Reviewer's report 
 Migraine, Fibromyalgia, and Depression Among People With IBS: A Prevalence Study Title: 
 1  13 May 2006 Version: Date: 
 Ami D. Sperber Reviewer: 
Reviewer's report: 
General 
This is a potentially important study on a timely issue, i.e., the association between IBS and 
nongastrointestinal symptoms and disorders. The very large study population and available database present the authors with a unique opportunity to study this issue. On the whole they have done a 
commendable job and I feel that the paper should be published. The assessments of bias and sensitivity 
analyses are particularly interesting and important. I am not very familiar with these analytical methods. 
Although they are clearly and thoroughly explained by the authors I feel that a statistician should review 
them for appropriateness, etc. With the data at their disposal it seems a pity that the authors limited their 
study to prevalence rates and missed an opportunity to look at the effects of these disorders (especially 
comorbidity) on variables such as work absenteeism, health care utilization, and health-related quality of life. There are also generalizability issues that I have detailed in my specific comments. Thus, I believe the study could be improved so as to make a much greater contribution to our knowledge than it does at the 
present. 
------------------------------------------------------------------------------ 
Major Compulsory Revisions (that the author must respond to before a decision on publication can be reached) 
1) Why did the authors specifically choose fibromyalgia, depression and migraine? With their database and 
study population they could have chosen many additional (or other) disorders or symptoms, e.g., sleep 
disturbances, chronic fatigue, PTSD, etc. There is no satisfactory explanation in the text. 2) With such a large and comprehensive database at hand why did the authors choose to look only at 
prevalence rates. A major concern with functional disorders is their socioeconomic burden and effect on 
quality of life. The authors seem to have a golden opportunity to access work absenteeism, health care use, doctor visits, health-related quality of life (e.g., sleep disturbances), etc. For example, do individuals with more than one disorder have a higher rate of absenteeism than those with none or only one? 
3) Study population: 
a) The population is selected. Workers are usually healthier than the general population and may have a 
higher mean SES level. Workers with functional disorders could be expected to have less severe disease or 
better coping skills than those with the same disorders who are not able to work as a result. The authors do 
not discuss these potential biases. 
b) Failure to match the study and control populations for sex is a serious problem, since all the disorders 
studied are known to have a significant preponderance of women, as do most other functional disorders and 
unexplained symptoms. 
c) The 8 geographical areas are not described. Are they representative of the US as a whole? This 
question, together with the 2 previous comments raises generalizability issues. d) If there were 97,593 individuals with IBS, the entire study population must be huge, but we are not given this information. What was the prevalence of IBS? Is it consistent with other studies that have used more 
rigid diagnostic criteria? 
4) Diagnosis of IBS: a) As the authors allude in the paper the diagnosis of IBS is not based on commonly accepted diagnostic 
criteria. The same appears to be the case for fibromyalgia and depression. Only migraine appears to have a 
strong diagnostic basis. 
b) This problem may be compounded by the long study period and "flagging" method. If I understood correctly (and I'm not sure I did), if an individual was flagged at any month over the 6+ years study period 
with IBS, all subsequent months were marked as IBS. Thus, theoretically an individual who had a short-lived 
IBS related incident at an early stage of the study and nothing to hint at IBS for the next years would be give 
the same weight as an individual who has IBS-related incidents throughout the study period. 
c) The misclassification analyses, which are a strong point of this study, actually show how probelmatic the diagnosis issue is. 
5) If the authors cannot address the comments above by revising the text, then at least they should 
considerably expand the limitations section of the Discussion to reflect these problems. 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author 
can be trusted to correct) 
1) Title page: The affiliations are mistaken. For example, there is a #6 for Gastroenterology, but no author has a superscript 6 next to their name. 2) The aim of the study should be stated in the Background section of the Abstract. 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
1) Table 3 is fully described in the text. It should either remain as a table with the text reduced, or be deleted 
without change to the text. 
 Unable to decide on acceptance or rejection until the authors have responded to the major What next?: 
compulsory revisions 
 An article whose findings are important to those with closely related research interests Level of interest: 
 Acceptable Quality of written English: 
 Yes Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests 
Reviewer's report 
 Migraine, Fibromyalgia, and Depression Among People With IBS: A Prevalence Study Title: 
 1  13 May 2006 Version: Date: 
 Ami D. Sperber Reviewer: 
Reviewer's report: 
General 
This is a potentially important study on a timely issue, i.e., the association between IBS and 
nongastrointestinal symptoms and disorders. The very large study population and available database present the authors with a unique opportunity to study this issue. On the whole they have done a 
commendable job and I feel that the paper should be published. The assessments of bias and sensitivity 
analyses are particularly interesting and important. I am not very familiar with these analytical methods. 
Although they are clearly and thoroughly explained by the authors I feel that a statistician should review 
them for appropriateness, etc. With the data at their disposal it seems a pity that the authors limited their 
study to prevalence rates and missed an opportunity to look at the effects of these disorders (especially 
comorbidity) on variables such as work absenteeism, health care utilization, and health-related quality of life. There are also generalizability issues that I have detailed in my specific comments. Thus, I believe the study could be improved so as to make a much greater contribution to our knowledge than it does at the 
present. 
------------------------------------------------------------------------------ 
Major Compulsory Revisions (that the author must respond to before a decision on publication can be reached) 
1) Why did the authors specifically choose fibromyalgia, depression and migraine? With their database and 
study population they could have chosen many additional (or other) disorders or symptoms, e.g., sleep 
disturbances, chronic fatigue, PTSD, etc. There is no satisfactory explanation in the text. 2) With such a large and comprehensive database at hand why did the authors choose to look only at 
prevalence rates. A major concern with functional disorders is their socioeconomic burden and effect on 
quality of life. The authors seem to have a golden opportunity to access work absenteeism, health care use, doctor visits, health-related quality of life (e.g., sleep disturbances), etc. For example, do individuals with more than one disorder have a higher rate of absenteeism than those with none or only one? 
3) Study population: 
a) The population is selected. Workers are usually healthier than the general population and may have a 
higher mean SES level. Workers with functional disorders could be expected to have less severe disease or 
better coping skills than those with the same disorders who are not able to work as a result. The authors do 
not discuss these potential biases. 
b) Failure to match the study and control populations for sex is a serious problem, since all the disorders 
studied are known to have a significant preponderance of women, as do most other functional disorders and 
unexplained symptoms. 
c) The 8 geographical areas are not described. Are they representative of the US as a whole? This 
question, together with the 2 previous comments raises generalizability issues. d) If there were 97,593 individuals with IBS, the entire study population must be huge, but we are not given this information. What was the prevalence of IBS? Is it consistent with other studies that have used more 
rigid diagnostic criteria? 
4) Diagnosis of IBS: a) As the authors allude in the paper the diagnosis of IBS is not based on commonly accepted diagnostic 
criteria. The same appears to be the case for fibromyalgia and depression. Only migraine appears to have a 
strong diagnostic basis. 
b) This problem may be compounded by the long study period and "flagging" method. If I understood correctly (and I'm not sure I did), if an individual was flagged at any month over the 6+ years study period 
with IBS, all subsequent months were marked as IBS. Thus, theoretically an individual who had a short-lived 
IBS related incident at an early stage of the study and nothing to hint at IBS for the next years would be give 
the same weight as an individual who has IBS-related incidents throughout the study period. 
c) The misclassification analyses, which are a strong point of this study, actually show how probelmatic the diagnosis issue is. 
5) If the authors cannot address the comments above by revising the text, then at least they should 
considerably expand the limitations section of the Discussion to reflect these problems. 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author 
can be trusted to correct) 
1) Title page: The affiliations are mistaken. For example, there is a #6 for Gastroenterology, but no author has a superscript 6 next to their name. 2) The aim of the study should be stated in the Background section of the Abstract. 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
1) Table 3 is fully described in the text. It should either remain as a table with the text reduced, or be deleted 
without change to the text. 
 Unable to decide on acceptance or rejection until the authors have responded to the major What next?: 
compulsory revisions 
 An article whose findings are important to those with closely related research interests Level of interest: 
 Acceptable Quality of written English: 
 Yes Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests 
Please review this paper.
user
Reviewer's report 
 Migraine, Fibromyalgia, and Depression Among People With IBS: A Prevalence Study Title: 
 1  13 May 2006 Version: Date: 
 Ami D. Sperber Reviewer: 
Reviewer's report: 
General 
This is a potentially important study on a timely issue, i.e., the association between IBS and 
nongastrointestinal symptoms and disorders. The very large study population and available database present the authors with a unique opportunity to study this issue. On the whole they have done a 
commendable job and I feel that the paper should be published. The assessments of bias and sensitivity 
analyses are particularly interesting and important. I am not very familiar with these analytical methods. 
Although they are clearly and thoroughly explained by the authors I feel that a statistician should review 
them for appropriateness, etc. With the data at their disposal it seems a pity that the authors limited their 
study to prevalence rates and missed an opportunity to look at the effects of these disorders (especially 
comorbidity) on variables such as work absenteeism, health care utilization, and health-related quality of life. There are also generalizability issues that I have detailed in my specific comments. Thus, I believe the study could be improved so as to make a much greater contribution to our knowledge than it does at the 
present. 
------------------------------------------------------------------------------ 
Major Compulsory Revisions (that the author must respond to before a decision on publication can be reached) 
1) Why did the authors specifically choose fibromyalgia, depression and migraine? With their database and 
study population they could have chosen many additional (or other) disorders or symptoms, e.g., sleep 
disturbances, chronic fatigue, PTSD, etc. There is no satisfactory explanation in the text. 2) With such a large and comprehensive database at hand why did the authors choose to look only at 
prevalence rates. A major concern with functional disorders is their socioeconomic burden and effect on 
quality of life. The authors seem to have a golden opportunity to access work absenteeism, health care use, doctor visits, health-related quality of life (e.g., sleep disturbances), etc. For example, do individuals with more than one disorder have a higher rate of absenteeism than those with none or only one? 
3) Study population: 
a) The population is selected. Workers are usually healthier than the general population and may have a 
higher mean SES level. Workers with functional disorders could be expected to have less severe disease or 
better coping skills than those with the same disorders who are not able to work as a result. The authors do 
not discuss these potential biases. 
b) Failure to match the study and control populations for sex is a serious problem, since all the disorders 
studied are known to have a significant preponderance of women, as do most other functional disorders and 
unexplained symptoms. 
c) The 8 geographical areas are not described. Are they representative of the US as a whole? This 
question, together with the 2 previous comments raises generalizability issues. d) If there were 97,593 individuals with IBS, the entire study population must be huge, but we are not given this information. What was the prevalence of IBS? Is it consistent with other studies that have used more 
rigid diagnostic criteria? 
4) Diagnosis of IBS: a) As the authors allude in the paper the diagnosis of IBS is not based on commonly accepted diagnostic 
criteria. The same appears to be the case for fibromyalgia and depression. Only migraine appears to have a 
strong diagnostic basis. 
b) This problem may be compounded by the long study period and "flagging" method. If I understood correctly (and I'm not sure I did), if an individual was flagged at any month over the 6+ years study period 
with IBS, all subsequent months were marked as IBS. Thus, theoretically an individual who had a short-lived 
IBS related incident at an early stage of the study and nothing to hint at IBS for the next years would be give 
the same weight as an individual who has IBS-related incidents throughout the study period. 
c) The misclassification analyses, which are a strong point of this study, actually show how probelmatic the diagnosis issue is. 
5) If the authors cannot address the comments above by revising the text, then at least they should 
considerably expand the limitations section of the Discussion to reflect these problems. 
------------------------------------------------------------------------------- 
Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author 
can be trusted to correct) 
1) Title page: The affiliations are mistaken. For example, there is a #6 for Gastroenterology, but no author has a superscript 6 next to their name. 2) The aim of the study should be stated in the Background section of the Abstract. 
------------------------------------------------------------------------------- 
Discretionary Revisions (which the author can choose to ignore) 
1) Table 3 is fully described in the text. It should either remain as a table with the text reduced, or be deleted 
without change to the text. 
 Unable to decide on acceptance or rejection until the authors have responded to the major What next?: 
compulsory revisions 
 An article whose findings are important to those with closely related research interests Level of interest: 
 Acceptable Quality of written English: 
 Yes Statistical review: 
Declaration of competing interests: 
I declare that I have no competing interests 
assistant