Review for 10.1186/1471-230X-13-39 (2013)

Reviewer's report
Title:Cost and burden of gastroesophageal reflux disease among patients with
persistent symptoms despite proton pump inhibitor therapy: an observational
study in France
Version: 1Date:10 October 2012
Reviewer: Wieslaw Bochenek
Reviewer's report:
Cost burden of gastroesophageal reflux disease among patients with persistent
symptoms despite proton pump inhibitor therapy: observational study in France
Stanislas Bruley des Varannes et al.
This observational 12 months study was designed and undertaken to address
specific issue of cost and burden of GERD in population of patients who did not
respond adequately to treatment with PPI agents. Total of 262 patients were
enrolled and followed at various intervals using a number of assessment
instruments that included RESQ-7 at baseline, 3, 6, 9 and 12 months; HADS at
baseline and 12 months; HRQL using SF-36v2 and EQ-5D at baseline, 6 and 12
months; and WPAI-GERD at baseline 3, 6, 9 and 12 months.
Following are my comments and suggestions related to the study design,
evaluation of results and discussion.
Patients for the study were recruited from primary care physician (PCP) and
gastroenterology practices. It is likely that the diagnosis and treatment used by
these two types of practices are different with gastroenterologists evaluating
patients more thoroughly, likely to scope patients and then more carefully
applying treatment. Patient visits reported for PCPs were almost double
compared to patient visits for gastroenterology sites. Some 76% of patients had
endoscopy within 6 month prior to entering the study and only 50% were reported
as having characteristics of reflux esophagitis and another 16% with Barrett's
esophagus – most likely related to reflux. Is it then certain that the objective of
studying patients with GERD symptoms, as implied by study title was met, if only
66% were documented to have endoscopically confirmed GERD?
Information on PPI treatment states that the majority of patients (86%) reached
maximum dose. No explanation is given what constitutes maximum. Is it the
labeled use, is it the off-label use, is it once daily use or twice daily. For 29% of
patients the treatment was not optimized. Does this mean no maximum dose was
reached?
The treatment used is stated as essentially remaining unchanged over the 12
month period. Was this information collected or presumed and if collected how
reliable the information is?
Study information was collected using CRFs completed at all visits. Was this
paper CRF or CRF filled out electronically? Who checked the CRFs for
completeness of information and how complete were the CRFs and the survey
forms. How the two relate? How much information presented in the paper come
from CRFs and how much from survey forms?
Considerable effort was made to use questionnaires and other assessment
instruments yet no information is provided on the completeness of the
information collected. A recall method was used that is considered very
unreliable. The HADS was collected but no results are presented nor discussed.
Work productivity was assessed yet 51% of patients were not employed. It is
uncertain how reliable is the information and no details are provided which
patients were included in this assessment and how the data were analyzed. Was
productivity assessed in unemployed/retired, if not this should be stated?
The most interesting is the information on the cost per patient. The authors did
not discuss why the cost 1-12 months of the study is so much different from the
pre-study period. Is it because pre-study collected information for 6 month while
on the study information covers 12 month. If so, it might be more meaningful
averaging cost per month/patient for the two periods.
In the discussion, the authors state that the strength of the study relates to the
large sample size. This is doubtful given the demographic diversity of the study
population where the subgroups, if analyzed, would constitute rather small
numbers. This compares unfavorably with some other similar studies where
much larger number of patients participated. The recall method used in collecting
the questionnaire information is very unreliable and no information is provided on
the number of missing data and how the missing data were treated. Similarly no
information is provided if patients who dropped from the study were considered in
the overall assessment.
It is my opinion that the study has significant methodological issues aside from
the fact that the study population and its size do not allow for meaningful analysis
of the data. Novelty of the information is questionable as well and for these
reasons I recommend that the paper should not be accepted for publication.