PONE-D-21-35970Understanding patient preferences in anti-VEGF treatment options for age-related macular degenerationPLOS ONE

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Dear Dr. Ozdemir,

This is an interesting paper. Please Review and address the comments from Reviewers #1 and #2.

Some passages might benefit from professional language editing. Please contact a professional language editor in order to address this issue.

My own comments are below:

Page 20 line 240. The reader does not really understand what means Class 2,1 etc… when not familiar with the LCL model. Would it be possible to explain a little bit to what these classes correspond to “subset of Pts with comparable answers to question…” “subgroup of patients with ….” Clusters of patients based on the similar questions answers ….. or who have similar …”

I see that you explain it later in Discussion line 292 “We found two groups of patients with distinct preferences.” You should explain it earlier as well to facilitate the reader work.

“Among 2, 3, and 4-class LCL models, the 2-class LCL model was chosen based on the significance of estimates, the number of low prevalence classes, and Akaike information criterion. Classes 1 and 2 constituted 56.5% and 43.5% the sample.”

First line of Discussion, “Compared to current anti-VEGF agents (e.g. aflibercept), New nAMD therapies (e.g., broluciuzmab,…” change for “new”.

Page 34 line 321 What do you mean by “We found two groups of patients with distinct preferences.”

Line 327: This sentence is unclear . “As out-of-pocket was much more important to the patients, the preference for an on-label medication is likely to be influenced by its relative price.”

Reviewers' comments:

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: I Don't Know

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3. Have the authors made all data underlying the findings in their manuscript fully available?

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Reviewer #1: Yes

Reviewer #2: No

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

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Reviewer #1: The authors present an interesting paper to help understand patient preferences for anti-VEGF therapy when they have neovascular AMD (nAMD). The authors found that patients prefer to have good vision as first preference followed by out of pocket cost as the most important factors in therapy. Other things like frequency of visits was third but not nearly as important as the other factors. They authors discovered this by means of a discrete choice experiment test they administered to their patients. Overall it is a well written and interesting paper. There are a few issues below to be rectified.

The main issue is that the authors split the data into classes 1 and classes 2. The authors should introduce the differences of classes 1 and 2 starting on line 244. The differences are explained starting on line 266. This should also be clarified to make the reasoning for the split more apparent.

In Table 2, I would reword Anti-VEGF prescription history to: Less than 1 year of treatment and Greater than 1 year of treatment.

More specific comments are below.

In the Introduction, line 59 aging is misspelled.

In the introduction, the authors mention that PRN treatment have demonstrated good outcomes as a treatment regimen for nAMD. Typically patients treated with a PRN fashion start to lose vision at the 2 year mark (HARBOR data) when compared with fixed interval dosing and patients in the SEVEN-UP study, at 7 years treated mainly by PRN did much worse than other studies that looked at fixed interval or treat and extend regimens. While PRN treatment is an option, it is inferior to fixed interval and treat and extend. The authors should clarify this point.

In the introduction, lines 68-70: This sentence should be reworded. Consider " These treatment regimens impose logistical and/or financial burden to the patients and their caregivers that often accompany the patients."

In the introduction, line 98-100, consider changing the sentence to "The results of this study may inform physicians on patient..."

On line 137, consider adding equivalent USD, Euros or Pounds to help international audiences to have an idea of cost.

On Table 2 , in the explanation, the authors mention that the percentages have been rounded to the nearest whole number. This is not correct. The authors have rounded the percentages to the nearest tenth. Correct this.

On line 223, change the sentence to " The vast majority of patients...

On line 226, remove the word "vast"

On line 241, consider changing the sentence to "No patients failed the attention test."

On line 298-300, This sentence should be reworded and clarified.

On line 320, the authors mention that injection frequency could be confounded by clinic visits. Another alternative that should be mentioned is that once patients are seen and evaluated, getting an intravitreal injection was already expected, so having another injection or not, was not a major factor.

On line 335, the authors mention that for about half of the patients in the sample, cost was most important attribute, but according to their percentages, it would be about one quarter of patients, and not total cost, but out of pocket cost. This should be clarified.

On line 347-349, the authors talk about home-monitoring, nothing in their study examined that variable and this conclusion cannot be drawn from their study. I would remove this sentence.

On line 349, "decentralized" is misspelled

Reviewer #2: Thank you very much for giving me the opportunity to review this interesting patient related outcome study. Ozdemir conducted a cross-sectional survey to identify which factors are most important for patients using established statistical techniques. Vision quality seemed to be the most important attribute, followed by out-of-pocket cost and convenience. Potential conflicts of interest have been clearly declared.

Overall, the study has been thoroughly designed and diligently conducted. There are some typos and some passages might benefit from professional language editing.

Minor issues:

Methods in abstract: bullet (3) should read >=21 years old, not <=

TnE is not a commonly used abbreviation for ‘treat-and-extend’.

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Reviewer #1: Yes: Sean Adrean

Reviewer #2: No

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Understanding patient preferences in anti-VEGF treatment options for age-related macular degeneration

PONE-D-21-35970R1

Dear Dr. Ozdemir,

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Marie-Helene Errera

Academic Editor

PLOS ONE

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