Letter: international IBD practice guidelines -- authors' reply.

SIRS, We thank Drs Mowat and Bloom for their comments concerning our manuscript 2 We agree that clinical practice guidelines require greater attention to transparency regarding potential conflicts of interest (COI) and grading of evidence for the recommendations. However, we do not agree with the critique regarding the decision to assign a Grade D to highlight recommendations that did not provide any indication of the supporting evidence. We felt that any statement marked with a bullet point separated from the body of the manuscript could be considered a recommendation. These statements could have been graded, even if the level of evidence was only expert opinion. When a guideline does not cite the level of evidence, there is no way for the clinician to know the quality of evidence or the strength of the recommendation. While many recommendations lack evidence from randomised control trials, we suggest that it is not acceptable to make recommendations without an indication of the grade of evidence. The example cited by Mowat and Bloom regarding methotrexate exemplifies this point. Despite a lack of randomised trials, there is an abundance of data concerning the dangers associated with taking methotrexate during pregnancy. Had the GRADE system (Grading of Recommendations, Assessment, Development and Evaluation) been used, it would have graded ‘methotrexate is absolutely contra-indicated in pregnancy’ as a strong recommendation based on the certainty of the available evidence. We disagree that we misquoted the BSG level of evidence regarding checking thiopurine methyltransferase levels. The British Society of Gastroenterology (BSG) cites evidence level EL4. Evidence level 4 refers to case– control study or poor/non-independent reference standards. This merges into a level C evidence – consensus opinions of experts, case studies or standard of care. With regard to use of methotrexate in ulcerative colitis (UC) and the BSG’s discordant recommendation, the European Crohn’s and Colitis Organisation (ECCO) guideline cites seven manuscripts related to methotrexate in UC. The additional paper that the BSG references is the Cochrane review from 2009 that comments “the available evidence is not sufficient to recommend the use of methotrexate,” which is identical to the ECCO guidelines. BSG is alone in recommending methotrexate in UC. Lastly, we fully agree that potential conflicts of interest (COI) do not equate to bias. However, when COI are present in the development process there is the potential for the COI to bias recommendations. 11 Having a rigorous review process of the manuscript’s drafts does not obviate the need for transparency regarding COI and a well-defined process to mitigate potential bias prior to guideline development. We all agree that the goal of practice guidelines is to create a safer and more effective medical system. To this end, the guidelines development process must be transparent regarding potential COI, have a system in place to minimise potential bias, base recommendations on the best available evidence, and provide a grading of the quality of the evidence for all recommendations.