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Comparisons of Interventions for Preventing Falls in Older Adults A Systematic Review and Meta-analysis Andrea C. Tricco, PhD; Sonia M. Thomas, MSc; Areti Angeliki Veroniki, PhD; Jemila S. Hamid, PhD; Elise Cogo, ND; Lisa Strifler, MSc; Paul A. Khan, PhD; Reid Robson, MSc; Kathryn M. Sibley, PhD; Heather MacDonald, MSc; John J. Riva, DC; Kednapa Thavorn, PhD; Charlotte Wilson, MSc; Jayna Holroyd-Leduc, MD; Gillian D. Kerr, MD; Fabio Feldman, PhD; Sumit R. Majumdar, MD; Susan B. Jaglal, PhD; Wing Hui, MSc; Sharon E. Straus, MD, MSc
IMPORTANCE Falls result in substantial burden for patients and health care systems, and given the aging of the population worldwide, the incidence of falls continues to rise.
OBJECTIVE To assess the potential effectiveness of interventions for preventing falls.
DATA SOURCES MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Ageline databases from inception until April 2017. Reference lists of included studies were scanned.
STUDY SELECTION Randomized clinical trials (RCTs) of fall-prevention interventions for participants aged 65 years and older.
DATA EXTRACTION AND SYNTHESIS Pairs of reviewers independently screened the studies, abstracted data, and appraised risk of bias. Pairwise meta-analysis and network meta-analysis were conducted.
MAIN OUTCOMES AND MEASURES Injurious falls and fall-related hospitalizations.
RESULTS A total of 283 RCTs (159 910 participants; mean age, 78.1 years; 74% women) were included after screening of 10 650 titles and abstracts and 1210 full-text articles. Network meta-analysis (including 54 RCTs, 41 596 participants, 39 interventions plus usual care) suggested that the following interventions, when compared with usual care, were associated with reductions in injurious falls: exercise (odds ratio [OR], 0.51 [95% CI, 0.33 to 0.79]; absolute risk difference [ARD], −0.67 [95% CI, −1.10 to −0.24]); combined exercise and vision assessment and treatment (OR, 0.17 [95% CI, 0.07 to 0.38]; ARD, −1.79 [95% CI, −2.63 to −0.96]); combined exercise, vision assessment and treatment, and environmental assessment and modification (OR, 0.30 [95% CI, 0.13 to 0.70]; ARD, −1.19 [95% CI, −2.04 to −0.35]); and combined clinic-level quality improvement strategies (eg, case management), multifactorial assessment and treatment (eg, comprehensive geriatric assessment), calcium supplementation, and vitamin D supplementation (OR, 0.12 [95% CI, 0.03 to 0.55]; ARD, −2.08 [95% CI, −3.56 to −0.60]). Pairwise meta-analyses for fall-related hospitalizations (2 RCTs; 516 participants) showed no significant association between combined clinic- and patient-level quality improvement strategies and multifactorial assessment and treatment relative to usual care (OR, 0.78 [95% CI, 0.33 to 1.81]).
CONCLUSIONS AND RELEVANCE Exercise alone and various combinations of interventions were associated with lower risk of injurious falls compared with usual care. Choice of fall-prevention intervention may depend on patient and caregiver values and preferences.
JAMA. 2017;318(17):1687-1699. doi:10.1001/jama.2017.15006
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Supplemental content
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Author Affiliations: Author affiliations are listed at the end of this article.
Corresponding Author: Sharon E. Straus, MD, MSc, Director, Knowledge Translation Program, Li Ka Shing Knowledge Institute, St Michael’s Hospital, 209 Victoria St, East Bldg, Room 716, Toronto, ON, M5B 1T8, Canada (sharon.straus @utoronto.ca).
Research
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D ata from the National Institute on Aging showedthat the 2-year prevalence of falls among individualsaged 65 years or older was 36% in 2010.1 Falls cause a substantial burden to patients and health care systems.2-4
In 2012, the cost of falls to Medicare was $31 billion.5 Not only can falls result in serious injury or death,6,7 but older adults who experience falls also report increased anxiety and depression and reduced quality of life.8,9 Given the aging of the population worldwide, the incidence of falls is expected to continue rising.5 As such, preventing falls among older persons is increasingly important for health care systems.
Previous randomized clinical trials (RCTs) and system- atic reviews have selectively examined fall-prevention programs.10-13 However, directly comparing more than 2 interventions using conventional meta-analysis has major limitations. The key elements of an effective fall-prevention program remain unclear, which has hampered implementa- tion of effective interventions. Furthermore, a network meta-analysis ranking all available fall-prevention interven- tions and their combinations has not been conducted. Therefore, a systematic review and network meta-analysis on all available fall-prevention inter ventions for older people were conducted.
Methods Protocol The systematic rev iew protocol was developed using guidance from the Preferred Reporting Items for System- at i c Re v i e w a n d Me t a - a n a l y s i s P ro to c o l s ( P R I S M A- P ) statement,14 registered in PROSPERO (CRD42013004151), and published. 1 5 B ec ause the methods were reported prev iously, they are desc ribed only briefly here. The PRISMA-network meta-analysis extension16 was used to report results.
Eligibility Criteria A l l t y p e s o f RC Ts (e g , c l u s t e r, c r o s s ove r ) ex a m i n i ng fall-prevention interventions (whether single or multifacto- rial) for adults aged 65 years or older in all settings (eg, com- munity, ac ute c are) were included. Potential compar- ators were usual care, other fall-prevention interventions, and placebo.
Outcomes The primary outcomes were the numbers of injurious falls and fall-related hospitalizations. The secondary outcomes were rate of falls, number of fallers, number of fall-related emergency department visits, number of fall-related physi- cian visits, number of fractures, costs (eg, to the health care system), number of intervention-related harms (eg, muscle soreness from exerc ise), and quality of life. Quality of life was measured with the SF-12 or SF-36 physical and men- tal summary component measures (range, 0-100) or the EuroQol-5D VAS (range, 0-100), where 0 indicates maxi- mum disability, and 100 indicates no disability.17-19
Data Sources MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Ageline databases were searched from inception until December 1, 2015 (see protocol for search strategy15). Reference lists of included RCTs and relevant reviews were scanned for additional RCTs. Study authors were contacted for unpublished studies or additional data. An updated search was conducted on April 19, 2017, which involved screening, abstraction, and risk-of-bias appraisal by 2 review- ers, working independently without additional reference scanning or author contact regarding conference abstracts, trial protocols, or non-English articles for any studies identi- fied in the update.
Study Selection After pilot-testing eligibility criteria for citations and full-text articles, screening was conducted independently by pairs of reviewers. Conflicts were resolved by a third reviewer.
Data Abstraction Data abstraction was completed by independent pairs of reviewers after pilot-testing of the data abstraction form. Conflicts were resolved by a third reviewer. Interven- tions were coded independently by a clinician (S.E.S.) and a methodologist (A.C.T.) using a preestablished coding guide (eTable 1 in the Supplement). Included interventions were classified into the following broad categories: basic f alls risk assessment, c alc ium supplementation, cog- nitive behav ioral therapy, dev ices, diet modific ation, electromagnetic field therapy and whole-body vibration, environmental assessment and modification, exercise, floor modifications, multifactorial assessment and treatment, osteoporosis medications, podiatry assessment and treat- ment, quality improvement strategies, social engagement, surgery, vision assessment and treatment, and vitamin D supplementation. Quality improvement strategies were focused on increasing use of research in practice and were classified at the health system, clinic and clinician, and patient levels (Box 1 and Table 1).20
Key Points Question What types of fall-prevention programs may be effective for reducing injurious falls in older people?
Findings In a network meta-analysis including 54 studies and 41 596 participants, exercise (odds ratio [OR], 0.51), combined exercise, vision assessment and treatment, and environmental assessment and modification (OR, 0.30), combined exercise, and vision assessment and treatment (OR, 0.17), and combined clinic-level quality-improvement strategies, multifactorial assessment and treatment, calcium supplementation, and vitamin D supplementation (OR, 0.12) were significantly associated with reductions in injurious falls.
Meaning The analysis identified combinations of interventions likely to be more effective than usual care for preventing injurious falls.
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Risk-of-Bias Appraisal The Cochrane Effective Practice and Organisation of Care (EPOC) Group’s risk-of-bias tool was used to appraise in- cluded studies.21 This appraisal was conducted by pairs of independent reviewers, with conflicts resolved by a third reviewer. Small study effects were assessed for each out- come (when >10 RCTs were available) using the comparison- adjusted funnel plot and the netfunnel command (Stata 13.0)22
with a fixed meta-analysis model and ordering treatments from most to least effective according to clinical insight.
Data Synthesis and Analysis Across all outcomes, pairwise random-effects meta-analysis was conducted. Effect estimates are reported as odds ratios (ORs) for dichotomous outcomes and mean differences for continuous outcomes. Studies reporting dichotomous out- comes with zero events across all groups were included in the systematic review, but excluded from analysis. Studies reporting continuous outcomes with the average effect esti- mate but not reporting the associated measure of variance (eg, standard deviation) were included in the analysis, with standard errors imputed when feasible.23,24
Random-effects network meta-analyses were con- ducted for connected networks of included RCTs when more than 10 RCTs were available and the number of RCTs was greater than the number of intervention nodes. To sur- mount small study effects,25 smaller trials (n <100 partici- pants) were excluded from analysis. Across all outcomes for which network meta-analysis was possible, the transitivity and consistency assumptions were assessed a priori.26-28
In both network meta-analysis and inconsistency models, common within-network, between-study variance across intervention comparisons was assumed because the treat- ments included in each network of trials were mostly nonpharmacological. Subgroup and sensitivity network meta-analyses were conducted for the primary outcome
with consideration of potential treatment effect modifiers. Interventions were ranked using P scores29 and presented in a rank-heat plot.30 For each network meta-analysis, the overall risk for the control group (considering usual care as the control) of the included studies was calculated via the variance-stabilizing Freeman-Tukey double arcsine approach.31 A random-effects pairwise meta-analysis was applied using inverse variance weights, and to facilitate interpretation, summary group risks were back-transformed to the initial scale. All network meta-analyses and consis- tency assessments were conducted with R software (version 3.3.3)32 using the netmeta package.33 Results were summa- rized using effect estimates (ORs or mean differences) and their associated 95% CIs. Overall ORs, derived from each network meta-analysis, were transformed to risk differ- ences to allow judgment of the clinical importance of statis- tically significant results.34 Analysis details are provided in eMethods in the Supplement.
Results Study Selection A total of 10 650 titles and abstracts and subsequently 1210 full-text articles were sc reened (Figure 1). Ac ross all outcomes, 283 RCTs and 20 companion reports were
Box 1. Components of Quality Improvement Strategies Classified by Level of Implementation
Clinic Level Quality improvement initiatives targeting the clinic or care team include case management, team changes, electronic patient registries, facilitated relay of information to clinicians, continuous quality improvement, audit and feedback, staff education, and clinician reminders
Patient Level Quality improvement initiatives targeting the patient include promotion of self-management, patient education, patient reminders, and motivational interviewing
Health System Level Quality improvement initiatives targeting the health system include interventions with positive or negative financial incentives directed at clinicians (eg, linked to adherence to some process of care or achievement of some target outcome), positive or negative financial incentives directed at patients, or system-wide changes in reimbursement systems
Table 1. Components of Interventions to Prevent Falls
Intervention Component Abbreviation Basic falls risk assessment bf
Calcium ca
Cognitive behavioral therapy cb
Clinic-level quality improvement cl-qi
Comprehensive podiatry assessment and treatment
cp
Device—alarm de-al
Device—hip protector de-hp
Device—orthosis de-or
Dietary modifcations di
Environmental assessment and modification
ea
Electromagnetic field therapy and whole-body vibration
em + wb
Exercise ex
Flooring fl
Lavender la
Multifactorial assessment and treatment mf
Osteoporosis treatment op-tx
Patient-level quality improvement pa-qi
Social engagement so
Surgery—cataract su-ey
Surgery—hip su-hi
Surgery—pacemaker su-pm
Health system–level quality improvement sy-qi
Usual care uc
Vision assessment and treatment va
Vitamin D vi-d
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included (citations in eReferences in the Supplement), with a total of 159 910 participants (mean age 78.1 years; 74% women). Two included studies were available only as conference abstracts,35,36 and 14 other studies were identi- fied by scanning reference lists of included studies and rel- evant reviews.37-50
Author Contact Fifty-four authors were contacted, and responses were re- ceived from 35 (response rate, 65%), which allowed inclusion of 2 additional studies.
Study and Participant Characteristics For 155 of the RCTs (54.8%), the mean age of participants was between 74 and 84 years (Table 2; eTable 2 in the Supplement). In 248 of the RCTs (87.6%), at least 50% of the participants were women. One hundred sixty-nine RCTs (59.7%) included a mixture of individuals with and without a history of falls. The number of medications taken was not reported in 172 RCTs (60.8%).
Two hundred fifty-five of the RCTs (90.1%) were pub- lished in 2001 or later, and the studies were conducted in Europe (121 [42.8%]), Australia or New Zealand (66 [23.3%]), and other regions (Table 3; eTable 3 in the Supplement). The setting for 142 studies (50.2%) was at home, 75 were in a clinic ([26.5%]), and 72 were in the community (25.4%), with some studies including multiple settings. One hundred and fifty-one RCTs (53.4%) had an intervention duration of 26 weeks or less, and 223 of the studies (78.8%) had a duration (ie, from recruitment to the end of follow-up) of 1 year or less.
Risk of Bias Most RCTs had a low risk of bias for random sequence gen- eration (187 [66.1%]), similar baseline outcome measures (212 [74.9%]), similar baseline characteristics (238 [84.1%]), incomplete outcome data (221 ( 78.1%]), blinding (267 [94.3%]), and other components of bias (171 [60.4%]) (eTable 4 and eFigure 1 in the Supplement). However, a high propor- tion had unclear risk of bias for allocation concealment
Table 2. Summary of Patient Characteristics
Characteristic No. (%) of Randomized Clinical Trials (N = 283)
Age, mean, y
64-73.9 56 (19.8)
74-83.9 155 (54.8)
≥84 36 (12.7)
Not reported 36 (12.7)
% Women
0-49.9 20 (7.1)
50-100 248 (87.6)
Not reported 15 (5.3)
History of falls
All 60 (21.2)
Mixed 169 (59.7)
None 0
Not reported 54 (19.1)
No. of medications takena
0-4 56 (19.8)
≥5 55 (19.4)
Not reported 172 (60.8)
a Refers to the reported mean or median number of medications taken by patients—not necessarily the number of medications taken daily.
Figure 1. Study Flow From Literature Search
9454 Excluded 9191 Not a falls-prevention
intervention
3 No relevant comparator
233 Not an RCT 27 Participants aged <65 y
907 Excluded 266 No relevant outcome
104 No abstractable data 99 Participants aged <65 y 35 Duplicate article 17 No relevant comparator
224 Not an RCT 162 Not a falls-prevention intervention
1210 Full-text articles assessed for eligibility
303 Studies included in meta-analysis 283 Primary publications
20 Companion reportsa
10 650 Records identified and screened through database search
14 Articles identified from scanning of reference lists
RCT indicates randomized clinical trial. a If multiple publications reported
data from the same trial (eg, reporting results at 1-year vs 2-year follow-up), the first was identified as the primary publication and any additional publications were referred to as companion reports to avoid double counting data from the same trial.
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(145 [51.2%]), contamination (190 [67.1%]), and selective out- come reporting (183 [64.7%]). All comparison-adjusted fun- nel plots suggested no evidence of publication bias (eFigure 2 in the Supplement).
Statistical Analysis The design-by-treatment interaction model showed no evi- dence of significant inconsistency across the network meta- analysis (eTable 5 in the Supplement). Because of the large number of results from the analysis, the overall results for each outcome are presented and focus on statistically signifi- cant intervention effects relative to usual care for network meta-analyses (summarized in Box 2). The results from all statistically significant treatment comparisons are available in eTable 5 in the Supplement, and the results from all analy- ses are posted on the Open Science Framework.50 P scores were used to summarize results for the primary outcome, and all results are presented in eTable 6, eTable 7, and eTable 8 in the Supplement. The rank-heat plot, presented in eFig- ure 3 in the Supplement, indicates that exercise is likely the most effective intervention in terms of numbers of fallers, injurious falls, fractures, and hip fractures.
Injurious Falls Network meta-analysis for the primary outcome of injurious falls included 54 RCTs (41 596 participants) with 39 interven- tions plus usual care (Figure 2). The event rate for injurious falls in the usual care group was 0.34 (95% CI, 0.24 to 0.44). Across all 780 network meta-analysis comparisons, 101 (12.9%) were statistically significant (eTable 5 in the Supple- ment). The following 4 interventions were associated with a reduced risk of injurious falls relative to usual care:
• Exercise (OR, 0.51 [95% CI, 0.33 to 0.79]; absolute risk dif- ference [ARD], −0.67 [95% CI, −1.10 to −0.24])
• Combined exercise and vision assessment and treatment (OR, 0.17 [95% CI, 0.07 to 0.38]; ARD, −1.79 [95% CI, −2.63 to −0.96])
• Combined exercise, vision assessment and treatment, and en- vironmental assessment and modification (OR, 0.30 [95% CI, 0.13 to 0.70]; ARD, −1.19 [95% CI, −2.04 to −0.35])
• Combined clinic-level quality improvement strategies, mul- tifactorial assessment and treatment, calcium supplemen- tation, and vitamin D supplementation (OR, 0.12 [95% CI, 0.03 to 0.55]; ARD, −2.08 [95% CI, −3.56 to −0.60])
The remaining 35 single or multifactorial interventions were not significantly associated with the risk of injurious falls relative to usual care. According to the P score results, com- bined exercise and vision assessment and treatment was prob- ably the most effective intervention (97% likelihood) to re- duce injurious falls.
The results of subgroup analyses are summarized in Table 4. For the 37 RCTs that had less than 75% women (20 354 participants), which examined 27 treatments plus usual care, the network meta-analysis results were consistent with the main analysis. For the 44 RCTs with duration of 12 months or less (32 890 participants; examined 28 interven- tions plus usual care), the network meta-analysis results
Table 3. Summary of Study Characteristics
Study Characteristic No. (%) of RCTs (N = 283) Year of publication
1990-1995 10 (3.5)
1996-2000 18 (6.4)
2001-2005 66 (23.3)
2006-2010 77 (27.2)
2011-2015 87 (30.7)
2016-2017 25 (8.8)
Continenta
Europe 121 (42.8)
Australia/New Zealand 66 (23.3)
North America 47 (16.6)
Asia 43 (15.2)
South America 4 (1.4)
Multicontinent 2 (0.7)
Study design
Parallel RCT 243 (85.9)
Cluster RCT 40 (14.1)
Site
Multicenter 155 (54.8)
Single center 127 (44.9)
Not reported 1 (0.4)
Settingsb
Home 142 (50.2)
Clinic 75 (26.5)
Community 72 (25.4)
Hospital 51 (18.0)
Long-term care facility 39 (13.8)
Retirement home 28 (9.9)
Not reported 9 (3.2)
Sample size (No. of patients)
Parallel RCTs
20-99 65 (23.0)
100-299 90 (31.8)
300-999 68 (24.0)
1000-9440 20 (7.1)
Cluster RCTs
68-500 21 (7.4)
501-1500 11 (3.9)
1501-5500 6 (2.1)
5501-10 558 2 (0.7)
No. of clusters, median (IQR) 17 (8.00-25.00)
Duration of Intervention, wk
<1-26 151 (53.4)
27-52 72 (25.4)
53-78 11 (3.9)
79-104 13 (4.6)
105-260 17 (6.0)
Not reported 19 (6.7)
Abbreviations: IQR, interquartile range; RCT, randomized clinical trial. a Continent refers to where the study was conducted; if not reported explicitly,
the location of the first author’s institution was used as a proxy. b The number of RCTs exceeds 283 and percents total more than 100% because
some studies involved multiple settings.
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were consistent with the main analysis for the interventions of exercise vs usual care and combined clinic-level quality improvement strategies, multifactorial assessment and treat- ment, calcium supplementation, and vitamin D supplemen- tation vs usual care; the remaining 2 significant comparisons from the main analysis (combined exercise and vision assess- ment and treatment vs usual care; combined exercise, vision assessment and treatment, and environmental assessment and modification vs usual care) were no longer included in the network. Network meta-analysis was conducted for the 32 RCTs with participants who were younger than 80 years old (24 869 participants), which examined 26 interventions plus usual care. Compared with the main analysis, the same interventions were associated with a reduced risk of injurious falls except for the combination of clinic-level quality improvement strategies, multifactorial assessment and treat- ment, calcium supplementation, and vitamin D supplemen- tation, which was no longer in the network. This finding was consistent in another network meta-analysis involving the 40 RCTs (37 010 participants) for people with a mixed fall his- tory (ie, some had fallen previously and some had not), which examined 34 interventions plus usual care. A network meta-analysis restricted to 11 RCTs involving 3830 patients who had fallen previously and examining 9 interventions plus usual care found that the combination of clinic-level quality improvement strategies, multifactorial assessment
and treatment, calcium supplementation, and vitamin D supplementation was associated with fewer injurious falls than usual care (OR, 0.12 [95% CI, 0.04 to 0.44]; ARD, −2.08 [95% CI, −3.34 to −0.83]), while the remaining 3 comparisons (exercise vs usual care; combined exercise and vision assess- ment and treatment vs usual care; combined exercise, vision assessment and treatment, and environmental assessment and modification vs usual care) were no longer in the net- work. Sensitivity analysis was conducted restricting the net- work meta-analysis to 24 RCTs with a low risk of contamina- tion bias (26 969 participants; 19 interventions plus usual care); no intervention was associated with a lower risk of injurious falls compared with usual care (eg, exercise vs usual care, OR, 0.59 [95% CI, 0.29 to 1.18]; ARD, −0.53 [95% CI, −1.23 to 0.17]), and 3 of the significant comparisons from the main analysis were no longer in the network (combined exercise and vision assessment and treatment vs usual care; combined exercise, vision assessment and treatment, and environmental assessment and modification vs usual care; combined clinic-level quality improvement strategies, multi- factorial assessment and treatment, calcium supplementa- tion, and vitamin D supplementation vs usual care).
Overall, each of the 4 interventions that was associated with better outcomes than usual care in the main analysis was also associated with fewer injurious falls in 2 or more of the additional analyses, although in some cases, an additional analysis was not feasible for a particular subgroup.
Hospitalizations For the primary outcome of fall-related hospitalizations, 20 RCTs (24 531 participants) with 25 interventions plus usual care were included. Two pairwise meta-analyses were pos- sible across all comparisons (eTable 9 in the Supplement). There were no significant associations with hospitalizations for combined clinic-level quality improvement strategies, patient-level quality improvement strategies, and multifacto- rial assessment and treatment relative to usual care (2 RCTs [516 participants]; OR, 0.78 [95% CI, 0.33 to 1.81]; ARD, −0.03 [−0.10 to 0.093]) or for combined patient-level quality improvement strategies and exercise relative to exercise alone (2 RCTs [2126 participants]; OR, 1.12 [95% CI, 0.38 to 3.25]; ARD, 0.02 [−0.09 to 0.22]).
Emergency Department Visits Eleven RCTs (2956 participants) with 12 interventions plus usual care reported on emergency department visits. Only 1 pairwise meta-analysis (2 RCTs; 499 participants) was pos- sible across all comparisons (eTable 9 in the Supplement). There was no significant association with emergency department vis- its for multifactorial assessment and treatment relative to usual care (OR, 1.24 [95% CI, 0.86 to 1.77]; ARD, 0.04 [−0.03 to 0.13]).
Outpatient Physician Visits Twenty-one RCTs (17 193 participants) with 32 interventions plus usual care reported on physician visits. Only 1 pairwise meta-analysis (2 RCTs; 681 partic ipants) was possible across all treatment comparisons (eTable 9 in the Supple- ment). There was no significant association with outpatient
Box 2. Interventions Associated With Reduction of Outcome Compared With Usual Care in Network Meta-analysis
Outcomes Number of Injurious Falls Exercise
Combined exercise and vision assessment and treatment
Combined exercise, vision assessment and treatment, and envi- ronmental assessment and modification
Combined clinic-level quality improvement strategies, multifacto- rial assessment and treatment, calcium supplementation, and vita- min D supplementation
Number of Fallers Exercise
Combined exercise, patient-level quality improvement strategies, clinic-level quality improvement strategies, and multifactorial as- sessment and treatment
Combined exercise, patient-level quality improvement strategies, hip protectors, and environmental assessment and modification
Combined patient-level quality improvement strategies, clinic- level quality improvement strategies, dietary modifications, cal- cium supplementation, and vitamin D supplementation
Combined orthotics and exercise
Number of Fractures Combined osteoporosis treatment, calcium supplementation, and vitamin D supplementation
Number of Hip Fractures Combined osteoporosis treatment, calcium supplementation, and vitamin D supplementation
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physician visits for exercise relative to usual care (OR, 0.62 [95% CI, 0.32 to 1.18]; ARD, −0.10 [−0.19 to 0.04]).
Number of Fallers Network meta-analysis for the outcome of number of fallers included 158 RCTs, 107 300 participants, and 77 interven- tions plus usual care (Figure 3). One RCT (0.6%) with 31 par- ticipants (0.03%) was excluded from the network meta- analysis because it had zero events across all groups. The event rate for falls in the usual care group was 0.38 (95% CI, 0.33 to 0.43). Across all 3003 network meta-analysis comparisons, 200 (6.7%) were statistically significant (eTable 5 in the Supple- ment). Of these, 5 interventions were associated with a lower risk of patients experiencing a fall relative to usual care:
• Exercise (OR, 0.83 [95% CI, 0.70 to 0.99]; ARD, −0.19 [95% CI, −0.36 to −0.01])
• Combined exercise, patient-level quality improvement strat- egies, clinic-level quality improvement strategies, and mul- tifactorial assessment and treatment (OR, 0.68 [95% CI, 0.49 to 0.94]; ARD, −0.39 [95% CI, −0.72 to 0.06])
• Combined exercise, patient-level quality improvement strat- egies, hip protectors, and environmental assessment and modification (OR, 0.53 [95% CI, 0.29 to 0.97]; ARD, −0.63 [95% CI, −1.22 to −0.03])
• Combined patient-level quality improvement strategies, clinic-level quality improvement strategies, dietary modifi- cations, calcium supplementation, and vitamin D supple- mentation (OR, 0.36 [95% CI, 0.14 to 0.93]; ARD, −1.03 [95% CI, −1.99 to −0.08])
• Combined orthotics and exercise (OR, 0.22 [95% CI, 0.07 to 0.67]; ARD, −1.54 [95% CI, −2.67 to −0.40])
The remaining interventions were not signific antly associated with a lower risk of falls than usual care. One inter vention (combined exerc ise, patient-level quality improvement strategies, and social engagement) was asso- ciated with a higher risk that patients would experience falls relative to usual care (OR, 5.13 [95% CI, 2.14 to 12.30]; ARD, 1.63 [95% CI, 0.76 to 2.51]).
Fractures Network meta-analysis for the outcome of fractures included 68 RCTs, 86 491 participants, and 43 interventions plus usual care (Figure 4). The event rate for fractures in the usual care group was 0.07 (95% CI, 0.05 to 0.10). Across all 946 network meta-analysis comparisons, 45 (4.8%) were statistically sig- nificant (eTable 5 in the Supplement). Of these, 1 intervention (combined osteoporosis treatment (eg, bisphosphonates), calcium supplementation, and vitamin D supplementation) was associated with a lower risk of fractures relative to usual care (OR, 0.22 [95% CI, 0.09 to 0.54]; ARD, −1.51 [95% CI, −2.41 to −0.62]). The remaining 42 interventions were not significantly associated with a lower risk of fractures than usual care.
Hip Fractures Network meta-analysis for the outcome of hip fractures included 39 RCTs, 52 281 participants, and 23 interventions plus usual care (Figure 4). Four RCTs (9.1%) with 1877 par- ticipants (3.5%) were excluded from the network meta- analysis because they had zero events across all groups. The event rate for hip fractures in the usual care group was 0.03 (95% CI, 0.02 to 0.04). Across all 276 network meta-analysis
Figure 2. Network Geometry for Injurious Falls
so
ex
ea
fl
va
pa–qi
cl–qi
mf
uc
de-al
ex+va
ex+vi–d
ex+pa–qi
ea+ex ea+va
ea+pa–qi
pa–qi+va
cl–qi+mf
bf+pa–qibf+cl–qi
mf+pa–qi
ex+mf+pa–qi
ea+ex+va
ea+ex+vi–d
ea+ex+mf
cb+ex+pa–qi cb+cl–qi+pa–qi
cl–qi+ex+pa–qi
cl–qi+ex+mf
cl–qi+mf+pa–qi
bf+cl–qi+pa–qi
bf+cl–qi+sy–qi
ea+ex+pa–qi+sy–qi
ca+ex+em+wb+vi–d
ca+cl–qi+mf+vi–d
cl–qi+ex+mf+pa–qi
cl–qi+mf+pa–qi+so
bf+cl–qi+ex+pa–qi cl–qi+de–al+ex+mf+pa–qi
bf+ea+ex+pa–qi+va
Network geometry for 54 randomized clinical trials (41 596 patients). Each treatment node indicates an intervention and is weighted according to the number of patients who received the particular intervention. Each edge (line connecting the nodes) is weighted according to the number of studies and directly compares the treatments it connects. See Table 1 for expansions of treatment abbreviations. The coding guide, which provides a description of each intervention component, can be found in eTable 1 of the Supplement.
Comparisons of Interventions for Preventing Falls in Older Adults Original Investigation Research
jama.com (Reprinted) JAMA November 7, 2017 Volume 318, Number 17 1693
© 2017 American Medical Association. All rights reserved.
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Research Original Investigation Comparisons of Interventions for Preventing Falls in Older Adults
1694 JAMA November 7, 2017 Volume 318, Number 17 (Reprinted) jama.com
© 2017 American Medical Association. All rights reserved.
comparisons, 9 (3.3%) were statistically significant (eTable 5 in the Supplement). Of these, 1 intervention (combined osteoporosis treatment, calcium supplementation, and vita- min D supplementation) was associated with a lower risk of hip fracture relative to usual care (OR, 0.18 [95% CI, 0.05 to 0.62]; ARD, −1.70 [95% CI, −2.92 to −0.48]). An additional 22 interventions were not significantly associated with a lower risk of hip fractures than usual care.
Quality of Life Although 32 RCTs (18 521 participants) provided data on quality-of-life measures (eTable 10 in the Supplement), only 2 pairwise meta-analyses were possible (eTable 9 in the Supplement). Exercise was not significantly associated with improvement in quality of life as measured by the SF-36 or SF-12 physical component summary score com- pared with usual care (mean difference, −0.06 [95% CI, −0.90 to 0.77]; 2 RCTs; 1206 participants). Similar results
were obtained for the SF-36 or SF-12 mental component summary score (mean difference, 0.29 [95% CI, −1.00 to 1.58]; 2 RCTs; 1206 participants).
Harms Fifty-seven of the RCTs (24 558 participants) reported no intervention-related harmful events in any study group, and another 62 RCTs (39 596 participants) reported 1 or more harms (eTable 11 in the Supplement). Only 2 pairwise meta- analyses were possible (eTable 9 in the Supplement). Exer- cise was not significantly associated with an increased risk of muscle soreness compared with usual care (OR, 4.97 [95% CI, 0.35 to 70.38]; ARD, 0.13 [95% CI, −0.02 to 0.70]; 2 RCTs; 1021 participants). Supplementation with calcium and vita- min D was not significantly associated with an increased risk of gastrointestinal harm compared with usual care (OR, 1.05 [95% CI, 0.52 to 2.09]; ARD, 0.001 [95% CI, −0.01 to 0.03]; 2 RCTs; 3853 participants).
Figure 3. Network Geometry for Fallers
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17 18 19
20
21
22
23
24
25 26
27
282930
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
4849
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77 78
Order Code
Treatment Abbreviation
1 uc 2 di 3 so 4 ex 5 em+wb 6 ea 7 fl 8 de-al 9 de-hp
10 va 11 su-ey 12 su-PM 13 ca 14 vi-d 15 op-tx 16 pa-qi 17 cb 18 cl-qi 19 bf 20 mf 21 di+ex 22 di+vi-d 23 ex+so 24 ex+va 25 ex+vi-d 26 ex+pa-qi 27 ex+sy-qi 28 ex+mf 29 ea+ex 30 ea+va 31 ea+pa-qi 32 de-hp+pa-qi 33 de-or+ex 34 ca+vi-d 35 op-tx+vi-d 36 pa-qi+va 37 pa-qi+vi-d 38 cb+ex 39 cb+pa-qi
Order Code
Treatment Abbreviation
40 cl-qi+de-hp 41 cl-qi+pa-qi 42 cl-qi+mf 43 bf+pa-qi 44 bf+cl-qi 45 mf+pa-qi 46 ex+pa-qi+so 47 ex+mf+pa-qi 48 ex+mf+sy-qi 49 ea+ex+va 50 ea+ex+vi-d 51 ea+ex+mf 52 ea+mf+sy-qi 53 cp+de-ft+pa-qi 54 ca+di+vi-d 55 ca+op-tx+vi-d 56 ca+pa-qi+vi-d 57 cb+ex+pa-qi 58 cb+cl-qi+pa-qi 59 cl-qi+ex+pa-qi 60 cl-qi+ex+mf 61 cl-qi+ea+pa-qi 62 cl-qi+de-hp+pa-qi 63 cl-qi+mf+pa-qi 64 bf+ex+pa-qi 65 bf+cl-qi+pa-qi 66 bf+cl-qi+sy-qi 67 ea+ex+pa-qi+sy-qi 68 de-hp+ea+ex+pa-qi 69 ca+cl-qi+mf+vi-d 70 ca+ea+pa-qi+vi-d 71 cl-qi+ex+mf+pa-qi 72 cl-qi+mf+pa-qi+so 73 bf+cp+ex+pa-qi 74 bf+cl-qi+ex+pa-qi 75 ca+cb+di+ex+vi-d 76 ca+cl-qi+di+pa-qi+vi-d 77 cl-qi+de-al+ex+mf+pa-qi 78 bf+ea+ex+pa-qi+va
Network geometry for 158 randomized clinical trials (107 300 patients). Each treatment node indicates an intervention and is weighted according to the number of patients who received the particular intervention. Each edge (line connecting the nodes) is weighted according to the number of studies and
directly compares the treatments it connects. See Table 1 for expansions of treatment abbreviations. The coding guide, which provides a description of each intervention component, can be found in eTable 1 of the Supplement.
Comparisons of Interventions for Preventing Falls in Older Adults Original Investigation Research
jama.com (Reprinted) JAMA November 7, 2017 Volume 318, Number 17 1695
© 2017 American Medical Association. All rights reserved.
Discussion
Exercise alone and various combinations of interventions were associated with lower risk of injurious falls compared with usual care. Choice of intervention may depend on
patient and caregiver values and preferences. Combinations of interventions, including exercise, vision assessment and treatment, environmental assessment and modification, multifactorial assessment and treatment, and vitamin D supplementation were associated with preventing injurious falls compared with usual care. The combination of exercise
Figure 4. Network Geometry for Fractures and Hip Fractures
uc
di
so
ex
fl
de–al
su–ey
ca
vi–d
op–tx
op–tx+vi–d
pa–qi
cl–qi
bf
mf
di+ex
ex+pa–qi
ex+mf
ea+va
ea+pa–qi
de–hp+pa–qi ca+vi–d pa–qi+vi–d
cl–qi+de–hp
cl–qi+mf
bf+su–pm
bf+cl–qi
ea+ex+mf
cp+de–ft+pa–qi
ca+op–tx+vi–d
ca+pa–qi+vi-d
cb+cl–qi+pa–qi
cl–qi+ex+pa–qi
cl–qi+ex+mf
cl–qi+mf+pa–qi
bf+cl–qi+pa–qi
de–hp+ea+ex+pa–qi
ca+ea+pa–qi+vi–d
ca+cl–qi+mf+vi–d
cl–qi+ex+mf+pa–qi
cl–qi+mf+pa–qi+so
bf+cp+ex+pa–qi
ca+cl–qi+di+pa–qi+vi–d
FracturesA
Hip fracturesB
uc
so
ex
fl
de–al
su–ey
ca
vi–d
pa–qi
bf
mf
ex+pa–qi
ea+va
de–hp+pa–qi
ca+vi–d cl–qi+de–hp
cl–qi+pa–qi
cl–qi+mfcp+de–ft+pa–qi
ca+op-tx+vi–d
cl–qi+de–hp+pa–qi
cl–qi+mf+pa–qi
de–hp+ea+ex+pa–qi
cl–qi+mf+pa–qi+so
cl–qi+de–al+ex+mf+pa–qi
A, Network geometry for 68 randomized clinical trials (86 491 patients). B, Network geometry for 39 randomized clinical trials (52 281 patients). Each treatment node indicates an intervention and is weighted according to the number of patients who received the particular intervention. Each edge (line connecting the nodes) is weighted according to the number of studies and directly compares the treatments it connects. See Table 1 for expansions of treatment abbreviations. The coding guide, which provides a description of each intervention component, can be found in eTable 1 of the Supplement.
Research Original Investigation Comparisons of Interventions for Preventing Falls in Older Adults
1696 JAMA November 7, 2017 Volume 318, Number 17 (Reprinted) jama.com
© 2017 American Medical Association. All rights reserved.
and vision assessment and treatment was probably the intervention most strongly associated with reduction in injurious falls.
These results suggest that encouraging patients to exer- cise, undergo a vision assessment, and consider osteoporo- sis therapy (for those at risk), given the potential impact of these interventions in preventing injurious falls. Other com- binations of interventions to consider include exercise, patient-level and clinic-level quality improvement strate- gies, multifactorial assessment and treatment; exercise, patient-level quality improvement strategies, hip protectors, and env ironmental assessment and modific ation; and orthotics and exercise in patients at risk for falls. The results suggest focusing on implementing patient-level quality improvement strategies (eg, patient education and patient reminders) and clinic-level quality improvement interven- tions (eg, audit and feedback) to increase uptake of this evi- dence. The results also suggest that calcium and vitamin D supplementation may decrease fractures, as may osteoporo- sis therapy plus calcium and vitamin D supplementation. However, the results indicate the need for a tailored ap- proach; subgroup analyses showed that the combination of exercise, environmental assessment and modification, and multifactorial assessment and treatment was associated with an increased risk of injurious falls among patients who had fallen previously. In addition, the combination of exer- cise, patient-level quality improvement strategies, and social engagement was associated with increased fall risk. Exercise may increase fall risk in some individuals because these people become more mobile as their strength increases; patients can be made aware of this situation, but any cau- tionary advice must be balanced with the need to improve mobility and avoid deconditioning. This finding also raises the issue of the type of exercise to recommend, such as exer- cise focused on enhancing balance.52 Health care managers might consider the use of clinic-level quality improvement strategies, such as clinician reminders and audit and feed- back, to increase uptake of multifactorial assessment and treatment and of vitamin D supplementation to reduce inju- rious falls. As well, for patients in long-term care settings, hip protectors, environmental assessment and modification, exercise, and patient-level quality improvement strategies are potential options to reduce falls.
A 2015 systematic review and network meta-analysis examining vision and risk factor interventions to prevent falls included 7 RCTs with 2723 participants; interventions combining vision assessment and treatment and multifacto- rial assessment and treatment were found to be the most effective.53 The current systematic review was much larger (with an additional 276 RCTs and 157 187 participants; eRef- erences in the Supplement) and includes information on the effectiveness of quality improvement strategies and multi- factorial assessment and treatment. Although the authors of a systematic review on exercise54 did not conduct network meta-analysis, their results were similar to those reported here, which suggests that exercise might be associated with decreased falls in older adults, but the type of exercise should be tailored to the individual.
The authors of RCTs included in this review could have improved their studies by conducting adequate allocation concealment (which is possible in any RCT), ensuring that results were not influenced by contamination bias, and reporting all outcomes. Most RCTs were completed within 6 months, but longer-term follow-up and confirmation of the sustainability of these interventions are required. In addi- tion, few studies were conducted in the acute care setting, despite falls in hospitals often being considered during hos- pital accreditation processes.
Strengths of the review process include reviewers work- ing in pairs across all levels of screening, data abstraction, and risk-of-bias appraisal; cleaning of the data by a third re- viewer; and following the guidance of the International Soci- ety for Pharmacoeconomics and Outcomes Research in con- ducting statistical analyses.55
This study had several limitations. The published protocol included both the falls rate and costs as secondary outcomes. However, because few studies reported these outcomes consistently, these outcomes could not be ana- lyzed directly; rather, data for falls rates were converted to number of falls. As well, another outcome, quality of life, as measured by SF-12 or SF-36 summary component measures or EuroQol-5D, was added.17-19 Some of the planned sub- group analyses and sensitivity analyses were not conducted bec ause of insuffic ient data. Although the point esti- mate was similar to the overall OR, the results were no lon- ger statistically significant for the injurious falls network meta-analysis when only studies with a low risk of contami- nation bias were included. However, because most of the studies (67%) were assessed as having an unclear risk of contamination bias, the power of this sensitivity analysis was limited by the lower number of studies that could be included. This limitation suggests that improvements in re p o r t i ng a re re q u i re d . Mo s t n e t wo r k m e t a - a n a l y s e s included numerous interventions, with sparse data for the treatment comparisons; additional analyses, using the mod- els suggested by Welton et al56 and Caldwell and Welton57
to account for sparseness, could be conducted in the fu- ture. Scanning the reference lists of 32 additional studies from the updated search and inclusion of an unpublished conference abstract58 and a non-English paper59 were not possible. Because of the large number of comparisons in the network meta-analyses, multiplicity may have elevated the rate of false positives in the statistically significant results (type I error).60,61 Although P scores are based on the treatment effect estimates and their associated CIs, it is recommended that the P score values be interpreted along with the network meta-analysis point estimates and their precision.29
Conclusions Exercise alone and various combined interventions were as- sociated with lower risk of injurious falls compared with usual care. Choice of intervention may depend on patient and care- giver values and preferences.
Comparisons of Interventions for Preventing Falls in Older Adults Original Investigation Research
jama.com (Reprinted) JAMA November 7, 2017 Volume 318, Number 17 1697
© 2017 American Medical Association. All rights reserved.
ARTICLE INFORMATION
Accepted for Publication: September 28, 2017.
Author Affiliations: Knowledge Translation Program, Li Ka Shing Knowledge Institute, St Michael’s Hospital, Toronto, Ontario, Canada (Tricco, Thomas, Veroniki, Hamid, Cogo, Strifler, Khan, Robson, MacDonald, Thavorn, Wilson, Kerr, Hui, Straus); Epidemiology Division, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada (Tricco); Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada (Strifler); Toronto Rehabilitation Institute, University Health Network, Toronto, Ontario, Canada (Sibley); Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada (Sibley); Department of Family Medicine, David Braley Health Sciences Centre, McMaster University, Hamilton, Ontario, Canada (Riva); Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada (Riva); Clinical Epidemiology Program, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada (Thavorn); Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada (Holroyd-Leduc); Older Adult Program, Fraser Health, Surrey, British Columbia, Canada (Feldman); Department of Medicine, University of Alberta, Edmonton, Alberta, Canada (Majumdar); Department of Physical Therapy, University of Toronto, Toronto, Ontario, Canada (Jaglal); Department of Medicine, University of Toronto, Toronto, Ontario, Canada (Straus).
Author Contributions: Drs Straus and Tricco had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: Tricco, Sibley, Holroyd-Leduc, Feldman, Majumdar, Jaglal, Straus. Acquisition, analysis, or interpretation of data: Tricco, Thomas, Veroniki, Hamid, Cogo, Strifler, Khan, Robson, Sibley, MacDonald, Riva, Thavorn, Wilson, Holroyd-Leduc, Kerr, Majumdar, Hui, Straus. Drafting of the manuscript: Tricco, Thomas, Veroniki, Cogo, Sibley, Straus. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Veroniki, Hamid, Hui, Straus. Obtained funding: Tricco, Sibley. Administrative, technical, or material support: Thomas, Cogo, Riva, Thavorn, Kerr, Straus. Supervision: Tricco, Straus. Other - Knowledge user input: Feldman. Other - Editing & content analysis: Wilson.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Tricco reports receiving a Tier 2 Canada Research Chair in Knowledge Synthesis grant. Dr Veroniki reports receiving a Canadian Institutes of Health Research (CIHR) Banting Postdoctoral Fellowship Program grant. Dr Sibley reports receiving a Tier 2 Canada Research Chair in Integrated Knowledge Translation in Rehabilitation Sciences grant. Dr Riva reports board membership with the Ontario Chiropractic Association. Dr Holyroyd-Leduc reports working as an associate editor for the Canadian Medical Association Journal. Dr Majumdar
reports support from the Faculty of Medicine and Dentistry and the Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta (holds the Endowed Chair in Patient Health Management). Dr Straus reports receiving a Tier 1 Canada Research Chair in Knowledge Translation grant. No other disclosures were reported.
Funding/Support: This research was funded by a CIHR Knowledge Synthesis Grant (KRS 289648).
Role of the Funders/Sponsors: CIHR had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Additional Contributions: We thank Joseph Beyene, PhD, McMaster University, for analyzing preliminary data; Alexander Leung, MD, University of Calgary, Sophia Tsouros, BHKin, University of Ottawa Evidence-based Practice Center, Alana Harrington, MSc, York University, Vera Nincic, PhD, St Michael’s Hospital, and Geetha Sanmugalingham, MSc, Tampa General Hospital, for screening and abstracting data from some studies; Laure Perrier, PhD, University of Toronto, for developing the literature search strategies; Patricia Rios, MSc, St Michael’s Hospital, for cleaning the data from the updated search and helping update statistics files and tables; Susan Le, HBSc, St Michael’s Hospital, for formatting the manuscript and managing the references; and Alissa Epworth, OCD, St Michael’s Hospital, for updating our search and obtaining the full-text articles. None of the aforementioned individuals received compensation for their role in the study beyond regular salary. Additionally, we thank Becky Skidmore, MLS, Ottawa Health Research Institute, who received compensation for peer-reviewing the MEDLINE search strategy; and Peggy Robinson, BSc, an independent editorial consultant, who received compensation for provision of copyediting services.
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