Ranibizumab versus Verteporfin for Neovascular Age-Related Macular Degeneration
2006 · paper · Clinical trials
A randomized trial of 423 patients comparing monthly ranibizumab injections with verteporfin photodynamic therapy for predominantly classic neovascular macular degeneration. At one year, 94–96% of ranibizumab patients lost fewer than 15 letters, versus 64% on verteporfin; ranibizumab was reported as superior.
3 findings
Substance Text says "The mean lesion area increased in the verteporfin group to 2.56 optic-disk areas", but Table 2 gives 2.56±3.09 as the mean change from baseline (baseline mean 1.88, Table 1). It should read 'by 2.56'.
- p. 7 Results, morphologic end points, left column
The mean lesion area increased in the verteporfin group to 2.56 optic-disk areas
- p. 8 Table 2, Change in size of lesion, Verteporfin
2.56±3.09
- p. 4 Table 1, Size of lesion mean, Verteporfin
1.88±1.40
Judge's note: Page 7 text uses "to 2.56". Page 8 Table 2 row "Change in size of lesion (optic-disk area)", Mean 2.56±3.09 for verteporfin. Page 4 Table 1 baseline lesion size for verteporfin is 1.88±1.40. In the same sentence the ranibizumab values 0.36 and 0.28 are described as increases, which matches the change values in the table. The preceding sentence also uses 'by' for the CNV change of 1.63. As printed, a reader would take 2.56 to be the 12-month area when it is the increase.
Second check: another model agreed
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Reference or label "In the MARINA study, with 2 years of study treatment, the rates of events classified as arterial thromboembolism according to APTC criteria were similar among the treatment groups.13". Reference 13 is the pegaptanib trial (Gragoudas et al.); MARINA is reference 14.
- p. 11 Discussion, right column
APTC criteria were similar among the treatment groups.13
- p. 13 Reference 13
Gragoudas ES, Adamis AP, Cunning-ham ET Jr, Feinsod M, Guyer DR. Pegap-tanib for neovascular age-related macular degeneration.
- p. 11 Discussion, paragraph 4
similar among the treatment groups.13
- p. 11 Discussion, paragraph on APTC events
similar among the treatment groups.13 Follow-up is continuing
Judge's note: Page 11 image shows superscript 13 on this sentence, while MARINA is cited as 14 twice in the same column. Page 13 reference list: 13 = Gragoudas ES et al., "Pegaptanib for neovascular age-related macular degeneration", NEJM 2004; 14 = Rosenfeld PJ et al., "Ranibizumab for neovascular age-related macular degeneration", NEJM 2006. The pointer is wrong.
Second check: another model agreed
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Wording Sample-size assumption: "assuming a rate of 84% in each ranibizumab group and 67% in the sham verteporfin group". The comparator arm received active verteporfin; the ranibizumab arms received the sham verteporfin.
- p. 4 Statistical analysis, sample size paragraph
group and 67% in the sham verteporfin group.
- p. 4 Statistical Analysis
67% in the sham verteporfin group
Judge's note: Page 4 image confirms the wording. Earlier in the same sentence the comparator is called "the verteporfin group", and that is its name throughout the paper. In this design the ranibizumab arms received sham verteporfin, so the label names the wrong arm. The intended arm is clear.
Second check: another model agreed
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3 minor (typos and the like; most checked by the judge only)
Wording Occult CNV defined as leakage that "appears in the late phases of disease", where the parallel classic definition refers to phases of the angiogram.
- p. 2 Introduction, first paragraph
leakage is less intense and appears in the late phases of disease)
- p. 2 Introduction, paragraph 1
leakage is less intense and appears in the late phases of disease).
Judge's note: Page 2 image: "classic (in which intensely bright fluorescence is seen in early phases of the angiogram and leaks in late phases) and occult (in which leakage is less intense and appears in the late phases of disease)". The definition is angiographic ("as seen on fluorescein angiography"), so 'late phases' should refer to the angiogram. 'Disease' looks like a slip. The meaning can still be recovered from context, so this is minor wording.
Second check: another model agreed
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Wording Text: "There was no increase in the ranibizumab groups in mean systolic or diastolic blood pressure". Table 3 gives the 0.5-mg mean change from baseline as "−2/1" mm Hg, a diastolic change of +1.
- p. 9 Results, adverse events, left column
There was no increase in the ranibizumab groups in mean systolic or diastolic blood pressure
- p. 10 Table 3, Mean change in blood pressure from baseline
−2/1
Judge's note: Page 9 text and page 10 Table 3 row "Mean change in blood pressure from baseline — mm Hg": verteporfin 0.1/0.3, 0.3 mg −2/−2, 0.5 mg −2/1. Taken literally, a +1 mm Hg diastolic change is an increase. The authors may mean no clinically meaningful increase, so this is a minor wording point.
Second check: another model agreed
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Typo Dr. Heier's disclosure reads "and grant support from Genentech, Eyetech, Pfizer, and Eli Lilly Theragenics.", where two company names run together with no separator or clause.
- p. 12 Disclosures, Dr. Heier
and Eli Lilly Theragenics.
Only the authors can say what is right here.
Judge's note: Page 12 image confirms the text as printed: no comma or other words between 'Eli Lilly' and 'Theragenics'. Theragenics appears separately in the consulting-fee list. A word or clause seems to be missing, and only the authors can say what was intended.
Second check: none (judge only)