Cost-Effectiveness of Drug Therapy for Diabetes Mellitus

– A Systematic ReviewYan-Jun Zhang, BS Pharmacy, MMS Pharmacology; Rashmi R. Nair, Ph.D.; Jinender Kumar, B.Pharm., D.M.M.

Department of Pharmacy Health Care Administration, College of Pharmacy, University of Toledo

According to the fact sheet issued by the Centers for

Disease Control and Prevention (CDC), in the year

2005, 20.8 million people are diabetics in the United

States which accounted for 7% of the population of the

US. Estimated diabetes costs in the US were $132

billion in 2002, of which direct medical expenditures

were $92 billion. The huge economic burden on

healthcare necessitates researchers and policy-makers

to conduct cost studies in order to reduce it.

To compare and contrast the cost-effectiveness of

various diabetes medications, we conducted the

systematic review of cost-effectiveness of antidiabetic

drugs including insulin.

Background and Objectives

Methods

A literature search using PubMed, OhioLINK,

SciFinder, EMBASE and Cochrane library was

conducted for cost-effectiveness studies on

hypoglycemic agents and insulin, combined with

reference lists of literatures and manual search of the

journals Pharmacoeconomics and Current Medical

Research and Opinion. The key terms used for

literature search were “diabetes”, and “cost-

effectiveness, cost-benefit, costs and cost analysis,

economics, pharmaceutical economics”. Two reviewers

independently assessed and identified the relevant

literatures using the following inclusion and exclusion

criteria.

Initial search resulted in 1402 abstracts. After applying the

inclusion/exclusion criteria, 13 studies were identified from

UK, Canada, USA, and Germany on either type 1 or type 2

diabetes mellitus. There is no cost-effectiveness study on

gestational diabetes. Except part of one study reported within-

trial cost-effectiveness, all the studies are modeling from the

short-term RCTs. The median sample size was 638 patients;

the median duration of trials was 39 weeks. Most studies

demonstrated overall positive effects in economic outcomes

and found that interventions improved the cost-effectiveness

and health care utilization over the comparators from their

individual perspectives. The studies focused on some

relatively new drugs which were approved to market in recent

years, such as insulin glargine, insulin detemir, exenatide and

rosiglitazone etc. These new antidiabetic drugs and insulin

analogues showed their cost-effectiveness. The more detailed

information are displayed in the following tables.

Results

There has been no cost-effectiveness review of pharmacotherapy for diabetes. However, there is growing evidence that these drug interventions may promote diabetic health with better economic outcomes.

There are few within-trial cost-effectiveness studies for diabetes drug therapy. Future RCTs should take within-trial economic evaluation into account.

There are some benefits of pharmacoeconomic modeling studies. The uncertainties and assumptions in model formalization process are made explicit and transparent. “To estimate costs and outcomes, existing data is frequently insufficient to allow optimal healthcare decision-making. Good modeling practice incorporates the best available evidence from all possible sources into a set of explicit parameters.” “Mathematical modeling allows a rational and scientific approach to overcoming the inherent limitations of RCTs, using the best available evidence.” [3]

However, “modeling study practical value is currently limited by insufficient standardization, meager documentation of practices and policies, no systematic quality surveillance, and a low level of acceptance by regulatory agencies and end users.”[3]

The results of this study should be interpreted with several limitations in mind. First, the heterogeneity of the studies including different countries and regions, different perspectives and diverse medications, weakened any general inferences. Second, only articles written in English language and conducted in RCTs were reviewed. However, double reviews were conducted to minimize errors and increase accuracy in data abstraction.

Future review should involve such databases as Science Citation Index (SCI), International Pharmaceutical Abstracts (IPA), Office of Health Economics Health Economic Evaluation Database (OHE-HEED), Health Technology Assessment (HTA) database, and UK National Health Service Economic Evaluations Database (NHS-EED).

Discussion and ConclusionsInclusion and Exclusion Criteria

Eligible studies were those focused on cost-effectiveness of

antidiabetic drugs based on randomized controlled trials

(RCTs), and published in English before January 2008. The

qualities of RCTs and economic evaluation were assessed

using the Cochrane standard[1] and British Medical Journal

checklist[2] respectively. Studies on preventive interventions of

diabetes and pharmacoeconomics of diabetes-related

complications were excluded.

Abbreviations: CORE, Center for Outcomes Research diabetes model; DCCT, Diabetes Control and Complications Trial; DES, Discrete Event Simulation; DiDACT, Diabetes Decision Analysis of Cost – type 2; ICER, Incremental Cost-Effectiveness Ratio; INITIATE, Initiate Insulin by Aggressive Titration and Education; NHS, (UK) National Health Service; NPH, Neutral Protamine Hagedorn; PROactive, PROspective pioglitAzone Clinical Trial In macroVascular Events; QALY, Quality-Adjusted Life Year; RCT, Randomized Controlled Trial; UKPDS, UK Prospective Diabetes Study.

Table: Characteristics of the Included Studies

Table: Characteristics of the Included Studies (continued)

1. Goudswaard AN, Furlong NJ, Valk GD, Stolk RP, Rutten GEHM. Insulin monotherapy versus combinations of insulin with oral hypoglycaemic agents in patients with type 2 diabetes mellitus. Cochrane Database of Systematic Reviews 2004, Issue 4. Art. No.: CD003418. DOI: 10.1002/14651858.CD003418.pub2.

2. Drummond MF, Jefferson TO. Guidelines for authors and peer reviewers of economic submissions to the BMJ. BMJ 1996 Aug; 313: 275-83.

3. Gagnon, J.P., M.D. Smith, and D. Rindress, Pharmacoeconomics: identifying the issues overview and advisory panel report summary. Value Health, 1999. 2(2): p. 67-72.

References

Study Types of diabetes Medication Interventions Country Perspective Clinical Data Year of Costing

Palmer AJ et al[19] Type 1 Insulin detemir vs. NPH insulin UK NHS A meta-analysis of results from four clinical trials 2003

Palmer AJ et al[20] Type 1 Insulin detemir + aspart vs. NPH + human soluble insulin UK NHS RCT by Hermansen et al. 2004

McEvan P et al[21] Type 1 Insulin glargine vs. NPH insulin UK NHS pooled data from RCTs including DCCT 2005

Valentine WJ et al[13] Type 1 Insulin detemir vs. NPH;Insulin detemir vs. glargine

US Medicare RCT 2005

Grima DT et al[8] Type 1 and type 2 Insulin glargine vs. NPH insulin Canada Canadian public payer RCT including UKPDS and DCCT 2005

Shearer AT et al[17] Type 2 Rosiglitazone + other oral agents vs. other + other oral agents Germany sickness funds RCT 2001

Tilden DP et al[22] Type 2 Pioglitazone + metformin vs. rosiglitazone + metformin UK NHS RCT 2004/5

Beale S et al[10] Type 2 Rosiglitazone + metformin vs. sulfonylurea + metformin UK NHS RCT 2003

Ray JA et al[12] Type 2 Exenatide vs. insulin glargine UK NHS RCT 2004

Valentine WJ et al[23] Type 2 Insulin aspart 30/70 vs. insulin glargine UK NHS INITIATE clinical trial 2004

McEvan P et al[24] Type 2 Insulin glargine vs. NPH insulin UK NHS pooled data from RCTs including DCCT 2005

Valentine WJ et al[25] Type 2 Pioglitazone + existing regimens vs. placebo + existing regimens UK health-care payer (NHS) PROactive Study 2005

Ray JA et al[26] Type 2 Insulin aspart 30 vs. insulin glargine US third-party payer INITIATE clinical trial 2004

Study Time Horizon (years) Discount Rate (%) Model ICER (/QALY)

Palmer AJ et al[19] Over patient lifetimes 3.5 CORE £19285

Palmer AJ et al[20] Over patient lifetimes 3.5 CORE £2500

McEvan P et al[21] over a maximum of 40 years 3.5 discrete event simulation (DES) £2695 to £10943

Valentine WJ et al[13] 35 3.0 CORE 100% probability below $50000 (vs. NPH);80% probability below $50000 (vs. glargine);

Grima DT et al[8] 36 5 Self-developed $Can20799 (type 1);$Can8618 (type 2)

Shearer AT et al[17] lifetime 5 (health outcomes not discounted) DiDACT Below international “willingness to pay” thresholds

Tilden DP et al[22] lifetime 3.5 Self-developed Pioglitazone dominate (0.0384 additional QALYs, costs lower £714)

Beale S et al[10] lifetime 3.5 DiDACT £16700 (obese cohort);£11600 (overweight cohort)

Ray JA et al[12] 35 3.5 CORE £22420/QALY (100% exenatide price of US)

Valentine WJ et al[23] 35 3.5 CORE £6951/QALY

McEvan P et al[24] Maximum: 40 3.5 DES £10027 to £13921

Valentine WJ et al[25] Modeling: 35 3.5 CORE (modified version) £5396/QALY (within-trial);£4060/QALY (modeling)

Ray JA et al[26] 35 3.0 CORE $46533