Dewey C. Scheid, MD, MPH Laine H. McCarthy, MLIS Frank H. Lawler, MD, MSPH Robert M. Hamm, PhD Kathryn E.H. Reilly, MD, MPH Oklahoma City, Oklahoma Submitted, revised, April 16, 2001. From the Department of Family and Preventive Medicine, University of Oklahoma Health Sciences Center. Reprint requests should be addressed to Laine H. McCarthy, 900 NE 10th Street, Oklahoma City, OK 73104. E-mail: laine-mccarthy@ouhsc.edu.
References
Criterion 5: Tests must be acceptable to the patient and available at reasonable cost. A major limitation of any annual screening program is the proportion of false-positive tests that occur. During the first years of an annual screening program in a previously unscreened population with a high prevalence of disease, the proportion of false positives would be low. For example, in the first year of screening a population with a 40% prevalence of MA,14 using a test that is 90% sensitive and specific, the probability of having true MA after a single positive test would be 86% (the positive predictive value [PPV]). During subsequent years of a screening program, the prevalence of MA should approach the annual incidence of new disease, 1% to 4% per year.14 Therefore, the PPV of a single screening test in subsequent years could be expected to range from 8% to 27%.
To reduce the number of false positives, the ADA recommends that 2 of 3 screening tests be positive over a 3- to 6-month period before beginning treatment.7,8,56 However, the degree of improvement that can be expected depends on the correlation between repeated tests. Although the UAE measure (in mg/minutes) has a high variance (coefficient of variation ranging from 33%-52%),57 there is no published information on the correlation between errors on repeated screens when each is simply categorized as positive or negative for MA. However, Feldt-Rasmussen57 calculated the probability of correct classification above or below 20 mg per minute using 1 sample compared with the median of 3 samples. Using 1 sample, specimens below 11 mg per minute and above 40 mg per minute had a greater than 95% probability of correct classification. By using the median of 3 samples, specimens below 13 mg per minute and above 32 mg per minute had a greater than 95% probability of correct classification. Most would agree that this is a clinically insignificant difference.
We analyzed the performance of a theoretical UAE test repeated up to 3 times according to ADA recommendations (considered negative if the first test is negative, or else the majority of 3 tests).8 Assuming an individual test sensitivity of 90%, a specificity of 90%, and a 10% prevalence of MA, we performed a sensitivity analysis of the effect of varying the correlations between repeated tests Figure 1.20 This pretest probability was selected because it was between the estimate of 40% prevalence for the first year of screening and a 1% to 4% annual incidence of new disease. If the tests are completely independent (correlation=0), the probability of true MA if the multiple screen is positive is 84%, an improvement compared with the PPV of 50% for a single positive test. However, as the correlation (phi) between tests increases, the PPV of repeated testing decreases, approaching the PPV for a single test. To keep the PPV of repeated testing as high as 75%, the correlation between tests would have to be lower than approximately 0.1, which is quite unlikely. Thus, although MA screening tests are noninvasive and relatively inexpensive, current recommendations may impose a significant burden on patient management without necessarily improving diagnostic certainty.
Criterion 6: Incidence of disease must justify screening cost. Seven cost-effectiveness analyses of MA screening and treatment with ACEIs to prevent end-stage renal disease (ESRD) have been published Table 3.58-64 Five of these studies estimated the cost-effectiveness of MA screening in persons with type 1 diabetes.59-63 Three of these 5 studies59,60,63 that found screening to be cost-saving assumed perfect testing for MA. In 1 study that considered false-positive tests, the additional cost of screening for MA was $27,042 per quality-adjusted year of life (QALY) saved, compared with simply screening for hypertension or macroalbuminuria.61
Because the incidence of a costly outcome such as ESRD is higher for persons with type 1 diabetes, MA screening is likely to be cost-effective in this population.62 However, the cost-effectiveness of screening persons with type 2 diabetes for MA, only 5% to 10% of whom will develop ESRD, has recently been analyzed.58,64 These analyses assumed perfect screening characteristics, and one study64 considered only Pima Indians, who have a higher incidence of ESRD. MA screening saved QALYs and reduced costs compared with screening for macroalbuminuria, but routine use of ACEIs for all persons with type 2 diabetes was cost-effective ($7500/QALY) when compared with screening.58 No cost-effectiveness analysis to date has included false-positive tests and studied a more typical population.
Discussion
We found no controlled trials of screening to prevent progression to nephropathy.3 Recommendations for screening persons with diabetes for MA are based on expert opinion; the evidence to support the specific components of these recommendations is lacking. Several studies have also demonstrated that UACR has little advantage over the measurement of UAC alone.25,29,47,65 Use of untimed urine samples avoids the need for 2 visits, collection equipment, the problems of inaccurate timing, urine storage at 4 °C, and transfer to laboratories.38
