PONE-D-21-00518

Factors indicating intention to vaccinate with a COVID-19 vaccine among older U.S. Adults

PLOS ONE

Dear Dr. Navar,

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.

Both reviewers agree that the paper is well written and addresses a relevant and timely question. However, they also raise a number of concerns and provide comments and suggestions that, if properly addressed, will help to further improve the quality of the paper. I also outline my comments below. 

First, both reviewers believe that more should be done to connect your research with the literature. They provide useful references, and you will certainly find recent work very relevant to the topic. Moreover, R2 is less satisfied than R1 regarding the importance of the research, and I encourage you to address this consideration. One way to do it could be to provide more information about the “high risk” that you refer to on page 4, which increases the relevance of improving our knowledge about elderly people and their responses to the crisis.

Second, and it is a crucial point: the reviewers raise a number of concerns with the timing. I see three issues. As mentioned by R1, you should address the news around the Moderna’s vaccine. R2 details some concerns about the representativeness of the sample in regard of the ‘treatment’ (i.e pre/post Pfizer news). Finally, I would also like you to address the possibility that the treatment (or the effect of the news) might have potential heterogenous effects across subsamples (for examples, groups that are less likely to trust scientists). 

Third, on top of the representativeness in the pre/post-Pfizer news samples, both reviewers raise fair questions about the whole sample with clear comments related to respondents’ income, the opt-in panel from an iPhone app, the external validity, etc. 

See also the other concerns outlined quite clearly by the reviewers below. 

Please submit your revised manuscript by Mar 14 2021 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.

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We look forward to receiving your revised manuscript.

Kind regards,

Jean-François Daoust

Academic Editor

PLOS ONE

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5.Thank you for stating the following in the Competing Interests section:

"I have read the journal's policy and the authors of this manuscript have the following competing interests:

JN, MK, GJW, JW, TS, JS, PB, RZ, NE, JT, RJ are employees of Janssen and Johnson and Johnson.

JS reports personal fees from Amgen, personal fees from Bayer, personal fees from Merck, personal fees from Novartis, personal fees from Janssen, personal fees from Myokardia, personal fees from Blue Cross Blue Shield of Kansas City,  outside the submitted work;  In addition, Dr. Spertus has a patent Copyright to the KCCQ with royalties paid and Equity in Health Outcomes Sciences.

MT reports grants from Janssen Inc, personal fees from Medtronic Inc, personal fees from Abbott, grants from Boehringer lngelheim, grants and personal fees from Cardiva Medical, personal fees from iRhythm, grants from Bristol Myers Squibb, grants from American Heart Association, grants from SentreHeart, personal fees from Novartis, personal fees from Biotronik, personal fees from Sanofi, personal fees from Pfizer, grants from Apple, grants from Bayer, personal fees from Myokardia, personal fees from Johnson & Johnson, personal fees from Milestone Pharmaceuticals, outside the submitted work; and Dr. Turakhia is an editor for JAMA Cardiology.

LS reports personal fees from J&J, outside the submitted work.

MG receives research grant support from Janssen.

AMN receives consulting fees from Janssen for serving on the steering committee of the Heartline study.  In addition, Dr. Navar receives funding for research to her institution from Amgen and Janssen, and honoraria and consulting fees from Amarin, Amgen, Astra Zeneca, BI, Esperion, Lilly, Sanofi, Regeneron, NovoNordisk, Novartis, The Medicines Company, New Amsterdam, Cerner, 89Bio, and Pfizer, outside the scope of this work."

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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: Partly

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: No

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 piece reviews the demographic and attitudinal correlates of intentions to refuse vaccination for COVID-19, among older US adults (aged 65+) . The authors find that Black respondents and women are significantly more likely to intend to refuse vaccination than the 65+ population more generally. The authors also find that concerns about vaccine safety and efficacy were correlated with vaccination intentions, that most individuals who intend to refuse vaccination would nevertheless be willing to consult with a medical professional prior to doing so, and that intentions to vaccinate significantly increased following news of Pfizer's positive Stage 3 clinical results.

In general, I found this paper to be well written, substantively important, and methodologically rigorous. However, while I find the piece suitable for publication in a journal like this one, there are several areas where I believe the authors can offer additional conceptual and analytical detail. I have listed each of those concerns in the order in which I encountered each one in the manuscript. I also suggest several actions the authors might take to remedy those concerns, when revising this manuscript.

1. p. 4 (final paragraph): The authors do an excellent job motivating why it is important to study vaccination intentions among older Americans -- i.e., because they are particularly at risk of experiencing severe complications from contracting COVID-19.

However, I think the authors could do much more to put their research into dialogue with other work on the demographic correlates of COVID-19 vaccine refusal, as well as individuals' reasons for planning to refuse to vaccinate. For example, Callaghan et al (2021) report a nearly identical pattern of demographic correlates of vaccine hesitancy (i.e., that women and Black respondents are less likely to intend to vaccinate) as well as individuals' reasons for intending to not vaccinate (e.g., concerns about safety and efficacy).

Why might we expect to observe a similar (or, different?) pattern of results among older Americans? What do we learn about either the nature of COVID-19 vaccine hesitancy, or its potential health policy implications, from studying this group? I encourage the authors to consider expanding on this point when discussing the importance and novelty of their research.

2. p. 7, (penultimate paragraph) and pp. 15-16 (final Results sub-section): While I found the results of the pre/post Pfizer Clinical Trial news to be both interesting and informative, I have two major conceptual and methodological concerns about this analysis.

A. First, the study's enrollment period (11/6-20, 2020) included not only the release of Pfizer's clinical trial data (11/9), but Moderna's as well (11/16). It was unclear to me why the authors analyze the former, but not the latter, when estimating the effects of attention to positive vaccine-related news. (see: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html)

If the authors have the ability to replicate this analysis for the Moderna news, I encourage them to do so. If not (e.g., due to statistical power concerns), I encourage them to instead state what those concerns are.

B. I am also somewhat concerned about the estimation of news "treatment" effects in the pre vs. post Pfizer announcement groups. Because this study is correlational, it could be the case that the group of respondents interviewed later on in the survey administration process was systematically different from the pre-treatment group on demographic on other factors associated with vaccine uptake. For example, if men were more likely to take the survey later on in the administration process than women, the appearance of a news treatment effect could actually be the result of methodological artifact: i.e., a gender effect.

Although the authors lack the ability to test these claims longitudinally (which would allow for the estimation of *within* subject treatment effects; potentially alleviating the concerns mentioned above), the authors could instead address this concern by showing that the pre and post treatment subgroups were balanced with respect to (1) demographic characteristics and (2) reasons provided for intending/not intending to vaccinate. This would help ensure that attention to the vaccine-related news, and not differences between the subsamples, is responsible for the effects documented in the piece.

3. p. 8 (Table 1, row 1): the authors observe much lower levels of vaccine hesitancy among older survey respondents than has been typically observed in existing research on COVID-19 vaccine hesitancy (e.g., see the Callaghan et al., piece referenced in #1). It is somewhat at odds with recent findings (e.g., Daoust 2020) suggesting that older and younger people tend to have similar attitudinal and behavioral responses to the pandemic.

If the authors had a priori expectations regarding why older individuals might be more likely to intend to vaccinate (e.g., increased risk of experiencing severe health complications), I encourage them to expand on that rationale. If not, I invite them to speculate, perhaps in the piece's discussion section, as to why this might be the case. Either way, I think the authors should make more of an effort to put these findings into conversation with types of research cited above; i.e., to note that older folks may be exceptional in their intentions to vaccinate, and that the effect of age on vaccination intentions may differ from the effects of age in other attitudinally and behaviorally relevant domains.

4. p. 19: the authors do an excellent job recognizing the limitations of collecting responses from an opt-in sample of mobile health app users. In addition to the concerns listed already in the document, I encourage the authors to discuss potential limits of the mobile app platform *itself* as a recruitment mechanism for this study. In addition to demographic differences in mobile phone access and representation in clinical trial enrollment, individuals who choose to download and regularly consult phone applications related to their health may be healthier and/or more health-conscious than individuals who do not.

Consequently, while observing higher-than-typical rates of vaccine compliance among older individuals could reflect an age cohort effect (see: point #3 above), it could alternatively reflect differences in who chooses to use the platform (vs. the remainder of the 65+ population). I.e., it could be the case individuals enrolled in this study and who regularly consult the app are more concerned about their health, and therefore more likely to vaccinate; or that they are more attuned to the possibility of experiencing adverse vaccination effects?

I encourage the authors to expand on this point in the piece's discussion. If possible, comparing the demographic characteristics of the 65+ sample to known subpopulation demographic benchmarks (e.g., from the US Census) would help further underscore the representativeness of this sample.

Minor points:

- The authors refer to study participants as "Adults" in the piece's abstract. I think it would be more informative to list the study's target population here; i.e., US Adults aged 65 or older.

- On p.5, the authors note that the study was approved by "an IRB." Which IRB, specifically, approved this research? I encourage the authors to provide additional information here.

References

Callaghan, Timothy, Ali Moghtaderi, Jennifer A. Lueck, Peter J. Hotez, Ulrich Strych, Avi Dor, Erika Franklin Fowler, and Matt Motta. "Correlates and disparities of COVID-19 vaccine hesitancy." Available at SSRN 3667971 (2020).

Daoust, J. F. (2020). Elderly people and responses to COVID-19 in 27 Countries. PloS one, 15(7), e0235590.

Reviewer #2: Thank you for the opportunity to review "Factors Indicating Intention to Vaccinate with a COVID-19 Vaccine among Older U.S. Adults" for possible publication in PLOS One. This article relies on an original survey sample of adults enrolled in the Heartline clinical study to examine vaccination intentions among U.S. adults over the age of 65. The authors find several factors influence the decision to vaccinate, include race, gender, and beliefs about the safety and efficacy of COVID-19. While this paper is written on a timely and vital topic, a few issues need to be resolved before publication.

My first concern with the manuscript in its current form is the generalizability of the findings. I am concerned the findings shown here may not be representative of the U.S. population. For example, examining Table 1 shows that 92% of the sample identifies as White and over 50% of the survey has income over $75,000. While I believe it is important to study the vaccine intentions of this vulnerable population, I don't believe the sample the authors use are representative of the older population in the U.S. The authors do make reference to the limitations of their study in the discussion but I believe the authors need to be more cautious about the inferences readers should take from the article.

My second concern with the manuscript is I would have liked to see more literature on vaccine hesitancy, specifically related to COVID-19, given all the recent literature done on the issue. I would encourage the authors to look at articles from Callaghan et al.; Motta et al. (just to name a few). I also would have liked to see more framing up front about the importance of studying this vulnerable population.

Thank you again for the opportunity to review this research letter. With these key changes, I believe this manuscript will make a valuable addition to our understanding of the factors influencing individual decisions to vaccinate against COVID-19.

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Reviewer #1: Yes: Matt Motta

Reviewer #2: No

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Factors indicating intention to vaccinate with a COVID-19 vaccine among older U.S. Adults

PONE-D-21-00518R1

Dear Dr. Navar,

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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Kind regards,

Jean-François Daoust

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Congratulations!

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 #1: All comments have been addressed

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 #1: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

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 #1: Yes

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 #1: Yes

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 #1: I thank the authors for addressing both my conceptual and methodological concerns about this manuscript. I especially appreciated the inclusion of revised/additional analyses regarding the Moderna vaccine news, and the assessment of demographic balance across conditions. I found the updated manuscript to be significantly improved, and I now recommend publication.

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 #1: Yes: Matt Motta

Reviewer #2: No