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Team Physicians Corner

Anterior Cruciate Ligament and M


Knee Injury Prevention Programs
for Soccer Players
A Systematic Review and Meta-analysis
Nathan L. Grimm,*y MD, John C. Jacobs Jr,z BS, Jaewhan Kim, PhD,
Brandon S. Denney,z BS, and Kevin G. Shea,|| MD
Investigation performed at the Duke University Medical Center, Durham, North Carolina, USA

Background: Soccer has one of the highest incidences of anterior cruciate ligament (ACL) injuries for both males and females.
Several injury prevention programs have been developed to address this concern. However, an analysis of the pooled effect has
yet to be elicited.
Purpose: To conduct a systematic review and meta-analysis of ACL and knee injury prevention programs for soccer players,
assess the heterogeneity among the studies, and evaluate the reported effectiveness of the prevention programs.
Study Design: Systematic review and meta-analysis.
Methods: A systematic search of the literature was conducted on PubMed (Medline), Embase, CINAHL, and Central-Cochrane
Database. Studies were limited to randomized controlled trials (RCTs) of injury prevention programs specific to the knee and/or
ACL in soccer players. The Cochrane Q test and I2 index were independently used to assess heterogeneity among the studies.
The pooled risk difference, assessing knee and/or ACL injury rates between intervention and control groups, was calculated by
random-effects models with use of the DerSimonian-Laird method. Publication bias was assessed with a funnel plot and Egger
weighted regression technique.
Results: Nine studies met the inclusion criteria as RCTs. A total of 11,562 athletes were included, of whom 7889 were analyzed
for ACL-specific injuries. Moderate heterogeneity was found among studies of knee injury prevention (P = .041); however, there
was insignificant variation found among studies of ACL injury prevention programs (P = .222). For studies of knee injury prevention
programs, the risk ratio was 0.74 (95% CI, 0.55-0.89), and a significant reduction in risk of knee injury was found in the prevention
group (P = .039). For studies of ACL injury prevention programs, the risk ratio was 0.66 (95% CI, 0.33-1.32), and a nonsignificant
reduction in risk of ACL injury was found in the prevention group (P = .238). No evidence of publication bias was found among
studies of either knee or ACL injury prevention programs.
Conclusion: This systematic review and meta-analysis of ACL and knee injury prevention program studies found a statistically
significant reduction in injury risk for knee injuries but did not find a statistically significant reduction of ACL injuries.
Keywords: anterior cruciate ligament injury prevention; knee injury; injury prevention; meta-analysis; systematic review

Soccer is the most popular sport in the world, with approx-


imately 265 million players as of 2006.1 The sport has seen
*Address correspondence to Nathan L. Grimm, MD, Department of
Orthopaedic Surgery, Duke University Medical Center, 8 Intuition Circle,
tremendous growth over the past decade in the United
Durham, NC 27705, USA (e-mail: nathan.grimm@duke.edu). States, especially in the youth and female populations,
y
Department of Orthopaedic Surgery, Duke University Medical Cen- which has led to an associated increase in injuries sus-
ter, Durham, North Carolina, USA.
z
tained by soccer players.2,11 The lower extremity repre-
University of Utah School of Medicine, Salt Lake City, Utah, USA.
sents a majority of soccer injuries in both male and
Division of Public Health, Study Design, & Biostatistic Center, Univer-
sity of Utah School of Medicine, Salt Lake City, Utah, USA. female athletes, with the knee being a frequently injured
||
St Lukes Intermountain Orthopaedics, Boise, Idaho, USA. body part.8,36,46 In particular, female athletes have a 3 to
The authors declared that they have no conflicts of interest in the 5 times higher risk of serious knee injury compared with
authorship and publication of this contribution. male athletes for soccer, basketball, volleyball, and other
sports.3-5,11,37
The American Journal of Sports Medicine, Vol. 43, No. 8
DOI: 10.1177/0363546514556737 Many intervention programs have been designed
2014 The Author(s) to reduce the risk of injury to the knee and anterior

2049
2050 Grimm et al The American Journal of Sports Medicine

cruciate ligament (ACL) in predominantly young ath- who has participated in previous studies (see Acknowledg-
letes.7,9,25,26,31,34 Studies that examine the efficacy of inter- ments).18 Briefly, the following search criteria were used:
vention programs are time consuming, expensive, and
((knee injuries[MeSH Terms] OR (knee[All
difficult to conduct. These limitations can lead to study
Fields] AND injuries[All Fields]) OR knee inju-
design and methodology flaws. These flaws subsequently
ries [All Fields] OR (knee[All Fields] AND injury
increase the risk for bias in the study and reduce the qual-
[All Fields]) OR knee injury[All fields]) AND (pre-
ity of evidence.
vention and control[Subheading] OR (prevention
The purpose of this systematic review and meta-
[All Fields] AND control[All Fields]) OR preven-
analysis was to identify level 1 evidence studies of ACL
tion and control[All Fields] OR prevention[All
and knee injury prevention programs for soccer players,
Fields])) AND Clinical Trial[ptyp] and (ACL[All
assess the internal validity of these studies, and evaluate
Fields] AND (Inj Prev[Journal] OR (injury
the quantitative pooled effectiveness of these prevention
[All Fields] AND prevention[All Fields]) OR injury
programs.
prevention[All Fields])) AND Clinical Trial[ptyp].
The search included supplemental bibliographic refer-
METHODS ence searches of articles to identify potentially missed,
relevant studies. For a more detailed list of the search
Criteria for Selecting Studies strategy used, see the Appendix (available online at
http://ajsm.sagepub.com/supplemental).
Types of Studies. Only evidence level 1 randomized con-
trolled trials (RCTs) of injury prevention programs as
defined by the Cochrane Handbook24 were included. Level Data Collection and Analysis
of evidence assessments were made based on the criteria
Study Selection Procedure. Two reviewers (N.L.G. and
described by the Oxford Centre for Evidence-Based Medi-
J.C.J.) independently conducted the article selection pro-
cine (http://www.cebm.net). Prospective, nonrandomized
cess. The reviewers initially screened these articles on
studies (level 2), retrospective studies (level 3), case series
the basis of title and abstract to determine whether the tri-
(level 4), and expert opinion (level 5) publications were not
al met inclusion criteria. The full text was retrieved and
included in the analysis. Non-English articles were
reviewed in detail if criteria were met. When disagree-
excluded from the study.
ments were noted, a third reviewer (K.G.S.) facilitated
Types of Participants. Only studies with participants who
group consensus agreement.
were limited to soccer players were included. Studies of
Data Extraction. Two reviewers (N.L.G. and J.C.J.)
cohorts containing multiple different sport athletes were
independently extracted data from studies that met inclu-
excluded. Studies were not excluded because of any of the fol-
sion criteria as described above. The following data were
lowing factors: sex, skill level of athletes, or age group.
extracted from each study: journal of publication, title,
Types of Interventions and Comparison Groups. The
author(s), publication year, subject sex, subject age, num-
only studies included were those that used interventions
ber of subjects in both intervention and treatment arm,
to prevent knee and/or ACL injuries. These interventions
type of intervention(s), characteristics of intervention(s),
included strengthening, stretching, proprioception, and
study design, follow-up time, and outcome data. Further-
neuromuscular exercises. Studies were excluded if they
more, the following outcome data elements were extracted
used an exogenous modality as used as a means of preven-
from each study: type of injury, frequency of injury occur-
tion (eg, bracing, taping).
rence, duration of follow-up, diagnostic methods for out-
Outcome Measures. Studies were eligible for inclusion if
comes of interest, number of dropouts, and compliance
either ACL and/or knee injury was reported as an out-
rate. If any of the data elements of interest were missing
come measure. We used the previously published defini-
or unclear, the study authors were contacted for
tion of knee injury as any trauma, whether contact or
clarification.
noncontact, whether acute or overuse, whether ligamen-
Risk-of-Bias Assessment. All randomized and cluster-
tous or nonligamentous, occurring to the knee. Acute inju-
randomized controlled trials that met inclusion were
ries were those with sudden onset with obvious trauma,
assessed for internal validity, and therefore risk of bias,
and overuse injuries were those occurring with an insidi-
by 2 independent reviewers (N.L.G. and J.C.J.) using the
ous onset.18
assessment algorithm described by van Tulder et al,51 and
each was assigned a risk-of-bias score based on its assessed
Search Method and Strategy internal validity (see Table 1). The van Tulder scale is one of
many critical appraisal tools used as an assessment for
The following major medical databases were searched from RCTs developed and used by the Cochrane Spine Group.51
inception through February 25, 2014: PubMed (Medline), This assessment focuses on several methodological criteria,
Embase, CINAHL, and Central (Cochrane Library). To including randomization method, concealment of allocation,
develop a sensitive and comprehensive search strategy, blinding, and intention-to-treat analysis, that have been
a medical library search strategist (M.M.) was consulted, shown to create an exaggeration of treatment effects and
Vol. 43, No. 8, 2015 Soccer Injury Prevention: Meta-analysis 2051

TABLE 1
Internal Validity Risk-of-Bias Assessment for Included Studies
Ekstrand Soderman Engebretsen Gilchrist Soligard Steffen Emery and van Beijsterveldt Walden
et al12 et al47 et al14 et al17 et al48 et al49 Meeuwisse13 et al50 et al52
(1983) (2000) (2008) (2008) (2008) (2008) (2010) (2012) (2012)

(A) Was the method of randomization Yesa Yesa Yesa Yesa Yesa Yes Yesa Yes Yes
adequate?
(B) Was the treatment allocation Yesa Yesa Yesa No Yes Yesa Yesa Yes Yes
concealed?
(C) Were the groups similar at Yes Yes No Yes Yes Yes Yes Yes Yes
baseline regarding the most
important prognostic indicators?
(D) Was the patient blinded to the No No No No No No No No No
intervention?
(E) Was the care provider blinded to No No No No No No No No No
the intervention?
(F) Was the outcome assessor blinded No No No No Yes Yes Yes No Yes
to the intervention?
(G) Were the cointerventions avoided No Yes Yes Yes Yes Yes Yes Yes Yes
or similar?
a a
(H) Was the compliance acceptable in Yes Yes No No Yes No No Yes Yes
all groups?
(I) Was the dropout rate described Noa No No Yes Yes Yes Yes Yes Yes
and acceptable?
(J) Was the timing of the outcome Yes Yes Yes Yes Yes Yes Yes Yes Yes
assessment in all groups similar?
(K) Did the analysis include an Yesa No Yes No Yes Yes Yes Yes Yes
intention-to-treat analysis?
Risk-of-Bias score 6 6 5 5 9 8 8 8 9

a
Ascertained via direct communication with primary or secondary author.

lead to systematic bias.35,39,41-44,54 These instruments are effects meta-analyses with the DerSimonian-Laird method
recommended by PRISMA (Preferred Reporting Items for to estimate the between-study variance.10 The Cochrane Q
Systematic Reviews and Meta-analyses)29 and for reporting test, with a P value of .10 being considered significant, and
systematic reviews in the orthopaedic literature.55 the Higgins and the Thompson I2 index were indepen-
If any of the specific criteria of the van Tulder scale dently used to assess heterogeneity among the studies.23,24
were not explicitly stated in a studys manuscript, authors These analyses were conducted separately for knee and
were contacted for clarification. If disagreements arose, ACL injury. The estimated prospective statistical power
a third reviewer was consulted (K.G.S.). This process of analysis was calculated to reach a power greater than 90%.
assessment is consistent with the PRISMA statement for
conducting systematic reviews.29
Meta-analysis and Statistical Procedures. All studies RESULTS
injury rates concerning intervention and control groups
were evaluated and summarized in tabular form for knee Search Findings
and/or ACL injuries. Estimates of the intervention effect
on the incidence of knee and ACL injuries were expressed Using an a priori inclusion and exclusion criteria, our
as a relative risk (RR), which compared the knee/ACL inci- search yielded 9 RCTs of knee/ACL injury prevention pro-
dence rate in the intervention group (numerator) with the grams for soccer players from major medical literature
rate in the comparison group (denominator). databases. We screened a total of 3377 articles based on
The analysis of publication bias was performed with title and abstract, of which 79 full-text articles were
Stata statistical software (Release 13; StataCorp LP) using retrieved and reviewed in detail. This resulted in 9 RCTs
the Egger test, Harbord test, Peter test, and Begg test, that met both inclusion and exclusion criteria (Figure 1).
which are general approaches to test publication bias in Primary reasons for exclusion included nonrandomized
the meta-analysis. The Egger test has been widely used study design, no comparison group, and inclusion of sub-
and has become a standard procedure.24,33 The first 3 tests jects who were nonsoccer-playing athletes.
are the regression-based tests, which are parametric. How-
ever, the Begg test is based on a rank correlation method, Study Characteristics
which is nonparametric. This was represented qualita-
tively using a funnel plot derivation. All studies and sample sizes included in this systematic
With Stata, an inverse variance method was used to cal- review and meta-analysis are provided in Table 2. A total
culate the weight for each study included using random- of 11,562 athletes were included in the 9 studies analyzed.
2052 Grimm et al The American Journal of Sports Medicine

statistically significant individually (Figure 2B). Likewise,


the pooled effect size showed a nonsignificant protective
effect against ACL injuries (RR, 0.66; 95% CI, 0.33-1.32;
P = .238) (Figure 2B). For sensitivity analyses, the data
were analyzed with fixed-effects meta-analysis. In those
analyses, similar results in RR and CI were found.

Publication Bias
Using the methods for publication bias described above, for
studies that reported knee injuries, the estimated bias
coefficient from the Egger test is 20.97 with a standard
error of 1.14, giving a P value of .422. Other tests also
showed no small-study effects (P = .537 [Harbord test],
.463 [Peter test], and .532 [Begg test]). The test thus pro-
vides no evidence of publication bias and can be seen qual-
itatively in the funnel plot (Figure 3A). Similarly, for
studies that reported ACL injuries, the estimated bias coef-
ficient is 3.17 with a standard error of 0.89, giving a P
value of .071 with the Egger test and thus no evidence of
publication bias. Other tests provided similar results
Figure 1. PRISMA flow diagram for study selection. except the result based on the Peter test (P = .131 [Harbord
test], .022 [Peter test], and .174 [Begg test]). This can be
seen qualitatively in the funnel plot (Figure 3B).
Five studies included only females,17,47-49,52 3 studies
included only males,12,14,50 and 1 study included both
males and females13 (Table 2). All study designs were DISCUSSION
either prospective cluster-randomized controlled trials or
prospective RCTs. Of the studies that met the inclusion cri- For this systematic review and meta-analysis, we found 9
teria, 5 reported on knee injury alone and 4 reported both high-quality RCTs designed to prevent knee and/or ACL
knee and ACL injury (Table 3). injuries in athletic soccer players. The quantitative pooled
effect suggests a significant protective effect against over-
all knee injuries in this population (RR, 0.74; 95% CI,
Risk of Bias 0.55-0.98; P = .039); however, a nonsignificant protective
effect for ACL injuries was found (RR, 0.66; 95% CI,
The average risk-of-bias score for the included studies was 7
0.33-1.32; P = .238). Given the relatively small number of
of 11 (range, 5-9) (Table 1). Although all internal validity
studies meeting inclusion for our meta-analysis, we did not
elements of the van Tulder scale51 were obtained from
perform subgroup analyses based on sex, skill level, or spe-
each study, we contacted authors from 7 of the 9 included
cific intervention type. It has been shown that multiplicity
studies to clarify at least 1 element that was not readily
of analysis increases the risk of type 1 error, resulting in spu-
available or clear in the manuscript. Two studies adequately
rious results, and should be performed and interpreted with
reported all elements of internal validity within their
caution.28,45 Our study was designed a priori to have the sta-
respective manuscript.50,52 Methodological elements that
tistical power to detect a difference in knee and ACL effects
were not performed included cointervention avoidance,
using a random-effects model, and therefore the modifying
intention-to-treat analysis, care provider blinding, outcome
effects of individual covariates would not have sufficient
assessor blinding, and subject blinding. However, the latter
power for detection. Therefore, we cannot say which elements
is logistically difficult with this particular study design.
of the intervention were more or less effective. Neither are we
able to clearly comment on the effects of the interventions rel-
Study-Specific and Quantitative Analysis ative to gender.
Outside of the studies analyzed in this meta-analysis
For overall knee injuries, the estimated RR was less than 1 and systematic review, several injury prevention studies
(which is consistent with a protective effect) in 7 studies, of have been published regarding handball,31,32,53 soc-
which 2 were statistically significant individually (Figure cer,9,20,22,34 basketball,22,34 volleyball,22,34 football,7 and
2A). The pooled effect size was statistically significant in skiing.15 However, given the logistical, methodological,
favor of injury prevention interventions showing a protec- and financial complexity of conducting an injury preven-
tive effect against overall knee injuries (RR, 0.74; 95% CI, tion study in athletes, relatively few have been conducted
0.55-0.98; P = .039) (Figure 2A). For ACL injuries, the esti- at the highest methodological rigorthe RCT. To date,
mated RR was less than 1 in 3 studies, which is consistent all of the published systematic reviews and meta-analyses
with a protective effect. However, no study was on injury prevention programs have included both
Vol. 43, No. 8, 2015 Soccer Injury Prevention: Meta-analysis 2053

TABLE 2
Summary Table of Study Characteristicsa
No. of
Publication Subjects Age, y, Program Study Follow- Subjects
Study Journal Year LOE Sex Mean (Range) Exercises Design up at Follow-up

Ekstrand American Journal 1983 1 Male 24.0 (17-37) Multifaceted approach: Prospective, cluster- 6 mo 180
et al12 of Sports protective gear, taping, randomized
Medicine and warm-up and controlled study
b
flexibility program
Soderman Knee Surgery, 2000 1 Female 20.4 (NR) Proprioceptive (balance Prospective, cluster- 6 mo 140
et al47 Sports board) randomized
Traumatology, controlled study
Arthroscopy
Engebretsen American Journal 2008 1 Male NR Balance training Prospective 8 mo 131
et al14 of Sports randomized
Medicine controlled study
Gilchrist American Journal 2008 1 Female 19.9 (NR) Multifaceted approach: Prospective, cluster- 3 mo 1435
et al17 of Sports warm-up, stretching, randomized
Medicine strength, plyometrics, controlled study
and agility training
Soligard British Medical 2008 1 Female 15.4 (13-17) Multifaceted approach: Prospective, cluster- 8 mo 1892
et al48 Journal warm-up, stretching, randomized
plyometrics, and controlled study
balance training
Steffen Scandinavian 2008 1 Female 15.4 (13-17) Multifaceted approach: Prospective, cluster- 6 mo 2020
et al49 Journal of core stabilization, randomized
Medicine and balance, plyometrics, controlled study
Science in and strength training
Sports
Emery British Journal of 2010 1 Male and NR Dynamic stretching, Prospective, cluster- 12 mo 744
and Sports Medicine female (12-18) eccentric strength, randomized
Meeuwisse13 agility, jumping, controlled study
balance
van British Journal of 2012 1 Male 24.8 (20-29) Core stability, Prospective, cluster- 1 season 456
Beijsterveldt Sports Medicine proprioception, randomized
et al50 dynamic stabilization, controlled study
plyometrics, eccentric
muscle training
Walden British Medical 2012 1 Female 14 (12-17) Neuromuscular Prospective, cluster- 1 season 4564
et al52 Journal exercises, jump- randomized
landing technique controlled study

a
LOE, level of evidence; NR, not reported (data not reported and unable to contact primary or secondary author).
b
The use of protective gear and taping only applied to the shin and ankle. No exogenous interventions were applied to the knee.

TABLE 3
Injury Data for Included Studiesa

Knee Injuries, % (n/N) ACL Injuries, % (n/N)

Study Prevention Control P Value Prevention Control P Value


12
Ekstrand et al 1.1 (1/90) 18.9 (17/90) \.05 NR NR NR
Soderman et al47 12.9 (8/62) 7.7 (6/78) NR 6.5 (4/62) 1.3 (1/78) NR
Engebretsen 10.8 (7/65) 12.1 (8/66) .93 NR NR NR
et al14
Gilchrist et al17 6.9 (40/583) 6.8 (58/852) .86 1.2 (7/583) 2.1 (18/852) .2
Soligard et al48 3.1 (33/1055) 5.6 (47/837) .08 NR NR NR
Steffen et al49 3.4 (37/1073) 3.2 (30/947) ..05 0.4 (4/1073) 0.5 (5/947) .73
Emery and 0.8 (3/380) 2.2 (8/364) .232 NR NR NR
Meeuwisse13
van Beijsterveldt 10.8 (24/223) 17.2 (40/233) NR NR NR NR
et al50
Walden et al52 1.9 (48/2479) 2.1 (44/2085) .71 0.3 (7/2479) 0.7 (14/2085) .02

a
ACL, anterior cruciate ligament; LOE, level of evidence; NR, not reported (data not reported and unable to contact primary or secondary author).
2054 Grimm et al The American Journal of Sports Medicine

Figure 2. (A) Random-effects model with DerSimonian-Laird weighting method showing a statistically significant risk ratio in favor
of injury prevention programs for reducing knee injuries. (B) Random-effects model with DerSimonian-Laird weighting method
showing no statistically significant benefit for ACL injury prevention.

Figure 3. (A) Funnel plot with 95% confidence interval showing no evidence of publication bias for injury prevention programs
evaluating knee injury prevention. (B) Funnel plot with 95% confidence interval showing no evidence of publication bias for injury
prevention programs evaluating anterior cruciate ligament injury prevention.

randomized and nonrandomized studies.16,19,21,56 The data included several different athletic populations in their anal-
of these meta-analyses should therefore be evaluated with ysis (eg, soccer, handball, basketball, volleyball) and they
caution given the mixing of several study designs, cohorts, included both evidence level 1 randomized studies and lev-
and individual knee/ACL injury risks. els 2 and 3 nonrandomized studies. It is well published
For example, the recent meta-analysis by Gagnier et al16 that these individual sports have variable ACL and knee
on ACL injury prevention programs showed a statistically injury risks.46 Additionally, it is well understood that non-
significant reduction of ACL injuries through the use of randomized trials can lead to an exaggeration of treatment
injury prevention programs. However, the difference in effects and greater chance of an introduction of bias into
findings may be explained by noting that Gagnier et al16 a study.27,54 This exaggeration of treatment effects is
Vol. 43, No. 8, 2015 Soccer Injury Prevention: Meta-analysis 2055

perhaps suggested by the subgroup analysis by Gagnier


An online CME course associated with this article
et al16 showing that the pooled effect of the randomized
is available for 1 AMA PRA Category 1 CreditTM at
studies was not statistically significant; however, non-
http://ajsm-cme.sagepub.com. In accordance with the
randomized studies demonstrated significant benefit.
standards of the Accreditation Council for Continuing
In our study we attempted to control for this shortcom-
Medical Education (ACCME), it is the policy of The Amer-
ing by including only level 1 studies as they pertained to
ican Orthopaedic Society for Sports Medicine that
a single sport (soccer) and limiting the multiplicity of anal-
authors, editors, and planners disclose to the learners
yses. Although we adhered to a strict protocol, following
all financial relationships during the past 12 months
the PRISMA guidelines,29 for collection, interpretation,
with any commercial interest (A commercial interest is
and analysis, our study is not without limitations. First,
any entity producing, marketing, re-selling, or distribut-
we did not blind the reviewers (N.L.G. and J.C.J.) to study
ing health care goods or services consumed by, or used
author, institution, or journal in which the study was pub-
on, patients). Any and all disclosures are provided in
lished. Although the extra step of blinding the reviewed
the online journal CME area which is provided to all par-
manuscripts has been performed in other reviews, it is
ticipants before they actually take the CME activity. In
an onerous extra step with little evidence to support its
accordance with AOSSM policy, authors, editors, and
ability to protect against bias.6 Furthermore, with a small
planners participation in this educational activity will
number of studies (n \ 10), the assessment of publication
be predicated upon timely submission and review of
bias should be interpreted with caution.24 Although there
AOSSM disclosure. Noncompliance will result in an
are no strict guidelines on the absolute number of studies
author/editor or planner to be stricken from participating
needed to detect a true publication bias, the larger the
in this CME activity.
sample the more accurate the assessment of bias will be.
Nonetheless, we used recommended analytical techniques
for detection of publication bias.24,33,38 Additionally, one
of the authors (K.G.S.) has published on knee injury pre- REFERENCES
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