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Effectiveness of multifocal and monofocal intraocular lenses for cataract surgery and lens replacement: a systematic review and meta-analysis

  • Sumitra S. Khandelwal
  • Jason J. Jun
  • Selene Mak
  • Marika Suttorp Booth
  • Paul G. ShekelleEmail author
Open Access
Review Article

Abstract

Purpose

Multifocal intraocular lenses (IOLs) offer the possibility of spectacle-free vision following cataract surgery compared to standard IOLs. Existing systematic reviews have generally concluded that multifocal IOLs result in better uncorrected near vision and greater spectacle independence, but more unwanted visual phenomena such as glare and halos, compared to monofocal IOLs. However, the certainty of evidence has been low for most outcomes, and pooled analyses have grouped together technologically obsolete lenses with newer lenses, potentially obscuring differences in performance across different lens types.

Methods

We performed a systematic review searching for RCTs of a multifocal IOL to a standard IOL or monovision that reported spectacle independence, visual acuity, or quality of life. Databases were searched from 1/1/2006–4/30/2017. Existing reviews were used to identify older studies. Title/abstract screening and data extraction were done in duplicate. Where possible, random effects meta-analysis was performed to synthesize results. In addition to comparing multifocal IOLs as a group to monofocal IOLs, we also compared newer diffractive lenses to obsolete or refractive lenses.

Results

Twenty-five eligible studies were identified. There was no difference in pooled estimates of corrected or uncorrected distance vision between multifocal and standard IOLs. Compared to monofocal IOLs, multifocal IOLs had statistically significantly better pooled results for the outcome of near vision (10 studies, 1025 patients, mean difference in logMAR of ‐0.26 (95% CI ‐0.37, ‐0.15)); spectacle dependence (12 studies, 1237 patients, relative risk of 0.27 (95% CI 0.20, 0.38)) and borderline significantly better quality of vision (6 studies, 596 patients, standardized mean difference of ‐0.54, (95% CI ‐1.12, 0.04)). Compared to monofocal IOLs, multifocal IOLs had statistically significantly worse pooled results for the outcomes of glare (9 studies, 847 patients, risk ratio of 1.36 (95% CI 1.15, 1.61) and halos (7 studies, 754 patients, risk ratio of 3.14 (95% CI 1.63, 6.08). Newer multifocal lenses had statistically significantly better outcomes than older diffractive lenses or refractive lenses, when compared to monofocal IOLs, in near vision, quality of vision, and risk of halos.

Conclusions

Multifocal IOLs compared to standard IOLs or monovision result in better uncorrected near vision and a higher proportion of patients who achieve spectacle independence, but greater risk of unwanted visual phenomena. Newer diffractive lenses may be better than refractive lenses in near vision and quality of vision outcomes, with less risk of halos than older diffractive lenses and refractive lenses.

(PROSPERO registration CRD42017069949)

Keywords

Multifocal intraocular lenses Cataract surgery Systematic review Meta-analysis 

Introduction

Expectations following cataract surgery have become increasingly high with many patients now desiring spectacle independence as an outcome. Multifocal intraocular lenses (MFIOL) may offer improved uncorrected near vision (UCVA) and spectacle independence, there may also be downsides including increases in unwanted visual symptoms such as glare, halo, and decreased contrast sensitivity [1].

An early systematic review, published in 2003, identified 8 eligible randomized controlled trials (RCTs) [2], and concluded based on pooled analyses that there were no statistically significant differences in distance vision (corrected or uncorrected) but better near vision and spectacle independence for patients receiving MFIOLs compared to monofocal intraocular lenses (IOLs). Patients with MFIOLs had statistically significantly more glare/haloes and worse contrast sensitivity than patients receiving monofocal IOLs. However this review only included older lenses that are currently not used. Two more systematic reviews, published in 2011 [3] and 2012 [4], included 20 and 29 studies, respectively, but only 8 and 5 of these were RCTs, and the latter study did not perform statistical pooling of results. Meanwhile the most recent Cochrane review [5] included newer lenses but pooled the data from new and old lenses together, concluding that distance visual acuity was no different between multifocal IOLs and monofocal IOLs; there is low-certainty evidence that near visual acuity was better with multifocal IOLs; there is low-certainty evidence that multifocal IOLs resulted in less spectacle dependence; and moderate-certainty evidence that visual phenomena like halos are more common with multifocal IOLs.

We therefore undertook a systematic review and meta-analysis to assess visual outcomes in patients receiving MFIOLs compared to either monofocal IOLs or monovision, and to compare results between newer and older IOLs. The key questions for this review were (1) What is the rate of spectacle independence of multifocal lenses compared to monofocal lenses; (2) What is the effectiveness in terms of distance and near vision; and (3) what are the harms of multifocal IOls versus monofocal IOLs in the setting of cataract surgery?

Methods

This is part of a larger review commissioned by the Department of Veterans Affairs [6]. A formal protocol was developed and submitted to PROSPERO (CRD42017069949) and exempt by the Institutional Review Board.

Search methods for identifying studies

We conducted searches in PubMed from 1/1/2006 to 4/30/2017 (Appendix for full search strategy) and included terms relating to “cataract” or “cataract extraction” and “lenses, intraocular” or “lens implantation, intraocular” and terms of multifocal lenses.

Study selection

Two team members independently screened the titles of retrieved citations. Inclusion criteria included RCTs of adults undergoing cataract extraction and comparing a multifocal lens with a standard monofocal lens or monovision and reporting spectacle independence. Additional outcomes were uncorrected and corrected distance vision, uncorrected near vision, validated measures of vision function (such as the VF-14) or quality of life. Harms included the harms of the surgery itself plus effects such as contrast sensitivity and aberrations like glare and halos. Outcomes could be measured at any time point following surgery. When multiple time points were reported, later time points were preferred to earlier time points.

Data collection and risk of bias assessment

Data extraction was completed in duplicate. All discrepancies were resolved with full group discussion. We abstracted data on the following: study design, single vs multi-site study, patient characteristics, intervention lenses, comparison monofocal lens, sample size, duration of follow-up, outcomes, and data needed for the Cochrane Risk of bias tool. RCTs were assessed for quality (risk of bias) with the Cochrane Risk of Bias tool [7] (see appendix).

Data synthesis and analysis

The sample size, mean, and standard deviation for each treatment group were extracted from articles that reported visual acuity using Snellen or logMAR measurements. Data that reported visual acuity using Snellen charts were converted into logMAR values. A mean difference (MD) was calculated for each comparison of multifocal and monofocal lenses. Similar data were collected for quality of life measures but since the scales varied, a standardized effect size (SMD) was calculated for each comparison. The sample size and number or percent of patients with spectacle independence was collected and a risk ratio (RR) was calculated for each comparison.

Meta-analyses were conducted for the visual acuity and quality of life outcomes using trials that reported a monofocal lens comparator. Because several trials reported comparisons of more than one intervention, two-level multilevel random effects models were estimated. [8] For the two trials that reported a monovision comparator, a fixed-effects meta-analysis was performed [9].

We categorized lenses as “refractive” (AMO Array SA40, AMO Rezoom NXG1, Storz Truevista, Hoya Isert PY60MV); “older diffractive” if they were no longer in use (3M 815LE, Pharmacia 808X, Laboratories Domilens Progress 3); or “newer diffractive” (AMO Tecnis ZM900, Alcon Restor SA60D3, Alcon Restor SN6AD1, Alcon Restor SN6AD3, Zeiss Acri-Lisa 366D, Zeiss Acri.tec Twin).

We pooled all eligible studies within outcome, and also performed stratified analyses that compared pooled results for newer diffractive lenses with refractive lenses and older diffractive lenses. We compared these pooled results using mixed-effects meta-regression.

Test of heterogeneity was reported using the I2 statistic [10]. Values of the I2 statistic close to 100% represent high degrees of heterogeneity. Begg rank correlation [11] and Egger regression asymmetry test [12] were used to examine publication bias. R version 3.4.1 was used for all statistical analyses.

Results

Description of the evidence

Our literature searches, expert recommendations, and reference mining identified 760 potentially relevant citations, of which 93 were included at the abstract screening. All 93 abstracts were included and obtained as full-text publications. Sixty-eight studies were excluded for the following reasons: No monofocal comparison group (n = 35); no multifocal comparison group (n = 8); not outcome of interest (n = 2); not RCT (n = 18); commentary (n = 1); background (n = 1); and duplicate (n = 3). A total of 25 publications were identified at full-text review that contributed to our final sample (Fig. 1). Details of included studies are provided in the Evidence Table (Appendix). A full list of excluded studies from the full-text review is included in Appendix D of the report [6].
Fig. 1

Literature flow chart

All of the studies were single-site with seven exceptions [13, 14, 15, 16, 17, 18, 19, 20]. Two studies were performed in the USA [16, 19], 4 studies were performed in China [22, 23, 24, 25]. Sample sizes were modest, 9 studies enrolled 75 patients or less [17, 21, 23, 26, 27, 28, 29, 30, 31], and only 2 studies enrolled more than 200 patients [13, 19]. The mean age of patients enrolled was 60–75 years of age, and patients were 50–60% female. Two studies compared the intervention lenses to monovision or mini-monovision [13, 28], where the two eyes have monofocal IOLs of different focal lengths, such that one eye sees predominantly distance vision and the other eye sees predominantly near vision. Nearly all studies reported visual acuity, 14 studies reported spectacle independence [13, 16, 18, 19, 20, 21, 24, 25, 26, 28, 30, 31, 32, 33] other outcomes were variably reported. We considered the two studies by Alio and colleagues [14, 27] and Allen and Haaskjold [17, 18] to potentially have overlapping patients. For the purpose of statistical pooling, we only used the Alio study with larger sample size and the Allen study because it had the outcomes of interest.

The quality of studies was in general low—one study was judged to be at low risk of bias across all domains [19] and three studies were at low risk of bias in all domains except one (Table 1) [16, 26, 31]. Since only two studies were reported as having had their protocol prospectively registered [13, 28], for example on clinicaltrials.gov, our ability to assess selective reporting bias is limited.
Table 1

Risk of bias for included studies

Effectiveness outcomes

Multifocal IOLs compared to monofocal IOLs—corrected and uncorrected distance vision

We identified 13 studies (with 24 comparisons and 1640 patients) [14, 18, 19, 20, 21, 22, 23, 24, 26, 31, 32, 34, 35] and 13 studies (with 23 comparisons and 1636 patients) [14, 16, 19, 20, 21, 24, 25, 26, 31, 32, 34, 35, 36] that reported corrected and uncorrected distance vision comparing multifocal IOLs to monofocal IOLs (that were not used for monovision). Figure 2 presents the data for uncorrected distance vision. The appendix presents the data for corrected distance vision. For both outcomes, there were no statistically significant differences in vision between the multifocal and monofocal IOLs.
Fig. 2

Multifocal IOLs compared to monofocal IOLs uncorrected distance VA (logMAR)

Five older studies were not included in this analysis because they reported visual acuity outcomes as binary data, the proportion of patients seeing equal or better than some certain value [23, 29, 30, 37]. Pooled analyses of these 4 studies were consistent with the pooled results from the studies with logMAR outcomes, namely that there were no statistically significant differences between multifocal and monofocal IOLs for this outcome (appendix Figs. B and C).

Newer diffractive lenses compared to refractive lenses

There were no statistically significant differences between results for newer diffractive lenses as compared to refractive lenses.

Multifocal IOLs compared to monofocal IOLs—uncorrected near vision

We identified 10 studies (with 13 comparisons and 1025 patients) that reported uncorrected near vision comparing multifocal IOLs to monofocal IOLs (that were not used for monovision) [16, 19, 20, 21, 23, 24, 25, 26, 31, 35]. Figure 3 presents the results. The random effects pooled estimate of effect in logMAR was − 0.26 (95% CI − 0.37, − 0.15) favoring multifocal IOLs. There was significant heterogeneity (I2 = 94.0%). There was no statistical evidence of publication bias (Begg’s test p = 0.86, Eggar’s test p = 0.30).
Fig. 3

Multifocal IOLs compared to monofocal IOLs uncorrected near VA (logMAR)

Six studies, four of which were not included in this analysis, reported their uncorrected near visual acuity outcomes as binary results, the proportion of patient seeing equal or better than some certain value [18, 23, 29, 33, 36, 37]. The pooled result of these studies was consistent with the pooled result of the studies with logMAR outcomes, with statistically significant benefits favoring multifocal IOLs (appendix Fig. D).

Newer diffractive lenses compared to refractive lenses

There was statistically significant evidence that newer diffractive lenses were better than refractive lenses (p = 0.01).

Multifocal IOLs compared to monofocal IOLs—spectacle independence

We identified 12 studies (with 17 comparisons and 1237 patients) that reported spectacle independence comparing multifocal IOLs to monofocal IOLs (that were not used for monovision) [16, 18, 19, 20, 21, 24, 25, 26, 30, 31, 32, 33]. Figure 4 presents the results. The random effects pooled estimate was a relative risk of 0.27 (95% CI 0.20, 0.38) favoring spectacle independence with multifocal IOLs. There was moderate heterogeneity (I2 = 40.2%). Begg’s and Eggar’s test for publication bias were p = .052 and .001, respectively. Removing the studies by Palmer and Kamlesh (showing 3x–10x greater benefits for spectacle independence than the other studies) made both publication bias tests nonsignificant while the result of better spectacle independence remained statistically significant.
Fig. 4

Multifocal IOLs compared to monofocal IOLs spectacle independence

Newer diffractive lenses compared to older lenses or refractive lenses

There was no evidence that newer diffractive lenses were better than refractive lenses or older diffractive lenses (p = 0.40 and 0.16, respectively).

Multifocal IOLs compared to monofocal IOLs—visual function/quality of life

Six studies presented data on visual function or quality of life for multifocal IOLs compared to monofocal IOLs [20, 24, 25, 26, 33, 35]. These studies included 9 comparisons and 596 patients. In 4 studies this outcome was measured with the VF-7 of VF-14, and in 2 studies it was measured as satisfaction with vision. The pooled random effects standardized mean difference was − 0.54 (95% CI − 1.12, 0.04) favoring multifocal IOLs (Fig. 5). There was substantial heterogeneity (I2 = 87.9%). There was no statistical evidence for publication bias (Begg’s test p = 0.35, Eggar’s test p = 0.58).
Fig. 5

Multifocal IOLs compared to monofocal IOLs quality of life

Newer diffractive lenses compared to refractive lenses

There was statistically significant evidence that newer diffractive lenses resulted in better visual function/satisfaction than refractive lenses (p < 0.01).

Multifocal IOLs compared to monofocal IOL as monovision

We identified 2 RCTs that compared multifocal IOLs to monofocal IOLs as monovision [13, 28]. We pooled these studies with a fixed-effect model. There was no statistically significant difference in uncorrected distance vision. Corrected distance vision was not reported. The pooled fixed-effect logMAR for uncorrected near vision was − 0.03 (95% CI − 0.07, 0.00) favoring multifocal IOLs. For spectacle independence, the pooled fixed-effect was a risk ratio of 0.40 (95% CI 0.29, 0.53) favoring multifocal IOLs. There was no statistical evidence of publication bias.

Harms

Surgical complications

Twelve of the 25 multifocal IOL studies specifically commented on the presence (or absence) of surgical adverse events, with varying degrees of detail [13, 18, 19, 22, 24, 25, 26, 27, 29, 31, 35, 37]. These outcomes are presented in Table 2. We considered the two studies by Alio to have potentially overlapping patients, so we include here only the 1 study by Alio that reported adverse events.
Table 2

Surgical Complications Reported in RCTs of Multifocal IOLs

Study

Intraoperative Complications

Postoperative Complications

Additional detail

El-Maghraby 1992 [37]

None

Yes

Decentered MF-IOL without vision issues (3)

Posterior capsule haze (1)

High surgically induced astigmatism (1)

Percival 1993 [29]

None

Yes

Decentered MF-IOL (3)

Allen 1996 [18]

None

None

None

Javitt 2000 [19]

Yes

Yes

Zonular dehiscence requiring IOL exchange (1)

Posterior capsule rupture (PCR) (1)

Cystoid macular edema (CME) (2)

Leyland 2002 [31]

Yes

Yes

Iris prolapse (2)

Bent haptics (2)

Damaged optic (2)

Posterior capsule opacification requiring YAG capsulotomy during study period (1)

Sen 2004 [35]

None

Yes

Late decentration of MF-IOL requiring IOL exchange (1)

Zeng 2007 [22]

None

Not mentioned

None

Alio 2011 [27]

None

None

Posterior capsule clear at 3 months

Cillino 2008 [26]

None

None

Specifically stated no CME, corneal edema, increased IOP, infection, IOL decentration, PCO

Zhao 2010 [25]

None

None

Specifically stated no PCR, high IOP, endophthalmitis, corneal decompensation, CME, IOL decentration, PCO

Peng 2012 [24]

None

None

None

Wilkins 2013 [13]

Yes

Yes

MF-IOL damaged on insertion (13)

Post-operative LASIK to correct residual refractive error (2)

IOL exchange due to dissatisfaction with MF-IOL (6)

Contrast sensitivity

There were 16 of the 25 multifocal IOL studies that reported contrast sensitivity [13, 16, 17, 18, 22, 23, 24, 25, 26, 28, 29, 30, 31, 32, 33, 35]. In the older studies, Allen, Haaskjold, and Kamlesh showed worse contrast sensitivity with multifocal IOLs at all light levels compared with monofocal lenses. Zeng showed statistically significant contrast sensitivity issues for the Array SA40N compared to the monofocal lens. Cillino showed better contrast sensitivity with the monofocal lens (AR40) and multifocal lens (ZM900) compared to the Array and ReZoom lenses (p = 0.038). Palmer showed monofocal IOLs with statistically significant better contrast sensitivity compared to the ZM900 and TwinSet lens at all spatial frequencies and luminance. Meanwhile, the difference was only significant between the monofocal and ReZoom at high spatial frequencies in scotopic conditions.

Ji showed lower contrast sensitivity with the ReSTOR lens compared to monofocal lens under all 6 spatial frequencies with mesopic and photopic conditions. Compared to monovision, multifocal lenses had less contrast sensitivity according to Wilkins (2013). Meanwhile Steinert and Peng showed worse contrast with the multifocal lenses at low contrast but no difference at higher contrast. Rosetti showed no difference in contrast sensitivity. Percival, Sen, and Leyland both showed less contrast sensitivity with multifocal IOLs that did not reach statistical significance.

Zhao showed no difference in contrast sensitivity between the ReSTOR lens (SA60AD3) and the monofocal lens (SA60AT). Labiris and colleagues reported no difference in contrast comparing “mini-monovision” with a refractive multifocal lens.

Glare

There were 16 of 25 multifocal IOL studies reporting glare following surgery [13, 16, 18, 19, 20, 21, 22, 24, 25, 26, 28, 29, 30, 31, 33, 35]. We pooled the nine studies reporting binary outcomes for glare, which totaled 847 patients [14, 19, 22, 26, 27, 30, 31, 34, 36]. The random effects pooled estimate was a risk ratio of 1.36 (95% CI 1.15, 1.61) favoring monofocal IOLs in minimizing glare. (Fig. 6) There was no heterogeneity (I2 = 0.0%). Begg’s and Eggar’s test did not show any evidence of publication bias.
Fig. 6

Multifocal IOLs compared to monofocal IOLs glare

Newer diffractive lenses compared to older lenses or refractive lenses

There was no evidence of differences between newer diffractive lenses and refractive lenses or older diffractive lenses.

Halos

There were 8 of 25 multifocal IOL studies reporting halos following surgery [13, 18, 24, 25, 26, 30, 33, 35]. We pooled the seven studies reporting binary outcomes for halo/unwanted images, which totaled 754 patients [13, 18, 25, 26, 30, 33, 35]. The random effects pooled estimate was a risk ratio of 3.14 (95% CI 1.63, 6.08) favoring monofocal IOLs. Heterogeneity was high (I2 = 64.2%). Begg’s test was nonsignificant (p = 0.40) but Eggar’s test for publication bias was significant (p = 0.01) (Fig. 7).
Fig. 7

Multifocal IOLs compared to monofocal IOLs halo

Newer diffractive lenses compared to older lenses or refractive lenses

There was statistically significant evidence that newer diffractive lenses were associated with a lower risk of increased halos than older diffractive lenses (p = 0.02) and borderline evidence that newer diffractive lenses were better than refractive lenses (p = 0.054).

Other visual phenomena

Palmer noted that more patients had complaints of dysphotopsias in the ZM900 group (81%) compared to the TwinSet (47%) and ReZoom (53%) and monofocal groups (48%) [32]. The authors also point out that no patient in the monofocal group complained on their own about photopsias compared to 16–18% of the multifocal IOL patients. Labiris commented on complaints of shadows following surgery being higher in the multifocal IOL group compared to mini monovision [28]. The study also commented there was no difference in stereopsis between multifocal IOL and mini monovision. This was in contrast to Jusufovic which described less stereopsis in the monofocal IOL group compared to the multifocal IOLs at higher levels of but not in lower levels [36].

Discussion

The principal findings from our systematic review and meta-analysis are that compared to monofocal lenses, multifocal intraocular lenses have benefits for UNVA and spectacle independence but also increased risk for reduced contrast sensitivity and other visual phenomena such as glare and halo. In addition, compared to monofocal IOLs newer MFIOLs had statistically significantly better outcomes than older lenses or refractive lenses for improved near vision, quality of vision and reduced unwanted visual phenomena.

In a majority of studies, intraoperative complications were reported as either none or there was no difference between multifocal and monofocal groups. There were few reports of late-onset complications in eyes treated with multifocal IOLs such as IOL decentration and posterior capsule opacification requiring further treatment. In one study, 6 patients ultimately required IOL exchange due to dissatisfaction with the multifocal lens [13]. For surgeons planning to implant these lenses, knowledge on how to address these issues is important.

Our results amplify and augment prior systematic reviews. We were able to include more eligible RCTs than any prior review, and additionally were able to perform subgroup analyses on certain categories of lens types. We found that newer diffractive lenses may result in better near visual acuity, better visual function/quality of life, and less risk of halos than refractive or older diffractive lenses, when compared to monofocal IOLs.

There were insufficient data for us to perform a specific analysis of intermediate vision outcomes or defocus curves, nor could we directly compare refractive and diffractive IOLs included in our review. Most of the included studies excluded patients due to pre-existing ocular conditions such as corneal astigmatism and macular disease. Detecting these conditions requires additional pre-operative testing such as corneal topography/tomography and macular optical coherence tomography. Additional resources may also be needed to counsel patients on the risks/benefits of multifocal IOLs and to manage suboptimal post-operative outcomes.

Our study has several limitations. As in all systematic reviews and meta-analyses, the primary limitation is the quantity and quality of the original trials with possibility of compromised by one or more key elements of bias. Only four studies were at low risk of bias in all [19] or four of the five domains [16, 26, 31] and only two trials were prospectively registered [13, 28], increasing concern about potential hidden methodological bias. Studies did not systematically report operative events and the need for re-operation, or the need for any additional resources pre-operatively or post-operatively in patients receiving multifocal IOLs as compared to monofocal IOLs. Also, for some pooled results, unexplained heterogeneity was substantial. This could be due to differences in the lenses being studied, the methods of the trials, the presence of publication bias, or random chance. Nevertheless, we judged that for most outcomes there were no serious limitations in terms of the consistency of the results. Lastly, we recognize that IOL technology is ever-evolving and that our review could not include newer IOLs and technologies that are currently in use or in late-phase clinical trials, and have yet to publish controlled trials comparing them to standard IOLs.

In summary, our review has expanded our knowledge about the potential benefits and risks of multifocal IOLs as compared to monofocal IOLs. Multifocal IOLs provide clear benefit in terms of uncorrected near visual acuity and spectacle independence but can cause unwanted and bothersome visual symptoms and reduced contrast sensitivity. Newer diffractive lenses may have advantages to older diffractive lenses or refractive lenses in terms of improved near vision, quality of vision and reduced unwanted visual phenomena. Additional resources may be required to evaluate, counsel, and manage patients receiving multifocal IOLs as compared to monofocal IOLs and these have not been quantified. Future research will be required to evaluate not only the potential benefits and risks but also the trade-offs of varying IOL technologies.

Notes

Funding

The Veterans Affairs Quality Enhancement Research Initiative provided financial support. The sponsor had no role in the design or conduct of this research.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This type of study is exempt by the Institutional Review Board.

Informed consent

For this type of study, formal consent is not required.

Supplementary material

417_2018_4218_MOESM1_ESM.docx (624 kb)
ESM 1 (DOCX 623 kb)

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© The Author(s) 2019

OpenAccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Authors and Affiliations

  • Sumitra S. Khandelwal
    • 1
    • 2
  • Jason J. Jun
    • 3
  • Selene Mak
    • 3
    • 4
  • Marika Suttorp Booth
    • 5
  • Paul G. Shekelle
    • 3
    Email author
  1. 1.Baylor College of MedicineHoustonUSA
  2. 2.Michael E DeBakey Veterans Affairs Medical CenterHoustonUSA
  3. 3.West Los Angeles Veterans Affairs Medical CenterLos AngelesUSA
  4. 4.Fielding School of Public HealthUniversity of CaliforniaLos AngelesUSA
  5. 5.Southern California Evidence-based Practice CenterRAND CorporationSanta MonicaUSA

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