Title:Adverse events after naprapathic manual therapy among patients seeking care for neck and/or back pain. A randomized controlled trial

Transcription

1 Author's response to reviews Title:Adverse events after naprapathic manual therapy among patients seeking care for neck and/or back pain. A randomized controlled trial Authors: Kari J Paanalahti (kari.paanalahti@ki.se) Lena W Holm (lena.holm@ki.se) Margareta Nordin (dmn2@nyu.edu) Martin Asker (martin@specialistgruppen.se) Jessica Lyander (jessica.lyander@comhem.se) Eva Skilllgate (eva.skillgate@ki.se) Version:2Date:17 January 2014 Author's response to reviews: see over

2 Author Response to Editor and Reviews: Thank you very much for your thoughtful and thorough review of our paper Adverse events after naprapathic manual therapy among patients seeking care for neck and/or back pain. A randomized controlled trial. We have tried to address your concerns as detailed in the table below. Reviewer: Michele Maiers Reviewer Comments: 1. Was there any assessment of the use of individual therapies in each of the three treatment arms? For example, although allowed in G1, did providers actually use SMT or massage at a rate that makes this group is sufficiently different from the comparator groups? This information seems fundamental to your study question. 2. P5: Please clarify the contrast between the parent RCT and the overall aim of this study (described in the last paragraph of the Background as the occurrence and severity of AE after naprapathic manual therapy, and then in the second paragraph of the Design section as the secondary objective ). Response: A random sample of 6% was taken from the patient records to assure that the treatments in G1 was performed right (e.g SMT was used when indicated and no contra indications were present (p10, second paragraph). We have added the result of that test and extended the discussion about that in the Discussion section, at page 19, second paragraph. The RCT on which this study is based on had a primary objectives to examine the difference in treatment effect between different combinations of Naprapathic manual therapy outcomes for patients seeking care for neck and/or back pain. These results will be reported on in a coming publication, when the data collection is completed (one year follow-up). The secondary objective; to describe the occurrence and severity of adverse events directly after naprapathic manual therapy for patients seeking care for neck and/or back is reported in this study. 3. P6: Exclusion criteria #7, what is meant by requiring in requiring/refusing spinal? It would seem requiring the treatment is met by the exclusion criteria #9. We agree that this was not clearly stated in the manuscript and we have tried to clarify this in the revised manuscript in the Materials and Methods/Design section at page 6. If the patient requires/refuses SMT at the first contact with the educational clinic or with the first contact with the therapist then this patient was not considered as a suitable

3 study person since this patient could be randomized in to group 1 (e.g spinal manipulation) or group 2 (e.g spinal mobilization). Exclusion criteria #9; if the therapist find out after physical examination that there is no need for spinal manipulation then the patient is not considered as suitable person for this study since treatment given in the group 1 consist spinal manipulation. 4. P7. Provide a reference for the contraindications for SMT according to the Swedish Board of Social Welfare 5. P10: What were the methods for collecting serious AE (it is reported in results that there were none, but I only see methods for classifying minor versus moderate)? Reference is added in the revised manuscript p 7, under exclusion criteria This comment has led to a change We have added this information in the abstract, under method section and at p11 third paragraph in the method section. Major adverse event was present if the patient had a loss of bowel/bladder function, stroke, fracture or where hospitalized. The collection of these serious events where collected by the adverse event questionnaire, question 8 ( something else ). To make sure not to miss any information about adverse events we did the following: 1. if the patient did not showed up at the scheduled visit the therapist contacted the patients to clarify why and to book a new appointment, 2. if this was not possible for any reason the research assistant contacted the patient to collect the information regarding potential adverse events after the latest visit. 6. P15: The number of therapists participating belongs in the results section. 7. P15: blinded randomization, data collection, and quality management should be noted in the results section. The number of therapists is written in the result section at p13, second paragraph This comment had led to a change. Information required is added in the result section p13, first paragraph.

4 8. P18: any difference in baseline and demographic characteristics among your pilot sample, which was then merged with the large sample? 9. Figure 1: missing n for Age, 18 or>65 years. Only non-significant differences differences were found. -n=16, is added in Figure 1. Discretionary Revisions 1. P 11: What is meant by controlling the data input of baseline and AE questionnaires? Does this mean quality control, and if so, how was that conducted? 2. Table 2: Use 0 instead of - if the dash is meant to denote zero. If it is missing data, indicate so. We have tried to clarify this at page 12 under the Data quality Assurance and Monitoring by the following text: Raw data input from the original, questionnaires was made by a trained research assistant. Validitycontrol for data input was performed at least once for every tenth questionnaire, comparing the information with the original baseline- and adverse event questionnaires to the registered data in the data base. This has led to a change. In Table 2. - is changed to 0. Reviewer: Greg Kawchuk ABSTRACT Terms such as manual therapy and spinal manipulation are used interchangeably confusing. There is never a definition or hierarchy explaining the terms in the main manuscript The first statement indicates there is a need to be more aware about this topic which suggests this is a paper about knowledge translation or will test a hypothesis about awareness - please rewrite to say there is a need for better information about AE rates etc. We would like to keep manual therapy in the abstract. - According to our opinion manual therapy is a standard expression internationally for this kind of treatment and we would like to keep it like that. This comment has led to a change in the abstract. The word information is used instead of awareness in the abstract. There is no evidence that manipulation is provided differently, better, worse etc.between various This comment has led to a change We agree with Dr Kawchuk and have

5 regulated professional who provide manual therapy. Therefore, the need to describe this as naprapathic manual therapy is dubious. It should be described as manual therapy without any reference to a specific profession other than a note in the methods that in this study, the intervention was provided by naturopaths. changed naprapathic manual therapy to manual therapy, whenever it is appropriate in the manuscript. Naprapath is a registered health profession in Sweden since 1994 and is controlled by The National Board of Health and Welfare. Naturopath is not same profession as Naprapath. BACKGROUND Not all guidelines that recommend SMT are linked to specific countries. Various guidelines that make this recommendation come from agencies, not countries. Need to define SMT, manual therapy etc We apologize, but we don t understand what Dr Kawchuck means. We have tried to define naprapathic manual therapy under background at p4, second paragraph. Would suggest that Naturopath also be used as a term as it is more common in the Americas than naprapath. Remove naprapathic as a preface of treatment description (e.g. naprapathic manual therapy) as there is no scientific evidence it differs from any other profession in its delivery Naprapath is a registered health profession in Sweden since 1994 and is controlled by The National Board of Health and Welfare. Naturopath is not same profession as Naprapath. We agree with Dr Kawechuck and have changed naprapathic manual therapy to manual therapy whenever it is appropriate in the manuscript.. I am unsure why unmasking was completed before treatment. Why was this necessary? Please change all references in the manuscript from patients to subjects It was necessary for the therapist to now which treatment group the patient belonged to, and how to treat the patient, because the study is based on different treatment options. We would like to call subjects for patients in this study. Persons in this study sought care at the

6 If the questionnaire was for AEs in last 24 hours after tx but the subject returned for treatment after a time greater than 24 hours, there is a problem with recall Please describe the times of when forms were completed (e.g. the percentage of subjects completing forms within 24 hours, 48 hours, 72 hours etc). educational clinic for neck and/or back pain and therefore we decided to call them for patients. According to previous studies most adverse events occurs 24 hour after the treatment and this is the reason why we decided to have this limitation. The treatment interval was approximately one week. There is always a possibility for recall bias but we have no reason to believe that patients in the different treatment groups recall differently. Forms were completed: 41% (1-8 days), 23% (9-14 days), 21% (15-30 days), 12% (>30 days) and 3% (data not available). This could cause a recall bias but we have no reason to believe that this is different between the treatment groups. We have added this under discussion section p 19, paragraph 4. How long could treatment go on for? 1 month? 1 year? How many treatments could be given? It is unclear if the anonymity of the subject or their comments were kept from the clinician. This is an important consideration as subjects may not report all AEs if they think the clinician would know what they said. We added within six weeks after maximum six visits (maximum six treatments within six weeks) p 10, under section Follow-up and clinical outcomes. The patient filled in the questionnaire before he/she met the therapist at each visit. But it probably is quite obvious that clinician asks the patient how he felt after previous visit and it is also important for clinician to know this. We agree that, at least theoretically, some patients may underestimate and others may overestimate the number and severity of AE, but we have no reason to believe that this is a differential misclassification of outcome that potentially bias our results. We have added this to the discussion part of the manuscript at page 19, second paragraph.

7 If bothersomeness is the same as severity, then use only 1 term in the paper. RESULTS It is unclear how many treatments were given and over what time period. What were the averages at least? We apologize, but we cannot see that we have used the word bothersomeness in the manuscript. The total numbers of visits were (mean 3.5 per patient (p 13, second paragraph). The time period is added to the revised manuscript; Time periods for treatments were between January 25 th December 2 nd 2010 and August 26 th December 3 rd (p 13, second paragraph). Please explore the effect of the duration of the complaint prior to enrollment in the study with outcomes. Were people with more chronic complaints more likely to report AEs? Please explore if AEs were more common early in treatment or latter in treatment. There are a number of factors that might be of importance for the risk of AEs, but we have chosen to report on one of these sex - based on results from previous studies Pain duration prior to enrollment in the study was not found to be a confounder in the final analysis of the association between treatment alternatives and AE. It seems that AE are more common early in the treatment series, see Table 2, and Table 6. This has been explored in the revised manuscript in the discussion section at page 16, first paragraph. Please explore if AEs were different between different anatomic regions (Cervicl, thoracic and lumbar). There are a number of factors that might be of importance for the risk of AEs, but we have chosen to report on one of these sex - based on results from previous studies. Anatomic regions was not found to be a confounder in the final analysis of the association between treatment alternatives and AE.

8 DISCUSSION On the form, how would subjects know if their AE was/was not caused by the treatment? How might this effect the results? There is a huge consideration here that is not discussed why data were included from subjects having a minimu of three treatments. Why at least 3 visits? This excludes subjects who had AE say in their first visit then never came back. This comment has led to a change This is an interesting discussion that we have added to the Discussion section at p19, second paragraph. The question in the adverse event questionnaire was - if the patient had experienced an event as an effect of the treatment given at the latest visit (yes/no). This could be a bias but in that case it should be non-differential misclassification of the outcome and have a dilutive effect on the results, towards to null. The main analysis concerns all patients. An additional analysis was done for 556 patients who had at least three treatments to be able to find out the number and proportion of patients who had experienced any kind of adverse events, regardless of severity and duration, after every visit, after any of the visits or who had no adverse events after any of the visits. To do this it is necessary to compare patients who have had several treatments. That is the reason for only including those who have had at least three treatments. This is described more clearly in the revised manuscript in the section Statistical Methods at p 11, last paragraph in the revised manuscript Don t define serious AE but say none were reported. We have added this information in the abstract, under method section and at p11 third paragraph in the method section. Major adverse event was present if the patient had a loss of bowel/bladder function, stroke, fracture or where hospitalized. The collection of these serious events where collected by the same questionnaire, question 8 ( something else ). We also considered that to not miss any information about adverse events; 1. if the patient did not showed up at the scheduled visit then the

9 therapist (in the first place) books a new appointment, 2. If this was not possible for any reason then the research assistant will contact the patients to collect the information regarding adverse events that the patient had after the latest visit.