Amandine Fauquembergue

Transcription

1 Author s response to reviews Title: Effect of a musical intervention on tolerance and efficacy of non-invasive ventilation in the ICU: study protocol for a randomized controlled trial (MUSique pour l'insuffisance Respiratoire Aigue - Mus-IRA) Authors: Jonathan Messika (jonathan.messika@aphp.fr) David Hajage (david.hajage@aphp.fr) Nataly Panneckouke (panadelle@hotmail.fr) Serge Villard (serge.villard@aphp.fr) Yolaine Martin (yolaine.martin@aphp.fr) Emilie Renard (milyrenard@gmail.com) Annie Blivet (annie.blivet@aphp.fr) Jean Reignier (jean.reignier@chu-nantes.fr) Natacha Maquigneau (natacha.maquigneau@chd-vendee.fr) Annabelle Stoclin (annabelle.stoclin@gustaveroussy.fr) Christelle Puechberty (christellepuechberty@hotmail.fr) Stéphane Guétin (s.guetin@music-care.com) Aline Dechanet (aline.dechanet@aphp.fr) Amandine Fauquembergue (amandine.fauquembergue@aphp.fr) Stephane Gaudry (stephanegaudry@gmail.com) Didier Dreyfuss (didier.dreyfuss@aphp.fr) Jean-Damien Ricard (jean-damien.ricard@aphp.fr) Version: 1 Date: 25 Mar 2016

2 Author s response to reviews: We sincerely thank Dr Weller for her thorough and precise review of our manuscript. R1: Thank you for submitting this interesting protocol to test music therapy in non ventilated patients. A1 Thank you for your positive appreciation. It is a pleasure to discuss these issues with you. The comments have help us improve the manuscript. R2 There a number of issue that would improve your manuscript before it can be considered for publication. Please review title to clearly articulate what this protocol will investigate. A2 The title has been modified, according to your suggestions. We now suggest : Effect of a musical intervention on tolerance and efficacy of non-invasive ventilation in the ICU: study protocol for a randomized controlled trial (MUSique pour linsuffisance Respiratoire Aigue - Mus-IRA). R3 What does (Mus-IRA) stand for? it is not clear in the title, abstract or text in your manuscript A3 Mus-IRA stands for MUSique pour linsuffisance Respiratoire Aigue. This has been added in the title and text of the manuscript. R4 please review CONSORT statement and follow item outline for your revised proposal. A4 As requested in the authors guidelines, the manuscript follows SPIRIT 2013 guidelines for the reporting of interventional trials, which has been filed and added as an additional file. CONSORT Guidelines will be followed to report the trials results. R5 Please note the term subject is not used in CONSORT statement and replace with 'participant' A5 The term subjects has been replaced by participants

3 R6: P4, L7, the reviewer asks to simplify the first sentence of the abstract to clearly outline what is meant. A6 This has been done, and the sentence has been changed in Noninvasive ventilation (NIV) intolerance is a source of premature cessation of NIV R7: P7, L15, the reviewer asks if we test a musical intervention to decrease anxiety. A7: Anxiety is part of the endpoints assessed, as it précised in the outcomes. Hospital anxiety and depression scale questionnaire is administered to the patient at ICU admission and at day-90. R8: Objectives need to be clearer, at present you interchange primary 'goals' 'endpoints' please review. A8: In order to simplify the objectives, a distinct study objectives has been added. The primary and secondary objectives have therefore been explicitly detailed. The word goal has been replaced (see your comment on P7, L34). R9: Please simplify Interventions section to allow the reader a clearer understanding of each intervention including how and when administered. A schedule of events may be helpful to show this more clearly (P10, L1). A9: As requested, a schedule of events has been added to the manuscript (table 1). In addition, the section has been simplified. Nonetheless, the description of NIV initiation and settings are important, so as to ensure that NIV is performed similarly across participating centres. Furthermore, to improve the details provided by figure1, the ventilator settings have been précised in the legend. R10: P9, L53, the reviewer underlines that figure 1 does not give enough details. The details of ventilator settings have been added to the legend of figure 1, and removed from the manuscript text. See figure 1.R1 R11: P10, L39, the reviewers asks if the physician orders the intervention.

4 A12: Indeed, the physician in charge prescribes the length of NIV sessions, and the number of sessions needed per day. This has been added in the revised version. R12: P10, L56, the reviewers asks if the NIV only group is the control group. A12: Indeed, it is the control group. Therefore, this has been added to the revised manuscript. R13: P11, L10 and L41, the reviewer asks to outline more clearly the interventions in the sensory deprivation group and in the Musical intervention group A13: this has been done in the revised manuscript. R14: Please outline more clearly the defined pre-specified primary and secondary outcome measures, including how and when assessed. A14: The pre-specified primary and secondary outcome measures have been more clearly outlined. Furthermore the timing of assessment for each outcome measure has been specified. IN addition, the schedule events asked by the reviewers (added in table 1) helps clarify when measures are assessed. R15: P15, Line 5: the reviewer suggests the blinding section to be moved to randomization section (section Methods and design of the study). A15: This has been done. R16: Sample size calculation needs to be added. How have you come to your total recruitment numbers? A16: We respectfully call the reviewers attention on the Sample size calculation section of the previous manuscript. This section exists in the manuscript. R17: Outline more clearly your statistical methods. A17: In order to clarify the manuscript, the sections have been named and numbered.

5 R18: is there any chance one or more interventions may cause harm? do you need to explain any interim analyses and stopping rules? A18: The section entitled safety considerations states that there is no anticipated risks or inconveniences. Nevertheless, as requested, we added that, for this reason, no safety interim analysis, nor stopping rules are planned. R19: The reviewer asks why data are assessed at day-28 (p13, L51). A19: We plan to assess some data until NIV discontinuation, ICU discharge or day-28 because it is a classical time-frame to assess interventions in the ICU. The number of patients who will stay in the ICU until day-28 should nevertheless be very limited. R20: The same question is asked for day-90 (p14, L5). A20: Patients who stay in the ICU for 90 days are scarce, but we plan to investigate some longterm outcomes such as post-icu depression, PTSD and quality of life (see Azoulay et al, JAMA 2013, Jun12;309(22):2386-7). R21: Please clarify mechanism used to implement the random allocation sequence, describing any steps taken to conceal the sequence until interventions were assigned. A21: Details regarding the randomization technique have been added to the randomization section. Cleanweb is a computer generated, interactive, web response system; the investigator fills the inclusion criteria and the absence of the non-inclusion criteria in the electronic Case Report Form and the participant can be randomized by this mean. These details have been added to the corrected manuscript. R22: Please revise CONSORT flow diagram. The relevance and meaning of Figure 2 and 4 are not clear Please review figures and tables. Each should stand-alone without reading the manuscript text. A22: The figures have been revised. - Figure 2 has been modified in order to stand alone and be understandable without referring to the manuscript.

6 - Figure 3 has been deleted and replaced by a table, as it clearly improves readability (the reviewer asks clarification P12, L31). - Figure 4: The figure is a classical representation of the Bonferroni-based chain procedure, which is used in the statistical analysis to compare the three intervention groups (See Dimitrienko et al. (2013). Key multiplicity issues in clinical drug development. Statistics in medicine, 32(7), ) R23: P22, L2 The reviewer asks who is the sponsor. A23: The sponsor is designed in the section funding/support. This study is promoted by the Assistance Publique-Hôpitaux de Paris. It has been added in the acknowledgment section, as requested (P28, L2) R24: P23, L4: the reviewer points that the first sentence of the discussion is different to the title. A24: This has been corrected in the revised manuscript. R25: P25, L1. The reviewer advises to improve language expression. A25: The sentence has been simplified. R26: P25, L10. The reviewer asks how we plan to investigate the respective effect of noise isolation and the effect of music. A26: The end of the section has been modified in order to clarify the sentence. R27: P27, L2. The reviewer asks when the recruitment is to begin. A27: As it is stated, the recruitment began on May I would be pleased to review your revised manuscript in the future.

7 Editorial requests: ER1: Please remove the word counts from the title page. A1: This has been done ER2: Please move the figure legend section below the reference list. A2: This has been done Author: we do hope all these changes will satisfy the reviewer and will allow a rapid response.