Review for 10.1186/s12876-017-0681-y (2017)

Reviewer ’s report  
 
Title:  Trends in Prevalence, Mortality, Health Care Utilization and Health Care Costs of Swiss 
IBD Patients: a claims data based study of the years 2010, 2012 and 2014  
 
Version: 0 Date: 22 Dec 2016 
 
Reviewer:  William  Bennett  
 
Reviewer’s report:  
 
The authors perform a large -scale retrospective analysis of prevalence, mortality, and cost 
associated with IBD in the Swiss population using a payer database containing claims from 
roughly 15% of the national population.  Overall, the methodology is sound and well applied, but 
the conclusions drawn need to better match the da ta.  
 
 
GENERAL COMMENTS:  
 
1. One primary weakness of the study is not sufficiently discussed:  low generalizability of 
the study conclusions to other populations.  The Swiss insurance system is distinct from 
that of the rest of Western Europe, Canada, or th e United States, since it is administered 
locally rather than federally.   
 
2. This is a long manuscript which probably needs to be edited to a more concise 
description of the data.  Many of the figures and tables seem superfluous.  
 
3. Methodology and stat istics are quite strong.  The regression model(s) need more detail 
about which variables were used when.  
 
4. Needs some English language editing for clarity and grammar.  
 
5. Two authors have extensive financial receipts from nearly a dozen pharmaceutical 
companies.  However, there does not appear to be a conflict with the data presented, 
although they do comment on the use of biologics.  
 
6. The authors have rather strong conclusions (e.g. "The prevalence of IBD in Switzerland 
is increasing") without suffici ent data (3 time points from 2010 -2014).  These 
conclusions should be softened considerably.  
 
SPECIFIC COMMENTS:  
 
Background:  
 
1. Page 4, Line 69 - "Seem to be higher..."  The rate of IBD is demonstrably higher in 
Western countries.   
 
2. Page 4, Line 81 - Source #19 is from 2006.  I'm not convinced that study showed what 
the authors claim, that is, that international differences were clearly due to divergent 
treatment strategies not divergent economics.  Area of practice variation is e xtremely 
complex, especially when assessing true costs in an international market.  Furthermore, 
the study was published more than a decade ago using data even older than that.  The use 
of biologics has increased substantially since then.  
 
Methods:  
 
3. Page 7, Line 141 - Was there Ethics Board / IRB approval from an institution other than 
the Helsana Group?  The academic institutions with which the authors are affiliated?  
Additionally, the reason for data protection in studies is not for the privacy of "ph ysicians 
and hospitals", but patients who are subject to research.  I'm confused why this language 
was used.  Is this a Switzerland -specific statute?  
 
4. Page 7, Line 158 - "All decedents…were excluded…"  I thought that mortality was one 
of your outcomes. So why are decedents specifically excluded?  This also is contrary to 
how your methodology is described elsewhere in the manuscript.  Please clarify.  
 
5. Page 8, Line 170 - "This mapping approach is frequency used…"  It's certainly not used 
as often as ICD -9/10 codes for diagnoses, and in most cases I believe it's used as part of a 
multimodal case finding approach.  I am surprised that ICD codes weren't used at all.  
Can you please clarify why the most common approach for case finding in administrative 
data sets was NOT used?  Why were ICD codes absent?  
 
6. Page 9, Line 192 - Your model includes multiple terms that have interaction (language 
and geography, among others), so there is not complete independence of the independent 
variables in your model.  From your description of the model, I don't have enough 
information to evaluate it.  Furthermore, sex is a genotype, and gender is a social 
construct.  I'm assuming gender is what is recorded, as in most databases.  
 
7. Page 11 - Your statistical methods are exc ellent, and it's clear the authors have experience 
using them effectively.  It would improve the manuscript to specify exactly which models 
were used, since you build several of them.  The results section is a bit confusing to me, 
because it's unclear exac tly which variables were used for which outcomes.   
 
Results:  
 
8. Page 12, Line 282 - Table 1 is excellent.  This rate is higher than in other pediatric 
studies, as you mention.  
 
9. Page 12, Line 287 - Table 2 data are interesting, but I'm confused how com parisons were 
done.  Were p -values obtained for all categorical variables or were specific individual 
comparisons made?  Please clarify.  
 
10. Page 13, Line 299 - I would be very careful here about overstating your conclusions here.  
A trend using 3 point e stimates from 3 years from 2010 -2014 using a 15% sample in a 
country is insufficient to establish a true increase in prevalence in that country.  
Furthermore, you use point prevalence in cross sectional comparisons over the course of 
a whole year.  Ideally , one would follow a cohort of patients to determine prevalence, 
otherwise you don't have any information on immigration / lost to system / etc.  I don't 
think you're wrong.  It's probably going up, but your effect size is small, and I don't think 
you have  the right research design (or a long enough time course) to definitively show 
this to be true.  In my opinion, this is a primary weakness of this manuscript, and would 
recommend softening your conclusions in this regard.  Furthermore, Figure 1 seems 
super fluous and is a bit confusing.  Consider eliminating.  
 
11. Page 14 - Cost analysis.  This is very well done and clear.  
 
12. Results in general - There are many examples of commentary on the results in your 
results section, including hypotheses about why re sults were the way they were.  This 
would more traditionally be located in the discussion / conclusion section.  It's a bit hard 
to see the authors' logic the way it's written.  
 
Discussion:  
 
In general, the discussion is quite long, and much of the commenta ry is repetitive.  The authors 
should consider editing for length and clarity.  
 
Page 19, Line 464 - It seems clear that the increasing rate of IBD in the Swiss population is the 
primary conclusion of this work, and I do not think that 3 years over a 5 -year period is sufficient 
to establish this.  Since use of medications is used to establish the rate of disease, I think that 
should have been analyzed more closely.  For instance, in Table 3, the authors report a drastic 
fall in use of 5 -ASAs from 96.8% to 84 .8% in 2 years.  Since this was the method of case -
finding, I'm worried they are reporting fluctuations in prescribing practice, which is quite 
complex, rather than true rate of disease.  Furthermore, in my opinion, a longitudinal cohort is 
the only clearl y effective way to show the changing rate of disease in a population, not the cross 
sectional finite design used in this study.  
 
Page 20, Line 470 - "Prevalence and mortality rates of IBD" - In my opinion, given the authors' 
method of case finding, the sma ll changes seen in prevalence could just have likely been 
differences in utilization, economics, insurance, and awareness of the diagnosis by both 
providers and patients.  The authors should comment on this.   
 
Page 20, Line 484 - "the prevalence rate seem s to be lower in the French speaking part of 
Switzerland."  More granular data are needed to make that much of a sweeping conclusion.  The 
authors should consider cutting this sort of conjecture, as I don't believe the data support it well.  
 
Page 20, Line 487 - This paragraph describes the many differences between this study and a 
similar Swedish study.  The differences described are far more likely to be the noise inherent in 
the study design, not true differences in the pattern of disease.   
 
Page 21, Line 500 - "to suffer from."  Avoid language that imply those with a chronic disease are 
"suffering."  
 
Page 22, Line 529 - The very fact that a large number of patients aren't on a medication makes 
your methodology for case finding highly suspect.   Furthermore, you cite research (#19) showing 
huge variations in medical treatment between countries.  This variation exists between 
institutions, between doctors, between cantons, between universities, all within a single country.  
As such, I'm again ske ptical that you are describing anything more than the noise in a messy data 
source.  
 
Page 27, Line 674 - "The major limitation…"  I disagree that the major limitation to your study 
was the inability to distinguish Crohn's vs. UC.  This is probably only rel evant as it relates to 5 -
ASAs, which don't work for maintenance in Crohn's but are often used anyway, or colectomy / 
surgery, which you don't discuss.  Otherwise, the indications for use of biologics or 
immunomodulators is no different.  The major limitati on of your study is the many comparisons 
you make in a data source with a large amount of noise and with a case finding methodology that 
only increases the amount of noise.  
 
Conclusions:  
 
This section would be better used indicating what new knowledge has b een generated by the 
study.   
 
Page 28, Line 701 - "The prevalence of IBD is higher than previously published, and is 
increasing in Switzerland."  Maybe, but I have reservations about over -interpretation of the data.   
 
Page 28, Line 703 - "costs…are consid erably higher in IBD patients."  This is well known.  
 
Page 28, Line 705 - "patients…comparatively younger."  This is also well known.  
 
Page 29, Line 706 - "They have an impaired quality of life and life -long morbidity, which can 
impact their work productivit y."  This is true in patients not in remission, but for the most part, 
not in those with quiescent disease, which is the majority of IBD patients.  Furthermore, you 
don't assess this outcome in your study, so you can't make a conclusion about it.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which  controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manuscript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further 
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an 
organisation that may in any way gain or lose financially from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in a n organisation that may in any way gain or lose 
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the 
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below. If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
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