X`PEER REVIEW HISTORY

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1 X`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. ARTICLE DETAILS TITLE (PROVISIONAL) AUTHORS Impulsivity-focused group intervention to reduce binge eating episodes in patients with binge eating disorder study protocol of the randomised controlled IMPULS trial Schag, Kathrin; Leehr, Elisabeth; Martus, Peter; Bethge, Wolfgang; Becker, Sandra; Zipfel, Stephan; Giel, Katrin VERSION 1 - REVIEW Deanna Schreiber-Gregory National University United States of America 11-Aug-2015 Overarching comment: Very well-thought out study and statistical analysis! I am looking forward to reading the results. Thank you for submitting! 1) Need to avoid labeling populations and groups. For example, dieters are referenced on page 5. This needs to be changed to something like individuals who diet. Along this line, I did not see any reference to Binge Eaters. This is excellent. Thank you for not labeling the target population. 2) What is the significance of expecting results within 4 weeks? Was this derived from a previous study? This seems like a rather short period of time to expect results. 3) I enjoyed seeing the variety of variables taken into account in the analysis. Variables such as other associated impulsive behaviors (substance use, etc.) could frequently be overlooked. However, I understand that by including too many variables the model can get off-focus. Was the degree of impact and appropriateness (to include) of each of these variables reviewed before including them in the final model? 4) The robustness of exclusion and inclusion criteria was very refreshing to see. Very appropriate. I was also impressed that a power calculation was included as an assessment of sample size. I was also impressed by the variability in recruitment strategies in order to reduce the impact of a convenience bias. Thank you for taking these into consideration. 5) It would be worthy to note as a limitation that, since this study was not conducted in a completely controlled environment, and that since participants were able to go home between therapeutic sessions, then most of the events taken place at home were self-report and therefore the reliability of self-reported therapy/study compliance cannot be confirmed. For example, I saw that participants were instructed to fast overnight, however, I did not see anything in the

2 protocol that could assess whether or not they were compliant. 6) In relation to the eye-tracking assessments, what was the length of time lapsed between each step in the eye-tracking task? For example, in the cued exploration paradigm, how much time lapsed between the cue appearance, disappearance, and then target appearance? For the antisaccade paradigm, how much time lapsed between the fixation cross disappearance and target appearance? If the time is too short, then the cue and fixation cross do not matter. If the time is too long, this can also affect the impact of the cue and fixation cross. What rationale do you have to use the times chosen? Also, was the cued exploration paradigm always presented before the antisiccade paradigm? Were they randomized for each participant? What were the directions given to the participants? Did they know that in the cued exploration paradigm that the cue indicated where the food target stimuli would appear? 7) I was very impressed to see the amount of thought put into the statistical analysis portion of this study. Many factors, potential bias, and assumption violations were taken into consideration. Excellent work. Very robust and well thought out. 8) I assume the data was analyzed using SPSS. Could you explicitly state that? Were any other statistical packages used? If so, what was your rationale for using them? 9) Thank you for including the note on manual publication intent. I look forward to reading it! Astrid Müller Hannover Medical School, Department of Psychosomatic Medicine and Psychotherapy, Hannover, Germany 12-Aug-2015 This interesting, well written manuscript presents the protocol of a randomized control CBT trial concerning food specific impulsivity in BED. I have only few comments that might be useful in improving the manuscript. - On page 6, the authors wrote that Additionally, we explore other impulsive behaviors (e.g. substance use, compulsive buying, irritability) in the past seven days but did not clarify how these other impulsive behaviors will be assessed. They should provide information on the measurement of these additional variables. Page 5, Sample size calculation: - What exact magnitude of change in BE frequency (%) was assumed based on longitudinal pilot data? - The assumed drop-out rate of 10% seems low to me. Could the authors please provide a reference or a rationale (e.g. own pilot data) for this rate? - On page 10, the authors very shortly describe the intervention. I assume that there is a typesetting error on line 10 in the paragraph Intervention. What exactly does the 2nd point of psychotherapeutic methods mean deviated self-control strategies? (derivation / development of adequate self-control strategies instead of deviated self-control strategies?).

3 VERSION 1 AUTHOR RESPONSE Reviewer: 1 Reviewer Name Deanna Schreiber-Gregory Institution and Country National University United States of America Please state any competing interests or state None declared : None Declared Please leave your comments for the authors below Overarching comment: Very well-thought out study and statistical analysis! I am looking forward to reading the results. Thank you for submitting! --> Thanks for this nice and helpful comments! 1) Need to avoid labeling populations and groups. For example, dieters are referenced on page 5. This needs to be changed to something like individuals who diet. Along this line, I did not see any reference to Binge Eaters. This is excellent. Thank you for not labeling the target population. --> You re right, we changed the spelling into people who diet two times at page 5. We checked the whole manuscript for similar mistakes, but did not find more of them. 2) What is the significance of expecting results within 4 weeks? Was this derived from a previous study? This seems like a rather short period of time to expect results. --> We decided to use the binge eating frequency within four weeks, i.e. item 10 of the Eating Disorder Examination (EDE) as primary outcome according to the multicenter trial INTERBED from De Zwaan and colleagues who used this item also (De Zwaan, M., Herpertz, S., Zipfel, S., Tuschen- Caffier, B., Friederich, H.-C., Schmidt, F., Gefeller, O., Mayr, A., Lam, T., Schade-Brittinger, C. & Hilbert, A. (2012). INTERBED: internet-based guided self-help for overweight and obese patients with full or subsyndromal binge eating disorder. A multicenter randomized controlled trial. Trials, 13, 220.). The EDE represents a semistructured interview which is regarded as the gold standard assessment of eating disorder psychopathology (De Zwaan et al., 2012). In the revision process, we remarked that it might be better to label the primary outcome more clearly as the difference between the binge eating frequency over the past four weeks at T0 and T1 and changed wording in the manuscript. We know from preceding studies that patients with BED are able to reduce binge eating episodes within weeks. Thus, we expect that the number of binge eating episodes over the past four weeks at the beginning of the study (T0) differs from that at the end of treatment (T1) and 3 months later (T2). 3) I enjoyed seeing the variety of variables taken into account in the analysis. Variables such as other associated impulsive behaviors (substance use, etc.) could frequently be overlooked. However, I understand that by including too many variables the model can get off-focus. Was the degree of impact and appropriateness (to include) of each of these variables reviewed before including them in the final model? --> Thanks for this comment! We decided to include subclinical and clinical impulsive behaviours into our process analysis questionnaire. All of these behaviours are listed as symptoms of impulse control disorders or Borderline personality disorder in ICD-10 and DSM-5. From these symptoms, we built 10 categories like imprudent/ compulsive buying, stealing, inconsideration in traffic, uncontrolled sexual behaviour, irritability / conflicts or excessive substance use and one category other (please describe):. We are aware that these are several variables, but we wanted to cover the most common impulsive behaviours and don t overlook some behaviours. Because of the number of variables, we plan to analyse data exploratively. We inserted additional information about other impulsive behaviours at p. 10 to make the variable selection more comprehensible. 4) The robustness of exclusion and inclusion criteria was very refreshing to see. Very appropriate. I

4 was also impressed that a power calculation was included as an assessment of sample size. I was also impressed by the variability in recruitment strategies in order to reduce the impact of a convenience bias. Thank you for taking these into consideration. --> Thanks! 5) It would be worthy to note as a limitation that, since this study was not conducted in a completely controlled environment, and that since participants were able to go home between therapeutic sessions, then most of the events taken place at home were self-report and therefore the reliability of self-reported therapy/study compliance cannot be confirmed. For example, I saw that participants were instructed to fast overnight, however, I did not see anything in the protocol that could assess whether or not they were compliant. --> That s right, as in most outpatient clinical studies, most of the events and experiences take place at home and we have to rely on self-reports in many variables, especially concerning compliance. Concerning the overnight fast, participants are instructed to fast overnight, but we did not include measures of insulin levels or something like that to check the compliance. We included this point as a limitation at p. 3. 6) In relation to the eye-tracking assessments, what was the length of time lapsed between each step in the eye-tracking task? For example, in the cued exploration paradigm, how much time lapsed between the cue appearance, disappearance, and then target appearance? For the antisaccade paradigm, how much time lapsed between the fixation cross disappearance and target appearance? If the time is too short, then the cue and fixation cross do not matter. If the time is too long, this can also affect the impact of the cue and fixation cross. What rationale do you have to use the times chosen? Also, was the cued exploration paradigm always presented before the antisaccade paradigm? Were they randomized for each participant? What were the directions given to the participants? Did they know that in the cued exploration paradigm that the cue indicated where the food target stimuli would appear? --> These are important questions! In the study protocol, we wanted to focus more onto the clinical trial and less onto the experimental paradigms, because we described them in details in our experimental cross-sectional eye tracking study (s. Schag et al., 2013 in the manuscript). However, we decided now to insert more information about the eye tracking paradigms: First, we show presentation times in figure 2. We chose these time intervals according to preceding experimental research (for example see Mulckhuyse & Theeuwes, 2010, Antoniades et al., 2013 from the manuscript. For further information see: Smyrnis, N. (2008). Metric issues in the study of eye movements in psychiatry. Brain and Cognition, 68(3), ). We also chose these time intervals because we had good experiences with similar presentation times before (e.g. Schag et al., 2013 and Giel, K. E., Friederich, H.-C., Teufel, M., Hautzinger, M., Enck, P. and Zipfel, S. (2011a). Attentional Processing of Food Pictures in Individuals with Anorexia Nervosa An Eye-Tracking Study. Biological Psychiatry, 69(7), ). Second, we cleared at page 9, that the two paradigms were presented in balanced order, so that half of the participants performed the cued exploration paradigm first and half of the participants the antisaccade paradigm. Third, the instructions given to the participants are similar to the description of figure 2, which we tried to display more clearly at p. 19: The participants get informed that the cue shows the position of the next food stimulus in the cued exploration paradigm. We implemented this instruction to ensure that the participants decide voluntary, if they want to look at the food picture or not. Especially Mulckhuyse & Theeuwes (2010) and Brignani et al. (2009) did basic experimental work concerning these endogenous cues. In the antisaccade paradigm, the participants get informed that they have to look away from the appearing food/nonfood picture as soon as possible. 7) I was very impressed to see the amount of thought put into the statistical analysis portion of this study. Many factors, potential bias, and assumption violations were taken into consideration. Excellent

5 work. Very robust and well thought out. --> Thanks! 8) I assume the data was analyzed using SPSS. Could you explicitly state that? Were any other statistical packages used? If so, what was your rationale for using them? --> You re right, the data will be analysed with SPSS. The information is given at p ) Thank you for including the note on manual publication intent. I look forward to reading it! --> That would be nice! Reviewer: 2 Reviewer Name Astrid Müller Institution and Country Hannover Medical School, Department of Psychosomatic Medicine and Psychotherapy, Hannover, Germany Please state any competing interests or state None declared : None declared Please leave your comments for the authors below This interesting, well written manuscript presents the protocol of a randomized control CBT trial concerning food specific impulsivity in BED. I have only few comments that might be useful in improving the manuscript. --> Thanks for this nice and helpful comments! - On page 6, the authors wrote that Additionally, we explore other impulsive behaviors (e.g. substance use, compulsive buying, irritability) in the past seven days but did not clarify how these other impulsive behaviors will be assessed. They should provide information on the measurement of these additional variables. --> Thanks for this comment! We inserted at p. 6 that we assessed the variables in an online questionnaire weekly. The process analyses questionnaire is described in more detail at p. 10. We included some additional information about the selection of the variables (please s. also the answer to comment 3 from reviewer 1). Page 5, Sample size calculation: - What exact magnitude of change in BE frequency (%) was assumed based on longitudinal pilot data? --> We inserted the magnitude of the reduction in binge eating frequency in the longitudinal pilot data at p. 7, which was 70%. This means that the patients with BED were able to reduce binge eating episodes after the CBT intervention in our pilot study from about 4 to 1 binge eating episode per week. The data is similar to other CBT trials in patients with binge eating disorder (see for example: Iacovino et al. (2012). Psychological Treatments for Binge Eating Disorder. Curr Psychiatry Rep, 14(4), doi: /s ; Brownley et al. (2007). Binge Eating Disorder Treatment: A Systematic Review of Randomized Controlled Trials. Int J Eat Disord, 40, ). We expect that a more specific impulsivity-focused intervention like our IMPULS programme should reduce binge eating episodes for the same amount as more general outpatient CBT interventions. - The assumed drop-out rate of 10% seems low to me. Could the authors please provide a reference or a rationale (e.g. own pilot data) for this rate? --> That s right, the dropout rates are normally somewhat higher with a dropout rate about 20%, ranging from 3-33% in CBT trials for patients with binge eating disorder (Iacovino et al., 2012). However, the treatment dose in these trials reaches from 8 weeks to 6 months and the attrition is lower in short-term interventions, e.g. the dropout rate in 8-week treatments like the IMPULS programme reaches from 6-12% (see Iacovino et al., 2012). To give another example, Boutelle and

6 colleagues (2011; 2014) had a dropout rate of 11% and they performed self-control and cue exposure interventions in a group format with 8 weeks duration. For these reasons, we decided to expect a dropout rate of 10% in the IMPULS trial. For a better understanding, we included the reference from Iacovino et al. (2012) at p On page 10, the authors very shortly describe the intervention. I assume that there is a typesetting error on line 10 in the paragraph Intervention. What exactly does the 2nd point of psychotherapeutic methods mean deviated self-control strategies? (derivation / development of adequate selfcontrol strategies instead of deviated self-control strategies?). --> Thanks a lot, this really was a typo which we changed immediately at p.10. VERSION 2 REVIEW Deanna Schreiber-Gregory National University, United States of America 09-Oct-2015 Thank you for the updated manuscript! All of my concerns seem to have been addressed adequately and I was happy with the author replies. I have some minor suggestions with wordage and typos which are outlined below: 1) Under the "Impulsivity-focused treatment influencing BED pathology" section on page 5, there is a sentence halfway through the first paragraph that states "Moreover, own pilot", I recommend reviewing this sentence again to make sure it is saying what you want it to say. Was the pilot data referenced gathered for this study or another? Is there a typo that is masking the meaning of the sentence? If the pilot data was gathered for this study, I suggest saying something along the lines of "pilot data gathered for the purposes of this study supported...". The sentence as it is now is a bit confusing. Along these lines as well, is the data referenced in the following sentence (Further, data...) also gathered through this pilot study? If so, it would be beneficial to state "Further, data from this same pilot study...". 2) In the "Data Analysis" section on page 11, the first sentence begins with the word "Date" but I assume this is a typo and that it is, in fact, supposed to be the word "Data". Overall, I'm very satisfied with this final draft. It is quite easy to follow and digest. Thank you for your submission! Astrid Müller Hannover Medical School, Germany 28-Sep-2015 The authors addressed all of my comments and I am satisfied with the revision of the manuscript. Minor comment: I am not a native Speaker but I got the impression that there are some typesetting errors in the changes (e.g., "date" instead of "data" on page 11).

7 VERSION 2 AUTHOR RESPONSE Reviewer: 1 Reviewer Name: Deanna Schreiber-Gregory Institution and Country: National University, United States of America Thank you for your attentive and helpful review! Concerning point 1, we tried to express these sentences more clearly and write now on p. 5: Moreover, pilot data from our workgroup shows in a longitudinal eye tracking study in women with BED and overweight/obese controls that reductions in impulsivity after an outpatient CBT programme are associated to the reduction of binge eating frequency. Further, data from this same pilot study indicates that rash-spontaneous behaviour compared to reward sensitivity seems to be more easily alterable: We didn t gather the data in this pilot study especially for the purpose of the IMPULS trial, but to explore changes in impulsivity and binge eating after CBT per se. Therefore, we decided to describe the study more conservatively and didn t include that the pilot data was gathered for the purposes of this study. Concerning point 2, this was truly a typo and we changed date into data on p. 11. Further, we checked the whole manuscript again for typos and grammar and made a few changes on p. 6 (we omitted ref. 9), p. 7 ( which computes ), p. 9 (we changed the description of the paradigm order from past into present), p. 14 ( These fundings ) and in the references (p ). Reviewer: 2 Reviewer Name: Astrid Müller Institution and Country: Hannover Medical School, Germany Thank you for your attentive and helpful review! This was truly a typo and we changed date into data on p. 11. Further, we checked the whole manuscript again for typos and grammar and made a few changes on p. 6 (we omitted ref. 9), p. 7 ( which computes ), p. 9 (we changed the description of the paradigm order from past into present), p. 14 ( These fundings ) and in the references (p ).