PONE-D-23-06022A prospective, cross-sectional study evaluating the psychological impact of the COVID-19 vaccination campaign in patients with cancer: The VACCINATE studyPLOS ONE

Dear Dr. Milella,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Jun 24 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

We look forward to receiving your revised manuscript.

Kind regards,

Suzanne Rose, PhD

Academic Editor

PLOS ONE

Journal requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at 

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and 

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Thank you for stating the following financial disclosure: 

   "YES. This work was supported by the ORCHESTRA project; the ORCHESTRA project has received funding from the European Union’s Horizon 2020 research and innovation program [grant number 101016167]."

Please state what role the funders took in the study.  If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." 

If this statement is not correct you must amend it as needed. 

Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf.

3. PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager. Please see the following video for instructions on linking an ORCID iD to your Editorial Manager account: https://www.youtube.com/watch?v=_xcclfuvtxQ

4. We note that you have included the phrase “data not shown” in your manuscript. Unfortunately, this does not meet our data sharing requirements. PLOS does not permit references to inaccessible data. We require that authors provide all relevant data within the paper, Supporting Information files, or in an acceptable, public repository. Please add a citation to support this phrase or upload the data that corresponds with these findings to a stable repository (such as Figshare or Dryad) and provide and URLs, DOIs, or accession numbers that may be used to access these data. Or, if the data are not a core part of the research being presented in your study, we ask that you remove the phrase that refers to these data.

5. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. 

Additional Editor Comments:

Please carefully review for readability in the English language to ensure sentence structure is solid and understandable. Please also avoid abbreviating pts or pt throughout and instead use the word patient or patients. 

I appreciate the novelty of the research you have provided and invite you to review the comments below from the two reviewers. I also do apologize for the length of time spent in securing reviewers for this important work. Thank you for your patience as high-quality reviewers were secured to provide the best possible feedback to your work. 

[Note: HTML markup is below. Please do not edit.]

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: Partly

Reviewer #2: Yes

**********

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

Reviewer #1: I Don't Know

Reviewer #2: Yes

**********

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

**********

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: No

Reviewer #2: Yes

**********

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: General comment: Thank you for the opportunity to revise the manuscript entitled “A prospective, cross-sectional study evaluating the psychological impact of the COVID-19 vaccination campaign in patients with cancer: The VACCINATE study”.

This paper surveyed a large cohort of adult cancer patients on their anxiety and distress symptomatology and attitude toward a COVID-19 vaccination. Participants were identified at two oncology wards in Italy (Verona and Veneto region). Patient reported outcomes were measured in patients who underwent the first or second dose of COVID-19 vaccination.

The topic is a valuable one and the paper can provide a contribution to the literature in this area, although there are some limitations in terms of methodology and results.

Comment 1: The article is reasonably well organized and written. While quite well-written in English, throughout the paper there are some linguistic inaccuracies and imprecision in language that makes the meaning unclear (esp. in the methods section). Editing for clarity of communication is needed.

Comment 2: The title is misleading since the term “prospective, cross-sectional study” is

contradictory.

Comment 3: Regarding Abstract/Background: Please name the term (patients) in full first before abbreviating it. The term "psychological status" is somewhat inaccurate and should be replaced with a more precise term that better describes the constructs being measured. Regarding Abstract/Methods and findings: Please add some information on patient sample size, response rate and sociodemographic characteristics like median age and sex.

Comment 4: Regarding Introduction: The authors occasionally speak of "a substantial body of evidence" or "a growing body of evidence" (p.3., ll. 72/92) but refer only to a single citation, which does not really support the claim thus made.

Comment 5: Regarding Introduction: The term "active cancer patient" (p.3, l. 99) is somehow misleading. "Patients with active cancer" does seem to be more appropriate.

Comment 6: Regarding Introduction: The authors should clarify the objective of the study, as it is not sufficiently compelling to state that "results will be reported" without stating the specific intent.

I am not sure what "patient characteristics" means. The term should be described in more detail, i.e., whether it is sociodemographic and clinical characteristics.

Comment 7: Regarding Methods, Study Design and participants: The authors stated that they have assessed patients who refused the vaccination. Were additional variables collected describing them in terms of age, sex, tumor-specific variables to compare them to patients who received the vaccination?

Please move the sentence "the number of patients who refused vaccination was calculated" to the statistical analyses section (p. 4, line 112).

Comment 8: Regarding Methods, Study Design and participants: The authors should specify the eligibility criteria ii) confirmed diagnosis of cancer, since the term “active cancer” was previously introduced. Where there any exclusion criteria in terms of treatment, cancer site, stage, etc.?

Comment 9: Regarding Methods, Questionnaires: Please provide the appropriate references for the questionnaires used.

Is there a rationale for why the metric scale of the DT was structured categorically? Research support a cut-off score of 5 on the DT to indicate patients with clinically elevated distress levels.

I don't quite understand how the item "Do you think the vaccine makes you less afraid of contracting COVID-19?" is supposed to represent an interference with cancer treatments.

Comment 10: Regarding Methods, Statistical analysis: Please change the term “categorical variables” to “continuous variables” (p.5, l.150). Item number 3 mentioned in the statistical analysis for the primary outcome does not match with the item number from the description of study measures (where “interferences with anticancer treatments” refers to item number 2).

It is unclear what the authors meant by “significant interference” (p.5, l.158) – please clarify.

Some expressions used to describe the statistical analyses seem inappropriate, i.e. “main determinants”.

This section contains the objectives of the study, which should be mentioned in the last paragraph of the introduction. This section needs to be revised for a detailed description of all statistical analyses used to test the research questions.

The authors considered two independent samples (first and second vaccination) as one sample (p.5, ll.163-66). It is unclear what the authors mean by this, as the following results are based on comparisons between the two groups.

Comment 11: Regarding results, patient sample: p.5-6, ll. 174-78 This sentence needs rephrasing. It is not clear what the authors mean by ”significant imbalances”. Please clarify.

Comment 12: Regarding results, table 1 and other tables including p values: Please do not include the zero before the decimalpoint reporting the p values.

Comment 13: Regarding results, suppl. Table S3: The abbreviation of the distress thermometer must be DT, not TD. Please rectify. The decimals points of the p value amounts to three not four as displayed in table S3.

Comment 14: Regarding results, Figure 2: It was a little difficult to capture the diagrams. Consider a similar color scheme for similar items to make visual comparisons easier.

Comment 15: Regarding results, logistic regression analysis: The heading does not summarize the content of the section below it. It is not clear how the variables are related to each other (direction of the correlation). To me, it is confusing that response frequencies are reported within the results of the regression analysis. This section needs restructuring.

Comment 16: Regarding results, comparison of hospitals: It would certainly be interesting to describe the patient characteristics of the second sample from Camposampiero Hospital.

Comment 17: Regarding discussion: I’m not sure what the term “overall figures” means. Please clarify.

Please remove the references for tables in the discussion.

Comment 18: Regarding discussion: Unfortunately, a detailed description of the nature and significance of the results and their implications is lacking. The authors should better elaborate the implications for practice and further research needs.

Reviewer #2: I have few comments for the authors:

1) It is not clear the meaning of "Prospective.." in the title given that the study design is cross-sectional. I suggest to delete it from the title.

2) Number of enrolled patients: if I correctly understood, out of 1794 patients invited for vaccination, 1763 accepted vaccination and 1089 accepted to take part in the study-i.e., a participation rate of 61.8%. What are the characteristics of vaccinated patients that refuse study participation? The authors should comment on this potential selection bias.

3) The authors made hundreds of statistical tests: a comment on the role of multiple testing before acceptance of statistical significant differences would be welcomed.

**********

6. 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 #1: No

Reviewer #2: No

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Cross-sectional survey evaluating the psychological impact of the COVID-19 vaccination campaign in patients with cancer: The VACCINATE study

PONE-D-23-06022R1

Dear Dr. Milella,

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.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

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,

Suzanne Rose

Academic Editor

PLOS ONE

Additional Editor Comments (optional): Thank you for adequately addressing all comments and revising the manuscript as requested. 

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

**********

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

**********

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

Reviewer #2: Yes

**********

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

**********

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

**********

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: The authors have made a sound revision of the article and they have answered to my comments. - I do not have further comments

**********

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: No

**********