Abstract

RESEARCH DESIGN AND METHODS

The study was approved by the Emory University Institutional Review Board and utilized data from 1,259 adults in the Screening for Impaired Glucose Tolerance (SIGT) study, described previously (13). Briefly, this study recruited participants without known diabetes between January 2005 and March 2008. The subjects' first visit was at different times of the day, without an overnight fast. Random capillary and plasma glucose (RCG and RPG) were measured, a 50 g glucose drink was given, and capillary and plasma glucose 1 h after a 50 g oral glucose challenge test (GCT-cap and GCT-pl) were measured. At a second visit, after an overnight fast, A1C was drawn and a 75 g OGTT was begun before 11:00 a.m.

RESULTS

The subjects had an average age of 48 years and BMI 30 kg/m²; they were 55% African American and 62% female; 19.5% had pre-diabetes (3.5% IFG₁₁₀ only, 12.5% IGT only, and 3.5% IFG+IGT), and 4.9% had diabetes. Dysglycemia (previously unrecognized pre-diabetes and diabetes) was present in 24.5%, and as reported previously (13) was identified with greatest accuracy by GCT-pl and least well by RCG. For the different tests, 70% specificity cutoffs (true positives, and false negatives), respectively, would be: GCT-pl 138 mg/dl (248, 61); GCT-cap 162 mg/dl (214, 95); RPG 100 mg/dl (195, 114); RCG 106 mg/dl (156, 153); A1C 5.5% (202, 107).

Table 1 shows base case health system and societal cost estimates for screening and 3 years of management in a system with Medicare fee-for-service reimbursement rates, with 70% specificity cutoffs, and assuming that false-negative costs (that could be prevented after detection of dysglycemia) amounted to 10% of 3-year medical costs. Cost components for these cost estimates are described in detail in online appendix Table A1. From both perspectives, total costs for testing (screening test + follow-up OGTT if indicated) were lowest for RCG because it was the least expensive test and had the fewest positive screens. Total true-positive costs were highest for GCT-pl from both perspectives, due to the higher numbers of true positives detected, while the cost of false negatives was highest for RCG because this test had the highest number of false negatives.

Table 1

Base case cost assessment in health system and societal costs

	Screen	Cost per screen	Screen cost total	Positives (n)	OGTT costs	Total cost of testing	Testing costs per TP	TP (n)	TP costs	FN (n)	Costs 10% FN	Average cost per FN	Total health system costs	Costs per TP
Health System costs					$17.99				$518
GCT-pl	1,254	$7.77	$9,744	535	$9,625	$19,368	$78.10	248	$128,464	61	$32,803	$538	$180,635	$728
GCT-cap	1,259	$6.75	$8,498	501	$9,013	$17,511	$81.83	214	$110,852	95	$54,617	$575	$182,980	$855
RPG	1,256	$5.48	$6,883	483	$8,689	$15,572	$79.86	195	$101,010	114	$66,198	$581	$182,780	$937
RCG	1,258	$3.27	$4,114	451	$8,113	$12,227	$78.38	156	$80,808	153	$93,054	$608	$186,090	$1,193
A1C	1,259	$13.56	$17,072	520	$9,355	$26,427	$130.83	202	$104,636	107	$61,198	$572	$192,261	$952
No screen	0	$0.00	$0.00	0	$0.00	$0.00	$0.00	0	$0.00	309	$205,966	$667	$205,966	NA
Societal costs					$48.61				$785.30				Total societal costs
GCT-pl	1,254	$10.13	$12,703	535	$26,006	$38,709	$156.09	248	$194,754	61	$39,375	$645	$272,839	$1,100
GCT-cap	1,259	$7.54	$9,493	501	$24,354	$33,846	$158.16	214	$168,054	95	$67,513	$711	$269,414	$1,259
RPG	1,256	$7.84	$9,847	483	$23,479	$33,326	$170.90	195	$153,134	114	$82,171	$721	$268,630	$1,378
RCG	1,258	$4.06	$5,107	451	$21,923	$27,031	$173.27	156	$122,507	153	$117,664	$769	$267,201	$1,713
A1C	1,259	$15.92	$20,043	520	$25,277	$45,320	$224.36	202	$158,631	107	$75,485	$705	$279,436	$1,383
No screen	0	$0.00	$0.00	0	$0.00	$0.00	$0.00	0	$0.00	309	$269,261	$871	$269,261	NA

Open in a separate window

Bold data indicate least expensive cost. TP, true positive; FN, false negative; NA, not applicable.

Total health system costs for all study subjects using base case assumptions would be GCT-pl $180,635, GCT-cap $182,980, RPG $182,780, RCG $186,090, and A1C $192,261; all were less than the cost of no screening, which was $205,966, with GCT-pl being the least expensive test. Societal costs with the same assumptions were GCT-pl $272,839, GCT-cap $269,414, RPG $268,630, RCG $267,201, and A1C $279,436; all were close to the cost for no screening, which was $269,261, with RCG being the least expensive test and slightly less expensive than no screening. However, GCT-pl was the least expensive test from both perspectives when costs were compared per true positive identified (Table 1).

Sensitivity analyses

Fig. 1 shows varied fractions of false-negative costs from health system and societal perspectives. When false-negative costs were over 10% of 3-year projected marginal costs for pre-diabetes and diabetes, both health system and societal projected costs for screening and management would be lower than costs of no screening. When false-negative costs were less than 10% (the DPP false-negative cost was slightly greater than 5%), costs for screening and management would be more than the cost of no screening. For false-negative costs higher than 10%, GCT-pl was the least expensive test from both perspectives, while for fractions less than 10%, RCG was least expensive. False-negative costs contributed most to total costs when higher fractions were used, while true-positive costs contributed more when lower fractions were used (online appendix Figure A1).

Open in a separate window

Figure 1

Health system and societal costs associated with varied fractions of false-negative costs. Total health system and societal costs for each screening test and for no screening, which include costs of testing, false negatives, and treatment of true positives, assuming different fractions of false-negative costs that could be prevented with early detection of conditions.

In the sensitivity analyses (Table 2), from a health system perspective, GCT-pl screening would be the least expensive test in most of the scenarios described. These scenarios include use of a glucose cutoff for pre-diabetes based on the optimality criterion, longer staff time for adminstering the screen, higher rates of progression from pre-diabetes to diabetes, and higher and lower prevalence of disease. From a societal perspective (Table 2), the least expensive test varied more depending on the scenario but tended to be either GCT-pl or RCG.

Table 2

Sensitivity analyses of health system and societal costs

	70% Specificity cutoff	Optimality cutoff	90% Sensitivity cutoff	Higher staff time	Higher patient time	Higher rate of progression	50% Higher prevalence	50% Lower prevalence	VA health system	VA-TP costs	DPP FN + VA-TP costs	Lifestyle costs
Health system costs
GCT-pl	$180,635	$180,908	$184,784	$183,469	N/A	$185,483	$263,214	$98,365	$162,639	$83,681	$71,934	$180,139
GCT-cap	$182,980	$183,171	$182,714	$185,825	N/A	$190,173	$266,656	$99,029	$164,718	$96,584	$76,184	$182,552
RPG	$182,780	$181,948	$183,480	$185,619	N/A	$191,335	$267,519	$98,494	$167,212	$105,128	$80,384	$182,390
RCG	$186,090	$185,094	$183,811	$188,933	N/A	$197,180	$273,743	$98,801	$173,334	$123,666	$87,529	$185,778
A1C	$192,261	$191,827	$192,987	$195,106	N/A	$200,388	$276,230	$108,597	$171,985	$91,997	$84,967	$191,857
No screen	$205,966	$205,966	$205,966	$205,966	N/A	$226,555	$309,192	$103,226	$205,966	$205,966	$122,059	$205,966
Societal costs
GCT-pl	$272,839	$269,253	$288,828	$275,673	$275,798	$281,342	$394,237	$151,373	$254,868	$131,915	$117,947	$585,493
GCT-cap	$269,414	$270,218	$284,990	$272,259	$270,409	$282,031	$389,725	$148,324	$251,173	$145,076	$118,851	$539,204
RPG	$268,630	$269,494	$290,917	$271,469	$271,594	$283,635	$389,080	$148,866	$253,081	$156,404	$124,255	$514,467
RCG	$267,201	$270,019	$295,126	$270,044	$268,195	$286,653	$388,899	$145,812	$254,461	$177,119	$128,136	$463,871
A1C	$279,436	$264,302	$299,313	$282,281	$282,407	$293,691	$398,958	$159,981	$259,180	$159,032	$129,996	$534,098
No screen	$269,261	$269,261	$269,261	$269,261	$269,261	$305,372	$404,168	$134,907	$269,261	$269,261	$147,287	$269,261

Open in a separate window

Bold data indicate least expensive cost. TP, true positive, FN, false negative; DPP-FN, Diabetes Prevention Program false negative; N/A, not applicable. VA-TP, alternative true positive cost in VA system.

We examined potential single-payer system costs, using VA-based costs as an example. Using base case assumptions, with VA costs for testing and metformin, health system costs for all tests would be less than costs for no screening, with GCT-pl being the least expensive test. Societal costs for all tests would also be less than no screening, with GCT-cap being least expensive. If VA-TP costs were used, the costs for screening with any of these tests would be substantially less than the cost of no screening, assuming either base case 10% false negative or DPP-false-negative costs, and GCT-pl would be the least expensive test (Table 2 and online appendix Figure A2).

Lifestyle intervention costs, using Medicare testing costs, 10% false-negative costs, and costs for a group intervention derived from the DPP, were similar from a health system perspective to the costs for treatment with generic metformin: screening with any test was less expensive than no screening, with GCT-pl being the least expensive test. Societal costs were much higher than costs for no screening and higher than costs associated with treatment with metformin due to the significant direct nonmedical costs associated with the lifestyle intervention.

There has been recent interest in using A1C as both a screening and a diagnostic test for diabetes. We calculated the costs of using A1C 6.0–6.4% to diagnose pre-diabetes and A1C ≥6.5% to diagnose diabetes, without confirmatory testing. Health system costs, with our base case assumptions and using metformin and lifestyle modification for management, would be $226,122 and $225,944, respectively—both higher than the costs with GCT or random glucose testing and higher than the cost of no screening, because of a large number of false negatives and treatment of false positives. Societal costs with metformin and lifestyle modification management would be $299,524 and $411,726, again higher than with other screening tests or with no screening.

CONCLUSIONS

This study evaluated the economic justification for a screening program that would detect both pre-diabetes and previously unrecognized diabetes. Over a 3-year horizon (typical of the duration of employer health insurance coverage for many workers), we compared the costs of no screening to the costs of screening with RPG, RCG, or A1C available today as well as novel GCT-pl and GCT-cap tests, and included the costs of management of detected cases. With Medicare-based costs and our base case assumptions, screening would be less expensive than no screening from a health system perspective and cost neutral or only slightly more expensive than no screening from a societal perspective; these results were robust to a variety of sensitivity analyses. GCT-pl screening had the greatest diagnostic accuracy, and, in many scenarios, would provide the lowest health system costs.

The sensitivity analyses performed include a wide range of assumptions and two ends of the spectrum of health system costs for treatment with metformin, Medicare- and VA-based. In both settings, the costs of testing would be only a minor portion of total costs, and testing costs with RCG would be least expensive. With more accurate tests (GCT-pl is best, RCG worst), the costs of true positives would rise and the costs of false negatives would fall. Overall, GCT-pl screening would be least expensive in settings with CMS reimbursement rates as well as in VA-based settings.

We estimated costs for treatment of true positives, both with metformin and lifestyle modification, based on the treatment protocol used in the DPP, but substituted drug costs to reflect current prices. However, some have suggested that such involved treatment might be impractical to implement in real-world settings. Recognizing this, we also examined an alternative care system: the VA. Costs in the VA are lower than Medicare testing and retail drug costs and might be representative of costs with a single-payer healthcare system. With these costs (VA-TP costs), screening with any of the tests would be cost-saving from both health system and societal perspectives.

Our analyses also revealed that screening for pre-diabetes and diabetes would involve a high cost for false negatives—a high cost for undetected and untreated pre-diabetes and diabetes. This was not unexpected, since costs attributable to diabetes (before and after diagnosis) are substantial due to a combination of costs of hospitalizations related to complications (particularly cardiovascular disease), pharmacy costs, and other medical visits (18–20,22,23).

The finding that treatment of detected cases might be cost-saving from a health-system perspective is at least partly driven by the findings from the DPP study in which those participants who were treated with metformin or lifestyle changes had reduced medical costs outside of the study compared to those in the placebo arm. We do not have a mechanism through which these cost-savings were obtained, but they may have resulted from improvements in cardiovascular risk factors which have been associated with both types of treatment.

Our study has limitations. The study subjects were volunteers, which may have caused some selection bias. However, the prevalence of pre-diabetes and diabetes in our study is similar to that found in other studies and lower compared to recent National Health and Nutrition Examination Survey (NHANES) estimates (24). We did not consider screening with fasting plasma glucose in this study; however, accuracy should be at least as good and health system costs should be similar to those with RPG testing, so costs should still be favorable compared to no screening. The ADA (25) has recommended that A1C be used for the diagnosis of diabetes and pre-diabetes, so screening with A1C measurements might involve either no follow-up testing or at most a repeat A1C if the first A1C were high, which differs from our main analysis, in which follow-up testing would involve an OGTT. Since A1C is a relatively inaccurate screening test, especially for pre-diabetes (13), an A1C-only screening strategy would increase screening costs but decrease both the projected costs for treatment (because fewer positives would be found), and the costs we attributed to patients who were A1C-negative but OGTT-positive (by defining such patients as true negatives). However, such an approach ignores the empirical findings of increased costs associated with pre-diabetes (above).

Our analysis also assumed that all adults would be screened for pre-diabetes/diabetes. If, however, screening targeted adults with one or more risk factors, the overall screening costs would decrease (due to fewer numbers being screened), and the relative proportion of true positives to false negatives should rise. In this case, the cost-effectiveness of screening should improve (7), and the costs of screening and 3 years of management should become even more favorable relative to no screening, since the cost of treatment of true positives, in our estimation, is less than the average cost of false negatives.

We focused our analysis on costs related to treatment with metformin, but this may not be the best treatment. Lifestyle interventions emphasizing diet and weight loss are a better treatment from a medical and, possibly, also from a cost perspective (12,16). However, metformin is a treatment that can be implemented in a consistent manner by most practitioners with fairly predictable results. Finally, the scope of our study was limited to the costs of one-time screening and did not incorporate the lifetime modeling needed to determine if the cost-savings we project over a 3-year period would continue with a program of repeated screening, as currently recommended by the ADA and the Centers for Disease Control and Prevention. However, a 3-year period might be an ideal representation from the perspective of a payer working with employers whose employees come and go, and who change healthcare plans every few years.

Our analyses indicate that screening programs and 3 years of management for pre-diabetes and previously unrecognized diabetes should be cost-effective, particularly from a health system perspective, and may be cost-saving.

Supplementary Material

Acknowledgments

Footnotes

References