PEER REVIEW HISTORY ARTICLE DETAILS VERSION 1 - REVIEW

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1 PEER REVIEW HISTORY BMJ Open publishes all reviews undertaken for accepted manuscripts. Reviewers are asked to complete a checklist review form ( and are provided with free text boxes to elaborate on their assessment. These free text comments are reproduced below. Some articles will have been accepted based in part or entirely on reviews undertaken for other BMJ Group journals. These will be reproduced where possible. TITLE (PROVISIONAL) AUTHORS REVIEWER REVIEW RETURNED ARTICLE DETAILS Acupuncture as analgesia for non-emergent acute nonspecific neck pain, ankle sprain and primary headache in an Emergency Department setting: a protocol for a parallel group, randomised, controlled pilot trial Kim, Kun Hyung; Ryu, Ji Ho; Park, Maeng Real; Kim, Yong In; Min, Mun Ki; Park, Yong Myeon; Kim, Yu Ri; Noh, Seung Hee; Kang, Min Joo; Kim, Young Jun; Kim, Jae Kyu; Lee, Byung Ryul; Choi, Jun Yong; Yang, Gi Young VERSION 1 - REVIEW Prof. Dr. med. Albrecht Molsberger Ruhr Universität Bochum, Germany University of North Carolina 12-Mar The reviewer completed the checklist but made no further comments. REVIEWER REVIEW RETURNED GENERAL COMMENTS Shefton Parker RMIT University, Australia 24-Mar-2014 The study is an interesting one and will add to existing research available in the research area. The manuscript itself has some vagueness in methodological design and how some aspects will be implemented and there are a couple of fundamental design flaws which seem evident from the manuscript. These may however actually have been addressed and just not clearly explained in the manuscript and I would recommend the researchers address them and edit the manuscript appropriately. If the flaws remain then they should be explained as limitations in the manuscript and how they may impact the results. The points I have raised in regards to the manuscript should be put to the researchers for response and action prior to further review and acceptance of this manuscript. 1. Is the research question or study objective clearly defined? - The abstract states it will assess effectiveness of the intervention, being a pilot study of small sample size this is unlikely. Pilot studies are typically designed to test the feasibility of a study design and assist in effect size calculation for sample size determination for statistical significance in a full scale RCT. Suggest rewording the abstract and protocol to ensure the focus of the pilot is to

2 assess feasibility rather than efficacy. Similarly this should be reflected in the title to the purpose of the acupuncture intervention and conventional treatment. Ie. pain reduction or analgesia. 2. Is the abstract accurate, balanced and complete? AND 3. Is the study design appropriate to answer the research question? - The abstract contains some minor grammatical errors and method discrepancies. Primary outcome is immediate pain reduction post discharge. It is unclear from this primary measure in the abstract and methods section: a) what scale is being used. b) whether it will be measured directly after acupuncture treatment or before discharge (2 very different time points as patients may remain in the ED hours after the acupuncture treatment. I am unsure how the researcher plan to detect a difference between the 2 groups if measurements are done at discharge as I assume the patients are not discharged until they have they reach a certain threshold of pain. Thus both groups will likely have very similar measurements for pain at discharge. Putting a time point (ie. 1 hour after acupuncture or (hourly measurements until discharge would like provide more of a comparator between the 2 groups for difference. This appears a significant flaw in the design unless the researchers can further clarify how they will circumvent this and explain it in the protocol. c) As mentioned earlier a pilot study should be focused on feasibility paramount with the primary and secondary measures assisting in the development of a full scale study by providing some evidence on potential effect size. I suggest the researchers frame the protocol this way otherwise reporting on all the outcome measures will likely provide negative or insignificant results that are not clinically relevant. Researcher need to be sure they don t overstate the pilot s potential outcomes. d) Outcome assessors at the primary outcome time point will not be blinded. This introduces high likelihood of bias in results and is a major limitation of the study design. This contributes to limiting the significance of any data comparisons between the groups. If possible the researches need to explain the significance of non-blinded assessors clearly in the protocol body and the abstract. 5. Are research ethics (e.g. participant consent, ethics approval) addressed appropriately? - The researchers mention a 30USD incentive for participation. Ethically incentives to participate in research are discouraged as it can create a degree of expectation and bias to results. I suggest the researchers instead consider the payment as a reimbursement for the participants time and should be reflected as such in the protocol.

3 6. Are the outcomes clearly defined? See previous responses re: pilot feasibility and query over the primary outcomes. The strengths and weaknesses of the study section state, the study is not intended to demonstrate clinical difference between the two interventions for pain as suggested then this should then be reflected in the title and protocol body. 8. Are the references up-to-date and appropriate? - Please remove the weblink for the IHC. Replace with the original publication manuscript. Headache Classification Committee of the International Headache Society. Cephalalgia. 2004;24: patients often present with non-emergent acute musculoskeletal symptoms, resulting in a delayed triage process and inefficiency in emergent management. Kim 2012 Needs explanation about why it is delayed and relate this to the present study. - In the introduction they refer to a recent multicentre study in Australia revealed the effectiveness and safety of acupuncture for acute pain management. Cohen 2011 This was just a protocol for the study and did not contain the results so does not fit here. Suggest a new search for a similar study with results which could be placed here instead. - It is unclear how this reference Arendts 2012 relates to acupuncture in the ED more explanation required this is an elderly population also so likely different population to the current proposed study. 12. Are the study limitations discussed adequately? - As mentioned previously the pilot nature of this study should be emphasized in the protocol similarly limitations of the design. i.e. Pragmatic point selection and why the current methodology was chosen despite limitations. i.e. not using sham acupuncture etc. 15. Is the standard of written English acceptable for publication? There are numerous grammatical and structural deficiencies in the manuscript I suggest the researchers have the manuscript reviewed by a proficient English language writer prior to resubmission. Ie. Putting text in a consistent future tense as it is a protocol for planned procedure eg. We will rather than is being Other (see relevant sections in the protocol) Randomisation and allocation concealment: The block size should not be known to protect blinding. It can be reported when the study is finished but not before or ensuring otherwise allocation concealment is compromised. i.e. 3 envelopes are opened 2 no

4 acupuncture the 3 rd acupuncture then the 4 th must be acupuncture. Study context Provide a reference for the population of Yangsan Selection of target conditions - Joint discussions among the study KMDs, ED physicians and investigators revealed that current ED management of such conditions seems suboptimal in terms of patient satisfaction. How was this determined and concluded from what evidence and why? More details required. - a study KMD will be called and will arrive within 10 minutes in the ED what happens if they are later than 10 minutes? How will this be measured? Why is this important? Eligibility criteria Eligible 2) Acute neck pain with no evidence of neurological abnormality - Should list what neurological abnormalities will consist of. (ie numbess.) is dizziness ok for example? More detail needed. Ineligible 2) Any suspected secondary headache classified by codes 5 to 12 in the International Classification of Headache Disorders 2nd edition - put in reference and delete 2 nd edition Acupuncture treatment protocol Electrical stimulation of the acupuncture needles will be added at the treating KMD s discretion. - This is quite an addition to the protocol that again is not explained in the abstract. Can acupuncture and electroacupuncture patients be included in the same group analysis? Researchers should consider how electro acupuncture may affect the results and calculation of subsequent effect sizes. Also there are no details re: safety and potential adverse events surrounding the electro acupuncture nor what equipment will be used and what wave type. Ie. constant, fast slow etc. The regimen was developed based on previous literature reviews and the consensus of three experts in Korean medicine and the ED physicians. - Were these li. Reviews published>? If so refs? If not what

5 did they cover i.e. text books only. Provide names of the text etc. - More detail required about the rescue medication. Ie what are they? What dosage will be given is there a protocol which will determine when rescue therapy is applied? i.e. if pain has not decreased more than 2 points on the pain scale after acupuncture. - How long after admission will the acupuncture be delivered? Are there limits? i.e. patients who were admitted 8 hours ago? Standard ED management protocol With pain scoring at least four points on the Wong-Baker pain scale (0 to 10) - Provide ref. brain computed tomography (CT) will be performed to exclude the possibility of stroke.. - Just stroke? What about brain lesions or other? Secondary outcomes Subjective pain The pain intensity NRS score at 72 hours after ED discharge - 72 hours exactly? What if you can t reach them? What is the cut-off ie +/- 8 hours. Should also be clear this will be assessed via phone call. This should also be placed in the abstract as in other parts of the protocol as it was not clear. (ie. 72 hour +/1? follow up phone call assessment) Adverse events The adverse events of acupuncture may include bleeding; needling pain; forgotten needles; - Suggest remove forgotten needles as an adverse event you mention it further down anyway as a procedure-related event. An adverse event may occur as a result of forgotten needles. Ie. pain but is not an adverse event itself. Patients perceived acceptability of acupuncture treatment How much do you agree that the acupuncture treatment that you have received was helpful for your condition? - This is not a question of acceptability. This is more perceived efficacy. Perceived acceptability would relate to the appropriateness of the acupuncture. Ie. Did the patient find the acupuncture an acceptable form of treatment for their condtion. Data management

6 A data monitoring committee (DMC) will regularly monitor patient safety - Who will this DMC consist of? Will they be independent to the researchers, how many and in what circumstances will they terminate the trial? - Data entry will it go into a database eg. Excel or similar, how often data will be entered, who will enter the data, will there be data checks in place. Ie double entry method. How will access to the data be controlled and how will changes to data be recorded. Sample size calculation the sample size was determined as the minimum required to achieve the pragmatic purpose of the trial (i.e., the collection of information such as aggregate values of the outcome results and their variation, safety data and feasibility-related information necessary for designing a future, full-scale clinical trial). - This responds to earlier queries about the title and abstract. This information should be stated clearly in the introduction and abstract. Trial status The trial is currently in the recruitment phase. The first patient was randomised on 08 January So how many in total are currently recruited and what is the anticipated time frame for the study? Table 1. Measurements of patient characteristics and outcomes - Remove informed consent as this is not a measurement - Please replace O with X for each time point be consistent with the time point acronyms eg. t1, 0, t1, t2 etc. NSAID injection Opioid injection (for headache) Other rescue medication (as needed) Discharge medication (optional) - Group with health resource utilization and make it clear the dosage details are what are being collected here (eg. IV, IM etc and 5mg, etc) Figure 1. Study flowchart

7 30 minute observation - This was detailed in the protocol if included needs to be explained. - Add exclusions sub boxes to screening boxes. Post- treatment assessment and ED discharge are separate in the flow chart. Will they be done at discharge>? If so should they be in the same box? Appendix 1. The revised STRICTA of acupuncture treatments 1b) reasoning of treatment The textbook of Acupuncture and Moxibustion Medicine. - Is this the literature review mentioned in the protocol>? Is so it should be in the protocol with a corresponding ref and detailed. Semi-indivisualized regimen including a set of mandatory points and other necessary points determined at the study KMD s discretion - How is discretion assessed by the KMD s ie based on traditional pulse and tongue diagnosis etc. 2b) Names of acupuncture points Location of classical acupuncture points refers to the WHO standard acupuncture point locations in the Western Pacific Region. - Provide a ref Alternating 2 to 100 Hz electrical stimulation - Provide details about the machine, what wave selection and why as well as how Hz will be determined. 4a) Details of other interventions - Details of rescue medication briefly 6b) precise description of the comparator Please see the method section Protocol of the standard ED management. - A brief overview should still be placed in this table for quick reference with the main details in the protocol body. Appendix 2. Adverse event questionnaire - Suggest removing this Appendix. The content is available in the protocol body and should the potential adverse events should be listed there in full. I notice some of those listed in

8 REVIEWER REVIEW RETURNED GENERAL COMMENTS the appendix were not mentioned in the protocol and should be added. Chien-Chang Liao Taipei Medical University Hospital Taiwan 26-Mar The sample size calculation should be addressed in detail. 2. Data collection should include more information, such as sociodemographics, and coexisting medical conditions. 3. Why do not include a group of shamed control plus conventional emergency care? 4. The sample size of 20 subjects in each group looks so small. VERSION 1 AUTHOR RESPONSE Reviewer: 2 Reviewer Name Shefton Parker Institution and Country RMIT University, Australia Please state any competing interests or state None declared : No competing interests to detail. The study is an interesting one and will add to existing research available in the research area. The manuscript itself has some vagueness in methodological design and how some aspects will be implemented and there are a couple of fundamental design flaws which seem evident from the manuscript. These may however actually have been addressed and just not clearly explained in the manuscript and I would recommend the researchers address them and edit the manuscript appropriately. If the flaws remain then they should be explained as limitations in the manuscript and how they may impact the results. The points I have raised in regards to the manuscript should be put to the researchers for response and action prior to further review and acceptance of this manuscript. 1. Is the research question or study objective clearly defined? Reviewer s comments 1-1) The abstract states it will assess effectiveness of the intervention, being a pilot study of small sample size this is unlikely. Pilot studies are typically designed to test the feasibility of a study design and assist in effect size calculation for sample size determination for statistical significance in a full scale RCT. Suggest rewording the abstract and protocol to ensure the focus of the pilot is to assess feasibility rather than efficacy. Similarly this should be reflected in the title to the purpose of the acupuncture intervention and conventional treatment. Ie. pain reduction or analgesia. Responses to the comments 1-1) Thank you for your comments. The title has changed as Acupuncture as analgesia combined with standard emergency department treatments~ based on your comments. The study objective in the abstract was also revised as follows This study aims to assess the feasibility of acupuncture as an add-on intervention ~. 2. Is the abstract accurate, balanced and complete? AND 3. Is the study design appropriate to answer the research question? Reviewer s comments 2-3a) The abstract contains some minor grammatical errors and method

9 discrepancies. Primary outcome is immediate pain reduction post discharge. It is unclear from this primary measure in the abstract and methods section: a) what scale is being used. Responses to the comments 2-3a) Thank you for your comments. We revised the sentence in the abstract as follows: Primary outcome will be pain reduction measured at discharge. Lack of blinding for primary outcome measurement was already described in the section of Blinding of participants, practitioners, other relevant healthcare staff, outcome assessors and data analysers in the methods section. Reviewer s comments 2-3b) whether it will be measured directly after acupuncture treatment or before discharge (2 very different time points as patients may remain in the ED hours after the acupuncture treatment. I am unsure how the researcher plan to detect a difference between the 2 groups if measurements are done at discharge as I assume the patients are not discharged until they have they reach a certain threshold of pain. Thus both groups will likely have very similar measurements for pain at discharge. Putting a time point (ie. 1 hour after acupuncture or (hourly measurements until discharge would like provide more of a comparator between the 2 groups for difference. This appears a significant flaw in the design unless the researchers can further clarify how they will circumvent this and explain it in the protocol. Responses to the comments 2-3b): Thank you for your comments. It is not uncommon to see a patient with pain even after receiving analgesics being discharged in the ED of our hospital. Previous research also shows that certain portion of patients (27% to 70%) have discharged with insufficient pain relief (please see references below). Thus, we thought that pain at discharge would be an important clinical outcome for measuring additional analgesic effects of acupuncture. We also think that this is not a flaw, but a difference between the Australasian study and ours. In our study, inclusion of this study can be considered when the standard pain management in the ED fails to provide certain level of pain relief. On the contrary, the Australasian trial does not have such inclusion criteria. So the study population differs. We revised the flowchart and the eligibility criteria to make the study process easier to understand. Eur J Anaesthesiol Feb;28(2): An audit of pain management in the Ed also presented that about two-third of patients with pain in the ED could not gain pain relief when measured at discharge. Eur J Emerg Med Aug;13(4): Reviewer s comments 2-3c): As mentioned earlier a pilot study should be focused on feasibility paramount with the primary and secondary measures assisting in the development of a full scale study by providing some evidence on potential effect size. I suggest the researchers frame the protocol this way otherwise reporting on all the outcome measures will likely provide negative or insignificant results that are not clinically relevant. Researcher need to be sure they don t overstate the pilot s potential outcomes. Responses to the comments 2-3c): Thank you for your comments. We are aware that the objective of the study is to assess the feasibility of acupuncture in the research context of ED, and that various outcomes are to explore the potential effects of acupuncture in different perspectives, rather than to selectively pick up certain outcome that can be positive by chance. Of course, we will calculate the required sample size for further full-scale RCT, based on the results of primary outcome. Reviewer s comments 2-3d) Outcome assessors at the primary outcome time point will not be blinded. This introduces high likelihood of bias in results and is a major limitation of the study design. This contributes to limiting the significance of any data comparisons between the groups. If possible the researches need to explain the significance of non-blinded assessors clearly in the protocol body and the abstract. Responses to the comments 2-3d): Thank you for your comments. We certainly agree with your

10 comments regarding the increased risk of bias due to unblinded outcome assessors. We have discussed this issue at the time of protocol development. We had no further required resource for the independent outcome assessor. Hospital staffs in the ED such as nurses or other paramedics who had not involved in the study could not be completely blinded because they were in the same place (i.e., somewhere in the ED room) at the time of allocation. We will clarify the unblindness of the study at the abstract and the protocol. Other researchers who are not involved in the treatment process will measure the primary outcome to reduce social-desirability bias. Reviewer s comments 5). Are research ethics (e.g. participant consent, ethics approval) addressed appropriately? - The researchers mention a 30USD incentive for participation. Ethically incentives to participate in research are discouraged as it can create a degree of expectation and bias to results. I suggest the researchers instead consider the payment as a reimbursement for the participants time and should be reflected as such in the protocol. Responses to the comments 5): Thank you for your comments. We agree your comments and will replace the term incentives into reimbursement for the participant s time. Reviewer s comments 6) Are the outcomes clearly defined? See previous responses re: pilot feasibility and query over the primary outcomes. The strengths and weaknesses of the study section state, the study is not intended to demonstrate clinical difference between the two interventions for pain as suggested then this should then be reflected in the title and protocol body. Responses to the comments 6): Thank you for your comments. We agree with your comments, and will reflect the nature of this study (a feasibility study) in the protocol body. We titled the study as a randomized controlled pilot trial, according to the CONSORT statement which recommends the clear description of random allocation of participants in the title. We think the term pilot means that this study is a feasibility study. If you would like to suggest better title that fits into the study, please let us know. Reviewer s comments 8) Are the references up-to-date and appropriate? - Please remove the weblink for the IHC. Replace with the original publication manuscript. Headache Classification Committee of the International Headache Society. Cephalalgia. 2004;24: PubMed. Responses to the comments 8): Thank you. The web-link reference was replaced into the suggested article. Reviewer s comments 9) patients often present with non-emergent acute musculoskeletal symptoms, resulting in a delayed triage process and inefficiency in emergent management. Kim 2012 Needs explanation about why it is delayed and relate this to the present study. Responses to the comments 9: Why triage is delayed and related this to the present study Thank you for your comments. We described the reason and the relevance of the delayed process to the study with proper references (please see below). Pines JM, Hollander JE. Emergency department crowding is associated with poor care for patients with severe pain. Ann Emerg Med Jan;51(1):1-5. Reviewer s comments 10) In the introduction they refer to a recent multicentre study in Australia revealed the effectiveness and safety of acupuncture for acute pain management. Cohen 2011 This was just a protocol for the study and did not contain the results so does not fit here. Suggest a new search for a similar study with results which could be placed here instead. Responses to the comments 9: Thank you for your comments. We revised the sentence and changed the reference accordingly.

11 Reviewer s comments 11) It is unclear how this reference Arendts 2012 relates to acupuncture in the ED more explanation required this is an elderly population also so likely different population to the current proposed study. Responses to the comments 9:Thank you for your comments. We replaced the reference into another one with more appropriate population (musculosketal conditions) with our systematic review. Gill SD, Stella J. Implementation and performance evaluation of an emergency department primary practitioner physiotherapy service for patients with musculoskeletal conditions. Emerg Med Australas Dec;25(6): Reviewer s comments 12) Are the study limitations discussed adequately? - As mentioned previously the pilot nature of this study should be emphasized in the protocol similarly limitations of the design. i.e. Pragmatic point selection and why the current methodology was chosen despite limitations. i.e. not using sham acupuncture etc. Responses to the comments 12) Thank you for your comments. Suggested issues are now described in the Strengths and weaknesses of this study and other sections in the manuscript accordingly. Reviewer s comments 15) Is the standard of written English acceptable for publication? There are numerous grammatical and structural deficiencies in the manuscript I suggest the researchers have the manuscript reviewed by a proficient English language writer prior to resubmission. Ie. Putting text in a consistent future tense as it is a protocol for planned procedure eg. Responses to the comments 15) Thank you for your comments. Although we have already let the manuscript to be reviewed by a professional English proofediting company, the revised manuscript is being reviewed again for English proficiency by American Journal Experts. The tense is now being revised with consistency. Other (see relevant sections in the protocol) Reviewer s comments Other-1) Randomisation and allocation concealment: The block size should not be known to protect blinding. It can be reported when the study is finished but not before or ensuring otherwise allocation concealment is compromised. i.e. 3 envelopes are opened 2 no acupuncture the 3rd acupuncture then the 4th must be acupuncture. Responses to the comments Other-1): Thank you for your comments. We agree that block size should not be revealed to protect blinding. We will remove the number of block size in the protocol. Information with regard to the size of block randomization had not been revealed to researchers who are responsible for random allocation, delivery of treatments and outcome assessments. We will keep the information secure until the study is finished as your suggestion. Study context Reviewer s comments Other-2) Provide a reference for the population of Yangsan Responses to the comments Other-2) : Thank you for your comments. We provided a web-link reference which presents the official statistics with regard to the population of Yangsan. ( Selection of target conditions Reviewer s comments Other-3)- Joint discussions among the study KMDs, ED physicians and investigators revealed that current ED management of such conditions seems suboptimal in terms of patient satisfaction. How was this determined and concluded from what evidence and why? More details required. Responses to the comments Other-3): Thank you for your comments. These were determined according to our clinical experiences. We supplemented this as follows:

12 Joint discussions among the study KMDs, ED physicians and investigators revealed that current ED management of such conditions seems suboptimal in terms of patient satisfaction, mainly on a basis of clinical experiences in the hospital. Reviewer s comments Other-4)- a study KMD will be called and will arrive within 10 minutes in the ED what happens if they are later than 10 minutes? How will this be measured? Why is this important? Responses to the comments Other-4): Thank you for your comments. This was to make sure that acupuncture will be timely provided for the acute management of pain in the ED patients. For the possible variation of the arrival time, we will allow minor delay of time as follows 10±5 minutes. In our hospital, full-time study KMDs are not available and the hospital KMDs who have other regular jobs should deliver acupuncture treatments. So a duty table for research is made and responsible KMDs at the time of the call should go and see the participant. We regard 10±5 minutes as a necessary time to respond the call and arrive at the ED. If a study KMD cannot respond to the call or cannot arrive at the ED within reasonable time delay (for instance, 10±5 minutes) due to other urgent situation, a patient cannot undergo the consent process and the ED physician will withdraw the suggestion to participate the trial. Eligibility criteria Eligible 2) Acute neck pain with no evidence of neurological abnormality Reviewer s comments Eligible 2)- Should list what neurological abnormalities will consist of. (ie numbess.) is dizziness ok for example? More detail needed. Responses to the comments Eligible 2): Thank you for your comments. We supplemented the example of neurological abnormalities in the eligibility criteria. Ineligible Reviewer s comments Ineligible 2) Any suspected secondary headache classified by codes 5 to 12 in the International Classification of Headache Disorders 2nd edition - put in reference and delete 2nd edition Responses to the comments Ineligible 2): Thank you for your comments. We revised the part as your suggestion. Acupuncture treatment protocol Electrical stimulation of the acupuncture needles will be added at the treating KMD s discretion. Reviewer s comments treatment protocol 1)- This is quite an addition to the protocol that again is not explained in the abstract. Can acupuncture and electro-acupuncture patients be included in the same group analysis? Researchers should consider how electro acupuncture may affect the results and calculation of subsequent effect sizes. Also there are no details re: safety and potential adverse events surrounding the electro acupuncture nor what equipment will be used and what wave type. Ie. constant, fast slow etc. Responses to the comments treatment protocol 1): Thank you for your comments. The optional use of electroacupuncture is now described in the abstract. Manual acupuncture is often provided with electrical stimulation on the certain subset of needled points. For example, we can combine electrical stimulation on the certain subset of needled points (LI11 and ST36) to enhance the analgesic effects of acupuncture. We will not perform a subgroup analysis based on the use of electrical stimulation in the study, although the number of patients underwent combined electrical stimulation can be descriptively summarized. Optional use of electrical stimulation is a part of acupuncture treatments in our study, so we do not feel to perform subgroup analysis. If we find potential clinical heterogeneity due to the optional use of electrical stimulation at the time of analyses, we may consider the potential effects of electrical stimulation on the overall results of the trial and describe it in the discussion section with appropriate caution. This is a small-size pilot study, so we do not expect this study to

13 provide enough information for subgroup analysis for us. Adverse events specific to the electrical stimulation of acupuncture will be of course collected by open-end questions, if any. Equipment information and the protocol of electrical stimulation are now provided in the methods and STRICTA table. Thank you. Reviewer s comments treatment protocol 2)-The regimen was developed based on previous literature reviews and the consensus of three experts in Korean medicine and the ED physicians. - Were these li. Reviews published>? If so refs? If not what did they cover i.e. text books only. Provide names of the text etc. Responses to the comments treatment protocol 2): Thank you for your comments. We supplemented references for literature reviews, including a textbook of acupuncture. Thank you. Reviewer s comments treatment protocol 3)- More detail required about the rescue medication. Ie what are they? What dosage will be given is there a protocol which will determine when rescue therapy is applied? i.e. if pain has not decreased more than 2 points on the pain scale after acupuncture. Responses to the comments treatment protocol 3): Thank you for your comments. Rescue medication will be selected among two types of opioid analgesics (pethidine HCl 25 mg/0.5 ml diluted with normal saline 10 ml or morphine 3mg IV boluses). Patients with pain equal or more than 4 points of Wong- Baker scale will be considered as a possible case of rescue medication administration. However, the final decision of administering rescue medicine will be on the ED physician. These are supplemented in the method section with the title of Use of rescue medication after group allocation. Reviewer s comments treatment protocol 4)- How long after admission will the acupuncture be delivered? Are there limits? i.e. patients who were admitted 8 hours ago? Responses to the comments treatment protocol 4): Thank you for your comments. According to the clinical experiences of the ED physicians, time from the admission to the administration of treatments has not exceeded 3 hours in the ED. Despite your reasonable comment regarding the possible case of exclusion, revision of eligibility criteria needs additional IRB approval and may delay the process of the trial. If a case you pointed occurs, the patient will be regarded not appropriate for participation in the trial. Standard ED management protocol Reviewer s comments treatment protocol 5) With pain scoring at least four points on the Wong-Baker pain scale (0 to 10) - Provide ref. Responses to the comments treatment protocol 5): Thank you for your comments. A reference was supplemented with regard to the threshold of moderate-to-severe pain intensity (generally at least 4 points on 0 to 10 pain intensity scales) (Jones 2007). Reviewer s comments treatment protocol 6) brain computed tomography (CT) will be performed to exclude the possibility of stroke.. - Just stroke? What about brain lesions or other? Responses to the comments treatment protocol 6): Thank you for your comments. The sentence is revised to reflect your suggestions. (such as other serious neurological conditions including brain tumor or other pathological lesions) Secondary outcomes Reviewer s comments secondary outcomes 1) Subjective pain The pain intensity NRS score at 72 hours after ED discharge - 72 hours exactly? What if you can t reach them? What is the cut-off ie +/- 8 hours. Should also be clear this will be assessed via phone call. This should also be placed in the abstract as in other parts

14 of the protocol as it was not clear. (ie. 72 hour +/1? follow up phone call assessment) Responses to the comments secondary outcomes 1): Thank you for your comments. We revised the follow-up time point as 72±12 hours accordingly. Phone call assessment is now also specified in the manuscript. Reviewer s comments secondary outcomes 2) Adverse events The adverse events of acupuncture may includebleeding; needling pain; forgotten needles; - Suggest remove forgotten needles as an adverse event you mention it further down anyway as a procedure-related event. An adverse event may occur as a result of forgotten needles. Ie. pain but is not an adverse event itself. Responses to the comments secondary outcomes 2): Thank you for your comments. As your suggestion, forgotten needles removed from description of adverse events. Reviewer s comments secondary outcomes 3)Patients perceived acceptability of acupuncture treatment How much do you agree that the acupuncture treatment that you have received was helpful for your condition? - This is not a question of acceptability. This is more perceived efficacy. Perceived acceptability would relate to the appropriateness of the acupuncture. Ie. Did the patient find the acupuncture an acceptable form of treatment for their condtion. Reviewer s comments secondary outcomes 4): Thank you for your comment. We accept your criticism, and the relevant description is now revised as perceived effectiveness of acupuncture. We will measure the acceptability of acupuncture in a more appropriate question in future studies. Reviewer s comments Data management 1) Data management A data monitoring committee (DMC) will regularly monitor patient safety - Who will this DMC consist of? Will they be independent to the researchers, how many and in what circumstances will they terminate the trial? Responses to the comments Data management 1) Thank you for your comments. Information on DMC members and trial termination criteria is now described in the manuscript. Reviewer s comments Data management 2)- Data entry will it go into a database eg. Excel or similar, how often data will be entered, who will enter the data, will there be data checks in place. Ie double entry method. How will access to the data be controlled and how will changes to data be recorded. Responses to the comments Data management 2): Thank you for your comments. Data entry method is now described in the Data management section. Sample size calculation Reviewer s comments sample size 1) the sample size was determined as the minimum required to achieve the pragmatic purpose of the trial (i.e., the collection of information such as aggregate values of the outcome results and their variation, safety data and feasibility-related information necessary for designing a future, full-scale clinical trial). - This responds to earlier queries about the title and abstract. This information should be stated clearly in the introduction and abstract. Responses to the comments sample size 1): Thank you for your comments. The information is now reflected in the abstract and the introduction part. Because of the word limit, the information cannot be further stated in the abstract. However, we expect that readers can understand the aim of this study (i.e., to test the feasibility of acupuncture and guide further randomized trials). Trial status Reviewer s comments Trial staus 1)The trial is currently in the recruitment phase. The first patient was randomised on 08 January 2014.

15 - So how many in total are currently recruited and what is the anticipated time frame for the study? Responses to the comments Trial staus 1): Thank you for your comments. We supplemented the recruitment status and anticipated time frame in the Trial status section. Reviewer s comments Table 1-1)Table 1. Measurements of patient characteristics and outcomes - Remove informed consent as this is not a measurement - Please replace O with X for each time point be consistent with the time point acronyms eg. t1, 0, t1, t2 etc. Responses to the comments Table 1-1): Thank you for your comments. Table 1 is now revised as your suggestion. Reviewer s comments Table 1-2) NSAID injection Opioid injection (for headache) Other rescue medication (as needed) Discharge medication (optional) - Group with health resource utilization and make it clear the dosage details are what are being collected here (eg. IV, IM etc and 5mg, etc) Responses to the comments Table 1-2): Thank you for your comments. Grouping and dosage details are now supplemented in Table 1. Figure 1. Study flowchart Reviewer s comments Figure 1) 30 minute observation - This was detailed in the protocol if included needs to be explained. - Add exclusions sub boxes to screening boxes. Responses to the comments Figure 1) Thank you for your comments. An exclusion sub-box is now added beside the screening box in Figure 1. For the 30 minute observation, it was already described in the 4th box, figure 1 in the draft manuscript version. For your convenience, it is highlighted without any change in Figure 1. We also found that descriptions on the study process in the manuscript were somewhat confusing. We revised it to reflect the 30 minutes of observation after the standard ED management before the eligibility test and allocation in the Pre-treatment assessment and participant recruitment process and Eligibility criteria section as well as Table 1, respectively. Reviewer s comments Figure 2) Post- treatment assessment and ED discharge are separate in the flow chart. Will they be done at discharge>? If so should they be in the same box? Responses to the comments Figure 2) Thank you for your comments. The post-treatment assessment box was removed and Outcome assessment at ED discharge was remained with highlight. Appendix 1. The revised STRICTA of acupuncture treatments Reviewer s comments STRICTA 1b) 1b) reasoning of treatment The textbook of Acupuncture and Moxibustion Medicine. - Is this the literature review mentioned in the protocol>? Is so it should be in the protocol with a corresponding ref and detailed. Responses to the comments STRICTA 1b): Thank you for your comments. References are now provided in the acupuncture treatment protocol section in the manuscript. Reviewer s comments STRICTA 1c)Semi-indivisualized regimen including a set of mandatory points and other necessary points determined at the study KMD s discretion -How is discretion assessed by the KMD s ie based on traditional pulse and tongue diagnosis etc. Responses to the comments STRICTA 1c): Thank you for your comments. The main discretion

16 criteria is based on the meridian diagnosis (site of pain or injury), pulse and tongue diagnosis, abdominal diagnosis (tenderness on epigastric region) and needle sensation tolerability (strong or mild stimulation). These are now described in the 1c item. Reviewer s comments STRICTA 2b) Names of acupuncture points Location of classical acupuncture points refers to the WHO standard acupuncture point locations in the Western Pacific Region. - Provide a ref Responses to the comments STRICTA 2b): Thank you for your comment. A reference is now added in the Appendix 1. Reviewer s comments STRICTA 2e) Alternating 2 to 100 Hz electrical stimulation - Provide details about the machine, what wave selection and why as well as how Hz will be determined. (instrument, wave selection, hz) Responses to the comments STRICTA 2e) Thank you for your comment. Suggested information is now described both in the manuscript and the Appendix. Reviewer s comments STRICTA 6a) Details of other interventions - Details of rescue medication briefly Responses to the comments STRICTA 6a): Thank you for your comments. They are now described both in the manuscript and the Appendix 6b). Reviewer s comments STRICTA 6b) precise description of the comparator Please see the method section Protocol of the standard ED management. - A brief overview should still be placed in this table for quick reference with the main details in the protocol body. Responses to the comments STRICTA 6b): Thank you for your comments. A brief overview is now described in the item 6b. Reviewer s comments Appendix 2) Adverse event questionnaire - Suggest removing this Appendix. The content is available in the protocol body and should the potential adverse events should be listed there in full. I notice some of those listed in the appendix were not mentioned in the protocol and should be added. Responses to the comments Appendix 2): Thank you. Appendix 2 is now removed as your suggestion. Detailed examples of adverse events are now described in the manuscript. Reviewer: 3 Reviewer Name Chien-Chang Liao Institution and Country Taipei Medical University Hospital, Taiwan Please state any competing interests or state None declared : None. Reviewer s comment 1) The sample size calculation should be addressed in detail. Response to the comment 1) Thank you for your comment. This is a pilot study to guide a full-scale randomized trial, there is no formal sample size calculation. This is described in the sample size calculation section. Reviewer s comment 2) Data collection should include more information, such as sociodemographics, and coexisting medical conditions. Response to the comment 2): Thank you for your comments. As this is already ongoing study, more question items for sociodemographic information and comrobidity is not possible unless IRB approves the collection of additional items. For the IRB approval of revised protocol, the delay of the study is

17 expected. Instead, we will consider collecting suggested information in future relevant study. Reviewer s comment 3) Why do not include a group of shamed control plus conventional emergency care? Response to the comment 3) Thank you for your comment. This is a pragmatic study and aims to guide further studies evaluating overall effectiveness of acupuncture combined with standard pain management in ED contexts. Thus, a sham-acupuncture intervention was not considered as a control group intervention because it is for assessing net efficacy of acupuncture (i.e., needling on the body) and it is not the purpose of our study. The rationale of not using sham intervention section is now provided in the manuscript. Reviewer s comment 4) The sample size of 20 subjects in each group looks so small. Response to the comment 4): Thank you for your comment. This is a feasibility study, so does not require a calculated sample size for assessing the effects of acupuncture compared to the control group. We call for a full-scale randomized trial with a formal sample size calculation using the information obtained from this study. REVIEWER REVIEW RETURNED GENERAL COMMENTS VERSION 2 REVIEW Shefton Parker RMIT University Australia 05-May-2014 The latest submission is a substantial improvement on the original and satisfies CONSORT, its extensions and STRICTA requirements. For the reference. BMJ referencing style should include: "For material published online, give the authors, title, date or year of publication as given on the web page, and URL." A couple of minor sentence structure changes are also included and recommended to improve the quality of the manuscript. Following these I would recommend publication of the manuscript and wish the researchers the best for their study. - The reviewer also provide a marked copy of the manuscript. Please contact the publisher for all the details. VERSION 2 AUTHOR RESPONSE All of your comments were reflected in the revised manuscript. The reference was corrected accordingly. The commented paragraph in the methods 'outcome' section, was modified and moved to the background section. The title was slightly shortened. All revised parts are highlighted.