Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Knee Surgery, Sports Traumatology, Arthroscopy
Published in: Knee Surgery, Sports Traumatology, Arthroscopy 8/2023

24-04-2023 | KNEE

The reverse fragility index: RCTs reporting non-significant differences in failure rates between hamstring and bone–patellar tendon–bone autografts have fragile results

Authors: Verdinand C. B. Ruelos, Raisa Masood, Richard N. Puzzitiello, Michael A. Moverman, Nicholas R. Pagani, Mariano E. Menendez, Matthew J. Salzler

Published in: Knee Surgery, Sports Traumatology, Arthroscopy | Issue 8/2023

Login to get access

Abstract

Purpose

The reverse fragility index (RFI) is a novel metric to appraise the results of studies reporting statistically non-significant results. The purpose of this study was to determine the statistical robustness of randomized controlled trials (RCTs) reporting non-significant differences in anterior cruciate ligament reconstruction (ACLR) graft failure rates, defined as re-rupture/revision ACLR rate, between hamstring tendon (HT) and bone–patellar tendon–bone (BTB) autografts by calculating RFIs.

Methods

A systematic review was performed to identify RCTs that compared HT to BTB grafts for ACLR through January 2022. Studies reporting non-significant differences in graft re-rupture and revision ACLR rate (n.s.) were included. The RFI, defined as the fewest number of event reversals needed to change the non-significant graft re-rupture/revision outcome to statistically significant (P < 0.05), was recorded for each study. In addition, the number of studies in which the loss to follow-up exceeded the RFI was recorded.

Results

Among the 16 included RCTs, the median (interquartile range [IQR]) sample size was 71 (64–114), and the median (IQR) total number of graft re-rupture/revision ACLR events was 4 (4–6). The median (IQR) graft re-rupture/revision ACLR rate was 4.3% (3.0–6.4) overall, 4.1% (2.6–6.7) in the BTB group, and 5.4% (3.0–6.3) in the HT group. The median (IQR) RFI was 3 (3–4), signifying that a reversal of the outcome in 3 patients in one arm was needed to flip the studies’ result from non-significant to statistically significant (P < 0.05). The median (IQR) number of participants lost to follow-up was 11 (3–13), and 13 (81.3%) of the included studies had a loss to follow-up greater than the studies’ RFI.

Conclusion

The results of RCTs reporting statistically non-significant re-rupture/revision ACLR rates between HT and BTB autografts would become significant if the outcome were reversed in a small number of patients—a number that was less than the loss to follow-up in the majority of studies. Thus, the neutrality of these studies is fragile, and a true statistically significant difference in re-rupture/revision rates may have been undetected.

Level of evidence

Level I.
Literature
1.
Ahmed W, Fowler RA, McCredie VA (2016) Does sample size matter when interpreting the fragility index? Crit Care Med 44(11):e1142–e1143PubMedCrossRef
2.
Aune AK, Holm I, Risberg MA, Jensen HK, Steen H (2001) Four-strand hamstring tendon autograft compared with patellar tendon-bone autograft for anterior cruciate ligament reconstruction. A randomized study with two-year follow-up. Am J Sports Med 29(6):722–728PubMedCrossRef
3.
Barenius B, Nordlander M, Ponzer S, Tidermark J, Eriksson K (2010) Quality of life and clinical outcome after anterior cruciate ligament reconstruction using patellar tendon graft or quadrupled semitendinosus graft: an 8-year follow-up of a randomized controlled trial. Am J Sports Med 38(8):1533–1541PubMedCrossRef
4.
Biau DJ, Tournoux C, Katsahian S, Schranz PJ, Nizard RS (2006) Bone-patellar tendon-bone autografts versus hamstring autografts for reconstruction of anterior cruciate ligament: meta-analysis. BMJ 332(7548):995–1001PubMedPubMedCentralCrossRef
5.
Björnsson H, Samuelsson K, Sundemo D, Desai N, Sernert N, Rostgård-Christensen L, Karlsson J, Kartus J (2016) A randomized controlled trial with mean 16-year follow-up comparing hamstring and patellar tendon autografts in anterior cruciate ligament reconstruction. Am J Sports Med 44(9):2304–2313PubMedCrossRef
6.
Bowman EN, Limpisvasti O, Cole BJ, ElAttrache NS (2021) Anterior cruciate ligament reconstruction graft preference most dependent on patient age: a survey of United States surgeons. Arthroscopy 37(5):1559–1566PubMedCrossRef
7.
Ciccotti MC, Secrist E, Tjoumakaris F, Ciccotti MG, Freedman KB (2017) Anatomic anterior cruciate ligament reconstruction via independent tunnel drilling: a systematic review of randomized controlled trials comparing patellar tendon and hamstring autografts. Arthroscopy 33(5):1062-1071.e5PubMedCrossRef
8.
9.
DeFazio MW, Curry EJ, Gustin MJ, Sing DC, Abdul-Rassoul H, Ma R, Fu F, Li X (2020) Return to sport after ACL reconstruction with a BTB versus hamstring tendon autograft: a systematic review and meta-analysis. Orthop J Sports Med 8(12):2325967120964919PubMedPubMedCentralCrossRef
10.
Drogset JO, Strand T, Uppheim G, Odegård B, Bøe A, Grøntvedt T (2010) Autologous patellar tendon and quadrupled hamstring grafts in anterior cruciate ligament reconstruction: a prospective randomized multicenter review of different fixation methods. Knee Surg Sports Traumatol Arthrosc 18(8):1085–1093PubMedCrossRef
11.
Ehlers CB, Curley AJ, Fackler NP, Minhas A, Rodriguez AN, Pasko K, Chang ES (2021) The statistical fragility of single-bundle vs double-bundle autografts for ACL reconstruction: a systematic review of comparative studies. Orthop J Sports Med 9(12):232596712110646CrossRef
12.
Eriksson K, Anderberg P, Hamberg P, Olerud P, Wredmark T (2001) There are differences in early morbidity after ACL reconstruction when comparing patellar tendon and semitendinosus tendon graft. A prospective randomized study of 107 patients. Scand J Med Sci Sports 11(3):170–177PubMedCrossRef
13.
Fackler NP, Ehlers CB, Callan KT, Amirhekmat A, Smith EJ, Parisien RL, Wang D (2022) Statistical fragility of single-row versus double-row anchoring for rotator cuff repair: a systematic review of comparative studies. Orthop J Sports Med 10(5):23259671221093390CrossRef
14.
Fukuda H, Ogura T, Asai S, Omodani T, Takahashi T, Yamaura I, Sakai H, Saito C, Tsuchiya A, Takahashi K (2022) Bone-patellar tendon-bone autograft maturation is superior to double-bundle hamstring tendon autograft maturation following anatomical anterior cruciate ligament reconstruction. Knee Surg Sports Traumatol Arthrosc 30(5):1661–1671PubMedCrossRef
15.
Gifstad T, Foss OA, Engebretsen L, Lind M, Forssblad M, Albrektsen G, Drogset JO (2014) Lower risk of revision with patellar tendon autografts compared with hamstring autografts: a registry study based on 45,998 primary ACL reconstructions in Scandinavia. Am J Sports Med 42(10):2319–2328PubMedCrossRef
16.
Gifstad T, Sole A, Strand T, Uppheim G, Grøntvedt T, Drogset JO (2013) Long-term follow-up of patellar tendon grafts or hamstring tendon grafts in endoscopic ACL reconstructions. Knee Surg Sports Traumatol Arthrosc 21(3):576–583PubMedCrossRef
17.
Guglielmetti LGB, Salas VER, Jorge PB, Severino FR, Duarte A, de Oliveira VM, de Cury RPL (2021) Prospective and randomized clinical evaluation of hamstring versus patellar tendon autograft for anterior cruciate ligament reconstruction in soccer players. Orthop J Sports Med 9(9):23259671211028170CrossRef
18.
Gupta PK, Acharya A, Mourya A, Mahajan P (2019) Comparison of patellar tendon versus hamstrings autografts for anterior cruciate ligament reconstruction in Indian population: a randomised control trial study. J Clin Orthop Trauma 10(3):581–585PubMedCrossRef
19.
20.
Holm I, Øiestad BE, Risberg MA, Aune AK (2010) No difference in knee function or prevalence of osteoarthritis after reconstruction of the anterior cruciate ligament with 4-strand hamstring autograft versus patellar tendon—bone autograft: a randomized study with 10-year follow-up. Am J Sports Med 38(3):448–454PubMedCrossRef
21.
Jaecker V, Drouven S, Naendrup J-H, Kanakamedala AC, Pfeiffer T, Shafizadeh S (2018) Increased medial and lateral tibial posterior slopes are independent risk factors for graft failure following ACL reconstruction. Arch Orthop Trauma Surg 138(10):1423–1431PubMedCrossRef
22.
Kautzner J, Kos P, Hanus M, Trc T, Havlas V (2015) A comparison of ACL reconstruction using patellar tendon versus hamstring autograft in female patients: a prospective randomised study. Int Orthop 39(1):125–130PubMedCrossRef
23.
Khan MS, Fonarow GC, Friede T, Lateef N, Khan SU, Anker SD, Harrell FE, Butler J (2020) Application of the reverse fragility index to statistically nonsignificant randomized clinical trial results. JAMA Netw Open 3(8):e2012469PubMedPubMedCentralCrossRef
24.
Krebs NM, Barber-Westin S, Noyes FR (2021) Generalized joint laxity is associated with increased failure rates of primary anterior cruciate ligament reconstructions: a systematic review. Arthroscopy 37(7):2337–2347PubMedCrossRef
25.
Maldonado DR, Go CC, Huang BH, Domb BG (2021) The fragility index of hip arthroscopy randomized controlled trials: a systematic survey. Arthroscopy 37(6):1983–1989PubMedCrossRef
26.
McCormick KL, Tedesco LJ, Swindell HW, Forrester LA, Jobin CM, Levine WN (2021) Statistical fragility of randomized clinical trials in shoulder arthroplasty. J Shoulder Elbow Surg 30(8):1787–1793PubMedCrossRef
27.
Mouarbes D, Menetrey J, Marot V, Courtot L, Berard E, Cavaignac E (2019) Anterior cruciate ligament reconstruction: a systematic review and meta-analysis of outcomes for quadriceps tendon autograft versus bone-patellar tendon-bone and hamstring-tendon autografts. Am J Sports Med 47(14):3531–3540PubMedCrossRef
28.
Murray DW, Britton AR, Bulstrode CJ (1997) Loss to follow-up matters. J Bone Jt Surg Br 79(2):254–257CrossRef
29.
Norquist BM, Goldberg BA, Matsen FA (2000) Challenges in evaluating patients lost to follow-up in clinical studies of rotator cuff tears. J Bone Jt Surg Am 82(6):838–842CrossRef
30.
31.
Parisien RL, Trofa DP, Cronin PK, Dashe J, Curry EJ, Eichinger JK, Levine WN, Tornetta P, Li X (2021) Comparative studies in the shoulder literature lack statistical robustness: a fragility analysis. Arthrosc Sports Med Rehabil 3(6):e1899–e1904PubMedPubMedCentralCrossRef
32.
Poehling-Monaghan KL, Salem H, Ross KE, Secrist E, Ciccotti MC, Tjoumakaris F, Ciccotti MG, Freedman KB (2017) Long-term outcomes in anterior cruciate ligament reconstruction: a systematic review of patellar tendon versus hamstring autografts. Orthop J Sports Med 5(6):232596711770973CrossRef
33.
Ruzbarsky JJ, Khormaee S, Daluiski A (2019) The fragility index in hand surgery randomized controlled trials. J Hand Surg Am 44(8):698.e1-698.e7PubMedCrossRef
34.
Sajovic M, Strahovnik A, Dernovsek MZ, Skaza K (2011) Quality of life and clinical outcome comparison of semitendinosus and gracilis tendon versus patellar tendon autografts for anterior cruciate ligament reconstruction: an 11-year follow-up of a randomized controlled trial. Am J Sports Med 39(10):2161–2169PubMedCrossRef
35.
Sajovic M, Stropnik D, Skaza K (2018) Long-term comparison of semitendinosus and gracilis tendon versus patellar tendon autografts for anterior cruciate ligament reconstruction: a 17-year follow-up of a randomized controlled trial. Am J Sports Med 46(8):1800–1808PubMedCrossRef
36.
Sajovic M, Vengust V, Komadina R, Tavcar R, Skaza K (2006) A prospective, randomized comparison of semitendinosus and gracilis tendon versus patellar tendon autografts for anterior cruciate ligament reconstruction: five-year follow-up. Am J Sports Med 34(12):1933–1940PubMedCrossRef
37.
Salem HS, Varzhapetyan V, Patel N, Dodson CC, Tjoumakaris FP, Freedman KB (2019) Anterior cruciate ligament reconstruction in young female athletes: patellar versus hamstring tendon autografts. Am J Sports Med 47(9):2086–2092PubMedCrossRef
38.
Samuelsen BT, Webster KE, Johnson NR, Hewett TE, Krych AJ (2017) Hamstring autograft versus patellar tendon autograft for ACL reconstruction: is there a difference in graft failure rate? A meta-analysis of 47,613 patients. Clin Orthop Relat Res 475(10):2459–2468PubMedPubMedCentralCrossRef
39.
40.
Schuette HB, Kraeutler MJ, Houck DA, McCarty EC (2017) Bone-patellar tendon-bone versus hamstring tendon autografts for primary anterior cruciate ligament reconstruction: a systematic review of overlapping meta-analyses. Orthop J Sports Med 5(11):2325967117736484PubMedPubMedCentralCrossRef
41.
Shaieb MD, Kan DM, Chang SK, Marumoto JM, Richardson AB (2002) A prospective randomized comparison of patellar tendon versus semitendinosus and gracilis tendon autografts for anterior cruciate ligament reconstruction. Am J Sports Med 30(2):214–220PubMedCrossRef
42.
Shen X, Qin Y, Zuo J, Liu T, Xiao J (2021) A systematic review of risk factors for anterior cruciate ligament reconstruction failure. Int J Sports Med 42(8):682–693PubMedCrossRef
43.
Smith PA, Cook CS, Bley JA (2020) All-inside quadrupled semitendinosus autograft shows stability equivalent to patellar tendon autograft anterior cruciate ligament reconstruction: randomized controlled trial in athletes 24 years or younger. Arthroscopy 36(6):1629–1646PubMedCrossRef
44.
Svantesson E, HamrinSenorski E, Danielsson A, Sundemo D, Westin O, Ayeni OR, Samuelsson K (2020) Strength in numbers? The fragility index of studies from the Scandinavian knee ligament registries. Knee Surg Sports Traumatol Arthrosc 28(2):339–352PubMedCrossRef
45.
Tan SHS, Lau BPH, Krishna L (2019) Outcomes of anterior cruciate ligament reconstruction in females using patellar-tendon-bone versus hamstring autografts: a systematic review and meta-analysis. J Knee Surg 32(8):770–787PubMedCrossRef
46.
Taylor DC, DeBerardino TM, Nelson BJ, Duffey M, Tenuta J, Stoneman PD, Sturdivant RX, Mountcastle S (2009) Patellar tendon versus hamstring tendon autografts for anterior cruciate ligament reconstruction: a randomized controlled trial using similar femoral and tibial fixation methods. Am J Sports Med 37(10):1946–1957PubMedCrossRef
47.
Torrens C, Martínez R, Santana F (2022) Patients lost to follow-up in shoulder arthroplasty: descriptive characteristics and reasons. Clin Orthop Surg 14(1):112–118PubMedPubMedCentralCrossRef
48.
Walsh M, Srinathan SK, McAuley DF, Mrkobrada M, Levine O, Ribic C, Molnar AO, Dattani ND, Burke A, Guyatt G, Thabane L, Walter SD, Pogue J, Devereaux PJ (2014) The statistical significance of randomized controlled trial results is frequently fragile: a case for a fragility index. J Clin Epidemiol 67(6):622–628PubMedCrossRef
49.
Xie X, Xiao Z, Li Q, Zhu B, Chen J, Chen H, Yang F, Chen Y, Lai Q, Liu X (2015) Increased incidence of osteoarthritis of knee joint after ACL reconstruction with bone-patellar tendon-bone autografts than hamstring autografts: a meta-analysis of 1,443 patients at a minimum of 5 years. Eur J Orthop Surg Traumatol 25(1):149–159PubMedCrossRef
Metadata
Title
The reverse fragility index: RCTs reporting non-significant differences in failure rates between hamstring and bone–patellar tendon–bone autografts have fragile results
Authors
Verdinand C. B. Ruelos
Raisa Masood
Richard N. Puzzitiello
Michael A. Moverman
Nicholas R. Pagani
Mariano E. Menendez
Matthew J. Salzler
Publication date
24-04-2023
Publisher
Springer Berlin Heidelberg
Published in
Knee Surgery, Sports Traumatology, Arthroscopy / Issue 8/2023
Print ISSN: 0942-2056
Electronic ISSN: 1433-7347
DOI
https://doi.org/10.1007/s00167-023-07420-0

Other articles of this Issue 8/2023

Knee Surgery, Sports Traumatology, Arthroscopy 8/2023 Go to the issue

Knee

Mismatch between trochlear coronal alignment of arthritic knees and currently available prosthesis: a morphological analysis of 4116 knees and 45 implant designs

KNEE

Posterior rim loading of a low-conforming tibial insert in unrestricted kinematic alignment is caused by rotational alignment of an asymmetric baseplate designed for mechanical alignment

Knee

Favorable rates of return to activity and work following lateral closing wedge distal femoral osteotomy for femoral-based symptomatic varus malalignment: an analysis at a mean 6-year follow-up

Letter to the Editor

Response to letter to the editor of “posterior tibial plateau impaction fractures are not associated with increased knee instability: a quantitative pivot shift analysis”

KNEE

No difference in patient reported outcomes, laxity, and failure rate after revision ACL reconstruction with quadriceps tendon compared to hamstring tendon graft: a systematic review and meta-analysis

ANKLE

Favourable clinical, arthroscopic and radiographic outcomes after autologous osteoperiosteal transplantation for massive medial cystic osteochondral defects of the talus