Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus

 

## Step 3: identify key areas for revisions and define the structure and methodology of the updated guideline
The chairman of the guideline committee (D.B. Sacks) acted as editor and assigned lead authors to each section. Authors reviewed the 2002 edition of the NACB DM guideline (1) and identified key areas for revisions and updating. The guideline team discussed the scope and methods of the updating process at a face-to-face meeting, which was followed by numerous teleconferences and e-mail exchanges among authors that were coordinated by the editor and the NACB. The guideline group decided that the structure of the guideline would remain the same as the 2002 document and that it would cover virtually all key analytes that are used primarily in the diagnosis and management of individuals with DM. As before, the testing of lipids and related cardiovascular risk factors is not covered in this update but is addressed in a separate NACB guideline. For each area of testing discussed, the guideline highlights the clinical use and rationale for the test or tests; the preanalytical, analytical, and interpretive aspects of each test; and, where relevant, emerging considerations for future research.

## Step 4: define and prioritize key questions
The lead authors used the review process outlined above to define specific key questions to enter on a standard form developed for this process. These questions were sent to all members of the guideline committee for independent review and prioritization, a process that used preset criteria related to the relationship between testing and outcomes (see [fig_ref] Table 2: Criteria for prioritization of key questions [/fig_ref]. Authors used the categories and explanatory notes provided (see [fig_ref] Table 2: Criteria for prioritization of key questions [/fig_ref] to document the rationale for prioritization or individually provided their own reasoning. Authors assigned priority scores on a scale of 1 to 4 (most important, important, moderately important, or least important, respectively). The independent replies collected from all authors were the basis for drafting a consensus priority list. Final key questions with priority scores and categories of reasoning are presented in the evidence tables (see .

## Step 5: search the literature systematically for high-priority questions and select relevant key publications
Key questions that earned the highest priority score were covered by a more systematic approach during the search and evaluation of the evidence currently available in the literature. Other topics that were considered less important were dealt with in a less rigorous way. Because this guideline is an update of the 2002 version, authors limited their searches to the period beginning in January 2002. Guidelines related to the topic were searched in the Agency for Healthcare Research and Quality National Guideline Clearinghouse database (http://www.guideline.gov/). Systematic reviews and metaanalyses were searched by using the Clinical Queries-Find Systematic Reviews function of PubMed. If no such publications were found, PubMed, Embase, and other databases were used to search the primary literature. Because the group of authors included leading experts in their fields, the authors' personal files, communications with experts, and unpublished or ongoing-trial data were also made available to be used in the guideline-updating process. Additional literature citations were added during the comment periods (see below).
Authors selected relevant key publications for updating each section, and the editor of the guideline (D.B. Sacks) and lead authors of other sections (D.E. Bruns, M.S. Kirkman, D.M. Nathan) acted as independent expert reviewers to avoid biased selection of papers. When the guideline team retrieved and agreed with existing guideline recommendations that had already covered the key question comprehensively and had reached concordant conclusions, the guideline team simply adopted and referenced the published recommendations in order to avoid duplicate publication.

## Step 6: subject selected key publications to critical expert review; extract data into evidence tables
Critical review of selected key publications formed the basis for establishing the level and quality of the evidence underlying each recommendation (see STEP 7 for details). Section authors and a methodology expert (A.R. Horvath) extracted data into evidence tables (see . These tables list all key questions together with their priority scores (STEP 4). Related recommendations and their grades from the 2002 guideline were aligned with those of the new updated recommendations (see columns 1 and 2 in . In the updated recommendation, authors highlighted changes to the original text in boldface and provided explanation for the changes where necessary (column 3). Key references supporting the new recommendation were listed (column 4).

## Step 7: define the quality of evidence underlying each recommendation
To our knowledge, no uniformly accepted grading scheme exists for rating the quality of evidence and the strength recommendations when questions related to laboratory testing for the screening, diagnosis, prognosis, and monitoring of a condition are addressed [bib_ref] Grading quality of evidence and strength of recommendations for diagnostic tests and..., Horvath [/bib_ref]. The guideline group agreed that the grading scheme of the ADA, which was used in the 2002 version of this guideline (1), is applicable predominantly to therapeutic recommendations and that its use in this diagnostic guideline was thus impracticable. Therefore, we developed a grading system by adapting the key elements of evidence-rating frameworks employed by various international guideline agencies, the US Preventive Services Task Force, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group (6-12). In this system, the overall quality of the body of evidence (STEP 7) and the strength of recommendations (STEP 9) are graded separately. Rating the quality of the body of evidence is based on (a) the level of evidence of individual studies defined by their study design and methodological quality; (b) the consistency of results across various studies; (c) the directness of comparisons; and (d) the precision-of-effect estimates. Supplementary provides a detailed explanation of evidence-level categories and these elements of the rating scheme for the quality of evidence.
Members of the guideline committee received detailed explanations and guidance, as well as methodological support, on how to use the grading scheme. At this stage of the guideline-development process, section authors indicated the study design (see column 5 in and the level of evidence (column 6) of all individual studies listed in the evidence tables. The quality of the totality of the evidence underlying each recommendation was established by means of the criteria mentioned above (column 7).

## Step 8: release the first draft of the guideline for public comments
The first draft of the guideline was released on the NACB Web site for soliciting of public review and feedback. The still nongraded draft recommendations were sent to a number of external organizations (see for peer review and expert comments that could be submitted either via the NACB Web site or by mail. The draft guideline was also presented at the Arnold O. Beckman consensus conference in 2007, and the discussions at this conference were recorded.

## Step 9: incorporate comments, grade recommendations, and prepare the second draft of the guideline
The guideline team reviewed and discussed the comments that were received and made many changes to the first draft to reflect the views of external peers, organizations, or individuals. The amended draft of the guideline was also presented at the 2009 AACC annual meeting and used for grading recommendations.
The grade or strength of recommendation refers to the extent of collective confidence that the desirable effects of a recommendation outweigh the potential undesirable effects. Desirable effects of a recommendation may include improved health-related, organizational, or economic outcomes or aspects of care. The quality of evidence (STEP 7, Supplementary is only one element in making recommendations for practice. Scientific evidence was supplemented with considered judgment that balanced the potential clinical benefits and harms with perceived patients' preferences, bioethical considerations, and organizational and economic impacts of testing . Considered judgment therefore may have upgraded or downgraded a recommendation. Categories for grading recommendations are shown in .
During the considered-judgment process, the guideline committee was primarily driven by 2 core bioethical values-beneficence and nonmalevolence. The guideline group also observed the first principle of bioethics, i.e., respect for patients' autonomy and the decision-making capacities of individuals to make their own choices. The guideline group assumes that the target users will also deal with this core bioethical principle when using these guidelines in practice (13). The guideline committee acknowledges that it was not able to cover universally other bioethical principles, such as justice and equity. As mentioned above, the members of the guideline team, as well as individuals who commented on the recommendations, were mostly from North America and other developed countries. Their views and experiences therefore unavoidably affected the considered-judgment and consensus processes involved in formulating recommendations. The guideline team also could not consider explicitly the cost implications of the recommendations in various resource settings, although recommendations were formulated in a generic way and in a cost-conscious manner.
Recommendations in diagnostic guidelines frequently are supported primarily by expert consensus. This reflects the often poor quality of evidence, or the lack or indirectness of evidence that the intervention is relevant to patient outcomes. To avoid the influence of dominant personalities and overrepresentation of the individual opinions or views of experts, the guideline team reached consensus when the evidence base was inconsistent, weak, or lacking. The matrix in assisted in the assignment of final grades to recommendations. The methodology expert pregraded recommendations by using the information in columns 5, 6, and 7 of the evidence tables provided by committee members (see . Authors reviewed these grades and returned the amended evidence tables to the methodology expert for completion. Committee members added comments or explanatory notes when necessary (column 8) to enhance the transparency and reproducibility of the considered-judgment and consensus process of grading and to address the adaptability and applicability of the final recommendations. All sections were reviewed by the ADA representative (M.S. Kirkman), a clinical expert (D.M. Nathan), and a methodology expert (A.R. Horvath) and were edited by the chairman of the guideline committee (D.B. Sacks).

## Step 10: release the second draft of the guideline for public comments and submit the final draft to the nacb for review and approval
The second draft of the guideline with graded recommendations was posted on the NACB Web site for a last call for public comments. The guideline recommendations were also reviewed by the Professional Practice Committee of the ADA. Several comments were received and incorporated, and the final guideline draft was submitted for review by the joint Evidence-Based Laboratory Medicine Committee of the AACC and the NACB. After addressing the reviewers' comments, the guideline committee referred the guideline to the NACB Board of Directors, which approved it before its official release for publication.

## Implementation and review
To assist implementation, the guideline committee has listed the key recommendations of the guideline in an executive summary. Key diagnostic and risk-assessment criteria are presented in tables, and a diagnostic algorithm is provided for urinary albumin testing. Most recommendations are worded to represent standards of care and thus can be easily converted to key performance indicators for local audit purposes.
Although recommendations have been developed for national and international use and are intended to be generic, certain elements of this guideline will not reflect views that are universally held, and other elements may have limited applicability in healthcare settings that lack sufficient resources for adopting the recommendations. The guideline committee advises users to adapt recommendations to their local settings. During such adaptation processes, the evidence tables provided (see might assist users in making informed decisions.
The next review of this guideline is planned in 5 years, unless substantial new evidence emerges earlier for high-priority areas in the laboratory management of patients with DM. Low: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate and the recommendation. The body of evidence is of low level and comes from studies with serious design flaws or with evidence that is indirect.
Very low: Any estimate of effect is very uncertain. Recommendation may change when higherquality evidence becomes available. Evidence is insufficient to assess the effects on health outcomes because of limited number or power of studies, important flaws in their design or conduct, gaps in the chain of evidence, or lack of information.

## Supplementary table 5. grading the strength of recommendations.

## A. the nacb strongly recommends adoption
Strong recommendations for adoption are made when:
- There is high-quality evidence and strong or very strong agreement of experts that the intervention improves important health outcomes and that benefits substantially outweigh harms; or
- There is moderate-quality evidence and strong or very strong agreement of experts that the intervention improves important health outcomes and that benefits substantially outweigh harms.
Strong recommendations against adoption are made when:
- There is high-quality evidence and strong or very strong agreement of experts that the intervention is ineffective or that benefits are closely balanced with harms, or that harms clearly outweigh benefits; or
- There is moderate-quality evidence and strong or very strong agreement of experts that the intervention is ineffective or that benefits are closely balanced with harms, or that harms outweigh benefits.

## B. the nacb recommends adoption
Recommendations for adoption are made when:
- There is moderate-quality evidence and level of agreement of experts that the intervention improves important health outcomes and that benefits outweigh harms; or - There is low-quality evidence but strong or very strong agreement and high level of confidence of experts that the intervention improves important health outcomes and that benefits outweigh harms; or
- There is very low-quality evidence but very strong agreement and very high level of confidence of experts that the intervention improves important health outcomes and that benefits outweigh harms.
Recommendations against adoption are made when:
- There is moderate-quality evidence and level of agreement of experts that the intervention is ineffective or that benefits are closely balanced with harms, or that harms outweigh benefits; or - There is low-quality evidence but strong or very strong agreement and high level of confidence of experts that the intervention is ineffective or that benefits are closely balanced with harms, or that harms outweigh benefits; or
- There is very low-quality evidence but very strong agreement and very high level of confidence http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc11-9998/-/DC1 of experts that the intervention is ineffective or that benefits are closely balanced with harms, or that harms outweigh benefits.

## C. the nacb concludes that there is insufficient information to make a recommendation
Grade C is applied in the following circumstances:
- Evidence is lacking, scarce, or of very low quality, the balance of benefits and harms cannot be determined, and there is no or very low level of agreement of experts for or against adoption of the recommendation.
- At any level of evidence-particularly if the evidence is heterogeneous or inconsistent, indirect, or inconclusive-if there is no agreement of experts for or against adoption of the recommendation.

## Gpp. the nacb recommends it as good practice point
Good practice points (GPPs) are recommendations mostly driven by expert consensus and professional agreement and are based on the information listed below and/or professional experience, or widely accepted standards of best practice. This category applies predominantly to technical (e.g., preanalytical, analytical, postanalytical), organizational, economic, or qualitymanagement aspects of laboratory practice. In these cases, evidence often comes from observational studies, audit reports, case series or case studies, nonsystematic reviews, guidance or technical documents, non-evidence-based guidelines, personal opinions, expert consensus, or position statements. Recommendations are often based on empirical data, usual practice, quality requirements, and standards set by professional or legislative authorities or accreditation bodies, etc.
[fig] 3: and represented the NACB (D.B. Sacks, D.E. Bruns) and the ADA (M.S. Kirkman). The guideline committee included clinical experts (G.L. Bakris, A. Lernmark, B.E. Metzger, D.M. Nathan) and laboratory experts (D.B. Sacks, D.E. Bruns, M. Arnold, A.R. Horvath) whose key area of research and practice is DM. Some members of the committee provided additional support in evidence-based guideline-development methodology (D.E. Bruns, A.R. Horvath, D.B. Sacks). [/fig]
[table] Table 2: Criteria for prioritization of key questions [/table]