Coaching doctors to improve ethical decision-making in adult hospitalised patients potentially receiving excessive treatment: Study protocol for a stepped wedge cluster randomised controlled trial

Dominique D. Benoit; Stijn Vanheule; Frank Manesse; Frederik Anseel; Geert De Soete; Katrijn Goethals; An Lievrouw; Stijn Vansteelandt; Erik De Haan; Ruth Piers; on behalf of the CODE study group

doi:10.1371/journal.pone.0281447

Peer Review History

Original SubmissionSeptember 16, 2022
7 Dec 2022 Decision Letter - Oathokwa Nkomazana, Editor PONE-D-22-24774Coaching doctors to improve ethical decision-making in adult hospitalised patients potentially receiving excessive treatment: study protocol for a stepped wedge cluster randomised controlled trialPLOS ONE Dear Dr. Benoit, 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 21 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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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. 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 If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references.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 If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. Additional Editor Comments (if provided): Thank you for submitting a very interesting protocol on a novel method to improve ethical decision making among doctors. Please respond to the reviewers' comments. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions? The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field. Reviewer #1: Yes Reviewer #2: Partly Reviewer #3: Yes ******** 2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses? The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory. Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes ****** 3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable? Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible. Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes ****** 4. Have the authors described where all data underlying the findings will be made available when the study is complete? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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 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 #2: Yes Reviewer #3: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics. You may also provide optional suggestions and comments to authors that they might find helpful in planning their study. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Dear journal editor Before embarking further on a review, I stumbled upon rule of acceptance nbr 1 which is copied here 1. The study presents the results of original research. The study in the article has no results yet, the article is describing a trial in progress. Therefore it seems rule nbr1 is not fulfilled. On the other hand , if you waive this rule nbr 1, I am happy to comment and accept with minor revision the study which is interesting in itself Reviewer #2: This is a protocol paper describing a stepped-wedge design (SWRT) aimed to make system-level interventions to improve ethical decision-making by medical doctors. I have a few concerns that need to be addressed, 1. Picture in Figure 3 is extremely low quality and I can’t read it. 2. SWRT design described in Figure 3 seems not done properly as in SWRT once a unit goes to Intervention never comes back to its previous regime. But Figure 3 seems they revert back after 4 months’ time. That is not a typical SWRT. 3. The power analysis section needs further elucidation. For example, please mention which statistical model is used and what software is used to power the model. Also mention whether the primary analysis model and power analysis model is the same or different and why it is so. I.e. if the Linear mixed model is used for power analysis and using what program/software!! 3. Randomization in any Cluster randomized model is challenging and so does for SWRT. It is not clear who will perform it and where the randomization key will be kept. 4. Since SWRT is a longitudinal model, missing data is unavoidable. Any plan to handle that must be described. Also, describe its effect on power analysis. 5. Outcomes are described to come from various levels. This means this is an SWRT with a multi-level model. Statistical analysis model for such data is challenging, please describe some of it. Reviewer #3: Thank you for the opportunity to review this manuscript describing a study protocol for a stepped-wedge cluster RCT (SWT) for a novel intervention which involves coaching doctors to improve ethical decision making for hospitalized adult patients identified as receiving potentially excessive treatment. The authors adequately provide a description of the scientific and social value for the proposed study. I have a few observations for the authors to consider; 1. In the abstract, there is need to specify the actual endpoint of the questionnaire as the questionnaire itself is not an endpoint but a measurement tool to evaluate an endpoint. 2. Details on how the pilot study that informed this proposed SWT was conducted are needed for the benefit of the reviewers and readers (Line 127-129) 3. The implementation domain of the RE-AIM framework is generally categorised into "feasibility", "acceptibility" or "fidelity". As an implementation outcome,"experiences and satisfaction" best aligns with "Acceptibility" and this needs to be stated as such. Given that the intervention is defined by a protocol, it would be important to also evaluate "fidelity" to the protocol as an implementation outcome. [Table 2c] 4. It is not clear what informed the assumption of intra-departmental correlation [Line 444, Line 456-458]. These assumptions need to be stated and cited where possible. ****** 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 #2: No Reviewer #3: No ******** [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.0281447.r001
Revision 1
5 Jan 2023 Author Response Dear editor, We would like to thank the reviewers for sharing their expertise with us and for their useful comments. Please find below our answers to the comments. We have revised our manuscript accordingly. We have also uploaded an excel file with the names and affiliations of the members of the CODE study group as such that their co-author / membership can be acknowledged in pubmed. Kind regards, Dominique BENOIT on behalf of the CODE-study investigators. Reviewer 1 . The study presents the results of original research. The study in the article has no results yet, the article is describing a trial in progress. Therefore it seems rule nbr1 is not fulfilled. On the other hand , if you waive this rule nbr 1, I am happy to comment and accept with minor revision the study which is interesting in itself Thank you for sharing your expertise with us. Indeed this article describes a trial in progress. We are not aware of the fact that we uploaded our protocol in the wrong manuscript category. We will double check this during the uploading of our revised manuscript Reviewer 2 This is a protocol paper describing a stepped-wedge design (SWRT) aimed to make system-level interventions to improve ethical decision-making by medical doctors. I have a few concerns that need to be addressed, Thank you for sharing your expertise with us and for your comments. 1. Picture in Figure 3 is extremely low quality and I can’t read it. This is now a reconversion from an excel figure to tiff format which was checked in PACE. We changed the colours a bit to improve the readability. We hope the readability is better now 2. SWRT design described in Figure 3 seems not done properly as in SWRT once a unit goes to Intervention never comes back to its previous regime. But Figure 3 seems they revert back after 4 months’ time. That is not a typical SWRT. We believe that the label of SWRT is also appropriate here since we evaluate the effect of initiating the coaching intervention from a given point in time onwards. In our analysis, we do not `pretend’ as if the intervention comes back to the original regime, as there may – hopefully – be a lasting effect of the intervention. This analysis aligns with the usual intention-to-treat analysis. 3. The power analysis section needs further elucidation. For example, please mention which statistical model is used and what software is used to power the model. Also mention whether the primary analysis model and power analysis model is the same or different and why it is so. I.e. if the Linear mixed model is used for power analysis and using what program/software!! The statistical model is stated on lines 430-441. The phrase `Based on such analysis’ on line 432 confirms that the same model is used for the analysis and the power calculation. The software used is RStudio 2022.07.2+576 "Spotted Wakerobin" for macOS Mozilla/5.0. The paper states that a Monte Carlo (i.e., simulation-based) power calculation was made. No specific software is available for this is; instead, the power calculation was programmed in R. On Page 24 Lines 467-468: We added ‘The software used is RStudio 2022.07.2+576 "Spotted Wakerobin" for macOS Mozilla/5.0. 4. Randomization in any Cluster randomized model is challenging and so does for SWRT. It is not clear who will perform it and where the randomization key will be kept. We agree that this is challenging, that is why expert statistical advise was included for the design of the study. This is also stated in the manuscript on Page 25 Lines 471-473: Randomisation of the 10 departments was performed by the Ghent University Department of Applied Mathematics, Computer Science and Statistics based on a random number generator in the software R. 5. Since SWRT is a longitudinal model, missing data is unavoidable. Any plan to handle that must be described. Also, describe its effect on power analysis. We did not describe the effect of missing data on the power analysis because the expected sample size is 1680 patients, but only 605 patients are required. The planned analysis based on a linear mixed model adjusts for missing outcome data, provided that the missingness is `missing at random’. 6. Outcomes are described to come from various levels. This means this is an SWRT with a multi-level model. Statistical analysis model for such data is challenging, please describe some of it. To acknowledge the multilevel structure, we will fit linear mixed models with 2 random intercepts: 1 for department and 1 for clinician. Because such models are fairly standard, we are unsure what additional detail the reviewer is requesting. We added on page 28, Lines 544-545: ‘To acknowledge the multilevel structure, we will fit linear mixed models with two random intercepts: one for departments and one for clinicians.’ Reviewer 3 Thank you for the opportunity to review this manuscript describing a study protocol for a stepped-wedge cluster RCT (SWT) for a novel intervention which involves coaching doctors to improve ethical decision making for hospitalized adult patients identified as receiving potentially excessive treatment. The authors adequately provide a description of the scientific and social value for the proposed study. I have a few observations for the authors to consider; Thank you for sharing your expertise with us and for your comments. 1. In the abstract, there is need to specify the actual endpoint of the questionnaire as the questionnaire itself is not an endpoint but a measurement tool to evaluate an endpoint. We changed ‘ethical decision-making climate questionnaire’ to ‘quality of ethical decision-making climate’in the abstract 2. Details on how the pilot study that informed this proposed SWT was conducted are needed for the benefit of the reviewers and readers (Line 127-129) Thank you. We added some more explanation on the way the pilot study was conducted. In order to perform the power analysis for the current study, we measured the incidence of patients with two or more perceptions of excessive care by different clinicians in the wards of the Ghent University Hospital willing to participate in this study. A dedicated researcher actively surveyed all nurses and doctors during one week on every department asking for which patients the clinician was responsible and in which patients they perceived the care as excessive. The DNIR code for these patients was retrieved from the head nurse. Of the 258 patients admitted in these wards, 32 (12%) were perceived as receiving excessive care by two or more different clinicians and only 12 (38%) had a written DNIR order (Table 1). Page 7, Lines 129-132: We added ‘A dedicated researcher actively surveyed all nurses and doctors during one week on every department asking for which patients the clinician was responsible and in which patients they perceived the care as excessive. The DNIR code for these patients was retrieved from the head nurse.’ 3. The implementation domain of the RE-AIM framework is generally categorised into "feasibility", "acceptibility" or "fidelity". As an implementation outcome,"experiences and satisfaction" best aligns with "Acceptibility" and this needs to be stated as such. Given that the intervention is defined by a protocol, it would be important to also evaluate "fidelity" to the protocol as an implementation outcome. [Table 2c] Thank you for the remark. We adapted Table 2C on page 17 accordingly: (1) We added as outcome for adoption, implementation and maintenance: ‘experiences and satisfaction with the intervention; fidelity to the protocol and long-term perspectives’ (2) We changed the Legend accordingly to: Process measures based on RE-AIM framework, * Adoption = experiences with the intervention, Implementation = feasibility, acceptability (experiences and satisfaction) and fidelity to the protocol, Maintenance = long-term adaptation of the intervention 4. It is not clear what informed the assumption of intra-departmental correlation [Line 444, Line 456-458]. These assumptions need to be stated and cited where possible. Based on the data from the pilot study, we first fitted a logistic mixed effects model for the incidence of disproportionate care. This resulted in a between-unit standard deviation of 0.2385, which we rounded to 0.25 for the power calculation. This corresponds with an intraclass correlation of 0.25/(0.25+3.14152)=0.0247, which we rounded to 0.025. Page 23, Lines 446-449: We changed ‘In the power analysis, we assumed an intra-department correlation of 0.025.’to ‘Based on the data from the pilot study, we first fitted a logistic mixed effects model for the incidence of excessive treatment. This resulted in a between-unit standard deviation of 0.25, corresponding to an intraclass correlation of 0.025, used for the power analyses.’ https://doi.org/10.1371/journal.pone.0281447.r002
24 Jan 2023 Decision Letter - Oathokwa Nkomazana, Editor Coaching doctors to improve ethical decision-making in adult hospitalised patients potentially receiving excessive treatment: study protocol for a stepped wedge cluster randomised controlled trial PONE-D-22-24774R1 Dear Dr. Benoit, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Oathokwa Nkomazana, MD MSC PhD Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0281447.r003
Formally Accepted
31 Jan 2023 Acceptance Letter - Oathokwa Nkomazana, Editor PONE-D-22-24774R1 Coaching doctors to improve ethical decision-making in adult hospitalised patients potentially receiving excessive treatment: study protocol for a stepped wedge cluster randomised controlled trial Dear Dr. Benoit: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. 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 plosone@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. Oathokwa Nkomazana Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0281447.r004

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