in serum cholesterol level for patients with type 2 diabetes. Diabetes Study (UKPDS) and other studies were used to create a model of disease …
Cost-effectiveness of Intensive Glycemic Control, Intensified Hypertension Control, and Serum Cholesterol Level Reduction for Type 2 Diabetes
Online article and related content current as of November 16, 2008
The CDC Diabetes Cost-effectiveness Group
JAMA 2002;28719:2542-2551 doi:101001/jama287192542 http://jamaama-assnorg/cgi/content/full/287/19/2542
Correction Citations Topic collections
Contact me if this article is corrected This article has been cited 70 times Contact me when this article is cited
Nutritional and Metabolic Disorders; Lipids and Lipid Disorders; Nutritional and Metabolic Disorders, Other; Hypertension
Contact me when new articles are published in these topic areas
Related Articles published in the same issue
May 15, 2002
JAMA 2002;28719:2593
Subscribe
http://jamacom/subscribe
Email Alerts
http://jamaarchivescom/alerts
Permissions
permissions@ama-assnorg http://pubsama-assnorg/misc/permissionsdtl
Reprints/E-prints
reprints@ama-assnorg
Downloaded from wwwjamacom by guest on November 16, 2008
ORIGINAL CONTRIBUTION
Cost-effectiveness of Intensive Glycemic Control, Intensified Hypertension Control, and Serum Cholesterol Level Reduction for Type 2
Diabetes
The CDC Diabetes Cost-effectiveness Group 2 DIABETES IS A MAJOR public health problem 1 - 5 Although treatment for type 2 diabetes has traditionally focused on glycemic control for reducing microvascular complications, recent attention has also focused on reducing risks of macrovascular complications Persons with type 2 diabetes have twice the risk for coronary heart disease CHD and stroke as persons without diabetes6-8 Available interventions to reduce CHD and stroke incidence in this population include aggressive blood pressure control and reduction in serum cholesterol level Evaluating whether interventions are cost-effective and yield acceptable benefits is important9 In this study, we evaluated whether the benefits measured in quality-adjusted life-years [QALYs] for type 2 diabetes of intensive glycemic control, intensified hypertension control, or reduction in serum cholesterol level justified the costs We also evaluated the relative costeffectiveness of each intervention and whether it varied with age A Markov model of type 2 diabetes disease progression was used to calculate incremental cost-effectiveness ratios for the interventions Costs were measured from the
perspective of the health care system, and outcomes were measured in QALYs
YPE
Context Several treatment interventions can reduce complications of type 2 diabetes, but their relative cost-effectiveness is not known Objective To estimate the incremental cost-effectiveness of intensive glycemic control relative to conventional control, intensified hypertension control, and reduction in serum cholesterol level for patients with type 2 diabetes Design, Setting, and Patients Cost-effectiveness analysis of a hypothetical cohort of individuals living in the United States, aged 25 years or older, who were newly diagnosed as having type 2 diabetes The results of the United Kingdom Prospective Diabetes Study UKPDS and other studies were used to create a model of disease progression and treatment patterns Costs were based on those used in community practices in the United States Interventions Insulin or sulfonylurea therapy for intensive glycemic control; angiotensin-converting enzyme inhibitor or -blocker for intensified hypertension control; and pravastatin for reduction of serum cholesterol level Main Outcome Measures Cost per quality-adjusted life-year QALY gained Costs in 1997 US
dollars and QALYs were discounted at a 3 annual rate Results The incremental cost-effectiveness ratio for intensive glycemic control is 41384 per QALY; this ratio increased with age at diagnosis from 9614 per QALY for patients aged 25 to 34 years to 21 million for patients aged 85 to 94 years For intensified hypertension control the cost-effectiveness ratio is -1959 per QALY The costeffectiveness ratio for reduction in serum cholesterol level is 51889 per QALY; this ratio varied by age at diagnosis and is lowest for patients diagnosed between the ages of 45 and 84 years Conclusions Intensified hypertension control reduces costs and improves health outcomes relative to moderate hypertension control Intensive glycemic control and reduction in serum cholesterol level increase costs and improve health outcomes The cost-effectiveness ratios for these 2 interventions are comparable with those of several other frequently adopted health care interventions
JAMA 2002;287:2542-2551 wwwjamacom
T
METHODS Our model builds on previous diabetes models,10-13 but differs in several ways We used a Markov model structure that placed greater emphasis on macrovascular complications, and introduced
interdependencies among diabetes progression paths Earlier models used data on patients with type 1
diabetes, while our model used data on key transition probabilities and intervention effects from patients with type
Author Affiliations: The affiliations for the members of the CDC Diabetes Cost-effectiveness Group are listed at the end of this article Corresponding Author and Reprints: Thomas J Hoerger, PhD, Research Triangle Institute, 3040 Cornwallis Rd, PO Box 12194, Research Triangle Park, NC 27709 e-mail: tjh@rtiorg
2542 JAMA, May 15, 2002–Vol 287, No 19 Reprinted
2002 American Medical Association All rights reserved
Downloaded from wwwjamacom by guest on November 16, 2008
COST-EFFECTIVENESS OF INTERVENTIONS FOR TYPE 2 DIABETES
2 diabetes in the United Kingdom Prospective Diabetes Study UKPDS A technical report on the model is available from the authors
Model Structure
; and 0947, for angina29 Utility levels for all other health states were set to 1
Interventions
28
In the Markov framework, a series of patient cohorts newly diagnosed as having diabetes progressed through the model Cohorts were defined by 10year age groups 25 to 94 years, sex, race or ethnicity,
hypertension status, hypercholesterolemia status, and current smoking status Cohorts were followed-up along the disease paths until death or age 95 years Overall, 55 of newly diagnosed patients were women and 8 were aged 25 to 34 years; 8, 35 to 44 years; 26, 45 to 54 years; 18, 55 to 64 years; 23, 65 to 74 years; 13, 75 to 84 years; and 4, 85 to 94 years14-16 Patients progressed simultaneously through 5 different disease paths: nephropathy, neuropathy, retinopathy, CHD, and stroke FIGURE 1 Transition probabilities depended on time since diagnosis of diabetes, time between onset and diagnosis of diabetes, age, sex, race or ethnicity, glycemic level, smoking, serum cholesterol level, and hypertension Patients could die from lower extremity amputation, end-stage renal disease, CHD, stroke, or from other causes unrelated to diabetes12,17
Progression Parameters, Costs of Complications, and Health Utilities
Interventions affected transition probabilities, thereby changing the cumulative incidence of complications and costs All patients were assumed to receive conventional treatment to control blood glucose levels In the model, conventional treatment was based on resources and outcomes
associated with the conventional blood glucose control arm of the UKPDS,30 which produced an average glycosylated hemoglobin level of 79 over a median duration of 10 years
Intensive Glycemic Control
tient visits, self-testing, and case management that reflect clinical practice in the United States12,30-37 Total annual costs since diagnosis are shown in TABLE 2
Intensified Hypertension Control
The initial distribution of patients at diagnosis when the model begins and transition probabilities between states were based on data from the UKPDS, previous disease progression models of type 2 diabetes10-12 and CHD,17-19 and other studies see technical report Costs of diabetes complications were derived from the literature,12,20-24 and are described in the technical report Health utility values between 0 deceased and 1 perfect health were used to estimate QALYs for each disease state Utility levels were 0690 for blindness; 0610, endstage renal disease; 0800, lower extremity amputation25; 0500, stroke26-27; 0880, cardiac arrest/myocardial infarction MI
In the UKPDS, conventional treatment primarily involved obtaining the best possible fasting plasma glucose concentration with diet alone;
drug treatment was added if hyperglycemic symptoms or an excessive fasting plasma glucose concentration were present Intensive glycemic control patients were randomly assigned to receive a sulfonylurea or insulin, with a goal of reducing their fasting plasma glucose concentration to less than 108 mg/dL 6 mmol/L In our model, intensive glycemic control patients were initially treated with chlorpropamide, glipizide, and insulin, respectively, following trial proportions We incorporated intensive glycemic control by adjusting baseline hazard rates using the ratio of glycemic level under intensive control to glycemic level under conventional treatment raised to an exponent that varies across progression paths and stages Using a similar equation, researchers have shown that hazard rates for type 1 diabetes depend on glycemic levels31 We assumed this functional form also worked for type 2 diabetes Glycemic levels under conventional and intensive glycemic control and exponents were based on data from the UKPDS TABLE 1 The costs of glycemic control included 4 resource components: drug use based on the UKPDS and outpa-
We compared the cost-effectiveness of intensified hypertension control
treatment with an angiotensin-converting enzyme inhibitor or a -blocker with a more moderate hypertension control treatment with diet and drugs but without ACE inhibitors and -blockers In our model, intensified hypertension control affected the probability of stroke and reduced the transition probability for nephropathy and retinopathy Table 2 The model only applied intensified hypertension control to persons who had hypertension defined as systolic blood pressure of 160 mm Hg; diastolic blood pressure of 95 mm Hg; or by antihypertensive medication use14 Average blood pressure levels by age group for persons with diabetes were calculated using data from the third National Health and Nutrition Examination Survey NHANES III38 The efficacy of intensified hypertension control relative to moderate control came from the UKPDS39 Hypertensive patients with type 2 diabetes were randomized between intensified hypertension control and moderate hypertension control Average systolic/ diastolic blood pressure achieved was 144/82 mm Hg for persons receiving intensified control and 154/86 mm Hg for persons receiving moderate control Angiotensin-converting enzyme inhibitors and -blockers were
equally effective in reducing the likelihood of stroke, so we present results for a single intensified hypertension intervention Intensified hypertension control was assumed to reduce stroke risk by 44 relative to moderate hypertension control39 Because intensified hypertension control did not have a statistically significant effect on CHD, our base case analysis assumed that the intervention has no effect on the CHD transition probability Our model assumed that all pa2543
2002 American Medical Association All rights reserved
Reprinted JAMA, May 15, 2002–Vol 287, No 19
Downloaded from wwwjamacom by guest on November 16, 2008
COST-EFFECTIVENESS OF INTERVENTIONS FOR TYPE 2 DIABETES
tients with a history of CHD or stroke received hypertension treatment, which is the accepted practice in the United States Based on the UKPDS hypertension study,39 persons with type 2 diabetes
and hypertension were assumed to have faster rates of progression to microalbuminuria, clinical nephropathy, and photocoagulation than their normotensive counterparts
The costs of moderate and intensified hypertension control were estimated using UKPDS drug dosage data40 and drug cost data from the 1997 Red
Book35 Table 2 Treatment costs in-
Figure 1 States and Transition Probabilities: Microvascular and Macrovascular Complications
Nephropathy
Normal
Low Micro/ High Micro
Clinical Nephropathy
ESRD
ESRD Death
Neuropathy Peripheral Nephropathy History of LEA Subsequent LEA
Normal
LEA
LEA Death
Retinopathy
Normal
Photocoagulation
Blind
Coronary Heart Disease Angina
Normal
CHD
CA/MI
Death
History of CA/MI
Stroke
Normal
Stroke
History of Stroke
Death
Arrows represent transitions between states; there is a transition probability associated with each transition Micro indicates microalbuminaria; ESRD, end-stage renal disease; LEA, lower extremity amputation; CHD, coronary heart disease; and CA/MI, cardiac arrest/myocardial infarction 2544 JAMA, May 15, 2002–Vol 287, No 19 Reprinted
2002 American Medical Association All rights reserved
Downloaded from wwwjamacom by guest on November 16, 2008
COST-EFFECTIVENESS OF INTERVENTIONS FOR TYPE 2 DIABETES
cluded 2 physician visits and 3 chemistry panels annually
Reduction in Serum Cholesterol Level
To determine the cost-effectiveness of reduction in serum cholesterol level, we compared pravastatin with no drug treatment
for persons with a high serum cholesterol level but without a history of CHD TABLE 3 In the model, the reduction intervention of serum cholesterol level lowered the probability of CHD and had no effect on the transition probabilities for other complications The intervention was only applied to persons with a high serum cholesterol level, defined as a total serum cholesterol level of 200 mg/dL 518 mmol/L or higher 4 1 The NHANES III serum cholesterol level data for persons with diabetes was used in the Framingham calculations to determine CHD and stroke risks18 Our estimates of risk reduction 31 achieved for serum cholesterol level came from the West of Scotland Coronary Prevention Study,42 a randomized controlled trial comparing pravastatin with placebo in individuals without a history of CHD The risk reduction achieved by pravastatin was independent of diabetes43 The risk reduction was modeled as affecting the probability of developing CHD After persons incurred CHD, the serum cholesterol level risk reduction for pravastatin came from a subgroup analysis of diabetic patients in the Cholesterol and Recurrent Events CARE trial,44 in which pravastatin reduced CHD by 25 We assumed
that intervention patients would receive pravastatin for their remaining lifetime The cost of the first year of treatment with pravastatin 1398 was based on a 40-mg daily dose and 4 physician visits with blood test samples, lipid profiles, and biochemical profiles Subsequent yearly costs 1288 included pravastatin and 2 physician visits with tests
Cost-effectiveness
ventional glycemic control for all patients and moderate hypertension control for patients with hypertension Complications cost is the cost of nephropathy, neuropathy, retinopathy, CHD, stroke, or death Intervention cost is the incremental cost of the intervention, over and above standard treatment cost The total cost is the sum of the 3 components We report 2 health outcomes: remaining life-years the average undiscounted life expectancy for newly diagnosed patients and the number of discounted QALYs The incremental cost-effectiveness ratio was calculated as the difference in total cost between the intervention and standard treatment divided by the dif-
ference in QALYs between the intervention and standard treatment All measures were calculated per person Costs in 1997 US dollars and QALYs were discounted at a 3
annual rate9
One-Way Sensitivity Analyses
For intensive glycemic control, we dropped the base case analysis assumptions that patients became hypertensive once they reached microalbuminuria and that patients with hypertension progressed faster than nonhypertensive patients on the nephropathy and retinopathy disease paths We assumed that intensive glycemic control reduced the probability of CHD by 16, based on UKPDS reductions in MI that approached conventional levels of sig-
Table 1 Model Parameters and Costs for Intensive Glycemic Control
Conventional HbA1c Level, 68 Initial level at onset12 02 Annual rate of change before treatment12 Years between onset and diagnosis assumption 10 -20 Treatment affect30 02 Annual rate of change after treatment30 Maximum level12 Without treatment 120 With treatment 110 Hazard Rate Normal to microalbuminuria30 Microalbuminuria to clinical nephropathy30 Normal to peripheral neuropathy30 Normal to photocoagulation30 Year 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
HbA1C indicates glycosylated hemoglobin; NA, not applicable Reprinted JAMA, May 15, 2002–Vol 287, No 19 2545
Description of Parameter
Intensive 68 02 10 -29 02 120 90 002371 006561 002940
000790
Exponent NA NA NA NA NA NA NA 262 108 167 274
003253 007497 003600 001100
Cost of Treatment, in 1997 372 413 447 490 538 594 642 679 717 741 771 839 860 870 870 870 1490 1398 1442 1484 1531 1574 1621 1648 1683 1711 1738 1760 1788 1794 1800 1813 NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA
We report 3 cost components Standard treatment cost is the cost of con-
2002 American Medical Association All rights reserved
Downloaded from wwwjamacom by guest on November 16, 2008
COST-EFFECTIVENESS OF INTERVENTIONS FOR TYPE 2 DIABETES
Table 2 Model Parameters and Costs for Hypertension Control
Description of Parameter Risk Reduction Coronary heart disease Stroke Hazard Rate Normal to microalbuminuria39 Microalbuminuria to clinical nephropathy39 Normal to photocoagulation39 Year 0 1 2 3 4 5 6 7 8
Relative to no treatment18,39
Moderate 13 17 005584 015050 001660
Intensified 0, 21 44 003773 012810 001020
Cost of Treatment, in 1997 35,40 241 277 287 292 301 304 349 349 404 599 630 656 664 667 675 689 685 703
cations cost dropped by about 12 The intervention cost was 12 213 Combining these costs, the incremental total cost was 7927 The cost-effectiveness ratio was 41384 per
QALY Costeffectiveness ratios increased rapidly with age at diagnosis, starting at 9614 per QALY for patients aged 25 to 34 years and reaching 21 million for patients aged 85 to 94 years TABLE 5
Intensified Hypertension Control
Base analysis; sensitivity analysis Both are relative to moderate treatment39 Relative to moderate treatment39
Table 3 Model Parameters and Costs for Reduction in Serum Cholesterol Level
Description No of Parameter Pravastatin Treatment Risk Reduction 0 Coronary heart 31; 25 disease Cost of Treatment, in 1997 Year 0 1 1398 1288 0 0
For patients without coronary heart disease42
For patients with coronary heart disease44
nificance P 0530 Cost-effectiveness ratios are often sensitive to assumptions about costs We reestimated the cost-effectiveness ratio under the assumption of no case management costs The UKPDS did not report case management costs We then applied a cost scenario that only included resources specifically identified in the UKPDS cost study45 We used US unit costs to convert resource use into total costs The UKPDS cost scenario contained no case management costs, much less selftesting, and slightly fewer physician visits, yielding a
conventional control cost of about 150 and an intensive control cost of about 900 less annually than the US cost scenario
For intensified hypertension control, we first applied control to patients who developed hypertension after diagnosis and who received the intervention only after developing hypertension We dropped the assumption that patients with hypertension developed nephropathy and retinopathy faster than nonhypertensive patients In the UKPDS, hypertension control reduced the incidence of MI by 21, but the reduction was not statistically significant P1339 In a sensitivity analysis, we assumed a 21 risk reduction for CHD For reduction in serum cholesterol level, we assumed that the intervention required no additional office visits For all interventions, we varied the discount rate from 0 to 59 RESULTS
Intensive Glycemic Control
Intensified hypertension control increased undiscounted life expectancy by 04744 years, and discounted QALYs increased by 03962, relative to moderate hypertension control results were averaged for all patients newly diagnosed as having type 2 diabetes and hypertension On average, intensified hypertension control reduced complications cost by 4836
during the patients lifetime Intervention cost was 3708, and standard treatment cost increased by 351 because life expectancy increased, thereby increasing the cost of conventional glycemic control The incremental total cost was 776 lower The cost-effectiveness ratio was negative -1959/QALY, indicating that the intervention saved costs relative to moderate hypertension control ie, QALYs increased and total costs decreased Age had relatively little effect on the cost-effectiveness ratio Table 5
Reduction in Serum Cholesterol Level
Intensive glycemic control applied to all persons in the United States newly diagnosed as having type 2 diabetes and led to an undiscounted 03173-year increase in life expectancy and a discounted 01915-year QALY increase TABLE 4 Because patients lived longer, the standard treatment cost increased slightly; however, the compli-
Primary reduction in serum cholesterol level using pravastatin increased undiscounted life expectancy by 06722 years and discounted QALYs increased by 03475 Standard treatment costs increased slightly because life expectancy increased The increase in life expectancy also led to an increase in complications cost, as the cost of
living longer with neuropathy, nephropathy, and retinopathy complications outweighed cost reductions from CHD and stroke The incremental total cost was 18033 and the costeffectiveness ratio was 51 889 per QALY Cost-effectiveness ratios for re-
2546 JAMA, May 15, 2002–Vol 287, No 19 Reprinted
2002 American Medical Association All rights reserved
Downloaded from wwwjamacom by guest on November 16, 2008
COST-EFFECTIVENESS OF INTERVENTIONS FOR TYPE 2 DIABETES
duction in serum cholesterol level varied by age, with the lowest costeffectiveness ratios for patients aged 45 to 84 years Table 5
Incidence of Complications
As shown in FIGURE 2, interventions directly affected cumulative incidence of complications by reducing the transition probabilities for complications The direct effect of intensive glycemic control reduced the cumulative incidence
of nephropathy, neuropathy, and retinopathy complications by 11 to 27 Intensified hypertension control directly reduced the cumulative incidence of nephropathy, retinopathy, and stroke complications, whereas reduction in serum cholesterol level directly lowered the cumulative incidence of CHD complications Interventions also had indirect
effects For example, if reductions in directly affected complications caused pa-
tients to live longer, they had more time to develop other complications, causing the cumulative incidence of those complications to increase slightly All 3 interventions led to increases in life expectancy so that there were small increases in the cumulative incidence of complications not listed above
Sensitivity Analyses
For intensive glycemic control, dropping the assumptions about microal-
Table 4 Incremental Cost-effectiveness by Intervention
Cost, Standard Treatment Complications Intervention Intensive glycemic control Conventional glycemic control standard treatment Intervention Incremental Intensive hypertension control Moderate hypertension control standard treatment Intervention Incremental Reduction in serum cholesterol level Standard treatment Intervention Incremental 10 741 10 785 44 10 679 11 030 351 10 353 10 756 404 37 602 33 271 -4330 33 738 28 902 -4836 34 819 36 505 1687 0 12 213 12 213 0 3708 3708 0 15 942 15 942 Total 48 343 56 270 7927 44 417 43 641 -776 45 171 63 204 18 033 Incremental Remaining Quality-Adjusted Cost-effectiveness Life-Years Ratio Total Life-Years Not
Discounted Cost/QALY, QALYs 172067 175240 03173 144380 149124 04744 163187 169909 06722 118791 120707 01915 103990 107952 03962 114690 118165 03475
41 384
-1959
51 889
Discounted at 3 annual rate Costs are for patients lifetime and are reported in 1997 dollars
All patients who were newly diagnosed as having type 2 diabetes All patients who were newly diagnosed as having type 2 diabetes and hypertension All patients who were newly diagnosed as having type 2 diabetes and above normal serum cholesterol level
Table 5 Cost-effectiveness by Age Group
25-34 y Change QALY Total cost, Cost-effectiveness ratio cost/QALY, Change QALY Total cost, Cost-effectiveness ratio cost/QALY, Change QALY Total cost, Cost-effectiveness ratio cost/QALY, 35-44 y 45-54 y 55-64 y Intensive Glycemic Control 02527 9372 37 086 01270 9118 71 816 65-74 y 75-84 y 85-94 y
06482 6232 9614
04575 8377 18 309
00507 7821 154 376
00142 5726 401 883
00017 3668 21 million
Intensified Hypertension Control 06939 -6609 Cost saving 06154 -3328 Cost saving 05290 -1341 Cost saving 04350 -413 Cost saving 03566 -167 Cost saving 02282 -43 Cost saving 00830 66 790
Reduction in Serum Cholesterol Level 02032 28 805
141 728 03443 27 361 79 473 04491 23 604 52 554 04351 18 852 43 331 03398 13 752 40 471 01675 8618 51 459 00447 4928 110 124
QALY indicates quality-adjusted life-year
All patients who were newly diagnosed as having type 2 diabetes All patients who were newly diagnosed as having type 2 diabetes and hypertension All patients who were newly diagnosed as having type 2 diabetes and above normal serum cholesterol level
2002 American Medical Association All rights reserved
Reprinted JAMA, May 15, 2002–Vol 287, No 19
2547
Downloaded from wwwjamacom by guest on November 16, 2008
COST-EFFECTIVENESS OF INTERVENTIONS FOR TYPE 2 DIABETES
buminuria and progression with hypertension led to moderate increases in the cost-effectiveness ratio FIGURE 3
If intensive glycemic control reduced CHD risk, QALYs increased substantially incremental QALYs03325 and
Figure 2 Cumulative Incidence of Complications
Without Intervention, With Selected Intervention,
Intensive Glycemic Control Microalbuminuria Nephropathy End-Stage Renal Disease Peripheral Neuropathy Lower Extremity Amputation Photocoagulation Blindness Coronary Heart Disease Stroke
0 10 20 30 40 50 60
Intensified Hypertension Control
Microalbuminuria Nephropathy End-Stage Renal Disease Peripheral Neuropathy Lower Extremity Amputation Photocoagulation Blindness Coronary Heart Disease Stroke
0 10 20 30 40 50 60
Reduction in Serum Cholesterol Level Microalbuminuria Nephropathy End-Stage Renal Disease Peripheral Neuropathy Lower Extremity Amputation Photocoagulation Blindness Coronary Heart Disease Stroke
0 10 20 30 40 50 60
the cost-effectiveness ratio decreased to less than 27000 per QALY Eliminating case management costs reduced intervention costs by 300 annually, causing the cost-effectiveness ratio to decrease to 22299 per QALY Under the UKPDS cost scenario, the intervention cost was only 3004, which was less than the reduction in complication costs; thus, the incremental total cost was 1309 lower, and the costeffectiveness ratio was negative, indicating that the intervention saved costs With a 0 discount rate, the costeffectiveness ratio decreased Conversely, with a 5 discount rate, the cost-effectiveness ratio increased For intensified hypertension control, applying the intervention to persons who developed hypertension after being diagnosed as having diabetes resulted in an incremental cost-effectiveness
ratio of 2091 per QALY Figure 3 Dropping the assumption that patients with hypertension progressed faster on the nephropathy and retinopathy disease paths increased the cost-effectiveness ratio If the intervention reduced the CHD transition probability by 21, the incremental QALYs associated with the intervention increased from 03962 to 06020 The total cost of the intervention increased by about 1000 because patients lived longer and the incremental cost-effectiveness ratio became 287 per QALY Changing the discount rate had little effect on the cost-effectiveness ratio For reduction in serum cholesterol level, eliminating extra office visits for the intervention lowered the costeffectiveness ratio to 47716 per QALY The cost-effectiveness ratio decreased with a 0 discount rate and increased with a 5 discount rate Figure 3 COMMENT The US Panel on Cost-effectiveness in Health and Medicine 9 notes that no absolute standard exists for deciding whether an interventions costeffectiveness ratio is cost-effective or not cost-effective Instead, the panel recommended describing interventions as more or less cost-effective than other
Cumulative Incidence of Complications,
Asterisk indicates
patients newly diagnosed as having type 2 diabetes; dagger, patients newly diagnosed as having type 2 diabetes and hypertension; and double dagger, patients newly diagnosed as having type 2 diabetes and an above normal serum cholesterol level 2548 JAMA, May 15, 2002–Vol 287, No 19 Reprinted
2002 American Medical Association All rights reserved
Downloaded from wwwjamacom by guest on November 16, 2008
COST-EFFECTIVENESS OF INTERVENTIONS FOR TYPE 2 DIABETES
interventions An exception occurs for interventions that reduce costs and improve health outcomes, thereby producing negative cost-effectiveness ratios Such interventions save costs and should be adopted Our results indicate that intensified hypertension control falls into the cost-saving category, relative to moderate hypertension control Both intensive glycemic control and reduction in serum cholesterol level improve health outcomes, but they also increase health costs Based on panel recommendations, these interventions cannot be characterized as either costeffective or not cost-effective Still, the cost-effectiveness ratios of 40881 per QALY for intensive glycemic control and 51889 per QALY for reduction in serum
cholesterol level are comparable with published cost-effectiveness ratios for commonly funded interventions, such as heart transplantation vs optimal conventional treatment among patients who need transplants 46000 per QALY, hypertension screening and therapy vs no screening among asymptomatic 20-year-old men 40000 per QALY, neonatal intensive care vs standard neonatal care among premature infants weighing 05 to 1 kg 47000 per QALY, and dual air bags vs driver-side air bag only 69000 per QALY46 From a policy perspective, it is possible to compare the 3 interventions in Table 4 Intensive hypertension control is the most cost-effective, followed by reduction in serum cholesterol level and intensive glycemic control Table 5 shows that the relative ranking varied somewhat with age, with intensive glycemic control performing better at younger than at older ages It should be noted that the interventions affect different subgroups of the population of patients newly diagnosed as having type 2 diabetes all patients receiving intensive glycemic control, those with hypertension receiving intensified hypertension control, and those with high serum cholesterol level seeking reduction Each
subsample has a different age and risk profile, affecting the potential gains from intervention
The comparison of cost-effectiveness ratios across interventions in Tables 4 and 5 should not be interpreted as minimizing the need for glycemic control in patients with type 2 diabetes Standard treatment for all interventions included conventional glycemic control that produced an average glycosylated hemoglobin level of 79 The cost-effectiveness analysis for intensive glycemic control examined the incremental costs and outcomes associated with more inFigure 3 Sensitivity Analyses
tensive control than conventional control In addition, sensitivity analyses indicate that if the incremental cost of the intensive glycemic control intervention can be reduced, the intervention will be more cost-effective The sensitivity analysis also shows that the cost-effectiveness ratio will decrease if glycemic control reduces patients risk for CHD The UKPDS found a 16 risk reduction for intensive glycemic control that was almost statistically significant30
Intensive Glycemic Control
Base Case Microalbuminuria Does Not Lead to Hypertension Persons With Hypertension Do Not Progress Faster
Microalbuminuria Does Not Lead to Hypertension and Persons With Hypertension Do Not Progress Faster Intensive Glycemic Control Reduces Risk of CHD by 16 No Case Management Costs UKPDS Cost Scenario Discount Rate Equals 0 Annually Discount Rate Equals 5 Annually 10 000 0 10 000 20 000 30 000 40 000 50 000 60 000 70 000
Intensified Hypertension Control
Base Case Intervention Provided to Persons Who Develop Hypertension Subsequent to Diagnosis of Diabetes Persons With Hypertension Do Not Progress Faster on Microalbuminuria and Retinopathy Paths Risk Reduction for CHD Equals 21 Discount Rate Equals 0 Annually Discount Rate Equals 5 Annually 4000 2000 0 2000 4000 6000 8000
Reduction in Serum Cholesterol Level
Base Case Intervention Requires No Additional Office Visits or Tests Discount Rate Equals 0 Annually Discount Rate Equals 5 Annually 0 10 000 20 000 30 000 40 000 50 000 60 000
Cost/QALY,
QALY indicates quality-adjusted life-year; CHD, coronary heart disease; and UKPDS, United Kingdom Prospective Diabetes Study Reprinted JAMA, May 15, 2002–Vol 287, No 19 2549
2002 American Medical Association All rights reserved
Downloaded from wwwjamacom by guest on November 16,
2008
COST-EFFECTIVENESS OF INTERVENTIONS FOR TYPE 2 DIABETES
Our cost-effectiveness estimates for intensive glycemic control and reduction in serum cholesterol level vary widely across age groups Intensive glycemic control is most cost-effective for younger patients In part, this is driven by the models assumption that the transition probabilities for nephropathy, neuropathy, and retinopathy are dependent on the duration of diabetes, not on patient age Because younger patients are less likely to die from other causes, they have more time to progress to these complications Given this assumption, intensive glycemic control has a greater potential to reduce complications in younger patients For reduction in serum cholesterol level, the costeffectiveness ratio initially decreases with age, as CHD risk increases
Limitations
Chronic disease modeling usually requires extrapolating the results of an intervention on intermediate outcomes, which occur within the duration of a randomized controlled trial, to longterm or end-stage health outcomes that are most likely to occur after the trial has ended Often, the intervention has a significant effect on intermediate outcomes, but the trial
ends before significant effects on long-term outcomes can be observed The UKPDS was an unusually long randomized controlled trial, with a median follow-up of 10 years, and intensive glycemic control that produced a 12 reduction P03 in the aggregate end point of any diabetes-related event30 However, intensive glycemic control did not produce significant reductions in such longterm outcomes as all-cause mortality, MI, stroke, renal failure, and amputation There were few cases of renal failure, blindness, or amputation under conventional glycemic control, virtually precluding a significant intervention effect on these outcomes Intensive glycemic control did significantly reduce progression to microalbuminuria, photocoagulation, and neuropathy When we incorporated into our model the effects of intensive glycemic control on these intermediate dis-
ease stages, the model indicated that such control would lead to long-term reductions in renal failure, blindness, and amputation Our results also rely on treatment compliance rates achieved during the UKPDS If compliance rates are lower outside the trial setting, the interventions will have less impact on health outcomes, QALYs, and
complications cost However, lower compliance will also reduce intervention cost because noncompliant patients will be less likely to take prescribed drugs, visit physicians, and perform self-testing The net impact on the cost-effectiveness ratio is uncertain Ideally, the model would combine resource use and health outcome data generated from the same study Although we performed a sensitivity analysis that combined the UKPDS cost scenario with UKPDS outcome results for intensive glycemic control, treatment patterns may vary between the United States and the United Kingdom Because the focus of our study was patients in the United States, our main analysis considered resource use associated with treatment patterns in the United States This approach may have produced more conservative higher cost-effectiveness ratios than would be found if the higher resource use for intensive glycemic control produced larger reductions in diabetes complications than those observed in the UKPDS Our study considers costs from the perspective of a health care system Because of data limitations, the model did not include nonmedical costs, such as lost productivity and the time provided by family and
friends in caring for patients with diabetes Thus, our model may underestimate the social costs of diabetes In turn, this could affect the estimated cost-effectiveness ratios
Implications
to evaluate the cost-effectiveness of interventions for type 2 diabetes that produce benefits years or even decades after the interventions begin The evaluation results provide information for policy makers as they decide whether to adopt the interventions
Affiliations of the Members of the CDC Diabetes Costeffectiveness Group: Thomas J Hoerger, PhD, Albert D Bethke, PhD, and Anke Richter, PhD, Research Triangle Institute, Research Triangle Park, NC; Stephen W Sorensen, PhD, Michael Engelgau, MD, Ted Thompson, MS, K M Venkat Narayan, MD, David F Williamson, PhD, Edward Gregg, PhD, and Ping Zhang, PhD, Division of Diabetes Translation, Centers for Disease Control and Prevention, Atlanta, Ga; Richard C Eastman, MD, Cygnus Inc; John Fuller, MD, University College, London, England; Claire B Gibbons, MPH, University of North Carolina School of Public Health, Chapel Hill; Steve Haffner, MD, University of Texas Health Center, San Antonio ; William H Herman, MD, University of Michigan Medical Center, Ann
Arbor; Barbara Howard, PhD, and Robert Ratner, MD, MedStar Research Institute, Washington, DC; and Trevor Orchard, MB BCh, University of Pittsburgh, Pittsburgh, Pa Author Contributions: Study concept and design: Hoerger, Bethke, Richter, Sorenson, Engelgau, Thompson, Narayan, Williamson, Gregg, Eastman, Fuller, Haffner, Herman, Howard, Orchard Acquisition of data: Hoerger, Bethke, Engelgau, Narayan, Gibbons, Orchard Analysis and interpretation of data: Hoerger, Richter, Engelgau, Narayan, Zhang, Gibbons, Herman, Ratner, Orchard Drafting of the manuscript: Hoerger, Bethke, Richter, Engelgau, Williamson, Gibbons, Haffner Critical revision of the manuscript for important intellectual content: Hoerger, Sorenson, Engelgau, Thompson, Narayan, Williamson, Gregg, Zhang, Eastman, Fuller, Herman, Howard, Ratner, Orchard Statistical expertise: Hoerger, Sorenson, Thompson, Orchard Obtained funding: Hoerger, Engelgau Administrative, technical, or material support: Hoerger, Bethke, Richter, Sorenson, Engelgau, Williamson, Gregg, Eastman, Gibbons, Haffner, Herman, Howard, Orchard Study supervision: Hoerger, Sorenson, Engelgau, Narayan Funding/Support: This work was suppported by Centers for
Disease Control and Prevention contract 20097-0621 Acknowledgment: We thank Mohan V Bala for additional assistance in the conception and design of the study; Kristine R Broglio for acquisition, interpretation, and analysis of data; Stephanie R Earnshaw for statistical expertise; Katherine A Hicks for analysis and interpretation of data; and Susan M Murchie for editorial support REFERENCES 1 Centers for Disease Control and Prevention National Diabetes Fact Sheet, 1997 Atlanta, Ga: Centers for Disease Control and Prevention, Division of Diabetes Translation; 1997 2 Harris MI, Flegal KM, Cowie CC, et al Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in US adults: the Third National Health and Nutrition Examination Survey, 1988-1994 Diabetes Care 1998;21:518-524 3 Alberti KGM, DeFronzo RA, Zimmet P, eds International Textbook of Diabetes Mellitus New York, NY: John Wiley Sons; 1995
Using common metrics, economic evaluations can estimate the relative value of various interventions The need for information usually dependent on long-term, expensive trials can partially be addressed by the modeling approach, which provides a feasible means
2550 JAMA,
May 15, 2002–Vol 287, No 19 Reprinted
2002 American Medical Association All rights reserved
Downloaded from wwwjamacom by guest on November 16, 2008
COST-EFFECTIVENESS OF INTERVENTIONS FOR TYPE 2 DIABETES
4 Rubin RJ, Altman WM, Mendelson DN Health care expenses for people with diabetes mellitus, 1992 J Clin Endocrinol Metab 1994;78:809A-809F 5 American Diabetes Association Economic consequences of diabetes mellitus in the US in 1997 Diabetes Care 1998;21:296-309 6 Wingard DL, Barrett-Connor E Heart disease and diabetes In: National Diabetes Data Group, eds Diabetes in America 2nd ed Bethesda, Md: National Institute of Diabetes and Digestive and Kidney Diseases; 1995:429-448 NIH publication 95-1468 7 Kuller LH Stroke and diabetes In: National Diabetes Data Group, eds Diabetes in America 2nd ed Bethesda, Md: National Institute of Diabetes and Digestive and Kidney Diseases; 1995:449-456 NIH publication 95-1468 8 Geiss LS, Herman WH, Smith PJ Mortality in noninsulin-dependent diabetes In: National Diabetes Data Group, eds Diabetes in America 2nd ed Bethesda, Md: National Institute of Diabetes and Digestive and Kidney Diseases; 1995:233-257 NIH publication 95-1468 9 Gold MR, Siegel
JE, Russell LB, Weinstein MC, eds Cost-effectiveness in Health and Medicine Oxford, England: Oxford University Press; 1996 10 Eastman RC, Javitt JC, Herman WH, et al Model of complications of NIDDM, I: model construction and assumptions Diabetes Care 1997;20:725-734 11 Eastman RC, Javitt JC, Herman WH, et al Model of complications of NIDDM, II: analysis of the health benefits and cost-effectiveness of treating NIDDM with the goal of normoglycemia Diabetes Care 1997;20: 735-744 12 Dong F, Orians C, Manninen D Economic evaluation of approaches to preventing diabetic endstage renal disease Seattle, Wash: Battelle/Centers for Public Health Research and Evaluation; 1997 13 CDC Diabetes Cost-effectiveness Study Group The cost-effectiveness of screening for type 2 diabetes JAMA 1998;280:1757-1763 14 Cowie CC, Harris MI Physical and metabolic characteristics of persons with diabetes In: National Diabetes Data Group, eds Diabetes in America 2nd ed Bethesda, Md: National Institute of Diabetes and Digestive and Kidney Diseases; 1995:117-164 NIH publication 95-1468 15 US Census Bureau National population estimates for the 1990s Available at: http://eirecensusgov/
popest/archives/national/nat_90s_detail/ nat_90s_1php Accessibility verified April 18, 2002 16 Centers for Disease Control and Prevention Diabetes Surveillance Atlanta, Ga: US Dept of Health and Human Services; 1997 17 Weinstein MC, Coxson PG, Williams LW, Pass TM, Stason WB, Goldman L Forecasting coronary heart disease incidence, mortality, and cost: the coronary heart disease policy model Am J Public Health 1987; 77:1417-1426 18 Anderson KM, Odell PM, Wilson PWF, Kannel WB Cardiovascular disease risk profiles Am Heart J 1990;121:293-298 19 Hunink MGM, Goldman L, Tosteson ANA, et al The recent decline in mortality from coronary heart disease, 1980-1990 JAMA 1997;277:535-542 20 OBrien JA, Shomphe LA, Kavanagh PL, Raggio G, Caro JJ Direct medical costs of complications resulting from type 2 diabetes in the US Diabetes Care 1998;21:1122-1128 21 Eckman MH, Greenfield C, Mackey WC, et al Foot infections in diabetic patients JAMA 1995;273:712720 22 Russell MW, Huse DM, Drowns S, Hamel EC, Hartz SC Direct medical costs of coronary artery disease in the United States Am J Cardiol 1998;81:11101115 23 Taylor TN, Davis PH, Torner JC, Homes J, Meyer JW, Jacobson MF Lifetime cost of stroke in
the United States Stroke 1996;27:1459-1466 24 Lubitz JD, Riley GF Trends in Medicare payments in the last year of life N Engl J Med 1993;328: 1092-1096 25 Diabetes Control and Complications Trial Research Group Lifetime benefits and costs of intensive therapy as practiced in the Diabetes Control and Complications Trial JAMA 1996;276:1409-1415 26 Shin AY, Porter PJ, Wallace MC, Naglie G Quality of life of stroke in younger individuals Stroke 1997; 28:2395-2399 27 Wolf PA, DAgnostino RB, ONeal A, et al Secular trends in stroke incidence and mortality Stroke 1992;23:1551-1555 28 Tsevat J, Goldman L, Soukup JR, et al Stability of time-tradeoff utilities in survivors of myocardial infarction Med Decis Making 1993;13:161-165 29 Nease RF, Kneeland T, OConnor GT, et al Variation in patient utilities for outcomes of the management of chronic stable angina JAMA 1995;273:11851190 30 UK Prospective Diabetes Study Group Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes UKPDS 33 Lancet 1998;352:837-853 31 Diabetes Control and Complications Trial Research Group The relationship of glycemic
exposure HbA1c to the risk of development and progression of retinopathy in the Diabetes Control and Complications Trial Diabetes 1995;44:968-983 32 UK Prospective Diabetes Study Group UKPDS 16 Overview of 6 years therapy of type II diabetes: a progressive disease Diabetes 1995;44:1249-1258 33 UK Prospective Diabetes Study Group UKPDS 24 A 6-year, randomized, controlled trial comparing sulfonylurea, insulin, and metformin therapy in patients with newly diagnosed type 2 diabetes that could not be controlled with diet therapy Ann Intern Med 1998; 128:165-175 34 Turner R, Holman R The UK prospective diabetes study Presented at: European Association for the Study of Diabetes Meeting; September 10, 1998; Barcelona, Spain Available at: http://wwwdtuoxacuk /indexhtml/maindoc /ukpds/ Accessed November 22, 1999 35 Red Book Montvale, NJ: Medical Economics Co Inc; 1997 36 Health Care Financing Administration Durable medical equipment regional carrier instructions to implement balanced budget act of 1997 provision 4105, to provide expanded coverage of blood glucose monitors, and testing strips for all diabetics Available at: http://wwwhcfagov/pubforms/transmit /b981760htm Accessibility
verified April 18, 2002 37 Aubert RE, Herman WH, Waters J, et al Nurse case management to improve glycemic control in diabetic patients in a health maintenance organization Ann Intern Med 1998;129:605-612 38 US Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Center for Health Statistics Vital and Health Statistics, Plan and Operation of the Third National Health and Nutrition Examination Survey, 1988-1994 Washington, DC: US Dept of Health and Human Services; 1994 DHHS publication 941308, series 1, No 32 4-0485 39 UK Prospective Diabetes Study Group Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes UKPDS 38 BMJ 1998;317:703-713 40 UK Prospective Diabetes Study Group Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes BMJ 1998;317:713-720 41 National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults Summary of the second report of the National Cholesterol Education Program NCEP expert panel on detection, evaluation, and
treatment of high blood cholesterol in adults JAMA 1993;269:3015-3023 42 Shepherd J, Cobbe SM, Ford I, et al Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia N Engl J Med 1995;333:13011307 43 West of Scotland Coronary Prevention Study Group Baseline risk factors and their association with outcome in the West of Scotland Coronary Prevention Study Am J Cardiol 1997;79:756-762 44 Goldberg RB, Mellies MJ, Sacks FM, et al Cardiovascular events and their reduction with pravastatin in diabetic and glucose-intolerant myocardial infarction survivors with average cholesterol levels Circulation 1998;98:2513-2514 45 Gray A, Raikou M, McGuire A, et al Cost effectiveness of an intensive blood glucose control policy in patients with type 2 diabetes: economic analysis alongside randomised controlled trial UKPDS 41 BMJ 2000;320:1373-1378 46 Chapman RH, Stone PW, Sandberg EA, Bell C, Neumann PJ A comprehensive league table of costutility ratios and a sub-table of panel-worthy studies Med Decis Making 2000;20:451-467
2002 American Medical Association All rights reserved
Reprinted JAMA, May 15, 2002–Vol 287, No 19
2551
Downloaded from wwwjamacom by guest on
November 16, 2008
Source:landminesurvivors.org
