Abstract

METHODS

COST-EFFECTIVENESS ANALYSIS

We evaluated a variety of different screening strategies for identifying children with diabetes and dysglycemia.

Identifying Diabetes

The initial strategy we considered was the 2-hour OGTT, with the assumption that all eligible participants were tested. No confirmatory screen was required for this strategy because it is considered the criterion standard and has been used to define diabetes and prediabetes in landmark trials, such as the Diabetes Prevention Program.^4,16 We assumed a test performance of 100% sensitivity and specificity, similar to previous studies.^12,18 Wethen tested 3 additional strategies using HbA1c, including thresholds of 6.5% (ADA definition of diabetes), 5.7% (ADA definition of prediabetes),¹⁹ and 5.5% (a threshold suggested as an optimal cutoff for detecting prediabetes in children).²⁰ For all the HbA1c strategies, we assumed a 2-step screening strategy in which only individuals with a positive initial test result (ie, above the defined threshold) receive a confirmatory 2-hour OGTT. Assumptions of test performance for HbA1c for the base case were based on a previously studied clinical cohort of children for whom the outcome of dysglycemia was studied.²¹ Because the diabetes test performance data were not previously published in that study, we conducted the analyses with the same pediatric cohort for the outcome of diabetes (see test performance results in the eTable; http://www.jamapeds.com), for which 3 children were identified as having diabetes.

Identifying Prediabetes

For prediabetes, we also evaluated a 2-hour OGTT, assuming 100% sensitivity and specificity. For the additional strategies, we assumed a 2-step screening strategy (confirmatory 2-hour OGTT after a positive initial test result) to evaluate HbA1c at thresholds of 5.5%, 5.7%, and 6.5%; random glucose test results (blood glucose level in a nonfasting state) at thresholds of 100 and 110 mg/dL (to convert to millimoles per liter, multiply by 0.0555); and a 1-hour glucose challenge test (GCT) result (blood glucose measurement 1 hour after ingestion of 50 g of Glucola in a nonfasting state) at thresholds of 110 and 120 mg/dL. We acknowledge that the random glucose test and the 1-hour GCT are not endorsed by the ADA; however, we thought that cost-effectiveness evaluation of these strategies was warranted given their improved test performance over HbA1c in a previously published study.²¹

Our analyses were conducted from the health care system perspective (direct costs) and the societal perspective (direct plus indirect costs). Table 1 gives the test performance assumptions used for the base-case analysis and sensitivity analyses. The direct and indirect cost assumptions for each screening strategy are listed in Table 2. Direct costs were calculated using Medicare reimbursement rates²² and included costs of the initial screening test, the follow-up 2-hour OGTT, and health care provider time.

Table 1

Test Performance Assumptions for Various Screening Strategies (at Selected Thresholds) for Identifying Children With Diabetes Mellitus and Dysglycemia for the Base-Case Analysis and Sensitivity Analyses

Screening Strategy and Cutoff Value	Sensitivity, %	Specificity, %
Base-Case Analysis
Diabetes mellitus
2-h OGTT (200 mg/dL)	100	100
HbAlc
5.5%	33	56
5.7%	33	71
6.5%	33	96
Dysglycemia (prediabetes and diabetes)
2-h OGTT (140 mg/dL)	100	100
Random glucose test
100 mg/dL	55	67
110 mg/dL	30	88
HbAlc
5.5%	45	57
5.7%	32	74
6.5%	7	98
1-h Glucose challenge test
110 mg/dL	63	63
120 mg/dL	44	81
Sensitivity Analyses
Diabetes mellitus
HbAlc
5.7%	71	79
6.5%	32	99
Dysglycemia (prediabetes and diabetes)
HbAlc
5.7%	34	83
6.5%	4	100

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Abbreviations: HbA_1c hemoglobin A_1c; OGTT, oral glucose tolerance test.

Table 2

Cost Assumptions for the Base-Case Analysis^a

Screening Strategy	Cost Per Screen, $	Additional Time for Testing, min
2-h OGTT	18.44	135
Random glucose test	5.62	15
HbA1c	13.90	15
1-h Glucose challenge test	6.80	75

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Abbreviations: HbA_1c hemoglobin A_1c; OGTT, oral glucose tolerance test.

^aThe half mean hourly wage for all occupations in 2010 was $10.68 per hour. Provider time was one-fifth the cost of a primary care visit ($20).

Provider time for identification of high-risk patients and interpretation of laboratory results was valued at one fifth the cost ($20) of a full primary care visit (25 minutes of face-to-face time) for all screening strategies. Indirect costs were calculated using wage data from the US Bureau of Labor Statistics²³ and accounted for the value of the patients’ time, which was calculated as the lost wages of the parent/guardian (who must accompany their child to the screening). As a conservative estimate, parent/guardian time was valued at half the mean hourly wage for all occupations in 2010.²⁴ All cost data were expressed in 2010 US dollars.

We conducted sensitivity analyses to assess the effect of differing levels of (1) adherence (75% adherence to the nonfasting screening strategies and 75% and 50% adherence to the 2-hour OGTT), (2) changes in the prevalence of dysglycemia or diabetes (±25% and adult prevalence estimates), (3) costs (doubling of provider time costs and reduction in HbA1c costs by half), and (4) alternate estimates of test performance for HbA1c from an additional pediatric study.²⁰

RESULTS

Table 3 gives the results of the base-case analysis from the societal and health care system perspectives. In the base-case model, there were 500 adolescents with diabetes and 400 000 adolescents with dysglycemia.

Table 3

Proportion of Cases and Costs Identified for the Different Screening Strategies for the Base-Case Analysis

Screening Strategy and Cutoff Value	Cases Identified, %	Total Costs (Direct), $	Total Costs (Direct and Indirect), $	Cost per Case Identified (Direct), $	Cost per Case Identified (Direct and Indirect), $
Diabetes mellitus
2-h OGTT(200mg/dL)	100	96 065 001	156 111 876	192 130	312 224
HbAlc
5.5%	33	105 182 379	138 513 737	631 157	831 166
5.7%	33	97 992 217	121 958 136	588 012	731 822
6.5%	33	86 377 340	95 214 473	518 316	571 344
Dysglycemia (prediabetes and diabetes)
2-h OGTT(140mg/dL)	100	96 065 001	156 111 876	240	390
Random glucose test
100mg/dL	55	80 850 720	109 451 714	368	498
110mg/dL	30	70 874 680	86 481 530	591	721
HbAlc
5.5%	45	104 685 520	137 369 701	582	763
5.7%	32	97 143 559	120 004 072	759	938
6.5%	7	86 005 799	94 358 987	3072	3370
1-h Glucose challenge test
110mg/dL	63	85 939 761	144 014 430	341	571
120mg/dL	44	77 568 001	124 738 157	441	709

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Abbreviations: HbA_lc hemoglobin A_lc; OGTT, oral glucose tolerance test.

Total costs for a one-time screening were in a similar range for dysglycemia and diabetes, between 94 million and 156 million US dollars, because the same pool of eligible children would need to be screened regardless of the disease prevalence. Total costs were highest for the 2-hour OGTT for both dysglycemia and diabetes, in part due to higher test costs and the patient time costs associated with a longer test (21/2 hours).

For diabetes, the 2-hour OGTT had the highest test effectiveness, detecting 100% of cases vs 33% for the HbA1c strategies. The cost per case was extremely high for all strategies because of the small number of children with diabetes: $312 000 per case for the 2-hour OGTT and $571 000 to $831 000 per case for the HbA1c strategies.

Figure 1 A shows effectiveness and efficiency for the base-case diabetes analysis from the societal perspective. The figure illustrates tradeoffs between 2 competing goals of screening efforts: identifying a greater proportion of cases and minimizing the cost per case identified. Preferred screening strategies are in the upper left, maximizing the percentage of cases identified and minimizing the total costs per case. In contrast, least preferred screening strategies are in the bottom right. On the basis of these criteria, the 2-hour OGTT was the most desirable strategy for diabetes. Effectiveness was similar across the various HbA1c thresholds; however, the cost per case was lowest for the HbA1c threshold of 6.5%.

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Figure 1

Screening effectiveness for diabetes (percentage of cases identified) plotted against screening efficiency (costs per case identified) from a societal perspective. A, Base-case analysis; B, alternative estimates of hemoglobin A_lc (HbA_lc) test performance. OGTT indicates oral glucose tolerance test.

For dysglycemia, the 2-hour OGTT strategy had the highest test effectiveness (100%) followed by a 1-hour GCT threshold of 110 mg/dL (63%), a random glucose threshold of 100 mg/dL (55%), and an HbA1c threshold of 5.5% (45%). The HbA1c thresholds of 5.7% and 6.5% had lower levels of effectiveness (32% and 7%, respectively). The 2-hour OGTT had the lowest total costs per case identified ($390), followed by a random glucose threshold of 100 mg/dL ($498), a 1-hour GCT threshold of 110 mg/dL ($571), and an HbA1c threshold of 5.5% ($763). In contrast, HbA1c thresholds of 5.7% and 6.5% had the highest costs per case identified, ranging from $938 to $3370.

Figure 2 A shows effectiveness plotted against efficiency for dysglycemia from the societal perspective. The 2-hour OGTT was the most desirable strategy, followed by a 1-hour GCT, a random glucose test, and an HbA1c level of 5.5%. The HbA1c thresholds of 5.7% and 6.5% were the least desirable strategies.

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Figure 2

Screening effectiveness for dysglycemia (percentage of cases identified) plotted against screening efficiency (costs per case identified) from a societal perspective. A, Base-case analysis; B, alternative estimates of hemoglobin A_1c (HbA_1c) test performance. GCT indicates glucose challenge test; and OGTT, oral glucose tolerance test.

In our sensitivity analyses, similar trends were seen for diabetes and dysglycemia. Lower adherence to the nonfasting strategies and to the 2-hour OGTT decreased total costs and screening effectiveness (Table 4). Cost per case identified was unchanged for the 2-hour OGTT but increased for the nonfasting strategies given an increasing number of missed cases.

Table 4

Proportion of Cases and Costs Identified for the Different Screening Strategies for 75% Adherence to Initial Nonfasting Screening Strategies and 75% or 50% Adherence to 2-Hour OGTT

Screening Strategy and Cutoff Value	75% Adherence to Nonfasting Screening and 75% Adherence to 2-Hour OGTT			75% Adherence to Nonfasting Screening and 50% Adherence to 2-Hour OGTT
	Cases Identified, %	Total Costs (Direct and Indirect), $	Cost per Case Identified (Direct and Indirect), $	Cases Identified, %	Total Costs (Direct and Indirect), $	Cost per Case Identified (Direct and Indirect), $
Diabetes mellitus
2-h OGTT (200 mg/dL)	75	117 083 907	312 224	50	78 055 938	312 224
HbAlc
5.5%	19	94 810 233	1011 410	12	86 053 541	1376994
5.7%	19	85 855 882	915 888	12	80 083 973	1281472
6.5%	19	70 931 963	756 683	12	70 134 694	1122 267
Dysglycemia (prediabetes and diabetes)
2-h OGTT (140 mg/dL)	75	117083 907	390	50	78 055 938	390
Random glucose test
100 mg/dL	31	74 820 378	605	21	67 551 971	819
110 mg/dL	17	61 899 650	917	11	58 938 152	1310
HbAlc
5.5%	25	94 405 496	932	17	85 783 716	1271
5.7%	18	84 637 329	1176	12	79 271 605	1651
6.5%	4	70 211 969	4458	3	69 654 698	6634
1-h Glucose challenge test
110 mg/dL	35	99 818 937	704	24	91 627 052	970
120 mg/dL	25	88 976 034	899	17	84 398 450	1279

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Abbreviations: HbA_1c hemoglobin A_lc; OGTT, oral glucose tolerance test.

A higher prevalence of disease slightly increased total costs but resulted in a lower cost per case, whereas a lower prevalence slightly decreased total costs and resulted in a higher cost per case (Table 5). When we assumed a population prevalence of diabetes and dysglycemia similar to adult levels, the cost per case decreased markedly for both outcomes but particularly for diabetes, which decreased from $312,000 to $831,000 per case to $781 to $2064 per case.

Table 5

Proportion of Cases and Costs Identified for the Different Screening Strategies for a 25% Increase in Prevalence, a 25% Decrease in Prevalence, or Adult Prevalence Assumptions

Screening Strategy and Cutoff Value	Cases Identified, %	25% Increase in Prevalence		25% Decrease in Prevalence		Adult Prevalence Assumptions (8% for Diabetes and 37% for Prediabetes)
		Total Costs (Direct and Indirect), $	Cost per Case Identified (Direct and Indirect), $	Total Costs (Direct and Indirect), $	Cost per Case Identified (Direct and Indirect), $	Total Costs (Direct and Indirect), $	Cost per Case Identified (Direct and Indirect), $
Diabetes mellitus
2-h OGTT(200mg/dL)	100	156111876	249779	156111876	416298	156111876	781
HbAlc
5.5%	33	138513150	664 930	138514325	1108225	137576050	2064
5.7%	33	121958377	585459	121957896	975 761	122 341851	1835
6.5%	33	95216051	457 083	95 212895	761 779	97732 759	1466
Dysglycemia (prediabetes and diabetes)
2-hOGTT(140mg/dL)	100	156111876	312	156111876	520	156111876	169
Random glucose test
100mg/dL	55	110385806	401	108517621	658	114 355 700	225
110mg/dL	30	87245787	582	85 717272	952	90493 882	326
HbA1c
5.5%	45	137454618	611	137284783	1017	137815518	331
5.7%	32	120258824	752	119749319	1247	121341523	410
6.5%	7	94 571280	2702	94146693	4483	95 473 529	1474
1-h Glucose challenge test
110mg/dL	63	145118357	461	142 910502	756	149810049	257
120mg/dL	44	125 799626	572	123 676688	937	130310868	326

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Abbreviations: HbA_1c hemoglobin A_1c; OGTT, oral glucose tolerance test.

Doubling of provider time resulted in higher total costs and higher cost per case identified (Table 6), and halving the price of HbA1c resulted in slightly lower total costs and lower cost per case, with no changes in the effectiveness estimates for either sensitivity analysis.

Table 6

Proportion of Cases and Costs Identified for the Different Screening Strategies for Doubling the Provider Costs or Cutting the HbA_1c Test Costs in Half

Screening Strategy and Cutoff Value	Cases Identified, %	Double Provider Costs, $		50%HbAlc Test Costs, $
		Total Costs (Direct and Indirect)	Cost per Case Identified (Direct and Indirect)	Total Costs (Direct and Indirect)	Cost per Case Identified (Direct and Indirect)
Diabetes mellitus
2-hOGTT(200mg/dL0	100	206076 8 76	412154
HbAlc
5.5%	33	188478737	1 130986	121138738	726905
5.7%	33	171923136	1 031 642	104 583137	627562
6.5%	33	145179473	871164	77 839474	467084
Dysglycemia (prediabetes and diabetes)
2-hOGTT(140mg/dL)	100	206076876	515
Random glucose test
100mg/dL	55	159416714	725
110mg/dL	30	136446530	1137
HbAlc
5.5%	45	187334701	1041	119994 702	667
5.7%	32	169969072	1328	102 629073	802
6.5%	7	144 323987	5154	76983 988	2749
1-h Glucose challenge test
110mg/dL	63	193 979430	770
120mg/dL	44	174 703157	993

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Abbreviations: HbA_1c hemoglobin A_1c; OGTT, oral glucose tolerance test.

Finally, when we assumed alternate test performance characteristics for HbA1c for diabetes,²⁰ the cost per case identified was lower ($320 000–$578 000) compared with the base case ($571 000–$831 000) due to improved test performance but still remained quite high (Figure 1B). For dysglycemia, the cost per case was lower for a threshold of 5.7% ($826 vs $938) because of improved test performance, and the cost per case was higher for a threshold of 6.5% ($5754 vs $3370) because of lower test performance (Figure 2B). Across the multiple sensitivity analyses for dysglycemia, the relative rankings of efficiency and effectiveness for the various screening strategies for dysglycemia were similar to the base case.

COMMENT

This study evaluated the total costs, effectiveness, and efficiency (cost per case identified) of a number of different screening strategies for identifying children with diabetes and dysglycemia. One of the most striking findings of our study was the very high cost per case of screening for T2D in adolescents regardless of test type, ranging from $312 000 to $831 000 per case identified. This finding is due to the low prevalence of T2D in the US pediatric population.¹¹

The ADA formulated the first screening guidelines for T2D in children in 2000 in response to an epidemic of obesity and increasing reports of a T2D phenotype in tertiary care clinics²⁵ and high-risk populations.²⁶ At the time that the recommendations were made, empirical data on screening efficacy and costs for T2D were not available; therefore, the recommendations were based on expert opinion. Since that time, a number of population-based studies^9–11,27 evaluating the epidemiology of pediatric diabetes have been conducted and suggest that the overall burden of T2D in children is still low, particularly compared with the burden among adults.

A similar study¹³ conducted in adults reported a cost per case identified of T2D, ranging from $600 to $850 per case across a variety of HbA1c thresholds and assuming a national T2D prevalence of 8%. When we assumed a similar prevalence for our pediatric population, the cost per case for children was reduced markedly, closer to the range reported in adults, suggesting that disease prevalence is the major determinant of cost-effectiveness for diabetes screening in children.

We did not explicitly calculate costs per quality adjusted life-year for our analysis, which makes determination of cost-effectiveness difficult, but the extremely high cost per case values would suggest that screening for T2D in children may not fall into the cost effective range. In contrast, our analyses for identification of dysglycemia resulted in much more reasonable cost-per-case ratios. A screening program for glucose abnormalities could therefore be considered more cost effective if dysglycemia were explicitly considered as a screening outcome. However, the ADA and AAP guidelines are focused on screening for diabetes as the primary outcome.

Screening for dysglycemia could be endorsed by the ADA and AAP because studies^28,29 such as the Diabetes Prevention Program in adults have demonstrated that early identification and treatment of individuals with prediabetes is both effective and cost-effective for reducing the rates of diabetes. However, it is unclear whether these conclusions could be extrapolated to the pediatric population, especially given the accelerated progression of disease reported in adolescents vs adults³⁰ and the fact that the benefits of early detection of dysglycemia in children are currently unknown.³¹

When comparing our cost-per-case ratios for identifying dysglycemia with adult studies,¹³ the cost-percase ratios were in a similar range but were higher for our pediatric population ($390–$3000 per case) compared with adults ($150–$500 per case). Again, this finding was likely in part due to the lower prevalence of prediabetes as shown by the results of our sensitivity analysis when we assumed a prevalence similar to the adult population (37%).

When comparing screening strategies for dysglycemia, the 2-hour OGTT (a fasting test) was the preferred strategy. However, previous studies^2,3,32 have shown remarkably low adherence with ADA-recommended screening tests among providers (4%–21%) in pediatric settings, most likely due to their onerous fasting requirement and associated increase in nonadherence rates among patients. Given these findings, the nonfasting 1-hour GCT and random glucose test may represent convenient and preferred screening alternatives for health care professionals. If efficiency (lower cost per case) were prioritized, then the random glucose test (100 mg/dL) would be a preferred strategy. Alternatively, if effectiveness (percentage of cases identified) were prioritized, then the 1-hour GCT (110 mg/dL) would be preferred.

The HbA1c thresholds of 5.7% and 6.5% were the least preferred strategies because they had the highest cost per case and the highest proportion of cases missed—a finding that has important policy implications given the recent ADA guidelines recommending the exclusive use of HbA1c for the diagnosis of prediabetes and diabetes in children. The guidelines will likely lead to increased use of HbA1c as a screening test. Given our findings, reconsideration of the new HbA1c guidelines or a lowering of the HbA1c threshold to 5.5% may be warranted.

We are unaware of previous studies that have compared the cost-effectiveness of different nonfasting screening strategies for identifying diabetes and dysglycemia in children. Previous studies¹³ have focused exclusively on adults for whom there are notable differences in test performance and disease prevalence.³³ Strengths of our study include the fact that our model simulation was based on empiric screening data in overweight and obese children^20,21 and the fact that our findings were robust to a variety of sensitivity analyses that explored changes in dysglycemia prevalence, testing adherence, provider time costs, lower test costs, and alternate test performance estimates for HbA1c.

We acknowledge several limitations of our study. First, we assessed the cost-effectiveness of a one-time screening of the pediatric population, despite the ADA recommendation that children receive biannual screenings because of a lack of longitudinal data regarding pediatric screening outcomes. Second, we used Medicare estimates for our cost assumptions. Testing costs may vary by payer; however, our objective was to evaluate the relative costs of different screening strategies. Third, our analysis included only costs associated with the detection of diabetes and dysglycemia, which represents just one aspect of the total costs associated with screening programs and did not consider the costs associated with treatment, health care utilization, or downstream productivity costs. Fourth, we did not address the benefits of early detection, including improvements in length and quality of life. Last, our test performance data relied on a single 2-hour OGTT to classify children as having dysglycemia. Although most studies of children and adults with dysglycemia rely on this definition,^9,18,34,35 we acknowledge that some studies³⁶ have reported a lack of reproducibility of the 2-hour OGTT results in children.

We recognize that all overweight and obese children likely require aggressive lifestyle management, regardless of their glycemic status, to reduce the risk of comorbidities. However, given limited health care resources, early identification of children with dysglycemia may represent a reasonable strategy for targeting the children at highest risk.

Since the recent guidelines recommending HbA1c for diagnosis of diabetes in children and adults, commentaries have highlighted testing costs as an important issue for determining which tests should be prioritized.³⁷ Total costs, efficiency (cost per case), and effectiveness (proportion of cases identified) of screening at-risk individuals are important criteria for determining optimal screening policy, and our findings highlight important tradeoffs to consider for the pediatric population. Future longitudinal studies are needed to evaluate the long-term outcomes (effectiveness and cost-effectiveness) of screening for pediatric glucose abnormalities, particularly for the most promising strategies (1-hour GCT and random glucose test). The high cost per case of screening for diabetes should inform future pediatric screening policy. The low effectiveness and high cost per case of current recommended HbA1c thresholds warrant reconsideration of the recent ADA guidelines recommending HbA1c measurement for the diagnosis of diabetes and dysglycemia in adolescents.

Acknowledgments

Footnotes

References