Appendix: Methods

The Research Triangle Institute-University of North Carolina Evidence-based Practice Center (EPC), with members of the US Preventive Services Task Force (USPSTF), sought to clarify issues concerning screening adults for type 2 diabetes by performing a systematic review of the relevant scientific literature on this topic.

Analytic Framework

The systematic evidence review examines the evidence for screening for diabetes, comparing systematic screening with no screening. Appendix Figure 1 presents the analytic framework that we used to guide our literature search.

The analytic framework describes the logical chain that evidence must support to link screening to improved health outcomes. Each arrow in the analytic framework represents a "Key Question." We searched systematically for evidence concerning each key question in the analytic framework.

The analytic framework begins on the left side of the figure with a sample at risk of undiagnosed diabetes and moves to the right. Key question 1 (represented by the overarching arrow) examines direct evidence that screening improves health outcomes. Because no such studies were found, we continued to examine the indirect evidence in the following key questions, represented as linkages in the analytic framework.

Key question 2 examines the yield of screening, involving both the accuracy and reliability of various screening tests as well as the prevalence of undiagnosed diabetes in the population. Farther to the right in the analytic framework, the third key question examines the efficacy of various treatments to prevent diabetic complications, including tight glycemic control, cardiovascular risk reduction, foot care, or enhanced counseling for lifestyle changes. It is important to note that the critical issue here is the efficacy of the treatment among persons who would be detected by screening. Some studies examine treatment for people with new clinically-detected diabetes; these are only useful insofar as they allow extrapolation to the efficacy of treatment at screening detection. In addition, key question 3 actually implies that the issue of interest is the added efficacy of initiating treatment after screening detection as opposed to initiation after clinical detection. An additional treatment (key question 4) is lifestyle intervention programs for persons with impaired fasting glucose or impaired glucose tolerance. These interventions may reduce the intermediate outcome of developing diabetes, but the critical question is the extent to which they improve health outcomes.

In between the treatment arrows and health outcomes are a variety of "intermediate outcomes," such as retinopathy and albuminuria. Although changes in these outcomes may herald later improved health outcomes, they may or may not be sufficient in themselves to allow estimation of the magnitude of health benefit with reasonable certainty.

At the far right in the analytic framework are the health outcomes—the outcomes that people can experience and care about. These include the major diabetic complications: severe visual impairment, ESRD, lower extremity amputation, and cardiovascular events. In the end, the indirect evidence must allow a reasonable estimation of the magnitude of benefit in these outcomes attributable to screening. At the bottom of the analytic framework is linkage and key question 5, the issue of the harms of screening (e.g., labeling) or harms of treatment (e.g., side effects).

Key Questions

Key question 1: Is there direct evidence from a randomized controlled trial (RCTs) of screening that screening for diabetes improves health outcomes?

Key question 2: What is the yield of screening, both in terms of the accuracy and reliability of screening tests and the prevalence of undiagnosed diabetes in the population?

Key Question 3: What is the added efficacy of initiating treatments (tight glycemic control, tight blood pressure control, lipid and aspirin treatment, foot care programs, counseling for lifestyle change) at screening detection compared with clinical detection in improving health outcomes?

Key question 4: What is the efficacy of lifestyle intervention for people with impaired fasting glucose or impaired glucose tolerance in improving health outcomes?

Key question 5: What are the harms of screening or treatment?

Eligibility Criteria for Admissible Evidence

The EPC staff and USPSTF liaisons developed eligibility criteria for selecting the evidence relevant to answer the key questions (Appendix Table 1):

• For key question 1, we required a well-conducted RCT of screening of adequate size and length to estimate health outcomes with reasonable accuracy.
• For key question 2, we required cross sectional or cohort studies in which screening tests were performed on a primary care or general unselected sample and compared with an acceptable reference standard.
• For key question 3, we accepted RCTs of treatments with health outcomes that provided information about disease duration and co-morbid conditions in persons with diabetes.
• For key question 4, we accepted RCTs of people with IFG or IGT treated with lifestyle or other interventions in which diabetes incidence or development of diabetic complications was an outcome.
• For key question 5, we required RCTs of screened (or treated) versus nonscreened (or nontreated) samples.

When we could not find such studies, we also examined cohort studies of screening-detected diabetics for evidence of quality of life or psychosocial harms.

Literature Search Strategy, Results, and Review of Abstracts and Articles

The analytic framework and key questions guided our literature searches. We examined the critical literature described in the previous review of this topic by the USPSTF (published in 1996) and used our eligibility criteria to develop search terms. We used the search terms to search MEDLINE® and the Cochrane Library for English-language articles that met inclusion criteria and were published between January 1, 1994, and July 30, 2002. We also examined the bibliographies of pertinent articles and contacted experts for other references. When we found that a key question could best be answered by older literature, we also examined these studies. The search strategies are given in Appendix Table 2. All searches started with the term "noninsulin dependent diabetes," and other terms were added as appropriate.

The first author and at least one other coauthor or trained assistant reviewed all abstracts found through our searches to find those that met eligibility criteria. When either reviewer thought that an abstract might meet criteria, the article was copied for full review. The first author and at least one other coauthor or trained assistant reviewed each full article. Those that met eligibility criteria after full review and, when necessary, discussion, were abstracted. Appendix Figures 2, 3, 4, 5, and 6 illustrate our selection process for each key question. We critically appraised each study using criteria developed by the USPSTF Methods Work Group. If we found an article that met criteria but had methodologically fatal flaws that invalidated its findings, it was excluded from further review. Abstracted articles that met eligibility criteria and had no fatal flaws were entered into predesigned evidence tables (go to Appendix B in the Systematic Evidence Review [SER]), Screening for Type 2 Diabetes Mellitis, on the AHRQ Web site at [www.preventiveservices.ahrq.gov]).

Development of the Systematic Evidence Review and Review of the Evidence Article

The authors presented an initial work plan including a provisional analytic framework and key questions to the entire Task Force. Interim reports were presented at subsequent meetings. The Task Force discussed and made important contributions to the review on several occasions. The two Task Force liaisons participated in every phase of the review, including multiple conference calls to discuss critical parts of the evidence.

A draft systematic evidence review was presented to the Task Force and then sent for broad peer review. The peer review included individual experts in the field, representatives of relevant professional organizations, and representatives of appropriate federal agencies. We made revisions to the evidence review as appropriate after receiving peer review comments. The Task Force reviewed all information and voted on a recommendation. We then finalized the SER for publication by AHRQ and separately adapted it for journal publication.

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