Implications for Precision Accelerated Clinically Embedded Research (PACER): A novel technology-enabled approach to conducting minimal-risk research in outpatient community healthcare settings

Emma Friedman; Kelly Nicole Michelson; Shruti Sehgal; Russell Steans; Mohammad Hosseini; Matthew J. Baumann; Amanda K. Venables; Theresa L. Walunas; Justin Starren

doi:10.1371/journal.pone.0318533

Peer Review History

Original SubmissionJune 7, 2024
7 Jun 2024 Author Response https://doi.org/10.1371/journal.pone.0318533.r001
14 Aug 2024 Decision Letter - Roberto Scendoni, Editor PONE-D-24-21081Implications for Precision Accelerated Clinically Embedded Research (PACER): a novel technology-enabled approach to conducting minimal-risk research in outpatient community healthcare settingsPLOS ONE Dear Dr. Michelson, 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 Sep 28 2024 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. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols . We look forward to receiving your revised manuscript. Kind regards, Roberto Scendoni Academic Editor PLOS ONE Journal Requirements: 1. When submitting your revision, we need you to address these additional requirements. 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 in the Acknowledgments Section of your manuscript: Research reported in this publication was supported, by The Greenwall Foundation and the National Institutes of Health's National Center for Advancing Translational Sciences, Grant Number UL1TR001422. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Greenwall Foundation or the National Institutes of Health. We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows: Author who received award: Justin Starren Funder: The Greenwall Foundation URL: https://greenwall.org/ The funder did not play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Author who received funding: Justin Starren Grant Number: UL1TR001422 Name of Funder: National Institutes of Health's National Center for Advancing Translational Sciences The funder did not play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript Please include your amended statements within your cover letter; we will change the online submission form on your behalf. 3. 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: Dr. Kelly Michelson has received funding for other work from the Patient Centered Outcomes Research Institute and the National Institutes of Health Mohammad Hosseini was supported by the National Institutes of Health’s National Center for Advancing Translational Sciences (UL1TR001422) Matthew Baumann's employment is supported by a grant from the National Evaluation Center of the Network of the National Library of Medicine (NEC/NNLM) We note that one or more of the authors are employed by a commercial company. a. Please provide an amended Funding Statement declaring this commercial affiliation, as well as a statement regarding the Role of Funders in your study. If the funding organization did not play a role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript and only provided financial support in the form of authors' salaries and/or research materials, please review your statements relating to the author contributions, and ensure you have specifically and accurately indicated the role(s) that these authors had in your study. You can update author roles in the Author Contributions section of the online submission form. Please also include the following statement within your amended Funding Statement. “The funder provided support in the form of salaries for authors, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.” If your commercial affiliation did play a role in your study, please state and explain this role within your updated Funding Statement. b. Please also provide an updated Competing Interests Statement declaring this commercial affiliation along with any other relevant declarations relating to employment, consultancy, patents, products in development, or marketed products, etc. Within your Competing Interests Statement, please confirm that this commercial affiliation does not alter your adherence to all PLOS ONE policies on sharing data and materials by including the following statement: "This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests) . If this adherence statement is not accurate and there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared. Please include both an updated Funding Statement and Competing Interests Statement in your cover letter. We will change the online submission form on your behalf. 4. In this instance it seems there may be acceptable restrictions in place that prevent the public sharing of your minimal data. However, in line with our goal of ensuring long-term data availability to all interested researchers, PLOS’ Data Policy states that authors cannot be the sole named individuals responsible for ensuring data access (http://journals.plos.org/plosone/s/data-availability#loc-acceptable-data-sharing-methods). Data requests to a non-author institutional point of contact, such as a data access or ethics committee, helps guarantee long term stability and availability of data. Providing interested researchers with a durable point of contact ensures data will be accessible even if an author changes email addresses, institutions, or becomes unavailable to answer requests. Before we proceed with your manuscript, please also provide non-author contact information (phone/email/hyperlink) for a data access committee, ethics committee, or other institutional body to which data requests may be sent. If no institutional body is available to respond to requests for your minimal data, please consider if there any institutional representatives who did not collaborate in the study, and are not listed as authors on the manuscript, who would be able to hold the data and respond to external requests for data access? If so, please provide their contact information (i.e., email address). Please also provide details on how you will ensure persistent or long-term data storage and availability. 5. Please include your full ethics statement in the ‘Methods’ section of your manuscript file. In your statement, please include the full name of the IRB or ethics committee who approved or waived your study, as well as whether or not you obtained informed written or verbal consent. If consent was waived for your study, please include this information in your statement as well. [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: Yes Reviewer #2: N/A ****** 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: Yes 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: Review • The introduction needs to be revised as it is unclear. The discussion on PACER is not adequately explained—what it is and what it entails are not clear without referring to bibliographic entry "7," which makes the paper difficult to read. Consequently, the authors present isolated statements about the system, which make it difficult for readers to understand what this system entails. Moreover, although the authors extol the system, these statements would benefit from better justification or even removal. • Were the participants adequately prepared before administering the questionnaire? Were they informed, even in broad terms, about the issues at hand? Was any information provided on this topic? • Please provide a better justification for the following statement: "However, obtaining written informed consent from participating patients could prolong the clinic encounter—reducing efficiency and potentially affecting participation" (line 483). • The results are not well aligned with the description. Given the description of the participants, were differences in viewpoints considered? • Overall, I find it challenging to understand the utility of the work, and the target audience of the article is not clear. Reviewer #2: Thank you for the oprtonuity to review this paper that qualitatively seeks to understand the ramifications of a distributive methodology to conduct low risk (human subject risk) research. This process may help in increasing equitable burden of research while still holding to the justice principles. Overall this was a well done description of interview methodology and provides a clear path to data collection and distillation. the only methodological concern i had was i was not clear in how the interviews were conducted, ie were they individual or group settings. if in groups, were the groups mixed with respect to the types of participants (ie ethicists, providers, regulatory) I also have a generalizability concern, subjects were restricted to the Chicago area. This concern is addressed in the limitations discussion, however, authors admit that the participants mirrored the Chicago mixture of society, but that does not necessarily mirror the greater American population. I would ask that authors make this limitation a little stronger instead of minimizing this area. overall this is a well done and well written report. Thank you for your contribution. ****** 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: Yes: David Wampler, PhD, LP, FAEMS ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] 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. https://doi.org/10.1371/journal.pone.0318533.r002
Revision 1
22 Oct 2024 Author Response Part I: Reviewer Comments and Responses Each reviewer comment is numbered. Our responses are below each comment, and all new and existing excerpts from the text are in quotation marks. All page and line numbers correspond to the new, edited version of the manuscript. Reviewer #1: (1) The introduction needs to be revised as it is unclear. The discussion on PACER is not adequately explained—what it is and what it entails are not clear without referring to bibliographic entry "7," which makes the paper difficult to read. Consequently, the authors present isolated statements about the system, which make it difficult for readers to understand what this system entails. We thank you for your comment requesting additional details about the functioning and technical aspects of PACER, citing bibliographic entry 7. To that end, we have made the following additions to the introduction section of the manuscript. We explain in additional detail related to what we hope PACER can achieve and how we envision the PACER architecture would function. Please see the manuscript pages 3-4 lines 47-74 and below and we have added the appropriate reference for this citation: "PACER’s mission is to maximize opportunities for broad and diverse participation in clinical research by expanding access to research studies and thereby improving the generalizability of results. This goal is shared by the National Institutes of Health, among other research organizations. The NIH’s newly appointed director has stated, “If we can build and support a research infra- structure that seamlessly integrates innovative science with routine clinical care, this will not only help us deliver high-quality results for people in a less resource-intensive way, but will allow us to get into diverse communities where we otherwise haven’t been.”[23] This aim is one our research team shares, and PACER is an embodiment of this aspiration. And with the increasing role of EHRs in clinical research, this new research infrastructure must interface with EHRs in non-AMC-affiliated and under-resourced clinics. PACER leverages recent advances in technology called CDS hooks [11] to enable researchers to create and deliver to clinicians very short (under two minutes) research prompts—such as asking a question or doing a brief exam—into the clinical encounter. In doing so, PACER seeks to enable high-speed, real-time, scalable, minimal-risk research through rapid bi-directional transmission of information between a central hub and many distributed electronic health records (EHRs). This distributed approach allows research prompts to be sent to any participating clinician across the country, regardless of their location or which EHR they use. The responses to the prompts (e.g., answers to questions or results of the medical exam) would be documented in the medical record, thereby providing data about a symptom not typically asked about or physical finding not regularly included in a clinic visit. This additional information could also be returned to the central hub to rapidly answer research questions. The following example about how PACER might have been useful during the recent COVID-19 pandemic further explains PACER and its potential impact. After clinicians noted that some patients with COVID-19 experienced anosmia, PACER could have sent prompts to clinicians around the country whose patients had symptoms suggestive of COVID-19 requesting that the clinician inquire about anosmia. This information could have been paired with COVID-19 test results to rapidly confirm or deny an association between anosmia and COVID-19." (2) Moreover, although the authors extol the system, these statements would benefit from better justification or even removal. Thank you for this important reminder to temper our statements. Throughout the paper, we are careful to use terms such as “could,” “hope,” “seek,” or “maybe.” We have edited the manuscript to moderate our statements and provide a more balanced perspective, and we note PACER’s limitations. Below, we list a few examples of how we moderated our statements. 1. On page 4 line 87, we deleted “enormous” regarding PACER’s potential. 2. On page 22 line 589, we changed “even” to “might” in the context of PACER’s potential to support improved resource allocation. 3. On page 32 line 854, we have removed the modifier, “enthusiastically” to describe our participants’ responses to PACER’s potential benefits. (3) Were the participants adequately prepared before administering the questionnaire? Were they informed, even in broad terms, about the issues at hand? Was any information provided on this topic? Thank you for these questions—participant preparation is an important issue that we appreciate clarifying. Participants were informed in broad terms of the subject of the study and the most salient features of the discussion through an information sheet provided to potential participants prior to interviews. Additionally, at the commencement of the interview, the interviewer gave an overview of PACER to contextualize the discussion. We added clarifying text on pages 7-8 lines 287-297 and here it is below: "Prior to confirming their involvement in the study, potential interviewees received an information sheet, sent electronically via email. The information sheet included a brief description PACER, of the study’s aims, the risks and benefits of participation, and study and institutional contact information. When the interviews commenced, the interviewer gave a brief description of PACER and how PACER would function and offered the participants the opportunity to ask their own questions prior to the interview questions." (4) Please provide a better justification for the following statement: "However, obtaining written informed consent from participating patients could prolong the clinic encounter—reducing efficiency and potentially affecting participation" (line 483). We apologize for the lack of clarity. The issue of consent, and how the consent process would interact with clinical workflow, is important. As is typical in surveys of research subject attitudes about consent, there was a heterogeneity of opinion. In the results we noted, “Some comments reflected the concern that truncating the consent process (e.g., requiring only oral permission) risks harming the process’s integrity and inhibiting patients from making well-informed choices. However other participants described how obtaining informed consent has its own associated burden” (page 29 line 761-765). In addition, in Table 2, Domain 2 Consent, Subtheme 1b Clinic factors, we report the quote, “A signed consent form adds time, complexity, interruption ...if the written information could be passed off like in the MA check right, and just say, ‘Hey, we're doing a little—we're doing some research on a medication you're taking. Here's just some information, right if you're comfortable, the provider may ask some questions, and you don't have to say, if you want to, and here's a little bit of information you can read while you wait for the provider to come into the room’ that's pretty fluid” (12). To further clarify this topic, we have changed the sentence to the following on page 29 lines 764-765. "However, other participants noted that obtaining written informed consent could prolong the clinical encounter—reducing efficiency and potentially affecting participation." (5) The results are not well aligned with the description. Given the description of the participants, were differences in viewpoints considered? In retrospect, we realize that the opening of the discussion section may not have captured the overall sense of the results. We have reworked this section including adding several clarifying statements including on page 28 at line 727-735: "Most reactions to PACER were positive. Participants indicated that PACER could improve clinical research processes and increase research participation, as well as advancing scientific knowledge. At the same time, the results demonstrated diverse views about implementing various aspects of PACER methodology. We discovered a diversity of opinions within each group of respondents. Although the responses were not amenable to a formal statistical analysis, we did not identify obvious trends within or among each category of interviewee. Thus, there was no unanimity regarding a single optimal design for a PACER implementation, and future implementers will need to weigh the various opinions." We also added at page 35 lines 908-911: "Additionally, we acknowledge that we may have failed to capture the full gamut of possible viewpoints as some participants expressed differing or contradictory opinions within one interview and certain demographic groups were insufficiently represented in this preliminary study." (6) Overall, I find it challenging to understand the utility of the work, and the target audience of the article is not clear. Thank you for bringing up the important issues of the utility of this work and our target audience. The primary goals of PACER are to increase the pace of and expand the access to biomedical research. In this particular work, we are exploring our interviewees’ viewpoints on a number of topics related to PACER’s design and implementation. To better describe the utility of the work, we have added the following to the introduction on page 5 at lines 217-219: "By exploring and describing diverse viewpoints related to PACER, and by identifying potential challenges imposed by PACER a priori, we intend for this work to inform the creation of guidelines for future PACER implementation." We feel these data will inform researchers interested in implementing PACER and clinicians and patients who may be involved in research that uses PACER methodology. To further clarify this we have included the following to the end of the first paragraph in the discussion on page 28-29 at lines 744-756. "We believe that this study of participants’ perceptions of PACER and its ethical implications, as well as how to implement PACER, can help guide the wider research and bioethics communities—including researchers, bioethicists, institutional review boards (IRBs), and others—who may wish to implement PACER." Reviewer #2: (1) Thank you for the opportunity to review this paper that qualitatively seeks to understand the ramifications of a distributive methodology to conduct low risk (human subject risk) research. This process may help in increasing equitable burden of research while still holding to the justice principles. Overall this was a well done description of interview methodology and provides a clear path to data collection and distillation. Thank you for these positive comments; we appreciate your vote of confidence and your sharing our vision. (2) The only methodological concern I had was I was not clear in how the interviews were conducted, e.g. were they individual or group settings. if in groups, were the groups mixed with respect to the types of participants (e.g. ethicists, providers, regulatory) Thank you so much for bringing this clarification question to our attention. All interviews were conducted individually (i.e., one-on-one) via teleconferencing (over Zoom). To make this clearer, we have added the following phrase--”one-on-one"to the manuscript—please see page 6 line 191 and also below: "We conducted one-on-one, qualitative semi-structured interviews with patients, clinicians, research experts, and bioethicists between February and August 2022." (3) I also have a generalizability concern, subjects were restricted to the Chicago area. This concern is addressed in the limitations discussion, however, authors admit that the participants mirrored the Chicago mixture of society, but that does not necessarily mirror the greater American population. I would ask that authors make this limitation a little stronger instead of minimizing this area. Generalizability is one of our top priorities, so we thank you for your comment on this subject. We more strongly acknowledge this limitation below, along with explaining our reasoning (that we hope that Chicago is a good starting off point on which to base future endeavors and that saturation from our Zipf analysis was reached). Please see page 36 lines 875-879 and below: "Given that Chicagoland is a highly diverse region, we felt it a good place to start this exploration of people’s view about PACER. Even so, it is clear that future studies with larger geographic coverage, and inclusion of ethnic groups not well represented in Chicagoland, e.g. Native American, Alaska Native, Native Hawaiian, and Pacific Islander, are needed." (4) Overall this is a well done and well written report. Thank you for your contribution. Thank you. We so appreciate the opportunity to resubmit this manuscript and feel it is much improved as a result of the requested revisions. Part II: Editor Comments and Responses The journal’s editor comments are listed below, and each comment is followed by a response. They are numbered for convenience, and the first sentence of each comment is bolded. Journal Requirements: 1. When submitting your revision, we need you to address these additional requirements. 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 Thank you so much for sharing these helpful resources with us. We are very grateful to have this information to consult. To that end, we have done the following: 1. We have deleted the address listed for the corresponding author and just kept the email address as instructed. 2. Headings: In keeping with sentence capitalization, we changed the “m” in “methods” in the heading in line 121 from uppercase to lowercase as the guide requires. On the same page at line 131, we changed the “g” in “Interview guide” from uppercase to lowercase. On the following page (at line 164), we changed from uppercase to lowercase several letters in the heading, “Participant recruitment and data collection.” We changed the “a” in the heading, “Data analysis” at line 194 from uppercase to lowercase. At line 261, we changed the heading “Impact on clinical research” to lowercase from uppercase. We also changed the “t” in type from uppercase to lowercase in heading “Consent type” at line 285. At line 321, we changed the “c” in “Consent” from uppercase to lowercase. At line 335, we changed the uppercase “P” to lowercase. At line 377, there is a heading with a slash in it. We changed the “c” in compensation from uppercase to lowercase, but we’re unsure if we are be permitted to keep the slash or the capitalization next to it. We also changed the “c” in compensation from uppercase to lowercase at lines 377 and 395. At line 409, we changed from uppercase to lowercase the “p” and “o” in “Impacts on people and organizations.” The “c” in “considerations” was changed from uppercase to lowercase at line 480. We also changed to lowercase letters in the heading on line 501, “Post-study contact.” The “q” in question at line 535 is also now lowercase. At line 549, the “t” in “topics” was changed to lowercase from uppercase. We also changed the headings in our tables to match this style. 2. Thank you for stating the following in the Acknowledgments Section of your manuscript: Research reported in this publication was supported, by The Greenwall Foundation and the National Institutes of Health's National Center for Advancing Translational Sciences, Grant Number UL1TR001422. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Greenwall Foundation or the National Institutes of Health. We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Fundin Attachments Attachment Submitted filename: PACER PLOS ONE Revisions Document final (1).docx https://doi.org/10.1371/journal.pone.0318533.r003
1 Dec 2024 Decision Letter - Roberto Scendoni, Editor PONE-D-24-21081R1Implications for Precision Accelerated Clinically Embedded Research (PACER): a novel technology-enabled approach to conducting minimal-risk research in outpatient community healthcare settingsPLOS ONE Dear Dr. Michelson, 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 Jan 15 2025 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. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols . We look forward to receiving your revised manuscript. Kind regards, Roberto Scendoni Academic Editor PLOS ONE Journal Requirements: Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. [Note: HTML markup is below. Please do not edit.] 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 #3: 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 #1: Yes Reviewer #3: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: N/A Reviewer #3: N/A ****** 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 #3: 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 #1: Yes Reviewer #3: 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 #1: Overall, the revisions result in a significant improvement of the manuscript. However, it is suggested to include some references in the text concerning the ethical section. De Micco F, Scendoni R. Three Different Currents of Thought to Conceive Justice: Legal, and Medical Ethics Reflections. Philosophies. 2024; 9(3):61. https://doi.org/10.3390/philosophies9030061 Van Biesen W, Decruyenaere J, Sideri K, Cockbain J, Sterckx S. Remote digital monitoring of medication intake: methodological, medical, ethical and legal reflections. Acta Clin Belg. 2021 Jun;76(3):209-216. doi: 10.1080/17843286.2019.1708152. Reviewer #3: It has been my pleasure to review this excellent paper, which qualitatively examines the ramifications of a distributive methodology to conduct low-risk (human subject risk) research. It is my hope that this process will help increase equitable burdens of research while at the same time adhering to justice principles. As a whole, this was a well-written description of interview methodology and provided a clear path for collecting and distilling data. ****** 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: No Reviewer #3: Yes: Ola Mousa ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] 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. https://doi.org/10.1371/journal.pone.0318533.r004
Revision 2
16 Dec 2024 Author Response Author Revisions and Replies Reviewer's Responses to Questions and 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 #3: All comments have been addressed We thank both Reviewer #1 and Reviewer #3 for this vote of confidence in our work and revisions. 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 #3: Yes We thank both Reviewer #1 and Reviewer #3 for their affirmation of this point. 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: N/A Reviewer #3: N/A 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 #3: Yes We are making these data available, submitting our data to deposit in the repository ICPSR. Upon acceptance of our manuscript for publication, we will provide you with the detailed information of our ICPSR deposit, including a DOI, which is currently in progress. 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 #3: 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 #1: Overall, the revisions result in a significant improvement of the manuscript. However, it is suggested to include some references in the text concerning the ethical section. De Micco F, Scendoni R. Three Different Currents of Thought to Conceive Justice: Legal, and Medical Ethics Reflections. Philosophies. 2024; 9(3):61. https://doi.org/10.3390/philosophies9030061 Van Biesen W, Decruyenaere J, Sideri K, Cockbain J, Sterckx S. Remote digital monitoring of medication intake: methodological, medical, ethical and legal reflections. Acta Clin Belg. 2021 Jun;76(3):209-216. doi: 10.1080/17843286.2019.1708152. We thank Reviewer #1 for the kind words regarding the improvement of the manuscript and the acknowledgement of our previous efforts. We also thank them for their suggestion to add references to the text, specifically in the ethical section and for pointing out these interesting articles. The Van Biesen, et al. article focuses primarily on the use of digital pills in clinical practice. The discussion of research mentions that the pill could be used in clinical trials and that FDA approval was based on non-randomized trials. The paper did not directly address potential bioethical issues related to point-of-care research as we describe, and it focuses exclusively on a particular intervention. Therefore, we feel that it is not applicable to our article. The paper by De Micco and Scendoni outlined the concept of justice, providing definitions in the broadest ethical terms. However, the article did not discuss justice in a specifically bioethical context. Since our area of investigation is bioethics, that context is crucial. Additionally, in our manuscript, justice is discussed in the context of compensation for research participation and includes a reference which more directly pertains to the comments made. Therefore, we have chosen not to include the suggested article. We did remove a repetitive sentence that emphasized justice starting at line 563 on page 30, “Thus an important aspect of patient compensation relates to bioethical principles justice and fairness.” Reviewer #3: It has been my pleasure to review this excellent paper, which qualitatively examines the ramifications of a distributive methodology to conduct low-risk (human subject risk) research. It is my hope that this process will help increase equitable burdens of research while at the same time adhering to justice principles. As a whole, this was a well-written description of interview methodology and provided a clear path for collecting and distilling data. We thank Reviewer #3 so much for these words of support. We are so pleased to have earned that approval. 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: No Reviewer #3: Yes: Ola Mousa Attachments Attachment Submitted filename: PACER PLOS ONE Revisions 2 final clean.docx https://doi.org/10.1371/journal.pone.0318533.r005
17 Jan 2025 Decision Letter - Emily Lund, Editor Implications for Precision Accelerated Clinically Embedded Research (PACER): a novel technology-enabled approach to conducting minimal-risk research in outpatient community healthcare settings PONE-D-24-21081R2 Dear Dr. Michelson, 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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, 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, Emily Lund Academic Editor PLOS ONE Additional Editor Comments (optional): The authors have adequately addressed all prior comments in their revision. Reviewers' comments: https://doi.org/10.1371/journal.pone.0318533.r006
Formally Accepted
Acceptance Letter - Emily Lund, Editor PONE-D-24-21081R2 PLOS ONE Dear Dr. Michelson, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Emily Lund Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0318533.r007

Open letter on the publication of peer review reports

PLOS recognizes the benefits of transparency in the peer review process. Therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. Reviewers remain anonymous, unless they choose to reveal their names.

We encourage other journals to join us in this initiative. We hope that our action inspires the community, including researchers, research funders, and research institutions, to recognize the benefits of published peer review reports for all parts of the research system.

Learn more at ASAPbio .