronic ENT. All other author(s) declare that there is no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Esophageal cancer remains a significant global health challenge. Several treatment modalities were explored in randomized controlled trials (RCTs) in recent decades. This study evaluates the robustness of RCTs focusing on esophageal cancer treatment using the fragility index (FI) and reverse fragility index (RFI)., Methods: A systematic review of RCTs studying different treatment modalities for esophageal cancer from 2000 to 2023 was conducted. The FI and RFI were utilized to gauge the robustness of statistically significant and non-significant outcomes, respectively. The FI represents the minimal number of patient outcomes that would need to alter to overturn a trial's statistical significance, while RFI indicates the minimal changes required to achieve significance in non-significant results., Results: Out of 4028 studies retrieved, 21 RCTs were included for final analysis. The studies spanned 2001 to 2023 with a mean followup of 66 months (range, 29-108 months) and median number of patients of 194 (range, 45-802). The most common treatment modalities examined in these studies were neoadjuvant chemoradiotherapy (n = 7, 33.3%), neoadjuvant chemotherapy (n = 4, 19.0%), and neoadjuvant immunotherapy (n = 2, 9.5%). Only 5 studies (23.8%) had a statistically significant primary outcome result with a median FI of 6 (IQR, 2.5-8.5). Non-significant primary outcomes were seen in 16 studies (76.2%) with a median RFI of 4 (IQR 1-11) and lost to followup of 0 (IQR 0-4). In the study with the highest FI (10), the FI was lower than the number of patients lost to followup (13)., Conclusion: Our findings demonstrate that most RCTs on esophageal cancer treatments did not report significant primary outcomes. The few studies that reported significant results had a low fragility index, suggesting a vulnerability in their findings., Competing Interests: Declarations. Disclosures: Drs. Noam Kahana, Elad Boaz, Nir Horesh, Sameh Hany Emile, Justin Dourado, Pauline Aeschbacher, Pete Rogers, Rachel Gefen, and Emanuele Lo Menzo have no conflicts of interest or financial ties to disclose. Dr. Raul Rosenthal receives speaker honoraria from Medtronics, serves on the Advisory Board and receives honoraria from Diagnostic Green; receives educational grants from Olympus, Stryker, Medtronic, Diagnostic Green, Arthrex, and Storz; is a shareholder in Medicad Simulation/Dendrite Imaging, and serves on the Advisory Board and as Interim CEO for Dendrite Imaging., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: This study aims to assess the robustness of cardiovascular disease randomized controlled trials (RCTs) with primary continuous outcomes from a clinical perspective, utilizing the concepts of continuous fragility index (CFI), reverse continuous fragility index (RCFI) and their corresponding quotients (CFQ, RCFQ)., Methods: A cross-sectional study was conducted, searching PubMed for cardiovascular RCTs published between January 1, 2018, to December 31, 2022, in eight high-impact journals. Inclusion criteria were phase III or IV trials with 1:1 randomization, reporting at least one primary continuous outcome. Data analysis involved altering each outcome until achieving the reversal of significance (ɑ = 0.05) to determine the CFI or RCFI. The fragility quotients were then calculated by dividing the CFI or RCFI by the sample size, and Spearman's correlation assessed correlation analyses., Results: Of 3983 records were screened, and 64 RCTs (76 outcomes) were included. The fragility index was analysed with 72 outcomes. The overall median CFI was 7, with an associated median CFQ of 0.032. Nonsignificant P values exhibited greater statistical instability (median RCFI = 5, RCFQ = 0.023) than significant P values (median CFI = 14, CFQ = 0.062). Interestingly, "fragile" values were found in 36% (9/25) of CFI or 46.7% (7/15) of RCFI. Additionally, fragility index showed a significant association with several variables., Conclusions: The findings suggest that changing only a small number of interventions (median of 7) could alter outcome significance. Reporting the fragility index alongside P values is recommended to provide a clearer understanding of statistical findings' robustness.HighlightsThe continuous fragility index (CFI) represents the minimum patient count needed to modify significance by altering their intervention.Among 72 primary continuous outcomes in 64 cardiovascular RCTs, the overall median CFI was 7, with a corresponding CFQ of 0.032.CFI demonstrated moderate to strong correlations with sample size, total dropouts, and patient numbers analyzed.

Introduction: Despite randomized controlled trials (RCTs) largely supporting volar locking plates (VLPs) for the management of distal radius fractures (DRFs), surgeons often opt for non-invasive interventions such as casting. This study used the fragility index (FI), reverse fragility index (rFI), and fragility quotient (FQ) to assess the statistical robustness of RCTs assessing the efficacy of VLP in DRF management., Methods: PubMed, Embase, and MEDLINE were queried for RCTs evaluating VLP versus casting for DRFs published from January 1st, 2000-June 30, 2024. FI and rFI were quantified for all dichotomous outcomes, and represent the number of event reversals required to alter statistical significance or non-significance, respectively. The FQ was then determined by dividing the FI or rFI by the sample size. A subanalysis was performed for outcomes pertaining to patient satisfaction, healing/function, and adverse events., Results: A total of 699 RCTs were identified in the initial literature search. 13 RCTs were eventually included in the final analysis, yielding 36 dichotomous outcomes. The median FI across these outcomes was 3 (IQR 3-5) and the median FQ was 0.037 (IQR 0.014-0.067). Among the 15 significant outcomes, the median FI was 2 (IQR 2-4) and the median FQ was 0.029 (IQR 0.013-0.055). The remaining 21 non-significant outcomes yielded a median rFI of 4 (IQR 2-5) and a median FQ of 0.042 (IQR 0.021-0.091). The most statistically fragile outcome category was patient satisfaction, with a median FI of 2 (IQR 2-3.5) and median FQ of 0.016 (IQR 0.013-0.030). Among 21 of the included outcomes (58.3 %), the number of patients lost to follow up exceeded the respective FI or rFI., Conclusion: A statistical fragility analysis of VLP versus casting for DRFs demonstrated fragile outcomes, reporting a median FQ of 0.037, or 3.7 %. Statistically significant outcomes and patient satisfaction results were particularly fragile, and large losses to follow up were found to be an important contributor to RCT fragility. Although VLP is largely recommended by level I evidence, its superiority may not be as ubiquitous as argued by contemporary literature., Competing Interests: Auston R. Locke has received royalty payments from Catheter Precision. Michael R. Hausman is a confounder and shareholder of Checkpo Surgical LLC. For the remaining authors none were declared., (© 2024 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

The results of randomized clinical trials (RCTs) are frequently assessed with the fragility index (FI). Although the information provided by FI may supplement the p value, this indicator presents intrinsic weaknesses and shortcomings. In this article, we establish an analysis of fragility within a broader framework so that it can reliably complement the information provided by the p value. This perspective is named the analysis of strength. We first propose a new strength index (SI), which can be adopted in normal distribution settings. This measure can be obtained for both significance and nonsignificance and is straightforward to calculate, thus presenting compelling advantages over FI, starting from the presence of a threshold. The case of time-to-event outcomes is also addressed. Then, beyond the p value, we develop the analysis of strength using likelihood ratios from Royall's statistical evidence viewpoint. A new R package is provided for performing strength calculations, and a simulation study is conducted to explore the behavior of SI and the likelihood-based indicator empirically across different settings. The newly proposed analysis of strength is applied in the assessment of the results of three recent trials involving the treatment of COVID-19., (© 2024 The Author(s). Pharmaceutical Statistics published by John Wiley & Sons Ltd.)

Background: Randomized controlled trials (RCTs) are the gold standard for treatment efficacy, but foot and ankle RCTs are often small or inconsistent. The Fragility Index (FI) evaluates the stability of significant findings. This study assessed the fragility of RCT outcomes for Achilles tendon pathology (ATP) interventions., Methods: This systematic review queried PubMed up to May 14, 2024, for RCTs on ATP interventions. RCTs with significant binary outcomes were included. Two reviewers assessed eligibility, extracted data, calculated FIs, and evaluated risk of bias. Frequency-weighted means were used for narrative synthesis., Results: Eleven RCTs with 4506 patients (mean cohort size: 409.64 ± 160.54) and a mean age of 36.97 ± 13.51 years (n = 4356; 96.67%) were included, covering 24 binary outcomes. The median FI across all outcomes was 3 (interquartile range 1-4; mean 3.92), indicating that changing the outcome of just a few patients could shift a study's results from statistically significant to nonsignificant. Trials having an FI ≤3 comprised 58.33%. Three outcomes (12.5%) had an FI of zero after recalculating P values using the two-sided Fisher exact test. Half of the outcomes were robust. No RCT reported FIs or adjusted significance for multiple testing. Most studies (81.82%) performed 2 or more statistical tests, with an average of 30.81 ± 41.28 P values reported per study. The overall risk of bias was low in 1 study (9.09%) and moderate in 7 (63.64%). Most studies had low risk of bias in randomization (72.73%) and missing outcome data (90.91%)., Conclusion: The FI assesses the fragility of statistically significant binary results, revealing that many ATP RCTs have fragile outcomes due to small sample sizes. A median FI of 3 means that changing the outcome of 3 patients could shift a study's results from statistically significant to nonsignificant., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Disclosure forms for all authors are available online., (© The Author(s) 2024.)

Purpose: To determine the statistical fragility of randomized controlled trials (RCTs) which compare the use of quadriceps tendon (QT) autografts to either hamstring tendon (HT) or bone-patellar tendon-bone (BPTB) autografts in anterior cruciate ligament reconstruction (ACLR)., Methods: A search was conducted across PubMed, MEDLINE and EMBASE databases for RCTs comparing QT autografts to HT or BPTB autografts in ACLR from inception to 21 April 2024. Studies that reported ≥1 statistically significant continuous outcome, statistically significant dichotomous outcome and/or nonsignificant dichotomous outcome were included for analysis. The fragility index (FI), continuous fragility index (CFI) and reverse fragility index (RFI) were calculated for significant dichotomous outcomes, significant continuous outcomes and nonsignificant dichotomous outcomes, respectively., Results: A total of 11 RCTs comprising 716 patients were included. The mean sample size was 65.8 patients. The median FI among nine outcomes from four studies was 1.0 (interquartile range [IQR], 0.5; 95% confidence interval [CI], 0.6-1.4; range 0.5-1.5). The number of patients lost to follow-up at the final follow-up period was more than the study-specific FI in three (75%) studies. The median CFI among 30 outcomes from six studies was 4.9 (IQR, 10.1, 95% CI, 3.9-8.2; range 0-18.2). The number of patients lost to follow-up at the final follow-up period was more than the study-specific CFI in four (66.7%) studies. The median RFI among 10 outcomes from five studies was 5.0 (IQR, 3.5; 95% CI, 3.4-6.6; range 1.0-9.0). The number of patients lost to follow-up at the final follow-up period was more than the study-specific RFI in four (80%) studies., Conclusion: This systematic review revealed that regardless of the metric used, RCTs comparing QT autografts to HT or BPTB autograft options in ACLR are statistically fragile. While the indices of statistical fragility evaluated in this study are important metrics of robustness to consider, their application in research and clinical practice needs to be further elucidated., Level of Evidence: Level I., (© 2024 The Author(s). Knee Surgery, Sports Traumatology, Arthroscopy published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Objectives: The sample sizes of phase I trials are typically small; some designs may lead to inaccurate estimation of the maximum tolerated dose (MTD). The objective of this study was to propose a metric assessing whether the MTD decision is sensitive to enrolling a few additional subjects in a phase I dose-finding trial., Methods: Numerous model-based and model-assisted designs have been proposed to improve the efficiency and accuracy of finding the MTD. The Fragility Index (FI) is a widely used metric quantifying the statistical robustness of randomized controlled trials by estimating the number of events needed to change a statistically significant result to non-significant (or vice versa). We propose a modified Fragility Index (mFI), defined as the minimum number of additional participants required to potentially change the estimated MTD, to supplement existing designs identifying fragile phase I trial results., Findings: Three oncology trials were used to illustrate how to evaluate the fragility of phase I trials using mFI. The results showed that two of the trials were not sensitive to additional subjects' participation while the third trial was quite fragile to one or two additional subjects., Conclusions: The mFI can be a useful metric assessing the fragility of phase I trials and facilitating robust identification of MTD.

Background: Based in part on the results of randomized controlled trials (RCTs) that suggest a beneficial effect over alternative treatment options, the use of platelet-rich plasma (PRP) for the management of knee osteoarthritis (OA) is widespread and increasing. However, the extent to which these studies are vulnerable to slight variations in the outcomes of patients remains unknown., Purpose: To evaluate the statistical fragility of conclusions from RCTs that reported outcomes of patients with knee OA who were treated with PRP versus alternative nonoperative management strategies., Study Design: Systematic review and meta-analysis; Level of evidence, 2., Methods: All RCTs comparing PRP with alternative nonoperative treatment options for knee OA were identified. The fragility index (FI) and reverse FI were applied to assess the robustness of conclusions regarding the efficacy of PRP for knee OA. Meta-analyses were performed to determine the minimum number of patients from ≥1 trials included in the meta-analysis for which a modification on the event status would change the statistical significance of the pooled treatment effect., Results: In total, this analysis included outcomes from 1993 patients with a mean ± SD age of 58.0 ± 3.8 years. The mean number of events required to reverse significance of individual RCTs (FI) was 4.57 ± 5.85. Based on random-effects meta-analyses, PRP demonstrated a significantly higher rate of successful outcomes when compared with hyaluronic acid ( P = .002; odds ratio [OR], 2.19; 95% CI, 1.33-3.62), as well as higher rates of patient-reported symptom relief ( P = .019; OR, 1.55; 95% CI, 1.07-2.24), not requiring a reintervention after the initial injection treatment ( P = .002; OR, 2.17; 95% CI, 1.33-3.53), and achieving the minimal clinically important difference (MCID) for pain improvement ( P = .007; OR, 6.19; 95% CI, 1.63-23.42) when compared with all alternative nonoperative treatments. Overall, the mean number of events per meta-analysis required to change the statistical significance of the pooled treatment effect was 8.67 ± 4.50., Conclusion: Conclusions drawn from individual RCTs evaluating PRP for knee OA demonstrated slight robustness. On meta-analysis, PRP demonstrated a significant advantage over hyaluronic acid as well as improved symptom relief, lower rates of reintervention, and more frequent achievement of the MCID for pain improvement when compared with alternative nonoperative treatment options. Statistically significant pooled treatment effects evaluating PRP for knee OA are more robust than approximately half of all comparable meta-analyses in medicine and health care. Future RCTs and meta-analyses should consider reporting FIs and fragility quotients to facilitate interpretation of results in their proper context., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: J.F.O. has received consulting fees from Kaliber.ai. A.P. has received support for education from Smith & Nephew and hospitality payments from Medical Device Business Services. S.M.S. has received consulting fees from Moximed, Smith & Nephew, Miach Orthopaedics, Vericel, and Flexion Therapeutics; research support from Vericel and JRF; speaking fees from Organogenesis and Vericel; and royalties from Organogenesis; and holds stock or stock options in Engage and Stryker. B.U.N. has received consulting fees from Stryker, Wright Medical, and Zimmer Biomet; support for education from Arthrex and Smith & Nephew; consulting fees from Figur8; and a grant from Arthrex; and holds stock or stock options in BICMD. C.L.C. has received consulting fees from Arthrex; research support from Major League Baseball; and publishing royalties from Springer. A.J.K. has received consulting fees from Joint Restoration Foundation, Arthrex, and Responsive Arthroscopy; honoraria from Joint Restoration Foundation; royalties from Arthrex and Responsive Arthroscopy; a grant from DJO; and research support from Aesculap/B.Braun; and serves on the medical board of trustees for the Musculoskeletal Transplant Foundation. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

OBJECTIVE: To determine the Fragility Index of hamstring injury risk factors, defined as the minimum number of participants who would need to change classification to make a hamstring injury risk factor statistically nonsignificant. DESIGN: Retrospective secondary data analysis. METHODS: Studies that investigated 1 or more risk factors for hamstring injury, and presented sufficient data to develop a 2 × 2 contingency table were included. A systematic literature search and reference screening of a recent hamstring injury systematic review were conducted to identify 78 articles. Relative risk and 95% confidence intervals were determined and then systematically recalculated by removing 1 observation from the high-risk injury count and adding it to the high-risk noninjury count. The Fragility Index for a risk factor was the number of observations required to be moved between groups until the relative risk was no longer significant. RESULTS: The median Fragility Index of all hamstring injury risk factors was 3 (Q1-Q3 = 2-6). The Fragility Index for nonmodifiable risk factors was 3 (Q1-Q3 = 2-6) and 3 (Q1-Q3 = 2-5) for modifiable risk factors. Over 35% of all included hamstring injury risk factors had a Fragility Index of ≤2. CONCLUSION: Most statistically significant hamstring injury risk factors are fragile associations. The interpretation of significant hamstring injury risk factors should consider a range of statistical metrics, and while the Fragility Index should never be considered in isolation, it is an intuitive measure to help assess the robustness of findings. J Orthop Sports Phys Ther 2024;54(10):672-678. Epub 4 September 2024. doi:10.2519/jospt.2024.12300 .

Background: The 2018 American Association of Hip and Knee Surgeons clinical practice guideline (CPG) 'tranexamic acid use in total joint arthroplasty' evaluated the efficacy and safety of tranexamic acid in primary total joint arthroplasty. The following review assessed the statistical fragility of the randomized controlled trial (RCT) outcomes on which the CPG recommendations were based using a fragility analysis., Methods: All dichotomous outcomes from the RCTs used to guide the CPG from its associated network, and direct meta-analyses were analyzed. Fragility and reverse fragility indices (FI and rFI) and quotients were calculated for each outcome. The mean indices and quotients were calculated for each guideline question, outcome category, and comparison of tranexamic dose, formulation, and administration timing., Results: This review evaluated 403 dichotomous outcomes on transfusion and complication rates associated with tranexamic acid (TXA) administration. The mean FI of significant outcomes of the CPG was 5.23, and the mean rFI of nonsignificant outcomes was 5.80. Outcomes assessing complication rates had a mean rFI of 6.48. Most outcomes on transfusion in categories comparing TXA to placebo administration had higher mean FIs than rFIs, and all outcomes comparing transfusion risk associated with different TXA formulations and doses had higher mean rFIs than FI or no associated significant outcomes., Conclusions: The rFI and FIs calculated for this CPG are comparable to or higher than mean values reported across orthopaedic literature, indicating the relative statistical stability of its included outcomes. As we learn more about fragility analyses and their potential applications, this type of statistical analysis shows promise as a useful tool to incorporate into future guidelines to assess the quality of RCTs and evaluate the strength of recommendations., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Overactive bladder (OAB) syndrome significantly impairs quality of life, often necessitating pharmacological interventions with associated risks. The fragility of OAB trial outcomes, as measured by the fragility index (FI: smallest number of event changes to reverse statistical significance) and quotient (FQ: FI divided by total sample size expressed as a percentage), is critical yet unstudied., Materials and Methods: We conducted a systematic search for randomized controlled trials on OAB medications published between January 2000 and August 2023. Inclusion criteria were trials with two parallel arms reporting binary outcomes related to OAB medications. We extracted trial details, outcomes, and statistical tests employed. We calculated FI and FQ, analyzing associations with trial characteristics through linear regression., Results: We included 57 trials with a median sample size of 211 participants and a 12% median lost to follow-up. Most studies investigated anticholinergics (37/57, 65%). The median FI/FQ was 5/3.5%. Larger trials were less fragile (median FI 8; FQ 1.0%) compared to medium (FI: 4; FQ 2.5%) and small trials (FI: 4; FQ 8.3%). Double-blinded studies exhibited higher FQs (median 2.9%) than unblinded trials (6.7%). Primary and secondary outcomes had higher FIs (median 5 and 6, respectively) than adverse events (FI: 4). Each increase in 10 participants was associated with a +0.19 increase in FI (p < 0.001)., Conclusions: A change in outcome for a median of five participants, or 3.5% of the total sample size, could reverse the direction of statistical significance in OAB trials. Studies with larger sample sizes and efficacy outcomes from blinded trials were less fragile., (© 2024 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Background: A P value of <.05 is often used to denote statistical significance; however, in many scenarios, this threshold is vulnerable to a small number of outcome reversals. This study joins a body of studies within the orthopaedic literature that evaluate the statistical fragility of existing research via metrics such as fragility index (FI) and fragility quotient (FQ)., Purpose/hypothesis: The purpose of this study was to investigate the statistical fragility of randomized controlled trials (RCTs) and comparative studies on the topic, given the resurgent interest in lateral extra-articular tenodesis (LET) to augment primary or revision anterior cruciate ligament reconstruction (ACLR). It was hypothesized that the outcomes reported in these studies would be statistically fragile., Study Design: Systematic review; Level of evidence, 4., Methods: Comparative studies and RCTs regarding LET as an adjunct procedure to ACLR published between 2000 and 2022 were analyzed. Descriptive characteristics, dichotomous outcomes, and continuous outcomes were extracted. The FI and continuous FI (CFI) were calculated by the number of event reversals to change significance; the FQ and continuous FQ (CFQ) were calculated to normalize the fragility metrics per sample size., Results: Of 455 studies screened, 29 studies were included (9 RCTs, 20 comparative); 79.3% of included studies were published after 2020. A total of 48 dichotomous and 265 continuous outcomes were analyzed. The median FI was 9.0 (IQR, 7.0-13.3), with FQ of 0.1 (IQR, 0.04-0.17); the median CFI was 7.8 (IQR, 4.2-19.6), with CFQ of 0.12 (IQR, 0.08-0.19). The FQ and CFQ for studies on LET with revision ACLR were larger (0.117 and 0.113, respectively) than those focused on primary ACLR (0.042 and 0.095, respectively)., Conclusion: Studies focused on LET with primary ACLR were more fragile than those on LET with revision, which suggests that further research on the indications for LET with primary ACLR is necessary. Future orthopaedic comparative research should include fragility metrics alongside traditional P values., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: B.D.O. has received consulting fees from DePuy/Medical Device Business Services, Vericel, Linvatec, and Musculoskeletal Transplant Foundation; royalties from Linvatec; and honoraria from Vericel; and is a paid associate editor for the American Journal of Sports Medicine. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2024.)

Objective: The fragility index (FI), which is the minimum number of changes in status from "event" to "non-event" resulting in a loss of statistical significance, serves as a significant supplementary indicator for clinical physicians in interpreting clinical trial results and aids in understanding the outcomes of randomized controlled trials (RCTs). In this systematic literature survey, we evaluated the FI for RCTs evaluating Chinese herbal medicine (CHM) for irritable bowel syndrome (IBS), and explored potential associations between study characteristics and the robustness of RCTs., Methods: A comprehensive search was conducted in four databases in Chinese and four databases in English from their inception to January 1, 2023. RCTs encompassed 1:1 ratio into two parallel arms and reported at least one binary outcome that demonstrated statistical significance were included. FI was calculated by the iterative reduction of a target outcome event in the treatment group and concomitant subtraction of a non-target event from that group, until positive significance (defined as P < 0.05 by Fisher's exact test) is lost. The lower the FI (minimum 1) of a trial outcome, the more fragile the positive result of the outcome was. Linear regression models were adopted to explore influence factors of the value of FI., Results: A total of 30 trials from 2 4118 potentially relevant citations were finally included. The median FI of total trials included was 1.5 (interquartile range [IQR], 1-5), and half of the trials (n = 15) had a FI equal to 1. In 12 trials (40%), the total number of participants lost to follow-up surpassed the respective FI. The study also identified that increased FI was significantly associated with no TCM syndrome differentiation for inclusion criteria of the patients, larger total sample size, low risk of bias, and larger numbers of events., Conclusions: The majority of CHM IBS RCTs with positive results were found to be fragile. Ensuring adequate sample size, scientifically rigorous study design, proper control of confounding factors, and a quality control calibration for consistency of TCM diagnostic results among clinicians should be addressed to increase the robustness of the RCTs. We recommend reporting the FI as one of the components of sensitivity analysis in future RCTs to facilitate the assessment of the fragility of trials., (© 2024. The Author(s).)

Background: Evidence-based care relies on robust research. The fragility index (FI) is used to assess the robustness of statistically significant findings in randomized controlled trials (RCTs). While the traditional FI is limited to dichotomous outcomes, a novel tool, the continuous fragility index (CFI), allows for the assessment of the robustness of continuous outcomes., Purpose: To calculate the CFI of statistically significant continuous outcomes in RCTs evaluating interventions for managing anterior shoulder instability (ASI)., Study Design: Meta-analysis; Level of evidence, 2., Methods: A search was conducted across the MEDLINE, Embase, and CENTRAL databases for RCTs assessing management strategies for ASI from inception to October 6, 2022. Studies that reported a statistically significant difference between study groups in ≥1 continuous outcome were included. The CFI was calculated and applied to all available RCTs reporting interventions for ASI. Multivariable linear regression was performed between the CFI and various study characteristics as predictors., Results: There were 27 RCTs, with a total of 1846 shoulders, included. The median sample size was 61 shoulders (IQR, 43). The median CFI across 27 RCTs was 8.2 (IQR, 17.2; 95% CI, 3.6-15.4). The median CFI was 7.9 (IQR, 21; 95% CI, 1-22) for 11 studies comparing surgical methods, 22.6 (IQR, 16; 95% CI, 8.2-30.4) for 6 studies comparing nonsurgical reduction interventions, 2.8 for 3 studies comparing immobilization methods, and 2.4 for 3 studies comparing surgical versus nonsurgical interventions. Significantly, 22 of 57 included outcomes (38.6%) from studies with completed follow-up data had a loss to follow-up exceeding their CFI. Multivariable regression demonstrated that there was a statistically significant positive correlation between a trial's sample size and the CFI of its outcomes ( r = 0.23 [95% CI, 0.13-0.33]; P < .001)., Conclusion: More than a third of continuous outcomes in ASI trials had a CFI less than the reported loss to follow-up. This carries the significant risk of reversing trial findings and should be considered when evaluating available RCT data. We recommend including the FI, CFI, and loss to follow-up in the abstracts of future RCTs., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: O.R.A. has received speaking fees from Conmed and is a tier 2 Canada Research Chair in Joint Preservation Surgery. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Purpose: FDA investigational device exemption (IDE) studies are considered a gold standard of assessing safety and efficacy of novel devices through RCTs. The fragility index (FI) has emerged as a means to assess robustness of statistically significant study results and inversely, the reverse fragility index (RFI) for non-significant differences. Previous authors have defined results as fragile if loss to follow up is greater than the FI or RFI. The aim of this study was to assess the FI, RFI, and robustness of data supplied by IDE studies in spinal surgery., Methods: This was a systematic review of the literature. Inclusion criteria included randomized controlled trials with dichotomous outcome measures conducted under IDE guidelines between 2000 and 2023. FI and RFI were calculated through successively changing events to non-events until the outcome changed to non-significance or significance, respectively. The fragility quotient (FQ) and reverse fragility quotient (RFQ) were calculated by dividing the FI and RFI, respectively, by the sample size., Results: Thirty-two studies met inclusion criteria with a total of 40 unique outcome measures; 240 outcomes were analyzed. Twenty-six studies reported 96 statistically significant results. The median FI was 6 (IQR: 3-9.25), and patients lost to follow up was greater than the FI in 99.0% (95/96) of results. The average FQ was 0.027. Thirty studies reported 144 statistically insignificant results and a median RFI of 6 (IQR: 4-8). The average RFQ extrapolated was 0.021, and loss to follow up was greater than the RFI in 98.6% (142/144) of results., Conclusions: IDE studies in spine surgery are surprisingly fragile given their reputations, large sample sizes, and intent to establish safety in investigational devices. This study found a median FI and RFI of 6. The number of patients lost to follow-up was greater than FIand RFI in 98.8% (237/240) of reported outcomes. FQ and RFQ tell us that changes of two to three patients per hundred can flip the significance of reported outcomes. This is an important reminder of the limitations of RCTs. Analysis of fragility in future studies may help clarify the strength of the relationship between reported data and their conclusions., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The P value has been used as a statistical tool in randomized controlled trials (RCTs) to establish significance but does not provide information on the robustness of a study when used alone. The fragility index (FI) provides a supplemental approach for demonstrating robustness in RCTs that report dichotomous outcomes. This study aims to determine the statistical fragility of RCTs that compare minimally invasive techniques with open techniques in managing benign and malignant colorectal diseases. Methods: Dichotomous outcomes of minimally invasive surgery versus open surgery in RCTs from 2000 to 2023 were assessed. The overall FI and fragility quotient (FQ) of each study were calculated. Results: Of the 1377 screened studies, 50 met the inclusion criteria. In total, 820 outcomes were recorded with 747 outcomes reported as not significant ( P ≥ .05) and 73 as significant ( P < .05). The overall FI for all studies including all outcomes was 5 (interquartile range [IQR] 4-7) with a FQ of 0.031 (IQR 0.014-0.062). Of the 50 RCTs, 6 (12%) reported a loss to follow-up that was greater than the overall FI of 5. Conclusions: As RCTs are judged increasingly beyond just the P value, practicing colorectal surgeons will benefit from using and interpreting the FI, FQ, and the P value of studies both in analyzing future RCTs and in determining whether or not to make a change in their clinical practice if there is an efficiently true discovery.

Background: Fragility analysis is a method of further characterizing outcomes in terms of the stability of statistical findings. This study assesses the statistical fragility of recent randomized controlled trials (RCTs) evaluating robotic-assisted versus conventional total knee arthroplasty (RA-TKA versus C-TKA)., Methods: We queried PubMed for RCTs comparing alignment, function, and outcomes between RA-TKA and C-TKA. Fragility index (FI) and reverse fragility index (RFI) (collectively, "FI") were calculated for dichotomous outcomes as the number of outcome reversals needed to change statistical significance. Fragility quotient (FQ) was calculated by dividing the FI by the sample size for that outcome event. Median FI and FQ were calculated for all outcomes collectively as well as for each individual outcome. Subanalyses were performed to assess FI and FQ based on outcome event type and statistical significance, as well as study loss to follow-up and year of publication., Results: The overall median FI was 3.0 (interquartile range, [IQR] 1.0 to 6.3) and the median reverse fragility index was 3.0 (IQR 2.0 to 4.0). The overall median FQ was 0.027 (IQR 0.012 to 0.050). Loss to follow-up was greater than FI for 23 of the 38 outcomes assessed., Conclusions: A small number of alternative outcomes is often enough to reverse the statistical significance of findings in RCTs evaluating dichotomous outcomes in RA-TKA versus C-TKA. We recommend reporting FI and FQ alongside P values to improve the interpretability of RCT results., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Reverse total shoulder arthroplasty (RTSA) has seen increasing utilization as an effective intervention for a wide variety of shoulder pathologies. The scope and indications for growth are often driven by findings from randomized controlled trials (RCTs) guiding surgical decision-making for RTSA. In this study, we utilized the fragility index (FI), reverse fragility index (rFI), and fragility quotient (FQ) to assess the robustness of outcomes reported in RCTs in the RTSA literature., Methods: PubMed, Embase, and MEDLINE were queried for RCTs (Jan. 1, 2010-Mar. 31, 2023) in the RTSA literature reporting dichotomous outcomes. The FI and rFI were defined as the number of outcome reversals required to alter statistical significance for significant and nonsignificant outcomes, respectively. The FQ was determined by dividing the FI by the sample size of each study. Subgroup analysis was performed based on outcome category., Results: One hundred seventy-six RCTs were screened with 18 studies included. The median FI across 59 total outcomes was 4 (interquartile range [IQR]: 3-5) with an associated FQ of 0.051 (IQR: 0.029-0.065). Thirteen outcomes were statistically significant with a median FI of 3 (IQR: 1-4) and FQ of 0.033 (IQR: 0.012-0.066). Forty-six outcomes were nonsignificant with a median rFI of 4 (IQR: 3-5) and FQ of 0.055 (IQR: 0.032-0.065). The most fragile outcome category was revision/reoperations with a median FI of 2.50 (IQR: 1.00-3.25), followed by clinical score/outcome (median FI: 3.00), complications (median FI: 4.00), "other" (median FI: 4.00), and radiographic findings (median FI: 5.00). Notably, the number of patients lost to follow-up was greater than or equal to the FI for 59% of outcomes., Conclusion: The statistical findings in RTSA RCTs are fragile and should be interpreted with caution. Reversal of only a few outcomes, or maintaining postoperative follow-up, may be sufficient to alter significance of study findings. We recommend standardized reporting of P values with FI and FQ metrics to allow clinicians to effectively assess the robustness of study findings., (Copyright © 2024 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Purpose: This study employs both the fragility index (FI) and fragility quotient (FQ) to assess the level of robustness in the cervical disc arthroplasty (CDA) literature. We hypothesize that dichotomous outcomes involving CDA would exhibit statistical vulnerability., Methods: A PubMed search was conducted to evaluate dichotomous data for randomized controlled trials (RCTs) in CDA literature from 2000 to 2023. The FI of each outcome was calculated through the reversal of a single outcome event until significance was reversed. The FQ was calculated by dividing each fragility index by the study sample size. The interquartile range (IQR) was also calculated for the FI and FQ., Results: Of the 1561 articles screened, 111 met the search criteria, with 35 RCTs evaluating CDA included for analysis. Six hundred and ninety-three outcome events with 130 significant (P < 0.05) outcomes and 563 nonsignificant (P ≥ 0.05) outcomes were identified. The overall FI and FQ for all 693 outcomes were 5 (IQR 3-7) and 0.019 (IQR 0.011-0.043). Fragility analysis of statistically significant outcomes and nonsignificant outcomes both revealed an FI of 5. All of the studies reported loss to follow-up (LTF) data where 65.7% (23) did not report or reported an LTF greater or equal to 5., Conclusions: The literature regarding CDA RCTs lacks statistical robustness and may misrepresent the conclusions with the sole use of the P value. By implementing the FI and FQ along with the P value, we believe the interpretation and contextualization of the clinical data surrounding CDA will be better understood., (© 2024. The Author(s).)

Background: Recently, there has been significant interest in, and adoption of, total neoadjuvant therapy (TNT) for locally advanced rectal cancer (LARC). We designed the present study to assess the robustness of the randomized controlled trials (RCTs) evaluating contemporary TNTs for LARC using the fragility index (FI)., Materials and Methods: Relevant articles were identified through a review article by Johnson et al. in the Canadian Journal of Surgery. Dichotomous outcomes within these RCTs were eligible for inclusion if the reported effect size had a p-value < 0.05. The main outcome was FI for each included outcome. Walsh et al.'s method of calculating FI was utilized. Correlations between FI and research characteristics were assessed using the Spearman's rank correlation coefficients. Risk of bias was assessed using Cochrane recommended tools., Results: Ten RCTs were identified with 25 outcomes having statistically significant differences between groups. Eleven outcomes were time-to-event outcomes, while the remainder were dichotomous outcomes. Approximately half (n = 13) were oncologic outcomes. The median FI was 2 (interquartile range [IQR] 1-16). The number of patients lost to follow-up exceeded the FI in 17 outcomes (68.0 %) and thus these results were considered "fragile". Lower FI was associated with high risk of bias (rho = -0.5594) and greater loss to follow-up (rho = -0.4394), while higher FI was associated with large study size (rho = 0.5120)., Conclusions: The robustness of outcomes from trials assessing TNT for LARC was found to be questionable. Most outcomes were fragile, as determined by the FI. This survey is limited by the number of included studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The fragility index is a statistical measure of the robustness or "stability" of a statistically significant result. It has been adapted to assess the robustness of statistically significant outcomes from randomized controlled trials. By hypothetically switching some non-responders to responders, for instance, this metric measures how many individuals would need to have responded for a statistically significant finding to become non-statistically significant. The purpose of this study is to assess the fragility index of randomized controlled trials evaluating opioid substitution and antagonist therapies for opioid use disorder. This will provide an indication as to the robustness of trials in the field and the confidence that should be placed in the trials' outcomes, potentially identifying ways to improve clinical research in the field. This is especially important as opioid use disorder has become a global epidemic, and the incidence of opioid related fatalities have climbed 500% in the past two decades., Methods: Six databases were searched from inception to September 25, 2021, for randomized controlled trials evaluating opioid substitution and antagonist therapies for opioid use disorder, and meeting the necessary requirements for fragility index calculation. Specifically, we included all parallel arm or two-by-two factorial design RCTs that assessed the effectiveness of any opioid substitution and antagonist therapies using a binary primary outcome and reported a statistically significant result. The fragility index of each study was calculated using methods described by Walsh and colleagues. The risk of bias of included studies was assessed using the Revised Cochrane Risk of Bias tool for randomized trials., Results: Ten studies with a median sample size of 82.5 (interquartile range (IQR) 58, 179, range 52-226) were eligible for inclusion. Overall risk of bias was deemed to be low in seven studies, have some concerns in two studies, and be high in one study. The median fragility index was 7.5 (IQR 4, 12, range 1-26)., Conclusions: Our results suggest that approximately eight participants are needed to overturn the conclusions of the majority of trials in opioid use disorder. Future work should focus on maximizing transparency in reporting of study results, by reporting confidence intervals, fragility indexes, and emphasizing the clinical relevance of findings., Trial Registration: PROSPERO CRD42013006507. Registered on November 25, 2013., (© 2024. The Author(s).)

Background: There is a lack of consensus in the use of open reduction internal fixation (ORIF) vs primary arthrodesis (PA) in the management of Lisfranc injuries. Statistical fragility represents the number of events needed to flip statistical significance and provides context to interpret P values of outcomes from conflicting studies. The current study evaluates the statistical fragility of existing research with an outcome-specific approach to provide statistical clarity to the ORIF vs PA discussion. We hypothesized that statistical fragility analysis would offer clinically relevant insight when interpreting conflicting outcomes regarding ORIF vs PA management of Lisfranc injuries., Methods: All comparative studies, RCTs, and case-series investigating ORIF vs PA management of Lisfranc injuries published through October 5, 2023, were identified. Descriptive characteristics, dichotomous outcomes, and continuous outcomes were extracted. Fragility index and continuous fragility index were calculated by the number of event reversals needed to alter significance. Outcomes were categorized by clinical relevance, and median FI and CFI were reported., Results: A total of 244 studies were screened. Ten studies and 67 outcomes (44 dichotomous, 23 continuous) were included in the fragility analysis. Of the 10 studies, 4 studies claimed PA to correlate with superior outcomes compared to ORIF with regard to functional scores and return to function outcomes. Of these 4 studies, 3 were statistically robust. Six studies claimed PA and ORIF to have no differences in outcomes, in which only 2 studies were statistically robust., Conclusion: The overall research regarding ORIF vs PA is relatively robust compared with other orthopaedic areas of controversy. Although the full statistical context of each article must be considered, studies supporting PA superiority with regard to functional scores and return to function metrics were found to be statistically robust. Outcome-specific analysis revealed moderate fragility in several clinically relevant outcomes such as functional score, return to function, and wound complications., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Disclosure forms for all authors are available online.

Background: Acellular dermal matrix (ADM) is commonly used in plastic and reconstructive surgery. With the abundance of randomized controlled trials (RCTs) reporting P-values for ADM outcomes, this study used the fragility index (FI), reverse fragility index (rFI), and fragility quotient (FQ) to evaluate the statistical stability of the outcomes in ADM RCTs., Methods: PubMed, Embase, SCOPUS, Medline, and Cochrane databases were reviewed for ADM RCTs (2003-present) reporting a dichotomous, categorical outcome. FI and rFI (event reversals influencing outcome significance) and FQ (standardized fragility) were calculated and reported as median. Subgroup analysis was performed based on intervention types., Results: Among the 127 studies screened, 56 RCTs with 579 outcomes were included. The median FI stood at 4 (3-5) and FQ was 0.04 (0.03-0.07). Only 101 outcomes were statistically significant with a median FI of 3 (1-6) and FQ of 0.04 (0.02-0.08). The nonsignificant outcomes had a median FI of 4 (3-5) and FQ of 0.04 (0.03-0.07). Notably, 26% of the outcomes had several patients lost to follow up equal to or surpassing the FI. Based on the intervention type, the median FIs showed minor fluctuations but remained low., Conclusions: Outcomes from ADM-related RCTs were statistically fragile. Slight outcome reversals or maintenance of patient follow-up can alter the significance of results. Therefore, future researchers are recommended to jointly report FI, FQ, and P-values to offer a comprehensive view of the robustness in ADM literature., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Introduction: Biologics and small molecules have been increasingly applied in Crohn's disease (CD) and ulcerative colitis (UC). But the robustness of their trials has not been evaluated., Methods: We initially collected all the approved biologics or small molecules for CD or UC up to December 1, 2022. Databases were then queried by keywords in chemical name and CD or UC. Randomized controlled trials (RCTs) in the two-arm, 1:1 design were included. Fragility index (FI) and fragility quotient (FQ) were subsequently calculated., Results: We included twenty-eight RCTs, including nine pivotal trials listed in approval labels, nineteen non-pivotal trials not included in the labels. The median sample size was 99 [IQR, 60-262] and the median number of loss-of-follow-up (LFU) was 14 [IQR, 8-43]. Pivotal trials in the labels had the median FI of 8 [IQR, 4-14, n = 6] that was marginally higher than non-pivotal trials (3 [IQR, 2-4], p = 0.08). The median FQ was 0.0330 [IQR, 0.1220-0.0466] and 0.0310 [IQR, 0.0129-0.0540] for pivotal and non-pivotal trials, respectively (p = 1.0). The sample size and FI were significantly correlated (Spearman correlation coefficient [r] = 0.56, 95 %CI 0.21-0.78, p = 0.003). The number of total events was also significantly correlated with FI (r = 0.53, 95 %CI 0.17-0.77, p = 0.006). Study p-values were significantly associated with FI (p = 0.01): trials with p-values < 0.001 had the highest median FI of 10 [IQR, 6-17]. No factor was found strongly correlated with FQ., Conclusion: Results from trials assessing administration-approved biologics or small molecules for treating CD or UC were vulnerable to small changes by measuring FI or FQ. Pivotal studies contributing to regulatory approvals exhibited a relatively higher degree of resilience compared to non-pivotal trials., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: This systematic review and meta-analysis aimed to conduct a thorough and contemporary assessment of maternal and neonatal outcomes associated with water birth in comparison with land-based birth., Data Sources: We conducted a comprehensive search of PubMed, EMBASE, CINAHL, and gray literature sources, from inception to February 28, 2023., Study Eligibility Criteria: We included randomized and nonrandomized studies that assessed maternal and neonatal outcomes in patients who delivered either conventionally or while submerged in water., Methods: Pooled unadjusted odds ratios with 95% confidence intervals were calculated using a random-effects model (restricted maximum likelihood method). We assessed the 95% prediction intervals to estimate the likely range of future study results. To evaluate the robustness of the results, we calculated fragility indices. Maternal infection was designated as the primary outcome, whereas postpartum hemorrhage, perineal lacerations, obstetrical anal sphincter injury, umbilical cord avulsion, low Apgar scores, neonatal aspiration requiring resuscitation, neonatal infection, neonatal mortality within 30 days of birth, and neonatal intensive care unit admission were considered secondary outcomes., Results: Of the 20,642 articles identified, 52 were included in the meta-analyses. Based on data from observational studies, water birth was not associated with increased probability of maternal infection compared with land birth (10 articles, 113,395 pregnancies; odds ratio, 0.93; 95% confidence interval, 0.76-1.14). Patients undergoing water birth had decreased odds of postpartum hemorrhage (21 articles, 149,732 pregnancies; odds ratio, 0.80; 95% confidence interval, 0.68-0.94). Neonates delivered while submerged in water had increased odds of cord avulsion (10 articles, 91,504 pregnancies; odds ratio, 1.75; 95% confidence interval, 1.38-2.24) and decreased odds of low Apgar scores (21 articles, 165,917 pregnancies; odds ratio, 0.69; 95% confidence interval, 0.58-0.82), neonatal infection (15 articles, 53,635 pregnancies; odds ratio, 0.64; 95% confidence interval, 0.42-0.97), neonatal aspiration requiring resuscitation (19 articles, 181,001 pregnancies; odds ratio, 0.60; 95% confidence interval, 0.43-0.84), and neonatal intensive care unit admission (30 articles, 287,698 pregnancies; odds ratio, 0.56; 95% confidence interval, 0.45-0.70)., Conclusion: When compared with land birth, water birth does not appear to increase the risk of most maternal and neonatal complications. Like any other delivery method, water birth has its unique considerations and potential risks, which health care providers and expectant parents should evaluate thoroughly. However, with proper precautions in place, water birth can be a reasonable choice for mothers and newborns, in facilities equipped to conduct water births safely., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: The fragility index (FI) measures the robustness of statistically significant findings in randomized controlled trials (RCTs) by quantifying the minimum number of event conversions required to reverse a dichotomous outcome's statistical significance. In vascular surgery, many clinical guidelines and critical decision-making points are informed by a handful of key RCTs, especially regarding open surgical versus endovascular treatment. The objective of this study is to evaluate the FI of RCTs with statistically significant primary outcomes that compared open vs endovascular surgery in vascular surgery., Methods: In this meta-epidemiological study and systematic review, MEDLINE, Embase, and CENTRAL were searched for RCTs comparing open versus endovascular treatments for abdominal aortic aneurysms, carotid artery stenosis, and peripheral arterial disease to December 2022. RCTs with statistically significant primary outcomes were included. Data screening and extraction were conducted in duplicate. The FI was calculated by adding an event to the group with the smaller number of events while subtracting a nonevent to the same group until Fisher's exact test produced a nonstatistically significant result. The primary outcome was the FI and proportion of outcomes where the loss to follow-up was greater than the FI. The secondary outcomes assessed the relationship of the FI to disease state, presence of commercial funding, and study design., Results: Overall, 5133 articles were captured in the initial search with 21 RCTs reporting 23 different primary outcomes being included in the final analysis. The median FI (first quartile, third quartile) was 3 (3, 20) with 16 outcomes (70%) reporting a loss to follow-up greater than its FI. Mann-Whitney U test revealed that commercially funded RCTs and composite outcomes had greater FIs (median, 20.0 [5.5, 24.5] vs median, 3.0 [2.0, 5.5], P = .035; median, 21 [8, 38] vs median, 3.0 [2.0, 8.5], P = .01, respectively). The FI did not vary between disease states (P = .285) or between index and follow-up trials (P = .147). There were significant correlations between the FI and P values (Pearson r = 0.90; 95% confidence interval, 0.77-0.96), and the number of events (r = 0.82; 95% confidence interval, 0.48-0.97)., Conclusions: A small number of event conversions (median, 3) are needed to alter the statistical significance of primary outcomes in vascular surgery RCTs evaluating open surgical and endovascular treatments. Most studies had loss to follow-up greater than its FI, which can call into question trial results, and commercially funded studies had a greater FI. The FI and these findings should be considered in future trial design in vascular surgery., (Copyright © 2023 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Fragility analysis supplements the p -value and risk of bias assessment in the interpretation of results of randomised controlled trials. In this systematic review we determine the fragility index (FI) and fragility quotient (FQ) of randomised trials in aneurysmal subarachnoid haemorrhage., Methods: This is a systematic review registered with PROSPERO (ID: CRD42020173604). Randomised controlled trials in adults with aneurysmal subarachnoid haemorrhage were analysed if they reported a statistically significant primary outcome of mortality, function (e.g. modified Rankin Scale), vasospasm or delayed neurological deterioration., Results: We identified 4825 records with 18 randomised trials selected for analysis. The median fragility index was 2.5 (inter-quartile range 0.25-5) and the median fragility quotient was 0.015 (IQR 0.02-0.039). Five of 20 trial outcomes (25%) had a fragility index of 0. In seven trials (39.0%), the number of participants lost to follow-up was greater than or equal to the fragility index. Only 16.7% of trials are at low risk of bias., Conclusion: Randomised controlled trial evidence supporting management of aneurysmal subarachnoid haemorrhage is weaker than indicated by conventional analysis using p -values alone. Increased use of fragility analysis by clinicians and researchers could improve the translation of evidence to practice., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Intensive Care Society 2023.)

Introduction: The purpose of this study was to utilize the fragility index to assess the robustness of randomized controlled trials (RCTs) evaluating the management of calcaneus fractures. We hypothesize that the dichotomous outcomes in calcaneus fracture literature will be statistically fragile and comparable to other orthopedic specialties., Methods: We performed a PubMed search for calcaneus fracture RCTs from 2000 to 2022 using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The fragility index (FI) of each outcome was calculated through the reversal of a single outcome event until significance was reversed. The fragility quotient (FQ) was calculated by dividing each fragility index by study sample size. The interquartile range (IQR) was also calculated for the FI and FQ., Results: Of the 3003 studies screened, 97 met the search criteria, with 19 RCTs evaluating calcaneus fractures included in the analysis. Seventy-nine dichotomous outcomes with 30 significant (P < 0.05) outcomes and 49 with nonsignificant (P> 0.05) outcomes were identified. The overall FI and FQ of all outcomes were 6 (IQR 3-8) and 0.067 (IQR 0.032-0.100), respectively., Conclusions: The literature surrounding calcaneus fractures may not be as statistically stable as previously thought. The sole reliance on the P value may depict misleading results. We, therefore, recommend reporting the P value in conjunction with the FI and FQ to give a robust contextualization of clinical findings in the calcaneus fracture literature., Competing Interests: Declaration of Competing Interest The authors did not receive support from any organization for the submitted work. Michael Megafu MPH, Hassan Mian MBA, Emmanuel Megafu BA, Sulabh Singhal BS, Katrina Nietsch MS, Avanish Yendluri BS, have no relevant financial or non-financial interests to disclose. Robert L. Parisien, MD has received grant support, hospitality, financial or material support from Anthrex Inc. Robert Parisien services committee roles and editorial roles on the following boards: American Orthopaedic Society for Sports Medicine, American Orthopaedic Society for Sports Medicine, Arthroscopy Association of North America, Arthroscopy Association of North America, Society of Military Orthopaedic Surgeons, Journal of Cartilage & Joint Preservation, Arthroscopy, Arthroscopy, Sports Medicine and Rehabilitation and Journal of Sport Rehabilitation. Paul Tornetta III, MD has received publishing royalties, financial and material from Wolters Kluwer Health – Lippincott Williams & Wilkins. Paul Tornetta III, MD also receives royalties from Smith & Nephew. Paul Tornetta III, MD is currently on the editorial and governing board for the Journal of Orthopedic Trauma. No animals or humans were used in this study and the Institutional Review Board was not notified due to the nature of the article., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: To identify and assess the clinical impact of randomised controlled trials (RCTs) assessing the surgical management of femoroacetabular impingement syndrome (FAIS) through a citation analysis., Methods: MEDLINE, EMBASE and CENTRAL were searched from inception to April 22, 2023 for RCTs assessing the surgical management of FAIS. Study characteristics were directly abstracted from included trials and citation metrics were obtained from the Clarivate Web of Knowledge database on May 19, 2023. The continuous fragility index (CFI) was calculated for eligible outcomes. Univariate regression models were used to explore correlations between total citations per year and various study characteristics., Results: Ten studies comprising one thousand two hundred ninetypatients were eligible for analysis. Studies were published from 2013 to 2023. Eight countries were represented across various trials with 91% being either North American or European. The mean journal impact factor of published studies was 39.684 (median 2.982; range 1.31-202.73). The mean citation density was 14.17 (range 0.33-48.67). The median CFI was 4.8 (range 1-32.2). Correlation analysis demonstrated strong and statistically significant correlations to study sample size (R = 0.75, p = 0.012), journal impact factor (R = 0.80, p = 0.006) and continuous fragility index (R = 0.95, p = 0.015)., Conclusion: Trials assessing the surgical management of FAIS present with a wide range of clinical uptake based on citation density and are published in journals of broadly variable impact factor. Despite promising citation metrics, high-quality evidence on arthroscopy for FAIS is limited to the United States and Europe with an unclear international impact. Future knowledge translation efforts are warranted to maximise the international uptake of evidence regarding arthroscopic management of FAIS., Level of Evidence: I., (© 2023. The Author(s) under exclusive licence to European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Purpose: To report the statistical stability of prospective clinical trials evaluating the effect of intramedullary reaming on rates of non-union in tibial fractures through calculation of the fragility metrics for non-union rates and all other dichotomous outcomes., Methods: Literature search was conducted for prospective clinical trials evaluating the effect of intramedullary reaming on non-union rates in tibial nailing. All dichotomous outcomes were extracted from the manuscripts. The fragility index (FI) and reverse fragility index (RFI) were calculated by determining the number of event reversals required for a statistically significant outcome to lose significance and vice-versa. The fragility quotient (FQ) and reverse fragility quotient (RFQ) were calculated by dividing the FI or RFI by the sample size, respectively. Outcomes were defined as "fragile" if the FI or RFI was found to be less than or equal to the number of patients lost to follow-up., Results: Literature search identified 579 results which produced ten studies meeting the criteria for review. There were 111 outcomes identified for analysis, of which 89 (80%) exhibited statistical fragility. For reported outcomes across the studies the median and mean FI was 2, the median FQ was 0.019, the mean FQ was 0.030, the median RFI was 4, the mean RFI was 3.95, the median RFQ was 0.045, and the mean RFQ was 0.030. Four studies reported outcomes which were found to have an FI of 0., Conclusions: The studies evaluating the effect of intramedullary reaming on tibial nail fixation demonstrate considerable fragility. On average, two event reversals for significant findings, and four event reversals for insignificant findings are sufficient to alter statistical significance., Level of Evidence: Level II, systematic review of Level I and Level II studies., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Objective: 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., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier Ltd.)

Background In biostatistics, assessing the fragility of research findings is crucial for understanding their clinical significance. This study focuses on the fragility index, unit fragility index, and relative risk index as measures to evaluate statistical fragility. The fragility indices assess the susceptibility of p-values to change significance with minor alterations in outcomes within a 2x2 contingency table. In contrast, the relative risk index quantifies the deviation of observed findings from therapeutic equivalence, the point at which the relative risk equals 1. While the fragility indices have intuitive appeal and have been widely applied, their behavior across a wide range of contingency tables has not been rigorously evaluated. Methods Using a Python software program, a simulation approach was employed to generate random 2x2 contingency tables. All tables under consideration exhibited p-values < 0.05 according to Fisher's exact test. Subsequently, the fragility indices and the relative risk index were calculated. To account for sample size variations, the indices were divided by the sample size to give fragility and risk quotients. A correlation matrix assessed the collinearity between each metric and the p-value. Results The analysis included 2,000 contingency tables with cell counts ranging from 20 to 480. Notably, the formulas for calculating the fragility indices encountered limitations when cell counts approached zero or duplicate cell counts hindered standardized application. The correlation coefficients with p-values were as follows: unit fragility index (-0.806), fragility index (-0.802), fragility quotient (-0.715), unit fragility quotient (-0.695), relative risk index (-0.403), and risk quotient (-0.261). Conclusion The fragility indices and fragility quotients demonstrated a strong correlation with p-values below 0.05, while the relative risk index and relative risk quotient exhibited a weak association with p-values below this threshold. This implies that the fragility indices offer limited additional information beyond the p-value alone. In contrast, the relative risk index and risk quotient exhibit independence from the p-value, indicating that they may provide important additional information about statistical fragility by evaluating the divergence of observed results from therapeutic equivalence, irrespective of the p-value-based statistical significance., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Heston et al.)

Background: Randomized clinical trials (RCTs) are considered the gold standard for evidence-based medicine. The Fragility Index (FI) is a tool to assess the robustness of RCT results. FI was validated for dichotomous outcomes and recent work expanded its use to continuous outcomes. Studying the robustness of RCTs in Pulmonary Arterial Hypertension (PAH) treatments is crucial due to the severity and mortality risks associated with this rare condition., Objectives: Analyze FI and Fragility quotient (FQ) of significant primary outcomes in PAH RCTs and study FI correlation with sample size and journal impact factor., Methods: FI and FQ calculation followed by Spearman correlation to assess the correlation between FI and sample size, and FI and impact factor., Results: The median sample size of the 21 trials was 202 patients (IQR 106-267), with 6 trials reporting primary outcomes as dichotomous and 15 reporting continuous primary outcomes. The median FI was 10 (IQR 3-20), and the median FQ was 0.044 (0.026-0.097). A moderate correlation was found between FI and sample size, with r = 0.56; P = 0.008 and FI and journal impact factor (r=0.50; P=0.019). The FI for continuous outcomes was similar to that for dichotomous outcomes., Conclusions: This study represents the first analysis of the FI and FQ of PAH treatment RCTs, and expands the use of FI to continuous outcomes in this context. The moderate correlation between FI and sample size suggests that increasing sample size alone is partially correlated to a higher FI. The similarity between FI for continuous and dichotomous outcomes supports the broader use of FI in PAH RCTs., Competing Interests: Declaration of Competing Interest none, (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: The P value is a widely used measure of statistical importance but has many drawbacks and limitations, one being that it does not reflect the robustness of the results of a clinical trial. The Fragility Index (FI) was developed as a measure of how many outcome events would need to change to nonevents to render a significant P value nonsignificant (P ≥ 0.05). The FI of trials from other medical specialties is typically < 5. We aimed to determine the FI of pediatric anesthesiology randomized controlled trials (RCT) and to test for association with various characteristics of the included trials., Methods: We conducted a comprehensive systematic search of high-impact anesthesia, surgical, and medical journals from the last 25 years for trials comparing an intervention between two groups with a statistically significant P value (< 0.05) for a dichotomous outcome. We also compared FI values for variables that reflect the quality and importance of a trial., Results: The median [interquartile range] FI was 3 [1-7] and correlated positively with the number of participants (r S = 0.41; P < 0.001) and events (r S = 0.42; P < 0.001), and negatively with the P value (r PB = -0.36; P < 0.001). Other measures of trial quality and impact or importance were not strongly associated with the FI., Conclusions: The FI of published trials in pediatric anesthesiology is similarly low as in other medical specialties. Larger trials with more events and P values ≤ 0.01 were associated with a higher FI., (© 2023. Canadian Anesthesiologists' Society.)

Purpose: The purpose of this study was to apply both the fragility index (FI) and fragility quotient (FQ) to evaluate the degree of statistical fragility in the distal femur fracture (DFF) literature. We hypothesized that the dichotomous outcomes within the DFF literature are statistically fragile., Methods: Using preferred reporting items for systematic reviews and meta-analyses, we performed a PubMed search for distal femur fractures clinical trials from 2000 to 2022 reporting dichotomous outcomes. The FI of each outcome was calculated through the reversal of a single outcome event until significance was reversed. The FQ was calculated by dividing each fragility index by study sample size. The interquartile range (IQR) was also calculated for the FI and FQ., Results: Of the 4258 articles screened, 92 met the search criteria, with eleven RCTs included for analysis. Ninety eight outcome events with 25 significant (P < 0.05) outcomes and 73 nonsignificant (P > 0.05) outcomes were identified. The overall FI and FQ for all 98 outcomes were 5 (IQR 4-6) and 0.130 (IQR 0.087-0.174), respectively. Three studies (33.3%) reported loss to follow (LTF) greater than 5., Conclusions: The randomized controlled trials in the peer-reviewed distal femur fracture literature may not be as robust as previously thought, as incorporating statistical analyses solely on a P value threshold is misleading. Standardized reporting of the P value, FI and FQ can help the clinician reliably draw conclusions based on the fragility of outcome measures., (© 2022. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Aim: The aim of this work was to evaluate the robustness of randomized controlled trials (RCTs) on anal fistula management using the news tools of Fragility Index (FI), Reverse Fragility Index (RFI) and their corresponding fragility quotients., Method: A systematic search was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines which utilized MEDLINE, EMBASE, Cochrane Library and Web of Science databases. Inclusion criteria included RCTs related to the management of anal fistula published from 2000 to 2022 with dichotomous outcomes measures and 1:1 allocation. Calculation of FI and RFI was performed by creating 2 × 2 contingency tables by successively changing one nonevent to an event for each outcome measure until the result was made nonsignificant or significant, respectively. The Fragility Quotients were calculated by dividing the FI or RFI by the total sample size. Fragile results were defined as those with a FI or RFI equal to or less than the number of patients lost to follow-up. Additionally, those with a FI or RFI less than 3 were also considered fragile. Studies were considered extremely fragile if FI was ≤1 or FQ was ≤0.01., Results: There were 36 RCTs that met our criteria, with 3223 patients. Among these, 19 (53%) were positive RCTs (p < 0.005) and 17 (47%) were negative RCTs (p > 0.05). The median FI was 2 (0-5). The analysis by categorical subgroup showed a strong correlation between FI and the p-value (p = 0.000) and the number of events (p = 0.011). The median RFI was 5 (3.5-9.5) and the subgroup analysis showed a strong correlation between RFI and the p-value (p = 0.000), sample size (0.021) and number needed to treat/number needed to harm (0.000). We considered 63.2% of positive RCTs to be fragile and 35.3% of negative RCTs., Conclusions: In the present study we demonstrated the lack of robustness of study findings in published RCTs in the field of anal fistula., (© 2023 Association of Coloproctology of Great Britain and Ireland.)

The Australian Placental Transfusion Study (APTS) randomised 1,634 fetuses to delayed (≥60 s) versus immediate (≤10 s) clamping of the umbilical cord. Systematic reviews with meta-analyses, including this and similar trials, show that delaying clamping in preterm infants reduces mortality and need for blood transfusions. Amongst 1,531 infants in APTS followed up at two years, aiming to delay clamping for 60 s or more reduced the relative risk of the primary composite outcome of death or disability by 17% (p = 0.01). However, this result is fragile because nominal statistical significance (p < 0.05) would be abolished by only 2 patients switching from a non-event to an event, and the primary composite outcome was missing in 112 patients (7%). To achieve more robust evidence, any future trials should emulate the large, simple trials co-ordinated from Oxford which reliably identified moderate, incremental improvements in mortality in tens of thousands of participants, with <1% missing data. Those who fund, regulate, and conduct trials that aim to change practice should repay the trust of those who consent to participate by doing everything possible to minimise missing data for key outcomes., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The purpose of this present study was to perform a fragility analysis to assess the robustness of randomized controlled trials (RCTs) evaluating the distal biceps tendon repairs. We hypothesize that the dichotomous outcomes will be statistically fragile, and higher fragility will exist among statistically significant outcomes comparable to other orthopedic specialties., Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), randomized controlled trials from 4 orthopedic journals indexed on PubMed from 2000 to 2022 reporting dichotomous measures relating to distal biceps tendon repairs were included. The fragility index (FI) of each outcome was calculated through the reversal of a single outcome event until significance was reversed. The fragility quotient (FQ) was calculated by dividing each fragility index by study sample size. The interquartile range (IQR) was also calculated for the FI and FQ., Results: Of the 1038 articles screened, 7 RCTs containing 24 dichotomous outcomes were included for analysis. The fragility index and fragility quotient of all outcomes was 6.5 (IQR 4-9) and 0.077 (IQR 0.031-0.123), respectively. However, statistically significant outcomes had a fragility index and fragility quotient of 2 (IQR 2-7) and 0.036 (IQR 0.025-0.091), respectively. The average number of patients lost to follow-up was 2.7 patients, with 28.6% of the included studies reporting loss to follow-up (LTF) greater than or equal to 6.5., Conclusions: The literature surrounding distal biceps tendon repair may not be as stable as previously thought and presents a similar fragility index to other orthopedic subspecialties. We therefore recommend triple reporting the P value, fragility index, and fragility quotient to aid in the interpretation of clinical findings reported in biceps tendon repair literature., (Copyright © 2023 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Background: Clinical decision-making often relies on evidence-based medicine, derived from objective data with conventional and rigorous statistical tests to evaluate significance. The literature surrounding rehabilitation after rotator cuff repair (RCR) is conflicting, with no defined standard of practice., Purpose: To determine the fragility index (FI) and the fragility quotient (FQ) of randomized controlled trials (RCTs) evaluating rehabilitation protocols after RCR., Study Design: Systematic review., Methods: A systematic review was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines by searching the PubMed, Cochrane Library, and Embase databases for RCTs evaluating rehabilitation protocols after arthroscopic RCRs from 2000 to June 1, 2022. The FI was determined by manipulating the dichotomous outcome events from each article until a reversal of significance with 2 × 2 contingency tables was achieved. The FQ was determined by dividing the FI by the sample size., Results: Fourteen RCTs with 48 dichotomous outcomes were ultimately included for analysis. The mean FI for the included dichotomous outcomes was 4 (interquartile range, 3-6), suggesting that the reversal of 4 events is required to change study significance. The mean FQ was 0.048. Of the RCTs that reported data regarding loss to follow-up, most studies (58.5%) indicated that >4 patients had been lost to follow-up., Conclusion: The results of RCT studies of RCR rehabilitation protocols are moderately fragile, something clinicians should be aware of when implementing study results into practice. We recommend the inclusion of FI and FQ in addition to standard P values when reporting statistical results in future RCTs with dichotomous outcome variables on this topic., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: M.A.W. has received education payments from Arthrex, Elite Orthopedics, Smith & Nephew, and Supreme Orthopedic Systems. A.M.M. has received education payments from Supreme Orthopedic Systems; consulting fees from Catalyst OrthoScience, DePuy/Medical Device Business Services, Globus Medical, Ignite Orthopedics, Stryker, and Zimmer Biomet; nonconsulting fees from Globus Medical; royalties from DePuy, Ignite Orthopedics, and Globus Medical; honoraria from Wright Medical; and has an investment interest in Ignite Orthopedics. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2023.)

Background: Debate centering on the management of anterior shoulder instability (ASI) in recent years has led to many randomized controlled trials (RCTs) being published on the topic. The fragility index (FI) has subsequently emerged as a novel method of assessing significant findings reported in RCTs, particularly those with small sample sizes., Purpose: To evaluate the FI of statistically significant findings in RCTs that reported the outcomes of management strategies of patients with ASI., Study Design: Systematic review; Level of evidence, 1., Methods: Using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, 2 independent reviewers performed a systematic review of RCTs focusing on the outcomes of management strategies of patients with ASI. There were 3 main categories of RCTs included: (1) nonoperative management in internal rotation (IR) versus external rotation (ER), (2) nonoperative management versus a surgical intervention, and (3) surgical management with arthroscopic Bankart repair versus open Bankart repair. The Fisher exact test was utilized to calculate the FI for the reversal of statistical significance in all statistically significant dichotomous outcomes., Results: A total of 21 RCTs were included, including 1589 shoulders (mean age, 29.4 years) with a mean follow-up of 26.8 months. There were 10 RCTs (831 shoulders) that reported outcomes after the nonoperative management of ASI in IR versus ER, with a mean FI of 6.8. There were 5 RCTs (324 shoulders) that reported outcomes comparing the nonoperative and operative management of ASI, with a mean FI of 3.5. There were 6 RCTs (434 shoulders) that reported outcomes after the operative management of ASI with either arthroscopic Bankart repair or open Bankart repair, with a mean FI of 9.6., Conclusion: The overall FI of RCTs reporting the outcomes of management strategies for patients with ASI was high, suggesting a moderate fragility of statistically significant outcomes including recurrence, revision stabilization, and return to play.

Aims: In randomized clinical trials (RCTs) rejecting the null hypothesis, the fragility index (FI) yields the minimum number of participants who would need to have had a different outcome for the results of the trial to become non-significant. We evaluated the robustness of RCTs supporting American College of Cardiology/American Heart Association (ACC/AHA) and European Society of Cardiology (ESC) clinical practice guidelines (CPGs) for ST-elevation myocardial infarction (STEMI) and non-ST-elevation acute coronary syndrome (NSTE-ACS) using the FI., Methods and Results: There were 407 RCTs among the 2128 studies cited in the 2013 and 2014 ACC/AHA and 2017 and 2020 ESC CPGs for STEMI and NSTE-ACS, respectively. The FI could be calculated in 132 RCTs (32.4%) meeting the needed criteria for its estimation (two-arm RCT, 1:1 allocation, binary outcome, P < 0.05). The median FI was 12 (interquartile range: 4-29). Hence, a change in the outcome status of 12 patients would be needed to reverse the statistical significance of the primary endpoint in 50% of the RCTs. The FI was ≤1% than their sample size in 55.7% RCTs, whereas in 47% of RCTs, the FI was lower than the number of patients lost to follow-up. Some study design features were associated with a higher FI (international, multicentre, private funding; all P < 0.05), whilst baseline patient characteristics were not substantially different by FI (e.g. age, female sex, white study participants; all P > 0.05), except for geographic enrolment (P = 0.042)., Conclusion: The FI might be useful to evaluate the robustness of those RCTs with statistically significant findings for the primary endpoint that have an impact on key guideline recommendations., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Utility of robotic over laparoscopic approach has been an area of debate across all surgical specialties over the past decade. The fragility index (FI) is a metric that evaluates the frailty of randomized controlled trials (RCTs) findings by altering the status of patients from an event to non-event until significance is lost. This study aims to evaluate the robustness of RCTs comparing laparoscopic and robotic abdominopelvic surgeries through the FI., Methods: A search was conducted in MEDLINE and EMBASE for RCTs with dichotomous outcomes comparing laparoscopic and robot-assisted surgery in general surgery, gynecology, and urology. The FI and reverse fragility Index (RFI) metrics were used to assess the strength of findings reported by RCTs, and bivariate correlation was conducted to analyze relationships between FI and trial characteristics., Results: A total of 21 RCTs were included, with a median sample size of 89 participants (Interquartile range [IQR] 62-126). The median FI was 2 (IQR 0-15) and median RFI 5.5 (IQR 4-8.5). The median FI was 3 (IQR 1-15) for general surgery (n = 7), 2 (0.5-3.5) for gynecology (n = 4), and 0 (IQR 0-8.5) for urology RCTs (n = 4). Correlation was found between increasing FI and decreasing p-value, but not sample size, number of outcome events, journal impact factor, loss to follow-up, or risk of bias., Conclusion: RCTs comparing laparoscopic and robotic abdominal surgery did not prove to be very robust. While possible advantages of robotic surgery may be emphasized, it remains novel and requires further concrete RCT data., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

BackgroundVaccines play a crucial role in the response to COVID-19 and their efficacy is thus of great importance.AimTo assess the robustness of COVID-19 vaccine efficacy (VE) trial results using the fragility index (FI) and fragility quotient (FQ) methodology.MethodsWe conducted a Cochrane and PRISMA-compliant systematic review and meta-analysis of COVID-19 VE trials published worldwide until 22 January 2023. We calculated the FI and FQ for all included studies and assessed their associations with selected trial characteristics using Wilcoxon rank sum tests and Kruskal-Wallis H tests. Spearman correlation coefficients and scatter plots were used to quantify the strength of correlation of FIs and FQs with trial characteristics.ResultsOf 6,032 screened records, we included 40 trials with 54 primary outcomes, comprising 909,404 participants with a median sample size per outcome of 13,993 (interquartile range (IQR): 8,534-25,519). The median FI and FQ was 62 (IQR: 22-123) and 0.50% (IQR: 0.24-0.92), respectively. FIs were positively associated with sample size (p < 0.001), and FQs were positively associated with type of blinding (p = 0.023). The Spearman correlation coefficient for FI with sample size was moderately strong (0.607), and weakly positive for FI and FQ with VE (0.138 and 0.161, respectively).ConclusionsThis was the largest study on trial robustness to date. Robustness of COVID-19 VE trials increased with sample size and varied considerably across several other important trial characteristics. The FI and FQ are valuable complementary parameters for the interpretation of trial results and should be reported alongside established trial outcome measures.

Purpose: The fragility index (FI) measures the robustness of randomized controlled trials (RCTs). It complements the P value by taking into account the number of outcome events. In this study, the authors measured the FI for major interventional radiology RCTs., Methods: Interventional radiology RCTs published between January 2010 and December 2022 relating to trans-jugular intrahepatic portosystemic shunt, trans-arterial chemoembolization, needle biopsy, angiography, angioplasty, thrombolysis, and nephrostomy tube insertion were analyzed to measure the FI and robustness of the studies., Results: A total of 34 RCTs were included. The median FI of those studies was 4.5 (range 1-68). Seven trials (20.6%) had a number of patients lost to follow-up that was higher than their FI, and 15 (44.1%) had a FI of 1-3., Conclusion: The median FI, and hence the reproducibility of interventional radiology RCTs, is low compared to other medical fields, with some having a FI of 1, which should be interrupted cautiously.