PONE-D-21-22827Correct use and ease-of-use of placebo ELLIPTA dry-powder inhaler in adult patients with chronic obstructive pulmonary diseasePLOS ONE

Dear Dr. Renu Jain,

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I have read the journal’s policy and the author of this manuscript have the following competing interests: RJ, KC, RS, LS, and JR report employment with, and stock/share ownership in, GlaxoSmithKline plc. during study conduct. KC is currently employed by AstraZeneca and LS is no longer employed by GlaxoSmithKline plc. TMS received research support from West-Ward Pharmaceuticals, Theravance Biopharma US, Inc., GlaxoSmithKline plc., Pearl Therapeutics, Chiesi, AstraZeneca, Novartis, Boehringer Ingelheim, Forest, Compleware, Evidera, Oncocyte, Teva, Vapotherm, Sunovion, Proterix BioPharma, Seer, and Sanofi. TMS has also received speaker fees from GlaxoSmithKline plc., Mylan Inc./Theravance Biopharma US, Inc., and Sunovion, and consulting fees from Vapotherm. DIB received grant/research/clinical trial support from GlaxoSmithKline plc., Teva, AstraZeneca, Pearl Therapeutics, Novartis, Genentech, Inc., Merck, Boehringer Ingelheim, Amgen, Aimmune, Shire, and Biocryst and consulted/participated in advisory boards for GlaxoSmithKline plc., ALK America, Gerson-Lehman, and Guidepoint Global.

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Additional Editor Comments:

This retrospective study on pooled data coming from 4 studies assessing use of Ellipta DPI in COPD patients is of clinical interest and well-written. Please, answer point by point to the two reviewers to increase the quality of the manuscript.

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Reviewers' comments:

Reviewer's Responses to Questions

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: Yes

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

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This is a retrospective study on pooled data coming from 4 studies assessing use of Ellipta DPI in COPD patients. The paper is of interest for the readers of the Journal and results sound.

I have the following question that the Authors need to address. Scrutiny of the figure 3 seems to indicate that there is a significant (and not a trend as reported in the text) difference in the % of patients using Ellipta correctly between patients aged 40-64 and those older than 75 yr (see CIs bewteen groups). Please check it with appropriate statiscal methods.

Reviewer #2: I would like to congratulate the authors for this interesting and well-written work. I have just

a few comments that should be addressed in the manuscript.

- The secondary endpoint was the percentage of patients rating the placebo

ELLIPTA DPI as “easy” or “very easy” to use at study end, as assessed by

questionnaires in patients deemed to be using the placebo ELLIPTA DPI correctly at

study end. What does it mean? Did the Authors consider only question 1 of the questionnaires?

- The secondary outcome has been assessed by mean of unvalidated tools. This is something that should be discussed. The use of unvalidated questionnaires to evaliutate the patient reported outcomes is a limit.

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Reviewer #1: Yes: Federico Lavorini

Reviewer #2: Yes: Ilaria Baiardini

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Correct use and ease-of-use of placebo ELLIPTA dry-powder inhaler in adult patients with chronic obstructive pulmonary disease

PONE-D-21-22827R1

Dear Dr. Renu Jain,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Manlio Milanese

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

The article, in its revised version, is suotable for publication

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

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2. 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 #2: Yes

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

Reviewer #2: Yes

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

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

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

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: (No Response)

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: Yes: Ilaria Baiardini

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