Global Guidelines in Dermatology Mapping Project (GUIDEMAP)—A systematic review of the methodological quality of contact dermatitis clinical practice guidelines

The Global Guidelines in Dermatology Mapping Project (GUIDEMAP) assesses the methodological quality of clinical practice guidelines (CPGs) for high‐burden skin diseases. This review focuses on contact dermatitis. We searched MEDLINE, Embase, PubMed, Web of Science, Cochrane Library, Emcare, Epistemonikos, PsycINFO and Academic Search Premier for CPGs published between 1 November 2018 and 1 November 2023. Prespecified guideline resources were hand searched. Two authors independently undertook screening, data extraction and quality assessments. Instruments used were the Appraisal of Guidelines for Research and Evaluation (AGREE) II Reporting Checklist, the U.S. Institute of Medicine's (IOM) criteria of trustworthiness, The Agency for Healthcare Research and Quality's National Guideline Clearinghouse Extent Adherence to Trustworthy Standards (NEATS) Instrument and Lenzer's Red Flags. Twenty five CPGs were included, exhibiting heterogeneity in both the topics they addressed and their methodological quality. Whereas the CPGs on management of hand eczema from Denmark, Europe and the Netherlands scored best, most CPGs fell short of being clear, unbiased, trustworthy and evidence‐based. Disclosure of conflicts of interest scored well, and areas needing improvement include ‘strength and wording of recommendations’, ‘applicability’, ‘updating’ and ‘external review’. Adhering to AGREE II and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) enhances methodological quality.


| INTRODUCTION
In 2021 we published a scoping review on clinical practice guidelines (CPGs) of the 12 most burdensome dermatological conditions measured with disability adjusted life years (DALYs), which included contact dermatitis. 1 Previously there was a notable concern recognised on the accessibility of CPGs. 1 A desire was expressed for the establishment of an online repository specifically for comprehensive dermatology guidelines, aiming to enable swift access in clinical settings.To address this, there was an acknowledged need to compile internationally available CPGs for common dermatological diseases.
An online repository may minimise research redundancy, identify high-quality CPGs and offer a summarised resource of methodological appraised CPGs for patients and clinicians.Additionally, it draws attention to areas that can be improved, such as accurate and comprehensive reporting and adherence to standards for guideline development.Furthermore, by providing a freely accessible global platform, this resource would significantly contribute to dermatological education and reference, particularly benefiting clinicians in resource-poor countries. 1The scoping review marked the commencement of the Global Guidelines in Dermatology Mapping project (GUIDEMAP). 2 The objective of GUIDEMAP is to collate the available CPGs, critically appraise their quality, and to create a global dermatology guidelines repository. 1 Teams were formed to identify and appraise the methodological quality of CPGs per condition.5][6] In this review we focussed on contact dermatitis, which is a prevalent inflammatory skin condition.The lifetime prevalence of contact dermatitis in the general population is estimated at 15%. 7 Contact dermatitis develops as a result of either repeated exposure to substances that cause an allergic reaction or by exposure to irritants that damage the skin barrier, both leading to inflammation of the skin. 8,9Contact dermatitis encompasses many different types, including allergic contact dermatitis, irritant contact dermatitis, photoallergic contact dermatitis, phototoxic contact dermatitis and protein contact dermatitis. 8,10- 124][15] It was estimated that in 2017 there were approximately 221 million new cases of contact dermatitis and 79 million people living with the condition in 195 countries and territories globally. 10,16The clinical symptoms of contact dermatitis can present in a variety of ways, and it is possible for patients to experience multiple subtypes of the condition simultaneously. 12,13,17The hands are most commonly affected, with irritant contact dermatitis (70%) being the leading cause followed by allergic contact dermatitis (25%) and to a lesser extent protein contact dermatitis (5%). 15,18The COVID-19 pandemic, due to mandatory use of antiseptics and personal protective equipment such as gloves, highlighted the importance of preventing and managing occupational skin disease, and its consequences. 19,208][19][20][21][22] Contact dermatitis can have a long-term negative impact on the quality of life of patients by adversely affecting their emotional well-being, social interactions, work productivity and daily activities. 8,12,15,17,18Considering all the aforementioned factors, CPGs have a pivotal role in managing contact dermatitis and improving the well-being of affected patients.The methodology for developing a CPG is laid down in the Appraisal of Guidelines for Research & Evaluation (AGREE) 23 and the Grading of Recommendations Assessment,

Development and Evaluation (GRADE) Evidence to Decision
Framework. 24e objective of this review is to critically appraise the methodological quality of available CPGs on contact dermatitis. 1

| METHODS
This systematic review adheres to the guidelines set out in the 2020 PRISMA statement. 25It follows the pre-established protocol available on the Open Science Framework. 26

| Eligible studies
All CPGs related to contact dermatitis, which had been created by various organisations at local, regional, national or international level, including those affiliated with governmental organisations were eligible for inclusion.We excluded consensus statements that were based solely on expert opinions, single-author documents, CPGs that did not provide recommendations, standalone treatment algorithms, summaries, reviews and duplicate publications. 26

| Literature search
We conducted a comprehensive search covering the period from 1 November 2018 until 1 November 2023 for relevant literature using multiple bibliographical databases, including MEDLINE (OVID version), Embase (OVID version), PubMed, Web of Science, Cochrane Library, Emcare (OVID version), Epistemonikos, PsycINFO (EbscoHOST version) and Academic Search Premier.Whenever possible, the Canadian Agency for Drugs and Technologies in Health (CADTH) filter was applied, which is specifically designed for identifying guidelines. 27The concept contact dermatitis was combined with the guidelines-terms from the CADTH-filter.We used not only controlled subject terms for contact dermatitis, but also several free text terms and synonyms.The search strategy was optimised for all of the databases, taking into account the differences of the various controlled vocabularies as well as the differences of database-specific technical variations (e.g., the use of quotation marks).Animal-only studies and conference abstracts were excluded.The search was performed on 7 November 2023 by an information specialist (JWS) and results were deduplicated before being presented to the reviewers.Appendix 1 in the Supplement provides a detailed description of the search strategy.Two reviewers (EJvZ/ZF) independently screened the search results based on title, abstract and keywords via the Rayyan platform. 28 assessed their eligibility, and any differences were resolved with a third reviewer (BWMA) to consolidate a joint decision.In addition, we checked all the references of included CPGs (EJvZ) for additional eligible reports.

| Methodologies for appraisal
In the protocol, 26 which was published in 2019 at the beginning of the scoping review, 1 it was outlined that three instruments would be used to assess the methodological quality of identified guidelines, modelled on a review by Eady et al. 29 : the AGREE II Reporting Checklist, 23 the US Institute of Medicine (IOM, since 2015 the National Academy of Medicine) criteria of trustworthiness 30 and Lenzer's Red Flags. 31 November 2022, GUIDEMAP decided to make an amendment to the protocol, replacing the IOM-criteria with the Agency for Healthcare Research and Quality's National Guideline Clearinghouse Extent Adherence to Trustworthy Standards (NEATS) Instrument, given its validation.32 The NEATS instrument builds upon the IOMcriteria and the AGREE II framework.See Table 1 for details on the four instruments that were used.
To maintain consistency with our earlier published work we chose to retain the IOM-criteria that we had previously included, making it also possible to calculate correlations between IOM and NEATS.
Blinded assessments were conducted independently by four authors (EJvZ, BWMA, SV and ZF), working in pairs.

| Data extraction and management
To describe the characteristics of the included CPGs, we used the datasheet of our previous systematic review of CPGs on atopic dermatitis. 3 extracted the following items: country; organisation producing the CPG; type of contact dermatitis; year of publication; geographical region; language; topics covered in CPG; publication source; sociodemographic index; funding source; accessibility of CPG; patient involvement; use of AGREE II; use of GRADE.The assessment of CPGs with the AGREE II tool was conducted through the online AGREE PLUS platform. 33Once the appraisals were completed, the scoring (ranging 1 to 7) was unblinded.In situations where there was a difference of more than two points in scoring of any of the 23 items, the reviewers discussed and resolved the discrepancy.The consolidated data obtained from AGREE PLUS were exported into a datasheet, with scores per item and domain scores expressed as a percentage (ranging from 0% to 100%, as per AGREE II methodology), and graded accordingly.The grading followed our protocol as: excellent (≥70%), average (≥50% and <70%) and poor (<50%).We deliberately did not assign an overall grade to the CPGs, as it would not adequately reflect the diverse strengths and weaknesses inherent in each guideline as we had justified previously. 3,29As for the IOM-criteria and Lenzer's Red Flags assessments, we reused earlier created evaluation forms for each reviewer, ensuring their assessments were blinded. 3A new Excel form was developed (BWMA) to evaluate each item of NEATS.Prior to its implementation, the form underwent piloting.After unblinding, any differences in scoring between the reviewers for IOM, Red Flags and NEATS were resolved by discussion.The NEATS overall scoring followed Burns et al., summing-up the 12 Likert scores and for three items add 5 points when scoring 'yes' and 0 points when scoring 'no' or 'unknown' (score range 12-75). 34e percentages for NEATS were calculated in exactly the same way as AGREE II does per domain (actual score minus minimum score, divided by maximum score minus minimum score; 0%-100%).
Guidelines in languages other than English, French, German, Spanish, Dutch, Polish and Arabic, were translated using Google translate.

| Statistical analyses
The descriptive statistics based on the datasheets were calculated with Microsoft's Office 365 Excel.Correlations between the four assessment instruments were calculated with the Pearson correlation coefficient, based on the AGREE II sum of domain percentages, the number of IOM items 'fully met', the NEATS total percentage scores, and the number of Red Flags, for which SPSS version 28.0 (IBM, Armonk, NY, USA) for Windows was used.

| RESULTS
The database search retrieved 1129 records as shown in Figure 1 and Appendix 1 in the Supplement.After removal of duplicate references (n = 465), we screened the titles, abstracts and keywords of 664 records, of which 639 were excluded.Full-text copies of the remaining 25 records were obtained for further evaluation.6][37][38][39][40][41][42][43][44][45][46] The manual search yielded 13 additional reports, one 47 of which did not meet the explicit criteria of a guideline.In total we identified 25 CPGs that met the inclusion criteria (see Figure 1).

| AGREE II scoring
Two CPGs on hand eczema (Denmark 52 and The Netherlands 65 ) and one on epicutaneous patch testing (Germany 58 ) scored 'excellent' for all six domains of the AGREE II reporting checklist.One CPG scored 'poor' on all domains. 69The remainder showed a large variety in scoring and grading per domain (Table 3).In-depth details per AGREE IIitem are presented in Table S1 in the Supplement.
e Sorting based on number of AGREE II domains scoring excellent, average and poor.This is not an absolute ranking from highest to lowest quality.

| IOM scoring
Two CPGs scored 'fully met' on all nine IOM criteria (Europe 53 and Germany 58 ) and two on eight criteria (Denmark 52 and The Netherlands 65 ).Six guidelines did not score 'Fully met' on any of the criteria: two from China, 48,50 Japan, 63 International, 61 ECRI 72 and Togo. 69See Table 3.
Ranking the IOM-criteria, 'Management of conflicts of interest' was the best scoring criterion (16/25 'fully met'), followed by 'Transparency' (9/25).The lowest three were 'Establishing evidence foundations', 'Rating strength of recommendations' and 'External review' with only four out of the 25 CPGs meeting these criteria fully.Sixteen did not meet the criteria 'Rating strength of recommendations' and 'External review', and 18 did not on 'Updating procedures'.More details are provided in Table S2 in the Supplement.

| Red Flags
Applying Lenzer's Red Flags methodology, two CPGs received no red flags of the possible eight, and scored no 'caution' or 'uncertain': The Netherlands 65 and Europe. 53The two lowest scoring CPGs were Germany 56 with five red flags and the international CPG 61 with six.  3 and Table S4 in the Supplement.

| Correlations between AGREE II, IOM, NEATS and Red Flags
From the outset, 26,29 it was decided that multiple instruments would be used, reflecting multiple angles, to assess the methodological quality of CPGs.Similar to our previous publication on CPGs for atopic dermatitis, 3 we were interested in exploring correlations between the four instruments, especially with the addition of NEATS and its possible correlation with IOM.We found very high correlations between AGREE II and NEATS (r = 0.95; p < 0.001) and between NEATS and the number of IOM items 'fully met' (r = 0.95; p < 0.001).AGREE II and NEATS correlated highly with fewer red flags (r = À0.74 and À0.75, respectively; p < 0.001).See Table S5 in the Supplement.

| Main findings and interpretation
Twenty five CPGs were included encompassing an array of topics such as hand dermatitis, Toxicodendron dermatitis, and contact dermatitis in its broader context.In addition we found CPGs focusing on diagnostics, management and/or prevention, as well as combinations of all three.As a result, the included CPGs are quite heterogeneous, both in topics, as in the aspects of care.Furthermore, the COVID-19 pandemic has had considerable impact on hand hygiene and use of personal protective equipment (PPE), with contact dermatitis emerging as a consequence of these measures, both for the general population and health care providers. 19,20,51,66,72Therefore, besides general public health information, specific recommendations regarding COVID-19 and its association with contact dermatitis have been developed.The profound influence of the pandemic was clearly evident in the latest developed guidelines. 51,66,725][56][57][58][59][60] The assessed methodological quality of these guidelines is directly related to their staging (indicated as S1-S3), 74 from consensus based (S1) to completely evidence based (S3).It is therefore not surprising that an S3 guideline 58 scored better than S1. 55,59,60e guidelines that scored the highest, as assessed with our four instruments, are the CPGs on management of hand eczema from Denmark, Europe and the Netherlands. 52,53,65This could be attributed in part to the fact that hand eczema is a relatively well-defined topic.
However, these guidelines also incorporated patient involvement, and adhered to the AGREE II and GRADE methodology, all contributing to their high scores.
In contrast to our appraisal of atopic dermatitis guidelines, 3  The IOM criteria 'Rating strength of recommendations', 'Updating procedures' and 'External review' were least met.The last two criteria were also found to be the least met in the review of the atopic dermatitis CPGs. 3 Still, those could be easily met by including an expiry date or updating statement, as well as seeking external review. 3e IOM criterion 'Guideline development composition group' (GDG), refers to a multidisciplinary group including methodological experts, as well as patient and public involvement. 30

| Applicability and future perspectives
CPGs on contact dermatitis are essential for healthcare providers in helping patients to make informed decisions about their care. 1,29veloping CPGs for contact dermatitis poses significant challenges.
First, the definition of contact dermatitis covers various types, each having distinct aetiologies, including causative factors like allergens and irritants, for instance. 11,12Second, accurately diagnosing, effectively managing and preventing contact dermatitis can be quite challenging. 11,75The applicability of these CPGs may vary across different regions and healthcare settings, considering factors such as the local healthcare system, diagnostic and treatment accessibility, locally prevalent contact allergens, and available resources.Ultimately these CGPs are intended to enhance the overall quality of care delivered to individuals and thus enhancing quality of life, including the ability to work.
With our systematic review we address the recognised need highlighted in the introduction.By synthesising the international CPGs which will be made available in the online repository (including the CPGs themselves), our review offers a high quality appraised resource for patients and clinicians reducing research waste particularly benefiting CPG development in resource-poor countries.
When using high-quality guidelines for another local situation, the GRADE-ADOLOPMENT, 76 ADAPTE 77 or RAPADAPTE 78 methodologies can also be used.These approaches are particularly applicable to contact dermatitis when the primary strategies involve allergen and irritant avoidance, and the use of topical treatments, all of which can be implemented in various settings, depending on feasibility, accessibility and affordability.However, local prevalent contact allergies may differ, as reflected in various standardised patch test series.

| Strengths and limitations
A comprehensive search was performed by an experienced information specialist (JWS), utilising multiple databases without any language restriction.In addition, six guideline repositories and over 200 websites of the members of the ILDS were hand searched, and 110 dermatological societies were contacted by email to enquire about their contact dermatitis guidelines.A further strength was that the assessors followed a directed approach for each guideline assessment: AGREE II first (23 items), then NEATS (15 items), then IOMcriteria (9 items), followed by Red Flags (8 items).By doing so, recall issues were reduced as much as possible.To further ensure a comprehensive approach, both in language and appraisal, we engaged in thorough discussions in pairs after unblinding to address any potential arising issues.
As not all societies' websites were online or freely accessible, and only a few have responded to our email, it is possible that some guidelines may have been missed.Although bibliographic databases typically index keywords, abstracts, and titles in the English language, irrespective of the article's original language, guidelines might not have been found as it was not feasible to incorporate terms from all languages spoken worldwide into our literature search.Additionally, guidelines that were not indexed in the predefined databases and online guideline repositories may not have been captured.Furthermore, as per protocol, we hand searched the websites of dermatological societies (ILDS) and not of others, such as occupational healthcare societies.Six guidelines [48][49][50]52,63,68 required translation, all others were within the language capabilities of the authors. For thesix we used Google Translate.This automated translation may have led to missing nuances which could have been important for the appraisal process.Regarding the correlations between the four instruments, there is also a limitation.All four instruments are intended to assess the methodological quality of a CPG.To calculate correlations between those instruments, we added the domain percentages of AGREE II as a total score.This is not advised by AGREE II, as the domains are not relatively weighed.
Therefore the sorting in Table 3 is based on the domain scores according to our grading system.For NEATS, of which only two peer-reviewed publications are available, we used the Burns et al.
method to calculate the scores. 34The correlations we found, however, were high to very high, confirming that all four instruments assess the methodological quality of these instruments and are quite in concordance.
In conclusion, we identified 25 CPGs on contact dermatitis that are less than 5 years old.These CPGs are highly heterogeneous in terms of their topics (aetiology of contact dermatitis) and aspects of care (diagnosis, prevention and treatment).Likewise, and not unexpectedly, the methodological quality of these guidelines is equally diverse.We also found that the four instruments used were quite This systematic review contributes to the establishment of a freely accessible global platform, aligning with the identified need and benefitting dermatological education by summarising these insights, particularly in resource-poor countries.
Any discrepancies were resolved by a third independent reviewer (BWMA).Additionally, two reviewers (EJvZ/BWMA) performed a manual search of guideline repositories, such as Guidelines International Network (G-I-N), National Institute for Health and Care Excellence (NICE), Scottish Intercollegiate Guidelines Network (SIGN), Turning Research into Practice (TRIP), DynaMed, and Emergency Care Research Institute (ECRI).These two reviewers also independently searched over 200 websites of Dermatological societies that are members of the International League of Dermatological Societies (ILDS), and contacted 110 societies per email to inquire about the availability of eligible guidelines.No language restrictions were applied.Reports deemed eligible were retrieved in full text (EJvZ).Two reviewers (EJvZ/ZF) Abbreviation: GDG, Guideline development group.
Records identified from databases (contact dermatitis (n = 1129): -MEDLINE (n =126) -Embase (n = 236) -PubMed (n = 320) -Web of Science (n = 251) -Cochrane Library (n = 77) -Emcare (n = 88) -Epistemonikos (n = 9) -PsycINFO (n = 1) -Academic Search Premier (n = 21) -Registers (n.a.) Records removed before screening: -Duplicate records removed by automation (n = 465) -Records marked as ineligible by automation tools (n = 0) -Records removed for other reasons (n The three best scoring Red Flag domains were 'Any suggestion of committee stacking that would pre-ordain a recommendation' (0 red flags), 'Sponsor(s) is a professional society that receives substantial industry funding' (1 red flag), and 'Committee chair(s) have any financial conflict' (3 red flags).Most of the red flags were for 'No external review' (17/25) and 'No inclusion of non-physician experts/patient representative/community stakeholders' (19/23).More information is found in Table the AGREE II domain of 'Editorial independence' scored excellent in more than half of the CPGs on contact dermatitis (14/25).This was consistent with the IOM criteria 'Transparency' and 'Management of conflicts of interest', the second item of NEATS ('Disclosure and Management of conflicts of interest'), and the low number of red flags for conflicts of interest.This may be due to the fact that most of the diagnostics and therapeutics for contact dermatitis do not pose a conflict of interest, unlike atopic dermatitis with new and emerging therapies.Similar to the atopic dermatitis CPGs review, the AGREE II domains 'Rigor of development' and 'Applicability' received the lowest scores.
concordant.We used NEATS for the first time, and it correlated very highly with AGREE II.Whereas the CPGs on management of hand eczema from Denmark,52 Europe 53 and the Netherlands scored best,65 most CPGs fell short of being clear, unbiased, trustworthy, and evidence-based to the extent they could and should be.There is ample room for improvement to enhance the methodological quality of CPGs by adhering to the AGREE II and GRADE directives.This includes incorporating quite simple elements such as specifying the date for guideline updates and seeking external review.Domains such as synthesis of evidence, strength and wording of recommendations, and applicability, need more resources to be addressed properly.It is important to note that while the methodological quality of certain CPGs may appear suboptimal for some, this does not necessarily imply that the content is not valuable or useful.Including methodologists and patient representatives during guideline development, would be very welcome, and could benefit patients with contact dermatitis and their quality of life.
Characteristics of included CPGs.
1 PRISMA 2020 flow diagram for new systematic reviews which included searches of databases, registers and other sources.ECRI, Emergency Care Research Institute; G-I-N, Guidelines International Network; ILDS, International League of Dermatological Societies; NICE, National Institute for Health and Care Excellence; SIGN, Scottish Intercollegiate Guidelines Network; TRIP, Turning Research into Practice.TA B L E 2 T A B L E 3 Scoring results for AGREE II, Institute of Medicine (IOM) criteria, NEATS and Red Flags.aAGREE II scores in percentages per domain; excellent (≥70%; green), average (≥50% and <70%; yellow) and poor (<50%; red).b IOM-scoring 'fully met' from 0 to 9 (higher is better).c NEATS-scoring 0%-100% (higher is better).d