-->PONE-D-25-38701-->-->Walking the tightrope of justifiable decision‑making: An exploratory qualitative study identifying barriers and solutions to efficient safety reporting-->-->PLOS One

Dear Dr. Thompson,-->-->

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.

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We look forward to receiving your revised manuscript.

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Ali Junaid Khan, PhD

Academic Editor

PLOS One

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

MSy:

• Grants/contracts from Astellas, Janssen, Sanofi-Aventis*

• Payments/honoraria: Eisai, Eli-Lily, Janssen*

• Independent member of many Independent Data Monitoring Committees but all for academic sponsors (unpaid)*

MLM:

• Member of Trial Steering Committee for TIPTOE Trial (unpaid)*

• Member of Trial Steering Committee for ASPIRING trial (unpaid)*

• MRC-NIHR Trials Methodology Research Partnership- PhD supervisor and TMRP rep for HDR UK on Executive Committee*

*not related to this project

JT, SBL and AS have declared that no competing interests exist

We note that one or more of the authors are employed by commercial companies: Astellas, Janssen, Sanofi-Aventis, Eisai, and Eli-Lily

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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: No

Reviewer #2: Yes

Reviewer #3: Partly

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

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: N/A

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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

Reviewer #3: 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: No

Reviewer #2: Yes

Reviewer #3: 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: Thank you for the opportunity to review your manuscript titled “Walking the tightrope of justifiable decision-making: An exploratory qualitative study identifying barriers and solutions to efficient safety reporting.” The topic is highly relevant and timely, particularly in light of the ongoing regulatory reforms in UK clinical trials. However, after a careful evaluation of the study design, methodological execution, and presentation, I am unable to recommend the manuscript for publication in its current form.

While the paper presents an important discussion of barriers to efficient safety reporting, several substantive issues limit its suitability for PLOS ONE at this stage:

Conceptual focus and originality:

The manuscript’s central theme—balancing efficiency with regulatory compliance—has been explored in prior qualitative and policy analyses. However, the contribution of this study relative to existing literature (e.g., Perez et al., 2017; Seltzer & Bhattacharyya, 2018) remains insufficiently articulated. The framing does not clearly demonstrate how this work advances current understanding of risk-adapted approaches or decision-making within CTUs.

Methodological depth:

Although Reflexive Thematic Analysis is appropriate, the description of analytic rigor is limited. The coding process, theme development, and strategies for ensuring analytic credibility (e.g., triangulation, member checking) are not sufficiently evidenced. The thematic structure appears largely descriptive, with limited interpretive depth or theoretical integration.

Researcher positionality and reflexivity:

The lead author’s close professional association with some participants introduces potential bias that is acknowledged but not adequately mitigated. Greater transparency about how reflexivity was incorporated into the analytic process—beyond acknowledgment of awareness—would be essential to ensure trustworthiness.

Sample representativeness and saturation:

The sample is heavily weighted toward oncology and academic CTUs, which restricts generalizability. Although “information power” is cited to justify sample size, this rationale is not convincingly demonstrated with respect to data richness or thematic sufficiency.

Analytical and structural concerns:

The over-arching theme of “Walking on a tightrope” is conceptually strong but lacks sufficient analytical integration among subthemes. Several findings are paraphrased rather than synthesized, and the discussion section reiterates results rather than advancing a deeper conceptual model of decision-making or systemic reform.

Presentation and formatting:

The manuscript contains formatting inconsistencies, lengthy quotations, and a very detailed methods section that could be condensed. Figures 1 and 2 are underdeveloped and do not clearly convey analytical structure. The reference list also requires standardization (missing DOIs and inconsistent citation formatting).

Given these issues, I recommend rejection at this stage, with encouragement to consider a substantial revision and resubmission after strengthening the theoretical framing, analytic rigor, and presentation clarity. The topic has merit, but the current draft does not yet meet PLOS ONE’s standards for methodological robustness and clarity.

Reviewer #2: This is a written and timely qualitative study on barriers and potential solutions to efficient safety reporting in CTIMPs, from the perspective of UK academic CTU staff. The focus on the “tightrope” of justifiable decision-making is compelling, and the five subthemes map well onto current debates about risk-proportionate approaches and bureaucratic burden. The paper is generally well structured, with appropriate use of reflexive thematic analysis and effective integration of participant quotes into the narrative. It has clear relevance for regulators, academic sponsors, and CTUs.

Reviewer #3: 1. Introduction and Objectives:

The introduction should clearly define the existing gap in knowledge regarding safety reporting in clinical trials. The manuscript does not provide a thorough review of past research to contextualize its study objectives. It is recommended that the authors expand the literature review, highlighting specific unresolved challenges and justifying why this study is necessary.

2. Methodology – Sampling:

The rationale for using convenience sampling is not adequately explained. The authors should clarify why this approach was chosen and discuss its limitations, particularly in terms of the potential for sampling bias and limited generalizability. Explicit acknowledgment of these limitations and any efforts to mitigate them would strengthen this section.

3. Discussion – Comparison with Previous Work:

The discussion section should systematically compare the study’s findings with those of previous research. Clearly identifying both similarities and differences will reinforce the credibility of the findings, show how they support or challenge past studies, and better highlight the novel contributions of this work.

Where new insights are presented, explicitly detail how these differ from or build upon previous literature.

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-->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.

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Reviewer #1: Yes: Shahar Yar

Reviewer #2: No

Reviewer #3: No

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NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications.

-->PONE-D-25-38701R1-->-->Walking the tightrope of justifiable decision‑making: An exploratory qualitative study identifying barriers and solutions to efficient safety reporting-->-->PLOS One

Dear Dr. Thompson,

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 Jul 16 2026 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 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.

As the corresponding author, your ORCID iD is verified in the submission system and will appear in the published article. PLOS supports the use of ORCID, and we encourage all coauthors to register for an ORCID iD and use it as well. Please encourage your coauthors to verify their ORCID iD within the submission system before final acceptance, as unverified ORCID iDs will not appear in the published article. Only  the individual author can complete the verification step; PLOS staff cannot  verify ORCID iDs on behalf of authors.

We look forward to receiving your revised manuscript.

Kind regards,

Farzana Chowdhury, PhD

Academic Editor

PLOS One

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If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise.

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.

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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

Reviewer #3: All comments have been addressed

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-->2. Is the manuscript technically sound, and do the data support the conclusions?

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

Reviewer #2: Yes

Reviewer #3: Yes

**********

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

Reviewer #2: Yes

Reviewer #3: N/A

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

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

Reviewer #2: Yes

Reviewer #3: Yes

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

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

Reviewer #2: Yes

Reviewer #3: Yes

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-->6. Review Comments to the Author

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

Reviewer #2: The manuscript is suitable for publication after minor revision. It makes a meaningful contribution to understanding why risk-proportionate safety reporting remains difficult to implement in practice. With clearer articulation of its contribution, stronger connection to UK regulatory reforms, and more actionable recommendations, the manuscript will be highly valuable for trial methodologists, regulators, sponsors, and academic clinical trials units.

Reviewer #3: All my comments were thoroughly addressed. The manuscript now meets the high-quality journal standards.

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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.

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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

Reviewer #3: No

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[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.]

To ensure your figures meet our technical requirements, please review our figure guidelines: https://journals.plos.org/plosone/s/figures

You may also use PLOS’s free figure tool, NAAS, to help you prepare publication quality figures: https://journals.plos.org/plosone/s/figures#loc-tools-for-figure-preparation.

NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications.

-->

Walking the tightrope of justifiable decision‑making: An exploratory qualitative study identifying barriers and solutions to efficient safety reporting

PONE-D-25-38701R2

Dear Dr. Thompson,

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

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

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

Kind regards,

Farzana Chowdhury, PhD

Academic Editor

PLOS One

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

-->Comments to the Author

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

Reviewer #2: All comments have been addressed

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-->2. Is the manuscript technically sound, and do the data support the conclusions?

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

Reviewer #2: Yes

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

Reviewer #2: (No Response)

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

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

Reviewer #2: Yes

**********

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

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

Reviewer #2: Yes

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-->6. Review Comments to the Author

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

Reviewer #2: The revised manuscript is suitable for publication after minor revision. The study makes a valuable contribution by identifying practical barriers to efficient, risk-proportionate safety reporting in UK academic clinical trials units. The manuscript is timely, especially in relation to recent UK regulatory changes, and the authors have strengthened the articulation of contribution, regulatory relevance, and practical recommendations. The qualitative design is appropriate, with 23 CTU staff participating across four focus groups, and the use of Reflexive Thematic Analysis is clearly described.

The central theme, “Walking on a tightrope: Making justifiable decisions,” is well developed and supported by meaningful participant quotations. The five subthemes provide a coherent explanation of why risk-proportionate safety reporting remains challenging in practice. The manuscript also offers relevant implications for regulators, sponsors, CTUs, and trial staff.

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

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

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

Reviewer #2: No

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