Evidence map›Paper›PMID 26875003›Full record

Trial reportOphthalmology2016

A Crossover Design for Comparative Efficacy: A 36-Week Randomized Trial of Bevacizumab and Ranibizumab for Diabetic Macular Edema.

Henry E Wiley, Darby J S Thompson, Clare Bailey, Emily Y Chew, Catherine A Cukras, Glenn J Jaffe, Richard W J Lee, Erin K Loken, Catherine B Meyerle, Wai Wong and 1 more

Registry-linked trialAbstract readComparative StudyMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Ophthalmology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01610557 (A Phase II Randomized Study to Compare Anti-VEGF Agents in the Treatment of Diabetic Macular Edema), which is not on this map. Cited by 14 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 3 pooled it
2.7field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01610557 phase2completednot on this map

A Phase II Randomized Study to Compare Anti-VEGF Agents in the Treatment of Diabetic Macular Edema (CADME)

TypeinterventionalSponsorNational Eye Institute (NEI)Ran2012 to 2015Enrolled56ConditionsDiabetic Macular EdemaArmsRanibizumab, Bevacizumab
3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 3 syntheses or guidelines pooled it, 20 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 5 institutions in 2 countries.

Henry E WileyNational Eye Institute, National Institutes of Health, Bethesda, Maryland. Electronic address: wileyhe@nei.nih.gov.
Darby J S ThompsonThe Emmes Corporation, Rockville, Maryland.
Clare BaileyUniversity Hospitals Bristol National Health Service Foundation Trust, Bristol, United Kingdom.
Emily Y ChewNational Eye Institute, National Institutes of Health, Bethesda, Maryland.
Catherine A CukrasNational Eye Institute, National Institutes of Health, Bethesda, Maryland.
Glenn J JaffeDuke Reading Center, Durham, North Carolina.
Richard W J LeeUniversity Hospitals Bristol National Health Service Foundation Trust, Bristol, United Kingdom; School of Clinical Sciences, University of Bristol, Bristol, United Kingdom; National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital, National Health Service Foundation Trust, and University College London Institute of Ophthalmology, London, United Kingdom.
Erin K LokenThe Emmes Corporation, Rockville, Maryland.
Catherine B MeyerleWilmer Eye Institute, Johns Hopkins Hospital, Baltimore, Maryland.
Wai WongNational Eye Institute, National Institutes of Health, Bethesda, Maryland.
Frederick L FerrisNational Eye Institute, National Institutes of Health, Bethesda, Maryland.
National Eye Institute · USEmmes (United States) · USJohns Hopkins Hospital · USUniversity College London · GBUniversity Hospitals Bristol NHS Foundation Trust · GB

Funding

Phase II Study to Compare Anti-VEGF Agents in Treatment of DME (12-EI-0134)ZIAEY000515 · NEI · NATIONAL EYE INSTITUTE · PI WILEY, HENRY · 2012 to 2016
$363k
NEI NIH HHS HHSN263201200001CNIH HHS HHSN263201200001E
6 · The paper itself

Abstract

purposeTo investigate the comparative efficacy of bevacizumab (Avastin) and ranibizumab (Lucentis; both Genentech, Inc, South San Francisco, CA) for diabetic macular edema (DME) using a crossover study design.

designRandomized, double-masked, 36-week, 3-period crossover clinical trial.

participantsFifty-six subjects with DME involving the center of the macula in one or both eyes.

methodsMonthly intravitreous injections of bevacizumab (1.25 mg) or ranibizumab (0.3 mg).

main outcome measuresComparison of mean changes in visual acuity and central retinal thickness, tested using a linear mixed-effects model.

resultsBased on the linear mixed-effects model, the 3-month estimated mean improvement in visual acuity was 5.3 letters for bevacizumab and 6.6 letters for ranibizumab (difference, 1.3 letters; P = 0.039). Estimated change in optical coherence tomography (OCT) central subfield mean thickness (CSMT) was -89 μm for bevacizumab and -137 μm for ranibizumab (difference, 48 μm; P < 0.001). Incorporating cumulative treatment benefit, the model yielded a predicted 36-week (9-month) average improvement in visual acuity of 7.1 letters (95% confidence interval [CI], 5.0-9.2) for bevacizumab and 8.4 letters (95% CI, 6.3-10.5) for ranibizumab, and a change in OCT CSMT of -128 μm (95% CI, -155 to -100) for bevacizumab and -176 μm (95% CI, -202 to -149) for ranibizumab. There was no significant treatment-by-period interaction (i.e., treatment difference was constant in all 3 periods), nor was there a significant differential carryover effect from one period to the next.

conclusionsThis trial demonstrated a statistically significant but small relative clinical benefit of ranibizumab compared with bevacizumab for treatment of DME, using a markedly reduced sample size relative to a full comparative efficacy study. The effects on visual acuity and central retinal thickness for the 2 drugs are consistent with those reported at 1 year for the concurrent parallel-group trial by the Diabetic Retinopathy Clinical Research Network testing bevacizumab, ranibizumab, and aflibercept for DME. The 3-period crossover design allowed for meaningful and efficient comparison, suggesting that this approach may be useful for future comparative efficacy studies of anti-vascular endothelial growth factor drugs for DME.

Indexed as

AdultAgedAged, 80 and overAngiogenesis InhibitorsBevacizumabCross-Over StudiesDiabetes Mellitus, Type 1Diabetes Mellitus, Type 2Diabetic RetinopathyDouble-Blind MethodFemaleHumansIntravitreal InjectionsMacular EdemaMaleMiddle AgedAngiogenesis InhibitorsBevacizumabRanibizumabVascular Endothelial Growth Factor AVEGFA protein, human

Identifiers

PMID26875003
PMCPMC4988394
OpenAlexW2253123730

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.