Prospective comparison of three guideline development methods for treatment of actinic keratosis Borgonjen, R.J.; van Everdingen, J.J.; Bik, C.M.; Tuut, M.K.; Spuls, P.I.; van de Kerkhof, P.C. General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. To compare three methods of guideline development, to see whether using alternative evidence-based methods resulted in variation of recommendations for treating actinic keratosis. Methods: Method 1 followed a standard multiple session evidence-based approach with a working group. In method 2 recommendations were formulated by a working group during a 2-day conference. Method 3 used one epidemiologist to summarise the evidence and one dermatologist to make clinical recommendations afterwards. Graded recommendations and levels of evidence were compared per therapy across three draft guidelines. The primary outcome was the extent of accordance or discordance. Secondary outcomes were total costs and time period necessary to make a draft guideline. Results: Therapeutic recommendations and levels of evidence differed in some occasions. However, intraclass correlations between levels of evidence were significant (method 1 vs 2: p¼0.003; method 1 vs 3: p<0.001).Regarding recommendation variation method 1 and method 2 correlated significant at 0.755 (p¼0.001). Method 1 versus 3 and method 2 versus 3 also showed significant, but lower, correlation coefficients (respectively, 0.493 (p¼0.026) and 0.673 (p¼0.007)). Method 3 was the cheapest and quickest (24 770 euro and 4 months) and method 1 was the most expensive and slowest method (€48 100 euro and 14 months). Conclusions:The value of a guideline using alternative evidence-based methods seems to at least equal that of a guideline composed in multiple sessions, that is, for topics with a monodisciplinary character and a relatively small number of conducted trials. In addition, the presented alternatives were more time-and cost-efficient.

If an authorized drug is prescribed for a use that is not described in the Summary of Product Characteristics, this is defined as 'off-label use.' Methotrexate is often used off-label for dermatological indications. Off-label use is permitted if physicians can justify the treatment based on scientific evidence available to them. Our objective here was therefore to summarize the evidence for the effectiveness, efficacy, and safety of the dermatological off-label use of methotrexate in a systematic review. We searched MEDLINE, EMBASE, and CENTRAL for studies for evidence on the effectiveness, efficacy, and safety of the off-label use of methotrexate in dermatological indications up to November 2019. We used the GRADE system to rate the quality of the evidence. The search retrieved 34,583 hits of which 3566 were selected after the title and abstract screening. After the full-text screening, 143 studies were included, which involved 3688 patients in total. We found low-quality evidence for the effectiveness, efficacy, and safety of the off-label use of methotrexate in 31 dermatological diseases.To optimize the quality of evidence to support off-label use, we need high-quality studies in which well-characterized patients are treated with standardized treatments regimens using well-validated outcomes relevant to patients and physicians.

No abstract