Review for 10.1186/1471-230X-13-23 (2013)

Reviewer's report
Title:Medication adherence and persistence in the treatment of Canadian
ulcerative colitis patients: analyses with the RAMQ database
Version: 2Date:10 October 2012
Reviewer: Maida Sewitch
Reviewer's report:
Re: Medication adherence and persistence in the treatment of Canadian
ulcerative colitis patients: analyses with the RAMQ database
Thank you for the opportunity to review the manuscript entitled, “Medication
adherence and persistence in the treatment of Canadian ulcerative colitis
patients: analyses with the RAMQ database”. The objectives of the study were to
estimate adherence and persistence to 5-ASA treatment and to its specific
treatments and to identify the potential determinants of adherence and
persistence in a ‘real-life setting’. The main study findings: High adherence was
predicted by male gender, older age, and current use of corticosteroids. High
persistence was predicted by male gender, current use of corticosteroids, and
presence of hypertension or respiratory diseases.
In general, the manuscript was well-written. However, the methods were not
well-described, and may have been inappropriate, leading to biased results.
First is the possibility for selection bias, as there was no information on the
diagnostic codes used to define ulcerative colitis (UC). Persons with a diagnostic
code of Crohn’s disease (CD) (the International Classification of Diseases, Ninth
Revision [ICD-9] diagnostic codes 555.0–555.9) were excluded. But patients are
often given both diagnostic codes in these databases; what was the algorithm
used to include/exclude patients? It is noteworthy that other investigators have
used validated algorithms to identify persons with UC and/or CD, implying
difficulty in this area.
The possibility for selection bias is also increased because the definition of new
users of medication was problematic. New users were operationalized as having
no prescription claim in the 3 months prior to the date of the first prescription fill’
[index date]) of a mesalamine treatment (Asacol® or generics, Pentasa®,
Salofalk®, or Mezavant®). However, these individuals may be poor adherers or
not persistent with medication; a longer time interval such as not having a
prescription fill in a 6–month or 1–year period is suggested.
Second, the definition of persistence was missing.
Third, is the possibility for confounding by indication, as patients who switched to
another mesalamine treatment were considered as non-persistent to the initial
medication. That the authors observed significantly better adherence and
persistence with Mezavant®, which is a new once daily oral treatment, seems to
confirm this suspicion. So does the observation that there were fewer users of
Mezavant compared to the other medications. Moreover, whereas the RAMQ
data for this study covered the years January 1, 2004 to December 31, 2009,
Mezavant only became available to Canadian UC patients for maintenance of
remission in June 2011.
(http://www.newswire.ca/en/story/733699/health-canada-grants-mezavant-new-expanded-indication-for-maintenance-of-remission-of-ulcerative-colitis)
It should be noted that the authors and the study were funded by Shire, the
manufacturer of Mezavant.
Minor points
I don’t think it is possible to calculate a mean age as RAMQ provides information
on age categories.
In conclusion, major methodological issues may have accounted for the findings
of this study.