ArticleLiterature Review

Cost Effectiveness of Dipeptidyl Peptidase-4 Inhibitors for Type 2 Diabetes

March 2015
PharmacoEconomics 33(6)

March 2015
33(6)

DOI:10.1007/s40273-015-0266-y

Source
PubMed

Authors:

Jinsong Geng

Nantong University

Hao Yu

RAND Corporation

Show all 5 authorsHide

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of antidiabetic drugs used for treating type 2 diabetes mellitus. While many studies have reported on the cost-effectiveness of DPP-4 inhibitors for treating type 2 diabetes, a systematic review of economic evaluations of DPP-4 inhibitors is currently lacking. The aim of this systematic review was to assess the cost effectiveness of DPP-4 inhibitors for patients with type 2 diabetes. MEDLINE, EMBASE, National Health Service Economic Evaluation Database (NHS EED), Web of Science, EconLit databases, and the Cochrane Library were searched in November 2013. Studies assessing the cost effectiveness of DPP-4 inhibitors for type 2 diabetes were eligible for analysis. DPP-4 inhibitor monotherapy or combinations with other antidiabetic agents were included in the review. The DPP-4 inhibitors were all marketed drugs. Two reviewers independently reviewed titles, abstracts, and articles sequentially to select studies for data abstraction based on the inclusion and exclusion criteria. Disagreements were resolved by consensus. The quality of included studies was assessed according to the 24-item checklist of the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. The costs reported by the included studies were converted to US dollars via purchasing power parities (PPP) in the year 2013 using the CCEMG-EPPI-Center Cost Converter. A total of 11 published studies were selected for inclusion; all were cost-utility analyses. Nine studies were conducted from a payer perspective and one used a societal perspective; however, the perspective of the other study was unclear. Four studies were of good quality, six were of moderate quality, and one was of low quality. Of the seven studies comparing DPP-4 inhibitors plus metformin with sulfonylureas plus metformin, six concluded that DPP-4 inhibitors were cost effective in patients with type 2 diabetes who were no longer adequately controlled by metformin monotherapy. Five studies compared DPP-4 inhibitors with thiazolidinediones, and whether DPP-4 inhibitors were cost effective was uncertain. Only two economic evaluations provided data to compare DPP-4 inhibitors versus insulin, and the results favored the use of DPP-4 inhibitors as second-line therapy. Synthesis of the data was impossible because of heterogeneity in the methodology and data sources of the economic evaluations, and the inclusion criteria excluded conference abstracts. It was difficult to find reliable weightings for each of the items of the CHEERS checklist, and the ratings were dichotomous. This study provides the first systematic evaluation of DPP-4 inhibitors for patients with type 2 diabetes. It found that, in patients with type 2 diabetes who do not achieve glycemic targets with antidiabetic monotherapy, DPP-4 inhibitors as add-on treatment may represent a cost-effective option compared with sulfonylureas and insulin. However, high-quality cost-effectiveness analyses that utilize long-term follow-up data and have no conflicts of interest are still needed.

Pharmacoeconomic evaluation of dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes mellitus: a systematic literature review

Article

Feb 2022

Introduction: Dipeptidyl peptidase-4 inhibitors (DPP-4i) are widely used oral antidiabetic agents that exert antihyperglycemic effects in type 2 diabetes mellitus (T2DM) without increased risk of weight gain or hypoglycemic events. The objective of this paper was to systematically review the latest evidence that were associated with the pharmacoeconomic evaluation of DPP-4i for the treatment of patients with T2DM. Areas covered: We conducted a systematic literature search of eligible articles published since inception up to March 2021 in Web of Science, MEDLINE (via PubMed), and ECONLIT. Fifty-four eligible articles were included in our review, in which DPP-4i were compared to metformin (4 studies), sulphonylurea (SU) (16 studies), alpha-glucosidase inhibitors (AGI) (3 studies), thiazolidinediones (TZD) (4 studies), other DPP-4i (3 studies), sodium-glucose co-transporter-2 inhibitors (SGLT-2i) (10 studies), glucagon-like peptide 1 receptor agonist (GLP-1RA) (18 studies), insulin (5 studies), and other antidiabetic therapies (5 studies). Expert opinion: This study provided the updated evidence of systematic pharmacoeconomic evaluation associated with DPP-4i for the treatment of patients with T2DM. The evidence from the literature suggested DPP-4i may be more cost-effective compared to SU and insulin as second-line therapy after metformin, but not a cost-effective alternative compared to SGLPT-2i and GLP-1RA.

Cost of Managing Type 2 Diabetes Before and After Initiating Dipeptidyl Peptidase 4 Inhibitor Treatment: A Longitudinal Study Using a French Public Health Insurance Database

Article

Full-text available

Jan 2020

IntroductionDiabetes is a growing epidemic that imposes a substantial economic burden on healthcare systems. This study aimed to evaluate the cost of managing type 2 diabetes (T2D) with dipeptidyl peptidase 4 inhibitors (DPP4Is) using real-world data.Method This longitudinal study used data from the French EGB (Echantillon Généraliste des Bénéficiaires) database. The annual average direct healthcare cost of treating patients with T2D was calculated 3 years prior and 3 years after initiation of DPP4I therapy. Actual total ambulatory and hospital care expenditure for the 3 years after DPP4I initiation was compared to projected costs. The distribution of costs across all care modalities was assessed over the 6-year period.ResultsAmbulatory and hospital care expenditure data for 919 patients with T2D starting DPP4I therapy alone or in combination in 2013 were analyzed. A total of 526 patients (57.2%) were still being treated with DPP4I 3 years after DPP4I initiation. Regardless of the treatment regimen, the ambulatory and hospital care costs increased above projected costs in the first year following DPP4I initiation, and then declined during the second and third years to levels in line with or below projected values for patients using DPP4Is as an add-on therapy. The increase in total expenditure in the first year following DPP4I initiation and the subsequent decline in costs in the second and third years were both associated with general trends in consumption across all aspects of patient care.Conclusion Despite an initial increase in healthcare expenditure, concomitant with reevaluation of patient care, this study showed that initiation of DPP4Is as an add-on therapy in French patients with T2D was associated with care expenditure that was in line or below predicted values within the 3 years following treatment initiation. Additional studies are required to evaluate the economic impact of the long-term treatment benefits.

Cost Utility of Sodium-Glucose Cotransporter 2 Inhibitors in the Treatment of Metformin Monotherapy Failed Type 2 Diabetes Patients: A Systematic Review and Meta-Analysis

Article

Full-text available

Nov 2019

Objectives: Type 2 diabetes mellitus (T2DM) and associated ailments are leading economic burdens to society. Sodium glucose cotransporter-2 (SGLT2) inhibitors are recent antidiabetic medications with beneficial clinical efficacy. This meta-analysis was conducted to quantitatively pool the incremental net benefit of SGLT2 inhibitors in T2DM patients who failed metformin monotherapy. Methods: Relevant economic evaluation studies of T2DM patients were identified from PubMed, Scopus, ProQuest, the Cochrane Library, and the Tufts Cost-Effective Analysis Registry until June 2018. Studies were eligible if they studied T2DM patients who failed metformin monotherapy and assessed the cost-effectiveness/utility between SGLT2 inhibitors and other treatments. Details of the study characteristics, economic model inputs, costs, and outcomes were extracted. Risk of bias was assessed using the biases in economic studies (ECOBIAS) checklist. The incremental net benefit was calculated with monetary units adjusting for purchasing power parity for 2017 US dollars. This was then pooled across studies stratified by the country’s level of income using a random-effect model if heterogeneity was present and with a fixedeffect model otherwise. Heterogeneity was assessed using the Q test and I2 statistic. Results: A total of 13 studies with 22 comparisons, mainly from high-income countries, were eligible. Six and 4 studies compared SGLT2 with dipeptidyl peptidase-4 inhibitors (DPP4i) and sulfonylureas, respectively. The pooled incremental net benefits (95% confidence interval) for these corresponding comparisons were $164.95 (–$534.71 to $864.61; I2 = 0%) and $3675.09 ($1656.46-$5693.71; I2 = 85.4%), respectively. These results indicate that SGLT2s were cost-effective in comparison with sulfonylureas but not DPP4i. Conclusion: SGLT2s were cost-effective as compared with sulfonylureas but not DPP4i. Most of the evidence was from highincome countries with few comparative drug groups, and the results might not be representative of the actual global scenario. Further studies from middle and lower economies and other comparators are still required.

The place of DPP-4 inhibitors in the treatment algorithm of diabetes type 2: a systematic review of cost-effectiveness studies

Article

Full-text available

Nov 2017
EUR J HEALTH ECON

Objective To conduct a systematic review of cost-effectiveness, cost-utility, and cost-benefit studies of DPP-4 inhibitors for diabetes treatment versus other antidiabetics. Methods Three investigators searched the CRD York, Tufts CEA Registry, and MEDLINE databases through 2015. We reviewed all potentially relevant titles and abstracts, and screened full-text articles, according to inclusion criteria. We established a quality score for each study based on a 35-item list. ResultsA total of 295 studies were identified, of which 20 were included. The average quality score was 0.720 on a 0–1 scale. All studies were performed in high- and middle-income countries, using a 3rd-party payer perspective and randomized clinical trials to measure effectiveness. Sitagliptin, saxagliptin and vildagliptin had an ICER below 25,000 €/QALY, as second-line and as add-ons to metformin, in comparison to sulfonylureas. When compared with sitagliptin, liraglutide (GLP-1 receptor agonist) had an ICER of up to 22,724 €/QALY for the 1.2-mg dosage, and up to 32,869 €/QALY for the 1.8-mg dosage. Insulin glargine was dominant when compared with sitagliptin. Conclusions According to the WHO threshold applied to the country and year of each study, DPP-4 inhibitors were highly cost-effective as second-line, as add-ons to metformin, in comparison with sulfonylureas. More recent therapies (GLP-1 receptor agonists and insulin glargine) were highly cost-effective in comparison to DPP-4 inhibitors. These results were obtained, however, on the basis of a limited number of studies, relying on the same few clinical trials, and financed by manufacturers. Further independent research is needed to confirm these findings.

Cost-Effectiveness of Dipeptidylpeptidase-4 Inhibitors Added to Metformin in Patients With Type 2 Diabetes in China

Article

Full-text available

Aug 2021

Purpose Dipeptidylpeptidase-4 (DPP-4) inhibitors, including linagliptin, alogliptin, saxagliptin, sitagliptin, and vildagliptin, are used for the treatment of type 2 diabetes mellitus (T2DM) patients in China. This study assessed the economic outcomes of different DPP-4 inhibitors in patients with T2DM inadequately controlled with metformin in the Chinese context. Materials and Methods In this study, the validated Chinese Outcomes Model for T2DM (COMT) was conducted to project economic outcomes from the perspective of Chinese healthcare service providers. Efficacy and safety, medical expenditure, and utility data were derived from the literature, which were assigned to model variables. The primary outputs of the model included the lifetime costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). One-way and probability sensitivity analysis was conducted to assess the potential uncertainties of parameters. Results Of the five competing strategies, alogliptin 25 mg strategy yielded the most significant health outcome, which associated with improvements in discounted QALY of 0.007, 0.014, 0.011, and 0.022 versus linagliptin 5 mg, saxagliptin 5 mg, sitagliptin 100 mg and vildagliptin50 mg, respectively. The sitagliptin 100 mg strategy was the cheapest option. The ICER of alogliptin 25 mg against sitagliptin 100 mg strategy was $6,952 per additional QALY gained, and the rest of the strategies were dominated or extended dominated. The most influential parameters were the cost of DPP-4 inhibitors and their treatment efficacy. Conclusions These results suggested that alogliptin was a preferred treatment option compared with other DPP-4 inhibitors for Chinese patients whose T2DM are inadequately controlled on metformin monotherapy.

Novel Therapeutics for Diabetes: Uptake, Usage Trends, and Comparative Effectiveness

Article

Full-text available

Apr 2016
Curr Diabetes Rep

The number of available therapies for treating type 2 diabetes has grown considerably in recent years. This growth has been fueled by availability of newer medications, whose benefits and risks have not been fully established. In this study, we review and synthesize the existing literature on the uptake, efficacy, safety, and cost-effectiveness of novel antidiabetic agents. Specifically, we focus on three drug classes that were introduced in the market recently: thiazolidinediones (TZDs), dipeptidyl peptidase-4 (DPP-4) inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists. Not surprisingly, we find that the usage trends reflect the efficacy and safety profile of these novel drugs. The use of TZDs increased initially but decreased after a black-box warning was issued for rosiglitazone in 2007 that highlighted the cardiovascular risks associated with using the drug. Conversely, DPP-4 inhibitors and GLP-1 receptor agonists gained market shares due to their efficacy in glycemic control as an add-on treatment to metformin. DPP-4 inhibitors were the most commonly prescribed agents among the three novel drug classes, likely because they are relatively less expensive, have better safety profile, are administered orally, and are weight neutral. Sitagliptin was the most preferred DPP-4 inhibitor. The level of evidence on the comparative effectiveness, safety, and cost implications of using novel antidiabetic agents remains low and further studies with long-term follow-ups are needed.

Cost-Effectiveness of Pharmacist Care in Diabetes Management: A Systematic Review

Article

Full-text available

Nov 2023

In recent years, the role of pharmacists has undergone significant transformation to become more patient-centered and involved in managing chronic diseases. Nonetheless, it remains unclear whether pharmacist involvement in diabetes management is cost-effective. This study aimed to systematically review the cost-effectiveness and reporting quality in comprehensive economic evaluations of pharmacist management compared to standard care in diabetes. Eligible studies included cost-effectiveness analyses employing pharmacist professional services as the intervention for diabetes. A literature search was conducted in the bibliographic databases Pubmed, Scopus, China National Knowledge Infrastructure (CNKI), and the International Health Technology Assessment (HTA) database from their inception until July 2023. Two independent reviewers performed title, abstract, full-text screening, and data abstraction and assessed the quality of reporting and methodological approaches using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS 2022) checklists. Twelve studies were identified with an average research quality score of 19.8, including cost-utility (n = 5) and cost-effectiveness (n = 7) analyses, with only four studies rated as high quality. The efficacy data were derived from randomized controlled trials (n = 7), retrospective studies (n = 2), and published literature sources (n = 2). Half of the included studies were conducted in high-income countries, while the other half was in upper-middle and lower-middle-income countries, respectively. Despite significant variations in the cost of pharmacist intervention, consistent findings demonstrate that pharmacist involvement in diabetes management is more cost-effective or even cost-saving than standard care, primarily attributed to better glycemic control, enhanced patient compliance, and reduced risks of medication-related problems. This systematic review substantiates that pharmacist involvement in diabetes management is cost-effective compared with standard care. However, the overall quality of reporting needs to be improved, and high-quality evidence is urgently needed to support healthcare decision-making in pharmacy practice.

Cost-Effectiveness of Newer Antidiabetic Drugs as Second-Line Treatment for Type 2 Diabetes: A Systematic Review

Article

Full-text available

Jul 2023
ADV THER

Introduction: Evidence from cardiovascular outcome trials (CVOTs) for newer antidiabetic drugs is increasingly influencing revised recommendations for second-line therapy in type 2 diabetes (T2D). This systematic review aimed to compare the cost-effectiveness of newer antidiabetic drugs specified as sodium-glucose cotransporter 2 inhibitor (SGLT2i), glucagon-like peptide 1 receptor agonist (GLP-1RA), and dipeptidyl peptidase 4 inhibitor (DPP-4i) for T2D in a second-line setting. Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines, and all relevant published studies were searched comprehensively in electronic databases, including PubMed, Embase, Web of Science, and International Health Technology Assessment database published from April 2023. The quality of the included studies was evaluated using Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 reporting checklists. Results: We included 28 studies that met the inclusion criteria. Overall reporting of the identified studies largely met CHEERS 2022 recommendations. The CORE and Cardiff models were the most frequently utilized for pharmacoeconomic evaluation in T2D. Four studies consistently discovered that SGLT2i was more cost-effective than GLP-1RA in T2D who were not adequately controlled by metformin monotherapy. Four studies compared GLP-1RA with DPP-4i, sufonylurea (SU), or insulin. Except for one that demonstrated SU was cost-effective, all were GLP-1RA. Five studies revealed that SGLT2i was more cost-effective than DPP-4i or SU. Eleven studies indicated that DPP-4i was more cost-effective than traditional antidiabetic drugs. Four additional studies explored the cost-effectiveness of various antidiabetic drugs as second-line options, indicating that SU, SGLT2i, or meglitinides were more economically advantageous. The most common driven factors were the cost of new antidiabetic drugs. Conclusion: Newer antidiabetic drugs as second line are the cost-effective option for T2D from the cost-effectiveness perspective, especially SGLT2i.

Were economic evaluations well reported for the newly listed oncology drugs in China’s national reimbursement drug list

Article

Full-text available

Dec 2022
BMC HEALTH SERV RES

Purpose To assess the reporting quality of published economic evaluations of the negotiated oncology drugs listed for China’s 2020 National Reimbursement Drug List (NRDL). Methods A comprehensive search was conducted to identify economic evaluation studies of negotiated oncology drugs listed in China’s 2020 NRDL using the PubMed/MEDLINE, Embase, Web of Science, CNKI, SinoMed, and WanFang Database up to March 31, 2021. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist scored the reporting quality between 0 and 100. A linear regression analysis was employed to examine the influence of various characteristics on the reporting quality scores. Results Eighty papers were included in the study, with the majority published during the past decade. Furthermore, more than half of the articles (57.5%, or 46 out of 80) were written in English. The average CHEERS score was 74.63 ± 12.75 and ranged from 43.48 to 93.75. The most inadequately reported items included choice of model, characterization of heterogeneity, and discussion, as well as currency, price date and conversion. Higher scores were associated with articles published from 2019 to 2021 and English publications. Conclusion The economic evaluation studies of negotiated oncology drugs listed in 2020 NRDL had moderate reporting quality. The Chinese economic evaluation publications could improve the reporting quality if the CHEERS checklist is consistently implemented. Also, the Chinese journals maybe explore introducing a reporting standard for economic evaluations.

Does health economics research align with the disease burden in the Middle East and North Africa region? A systematic review of economic evaluation studies on public health interventions

Article

Full-text available

Jul 2022

Abstract Introduction: Economic evaluation studies demonstrate the value of money in health interventions and enhance the efficiency of the healthcare system. Therefore, this study reviews published economic evaluation studies of public health interventions from 26 Middle East and North Africa (MENA) countries and examines whether they addressed the region’s major health problems. Methods: PubMed and Scopus were utilized to search for relevant articles published up to June 26, 2021. The reviewers independently selected studies, extracted data, and assessed the quality of studies using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Results: The search identified 61 studies. Approximately half (28 studies; 46%) were conducted in Israel and Iran. The main areas of interest for economic evaluation studies were infectious diseases (21 studies; 34%), cancers (13 studies; 21%), and genetic disorders (nine studies; 15%). Five (8%), 39 (64%), 16 (26%), and one (2%) studies were classified as excellent, high, average, and poor quality, respectively. The mean of CHEERS checklist items reported was 80.8% (SD 14%). Reporting the structure and justification of the selected model was missed in 21 studies (37%), while price and conversion rates and the analytical methods were missed in 21 studies (34%). Conclusions: The quantity of economic evaluation studies on public health interventions in the MENA region remains low; however, the overall quality is high to excellent. There were obvious geographic gaps across countries regarding the number and quality of studies and gaps within countries concerning disease prioritization. The observed research output, however, did not reflect current and upcoming disease burden and risk factors trends in the MENA region. Keywords: Cost-effectiveness, Economic evaluation, Middle East, North Africa, Public health

Safety of dipeptidyl peptidase-4 inhibitors in older adults with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials

Article

Full-text available

Jan 2022

Registration PROSPERO: CRD42020210645 Introduction We aimed to assess the safety of dipeptidyl peptidase-4 (DPP-4) inhibitors in older patients with type 2 diabetes with inadequate glycaemic control. Methods We included randomized controlled trials (RCTs) in older (⩾65 years) patients with type 2 diabetes. The intervention group was randomized to treatment with any DPP-4 inhibitors. A systematic search in MEDLINE and Embase was performed in December 2020. For assessing the risk of bias, RoB 2 tool was applied. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. We pooled outcomes using random effects meta-analyses. Results We identified 16 RCTs that included 19,317 patients with a mean age of greater than 70 years. The mean HbA1c level ranged between 7.1 and 10.0 g/dl. Adding DPP-4 inhibitors to standard care alone may increase mortality slightly [risk ratio (RR) 1.04; 95% confidence interval (CI) 0.89–1.21]. Adding DPP-4 inhibitors to standard care increases the risk for hypoglycaemia (RR 1.08; 95% CI 1.01–1.16), but difference in overall adverse events is negligible. DPP-4 inhibitors added to standard care may reduce mortality compared with sulfonylureas (RR 0.88; 95% CI 0.75–1.04). DPP-4 inhibitors probably reduce the risk for hypoglycaemia compared with sulfonylureas (magnitude of effect not quantifiable because of heterogeneity) but difference in overall adverse events is negligible. There is insufficient evidence on hospitalizations, falls, fractures, renal impairment and pancreatitis. Conclusion There is no evidence that DPP-4 inhibitors in addition to standard care decrease mortality but DPP-4 inhibitors increase hypoglycaemia risk. Second-line therapy in older patients should be considered cautiously even in drugs with a good safety profile such as DPP-4 inhibitors. In case second-line treatment is necessary, DPP-4 inhibitors appear to be preferable to sulfonylureas. Plain language summary Safety of dipeptidyl peptidase-4 inhibitors in older adults with type 2 diabetes Introduction: We performed the review to assess the safety of dipeptidyl peptidase-4 (DPP-4) inhibitors in older type 2 diabetes patients with blood sugar outside the normal level. Methods: To answer the question, we searched various electronic databases. We included studies in older (⩾65 years) patients with type 2 diabetes that assessed the safety of DPP-4 inhibitors. The data from the different studies were quantitatively summarized using statistical methods. We assessed the quality of the data to judge the certainty of the findings. Results: We identified 16 studies that included 19,317 patients with a mean age greater than 70 years. The average blood sugar level of patients in the included studies was slightly or moderately increased. Adding DPP-4 inhibitors to standard care alone may increase mortality slightly. Adding DPP-4 inhibitors to standard care increases the risk for hypoglycaemia, but difference in overall adverse events is negligible. DPP-4 inhibitors added to standard care may reduce mortality compared with sulfonylureas. DPP-4s probably reduce the risk of hypoglycaemia compared with sulfonylureas (magnitude of effect not quantifiable because of heterogeneity) but difference in overall adverse events is negligible. There is insufficient evidence on hospitalizations, falls, fractures, renal impairment and pancreatitis. Conclusion: There is no evidence that DPP-4 inhibitors in addition to standard care decrease mortality but DPP-4 inhibitors increase the risk that blood sugar falls below normal. Adding DPP-4 inhibitorss to standard care in older patients should be considered cautiously even in drugs with a good safety profile such as DPP-4 inhibitors. In case additional treatment is necessary, DPP-4 inhibitors appear to be preferable to sulfonylureas.

A Systematic Review on Economic Evaluation Studies of Diagnostic and Therapeutic Interventions in the Middle East and North Africa

Article

Full-text available

Dec 2021
Appl Health Econ Health Pol

Pramitha Esha Nirmala Dewi

Introduction Due to the increase in healthcare budget constraint, economic evaluation (EE) evidence is increasingly required to inform resource allocation decisions. This study aimed to systematically review quantity, characteristics, and quality of full EE studies on diagnostic and therapeutic interventions conducted in 26 Middle East and North Africa (MENA) countries. Methods PubMed and Scopus databases were comprehensively searched to identify the published EE studies in the MENA region. The quality of reviewed studies was evaluated using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Results The search identified 69 studies. The cost-utility approach was adopted in 49 studies (71 %). More than half (38 studies; 55 %) were conducted in Iran and Turkey. Sixteen countries (62 %) did not have any EE studies. The most frequently analyzed therapeutic areas were infectious diseases (19 studies; 28 %), cardiovascular diseases (11 studies; 16 %), and malignancies (10 studies; 14 %). Ten studies (14 %), 46 (67 %), 12 (17 %), and 1 study (1 %) were classified as excellent, high, moderate, and poor quality, respectively. The mean of items reported was 85.10 % (standard deviation 13.32 %). Characterizing heterogeneity, measurement of effectiveness, time horizon, and discount rate were missed in 21 (60 %), 22 (32 %), 20 (29 %) and 15 (25 %) studies, respectively. Data on effectiveness and utility relied primarily on studies conducted outside the region. Conclusions The quantity of EE studies in the MENA region remains low; however, overall quality is high to excellent. The availability of local data, capacity building, and national guidelines are vital to improve both the quantity and quality of EE studies in the region

Cost-Effectiveness of Aprepitant in Preventing Chemotherapy-Induced Nausea and Vomiting: A Systematic Review of Published Articles

Article

Full-text available

Aug 2021

Objectives: The aim of this systematic review is to assess the published cost-effectiveness analyses of aprepitant for patients with chemotherapy-induced nausea and vomiting (CINV). Methods: A systematic literature search was performed on PubMed, EMbase, the Cochrane Library, CNKI, WANFANG DATA, and CBM database. The date of publication is up to January 2019. Two reviewers independently reviewed titles, abstracts, and articles sequentially to select studies for data abstraction based on the inclusion and exclusion criteria. Disagreements were resolved and reviewers reached a consensus. The quality of the included studies was assessed according to the 24-item checklist of the consolidated health economic evaluation reporting standards (CHEERS). The costs reported by the included studies were converted to US dollars via purchasing power parities (PPP) in the year 2019 using the CCEMG–EPPI–Certer Cost Converter. Results: Thirteen articles were included based on the inclusion criteria for cost-effectiveness analysis and cost-utility analysis. Twelve studies were rated as good quality and one as a moderate quality based on the CHEERS checklist. Eight studies compared aprepitant plus 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA) and dexamethasone with the standard regimen (5-HT3RA and dexamethasone). It was concluded that aprepitant plus standard regimen was a cost-effective strategy for preventing CINV. Only one study that compared aprepitant plus 5-HT3RA with 5-HT3RA, concluded that the addition of aprepitant reduced the incidence of severe nausea, and it might also provide an economic benefit in the overall management. Four studies that compared aprepitant with other antiemetic drugs concluded that aprepitant is a cost-effective strategy for preventing CINV compared with metoclopramide. However, netupitan + palonosetron and olanzapine are cost-effective compared with aprepitant. Conclusion: This study is the first systematic evaluation of adding aprepitant to standard regimens for patients with CINV. Most economic evaluations of antiemetic medications are reported to be of good quality. Adding aprepitant to standard regimens is found to be a cost-effective strategy for preventing CINV.

Health utility of type 2 diabetes patients using basal insulin in China: results from the BEYOND II study

Article

Full-text available

Oct 2020

Objective To derive the health utility scores of type 2 diabetes (T2D) patients using basal insulin (BI) with diverse characteristics in China.Methods The study used the data of insulin-using T2D patients on BI treatment enrolled in the BEYOND II study, which is a multi-center, observational study from 78 hospitals nationwide. The 3-level EQ-5D (EQ-5D-3L) questionnaire was administered to each patient to derive their health utility scores using the EQ-5D-3L value set for China. Patients’ clinical and sociodemographic information were retrieved from their electronic case report form (eCRF). Ordinary least-square models with different specifications were explored to identify the best-fitting model to predict the utility scores.ResultsThe sample (n = 12,583) achieved a mean (standard deviation) EQ-5D-3L utility score of 0.936 (0.120). According to the model, a Chinese male who was younger than 59 years, not underweight, diagnosed with T2D shorter than 10 years, with controlled plasma glucose and free of diabetes complications/comorbidities, would have a mean utility of 0.993. Being female, older age, underweight, and higher plasma glucose, longer diabetes duration was negatively related to EQ-5D-3L scores. Comorbidities and seven of eleven complications were associated with utility decrement. Interactions between some complications were also discovered.Conclusions The derived health utility scores for diabetes complications could facilitate the assessment of the cost-effectiveness of health interventions for Chinese insulin-using T2D patients.

Glucagon-like peptide 1 agonists for treatment of patients with type 2 diabetes who fail metformin monotherapy: Systematic review and meta-analysis of economic evaluation studies

Article

Full-text available

Jul 2020

Objectives To conduct a systematic review and meta-analysis and to pool the incremental net benefits (INBs) of glucagon-like peptide 1 (GLP1) compared with other therapies in type 2 diabetes mellitus (T2DM) after metformin monotherapy failure. Research design and methods The study design is a systematic review and meta-analysis. We searched MEDLINE (via PubMed), Scopus and Tufts Registry for eligible cost–utility studies up to June 2018, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. We conducted a systematic review and pooled the INBs of GLP1s compared with other therapies in T2DM after metformin monotherapy failure. Various monetary units were converted to purchasing power parity, adjusted to 2017 US$. The INBs were calculated and then pooled across studies, stratified by level of country income; a random-effects model was used if heterogeneity was present, and a fixed-effects model if it was absent. Heterogeneity was assessed using Q test and I ² statistic. Results A total of 56 studies were eligible, mainly from high-income countries (HICs). The pooled INBs of GLP1s compared with dipeptidyl peptidase-4 inhibitor (DPP4i) (n=10), sulfonylureas (n=6), thiazolidinedione (TZD) (n=3), and insulin (n=23) from HICs were US$4012.21 (95% CI US$−571.43 to US$8595.84, I ² =0%), US$3857.34 (95% CI US$−7293.93 to US$15 008.61, I ² =45.9%), US$37 577.74 (95% CI US$−649.02 to US$75 804.50, I ² =92.4%) and US$14 062.42 (95% CI US$8168.69 to US$19 956.15, I ² =86.4%), respectively. GLP1s were statistically significantly cost-effective compared with insulins, but not compared with DPP4i, sulfonylureas, and TZDs. Among GLP1s, liraglutide was more cost-effective compared with lixisenatide, but not compared with exenatide, with corresponding pooled INBs of US$4555.09 (95% CI US$3992.60 to US$5117.59, I ² =0) and US$728.46 (95% CI US$−1436.14 to US$2893.07, I ² =0), respectively. Conclusion GLP1 agonists are a cost-effective choice compared with insulins, but not compared with DPP4i, sulfonylureas and TZDs. PROSPERO registration number CRD42018105193.

Systematic evidence of health economic evaluation of drugs for postmenopausal osteoporosis: A quality appraisal

Article

Full-text available

Jun 2020

This paper systematically and critically reviewed all published economic evaluations of drugs for the treatment postmenopausal osteoporosis. A systematic search was conducted using relevant databases for economic evaluations to include all relevant English articles published between January 2008 to January 2020. After extracting the key study characteristics, methods and outcomes, we evaluated each article using the Quality of Health Economic Studies (QHES) and the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) instruments. A total of 49 studies met the inclusion criteria. Majority of studies were funded by the industry and reported favorable cost-effectiveness. Based on the QHES total scores, studies (n = 35) were found to be industry-funded with higher QHES mean 82.44 ± 8.69 as compared with nonindustry funding studies (n = 11) with mean 72.22 ± 17.67. The overall mean QHES scores were found to be higher 79.06 ± 11.84, representing high quality (75–100) compared to CHEERS scores (%) 75.03 ± 11.21. The statistical pairwise comparison between CHEERS mean (75.03 ± 11.21) and QHES mean (79.06 ± 11.84) were not statistically significant (P = 0.10) whereas, QHES score showed higher means as compared to CHEERS. This study suggests the overall quality of the published literatures was relatively few high-quality health economic evaluation demonstrating the cost-effectiveness of drugs for postmenopausal osteoporosis, and the majority of the literature highlights that methodological shortcoming.

An Efficient and Practical Method for the Synthesis of Saxagliptin Intermediate 2-(3-Hydroxy-1-adamantane)-2-oxoacetic Acid and Its Optimization

Article

Full-text available

Oct 2019

A mild and relatively simple way for preparation of 2-(3-hydroxy-1-adamantane)-2-oxoacetic acid ( I ) was reported. It was prepared from 1-adamantanecarboxylic acid ( II ) via sulfuric acid/nitric acid to get 3-hydroxy-1-adamantanecarboxylic acid ( III ); treated with the one-pot method through acylation, condensation, and decarboxylation to obtain 3-hydroxy-1-acetyladamantane ( IV ); and finally oxidized by potassium permanganate (KMnO 4 ) to get the target compound ( I ). The overall yield was about 60%, which provides a new idea for commercial production of saxagliptin intermediate.

The Cost-Effectiveness of Digital Health Interventions on the Management of Cardiovascular Diseases: Systematic Review

Article

Full-text available

Jun 2019
J MED INTERNET RES

Background: With the advancement in information technology and mobile internet, digital health interventions (DHIs) are improving the care of cardiovascular diseases (CVDs). The impact of DHIs on cost-effective management of CVDs has been examined using the decision analytic model–based health technology assessment approach. Objective: The aim of this study was to perform a systematic review of the decision analytic model–based studies evaluating the cost-effectiveness of DHIs on the management of CVDs. Methods: A literature review was conducted in Medline, Embase, Cumulative Index to Nursing and Allied Health Literature Complete, PsycINFO, Scopus, Web of Science, Center for Review and Dissemination, and Institute for IEEE Xplore between 2001 and 2018. Studies were included if the following criteria were met: (1) English articles, (2) DHIs that promoted or delivered clinical interventions and had an impact on patients’ cardiovascular conditions, (3) studies that were modeling works with health economic outcomes of DHIs for CVDs, (4) studies that had a comparative group for assessment, and (5) full economic evaluations including a cost-effectiveness analysis, cost-utility analysis, cost-benefit analysis, and cost-consequence analysis. The primary outcome collected was the cost-effectiveness of the DHIs, presented by incremental cost per additional quality-adjusted life year (QALY). The quality of each included study was evaluated using the Consolidated Health Economic Evaluation Reporting Standards. Results: A total of 14 studies met the defined criteria and were included in the review. Among the included studies, heart failure (7/14, 50%) and stroke (4/14, 29%) were two of the most frequent CVDs that were managed by DHIs. A total of 9 (64%) studies were published between 2015 and 2018 and 5 (36%) published between 2011 and 2014. The time horizon was ≤1 year in 3 studies (21%), >1 year in 10 studies (71%), and 1 study (7%) did not declare the time frame. The types of devices or technologies used to deliver the health interventions were short message service (1/14, 7%), telephone support (1/14, 7%), mobile app (1/14, 7%), video conferencing system (5/14, 36%), digital transmission of physiologic data (telemonitoring; 5/14, 36%), and wearable medical device (1/14, 7%). The DHIs gained higher QALYs with cost saving in 43% (6/14) of studies and gained QALYs at a higher cost at acceptable incremental cost-effectiveness ratio (ICER) in 57% (8/14) of studies. The studies were classified as excellent (0/14, 0%), good (9/14, 64%), moderate (4/14, 29%), and low (1/14, 7%) quality. Conclusions: This study is the first systematic review of decision analytic model–based cost-effectiveness analyses of DHIs in the management of CVDs. Most of the identified studies were published recently, and the majority of the studies were good quality cost-effectiveness analyses with an adequate duration of time frame. All the included studies found the DHIs to be cost-effective.

Cost Effectiveness of Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors, Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists, and Dipeptidyl Peptidase-4 (DPP-4) Inhibitors: A Systematic Review

Article

Mar 2019

Objective This study aimed to systematically review cost-effectiveness studies of newer antidiabetic medications. Methods The PubMed/MEDLINE, EMBASE, CINAHL Plus, Cochrane Library–NHS Economic Evaluation Database (Wiley), Cochrane Library–Health Technology Assessment Database (Wiley), Cochrane Library–Database of Abstracts of Reviews of Effects (Wiley), and the Cost-Effectiveness Analysis Registry databases (from 1 January 2000 to 1 June 2018) were searched. The search strategies included the Medical Subject Heading (MeSH) term ‘economics’, and the MeSH entry terms ‘cost’, ‘cost effectiveness’, ‘value’, and ‘cost utility’, as well as all names for GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT2 inhibitors. Inclusion criteria included (1) cost-effectiveness studies of the newer antidiabetic medications, including sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and dipeptidyl peptidase-4 (DPP-4) inhibitors; and (2) full-text publications in English. Two reviewers independently screened the titles, abstracts, and full-text articles to select studies for data extraction. Discrepancies were resolved by discussion and consensus. The quality of reporting cost-effectiveness analyses was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) guideline. Results Among 85 studies selected, 82 clearly stated the types of diabetes model used (e.g. CORE model), and 70 studied used validated diabetes models. Seventy-four (87%) studies were funded by pharmaceutical companies, and 72 (85%) studies were conducted from a payer’s perspective. Seventy-six (89%) studies presented were of good quality (20–24 CHEERS items), and nine were of moderate quality (14–19 items). Thirty studies compared newer antidiabetic medications with insulin, 3 studies compared newer antidiabetic medications with thiazolidinediones (TZDs), 15 studies compared newer antidiabetic medications with sulfonylureas, 40 studies compared new antidiabetic medications with alternative newer antidiabetic medication, and 9 studies compared other antidiabetic agents that were not included above. Newer antidiabetic medications were reported to be cost-effective in 26 of 30 (87%) studies compared with insulin, and 13 of 15 (87%) studies compared with sulfonylureas. Conclusions Most economic evaluations of antidiabetic medications have good reporting quality and use validated diabetes models. The newer antidiabetic medications in most of the reviewed studies were found to be cost effective, compared with insulin, TZDs, and sulfonylureas.

Adjuvant breast radiotherapy: How to trade-off cost and effectiveness?

Article

Nov 2017
RADIOTHER ONCOL

Introduction: A series of health economic evaluations (HEE) has analysed the efficiency of new fractionation schedules and techniques for adjuvant breast radiotherapy. This overview assembles the available evidence and evaluates to what extent HEE-results can be compared. Methods: Based on a systematic literature review of HEEs from 1/1/2000 to 30/10/2016, all cost comparison (CC) and cost-effectiveness analyses (CEA) comparing different adjuvant breast radiotherapy approaches were analysed. Costs were extracted and converted to Euro 2016 and costs per QALY were summarized in cost-effectiveness planes. Results: Twenty-four publications are withheld, comparing different fractionation schedules and/or irradiation techniques or evaluating the value of adding radiotherapy. Normofractionation and intensity-modulated, interstitial or intraluminal techniques are important cost-drivers. Highest reimbursements are observed in the US, but may overestimate the real cost. Hypofractionation is cost-effective compared to normofractionation, the results of partial breast irradiation are less unequivocal. Intra-operative and external beam approaches seem the most cost-effective for favourable risk groups, but whole breast irradiation is superior in terms of health effect and omission of radiotherapy in terms of costs. Conclusion: Hypofractionation may be considered the most relevant comparator for new strategies in adjuvant breast radiotherapy, with omission of radiotherapy as an interesting alternative in the very favourable subcategories, especially for partial breast techniques. Although comparison of CC and CEA is hampered by the variability in clinical and economic settings, HEE-based evidence can guide decision-making to tailor-made strategies, allocating the optimal treatment in terms of effectiveness as well as efficiency to the right indication.

A systematic review of health economic evaluation in adjuvant breast radiotherapy: Quality counted by numbers

Article

Sep 2017
RADIOTHER ONCOL

Background: Evolving practice in adjuvant breast radiotherapy inevitably impacts healthcare budgets. This is reflected in a rise of health economic evaluations (HEE) in this domain. The available HEE literature was analysed qualitatively and quantitatively, using available instruments. Methods: HEEs published between 1/1/2000 and 31/10/2016 were retrieved through a systematic search in Medline, Cochrane and Embase. A quality-assessment using CHEERS (Consolidated Health Economic Evaluation Reporting Standards) was translated into a quantitative score and compared with Tufts Medical Centre CEA registry and Quality of Health Economic Studies (QHES) results. Results: Twenty cost-effectiveness analyses (CEA) and thirteen cost comparisons (CC) were analysed. In qualitative evaluation, valuation or justification of data sources, population heterogeneity and discussion on generalizability, in addition to declaration on funding, were often absent or incomplete. After quantification, the average CHEERS-scores were 74% (CI 66.9-81.1%) and 75.6% (CI 70.7-80.5%) for CEAs and CCs respectively. CEA-scores did not differ significantly from Tufts and QHES-scores. Conclusion: Quantitative CHEERS evaluation is feasible and yields comparable results to validated instruments. HEE in adjuvant breast radiotherapy is of acceptable quality, however, further efforts are needed to improve comprehensive reporting of all data, indispensable for assessing relevance, reliability and generalizability of results.

Cost-effectiveness analysis of different dipeptidyl-peptidase 4 inhibitor drugs for treatment of type 2 diabetes mellitus

Article

Jul 2017

Introduction: Type 2 diabetes mellitus (T2DM) has burdened health systems in the world to the value of 500 billion dollars/year. Dipeptidyl peptidase 4 inhibitors (DPP-4 Inhibitors) have been strongly associated with spending on the treatment of T2DM by the courts in Brazil. The aim of this study was to estimate the most cost-effective DPP-4 Inhibitor for T2DM treatment. A pharmacoeconomic study of cost-effectiveness was performed in a medium-sized municipality in Minas Gerais state, Brazil. Methods: The data are from legalization in municipal health in 2013. The effectiveness of DPP-4 Inhibitors was measured by the reduction in glycated hemoglobin (A1c). The direct medical costs of drug and adverse drug reactions were identified. With these data, a cost-effectiveness ratio (CER) and construction of the decision tree for sensitivity analysis were performed. Results: The representative of the most effective in reducing A1c gliptins was sitagliptin in combination with metformin, it was able to reduce A1c by 1.16% (1.09 to 1.22, CI 95%). The drug with the lowest cost was linagliptin, with a cost per patient/year of US$ 481.42. Sensitivity analysis performed by the decision tree shows that sitagliptin in association with metformin had the CER of US$ 1,506.75 per patient/year, to reduce A1c by 1%. Conclusion: The most cost-effective DPP-4 Inhibitor was sitagliptin with metformin.

Cost-effectiveness analysis of vaccinations and decision makings on vaccination programmes in Hong Kong: A systematic review

Article

Full-text available

May 2017
VACCINE

Objectives: To describe and systematically review the modelling and reporting of cost-effectiveness analysis of vaccination in Hong Kong, and to identify areas for quality enhancement in future cost-effectiveness analyses. Methods: We conducted a comprehensive and systematic review of cost-effectiveness studies related to vaccination and government immunisation programmes in Hong Kong published from 1990 to 2015, through database search of Pubmed, Web of Science, Embase, and OVID Medline. Methodological quality of selected studies was assessed using Consolidated Health Economic Evaluation Reporting Standards checklist (CHEERS). Decision making of vaccination was obtained from Scientific Committee on Vaccine Preventable Diseases (SCVPD) and Department of Health in Hong Kong. Results: Nine eligible studies reporting twelve comparative cost-effectiveness comparisons of vaccination programme for influenza (n = 2), pneumococcal disease (n = 3), influenza plus pneumococcal disease (n = 1), chickenpox (n = 2), Haemophilus influenzae b (n = 1), hepatitis A (n = 1), cervical cancer (n = 1) and rotavirus (n = 1) were identified. Ten comparisons (83.3%) calculated the incremental cost-effectiveness ratio (ICER) of a vaccination strategy versus status quo as outcomes in terms of cost in USD per life-years, cost per quality-adjusted life-years, or cost per disability-adjusted life-years. Among those 10 comparisons in base-case scenario, 4 evaluated interventions were cost-saving relative to status quo while the ICER estimates in 3 of the 6 remaining comparisons were far below commonly accepted threshold and WHO willingness-to-pay threshold, suggestive of very cost-effective. Seven studies were of good quality based on the CHEERS checklist; one was of moderate quality; and one was of excellent quality. The common methodological problems were characterisation of heterogeneity and reporting of study parameters. Conclusions: There was a paucity of cost-effectiveness models evaluating vaccination targeted to the Hong Kong population. All evaluated vaccinations and immunisation interventions in Hong Kong, except for Haemophilus influenzae b, hepatitis A and HPV vaccinations, were considered either cost-saving or very cost-effective when compared to status quo.

Adherence, Persistence, and Health Care Costs for Patients Receiving Dipeptidyl Peptidase-4 Inhibitors

Article

Mar 2017

Background: The dipeptidyl peptidase-4 (DPP-4) inhibitors are among the newer, yet more established, classes of diabetes medications. Objective: To compare adherence, persistence, and health care costs among patients taking DPP-4 inhibitors. Methods: Claims were extracted from Humana Medicare Advantage Prescription Drug (MAPD) or commercial plans for patients aged > 18 years with ≥ 1 prescription filled for a DPP-4 inhibitor between July 1, 2011, and March 31, 2013. The first prescription claim for a DPP-4 inhibitor established the index date and index medication; 12-month pre-index and post-index data were analyzed. The Diabetes Complications Severity Index (DCSI) was used to assess a level of baseline diabetes-related comorbidities. Adherence (proportion of days covered [PDC] ≥ 80%) and persistence (< 31-day gap) measures were compared before and after, adjusting for DCSI, pre-index insulin, age, and gender. Post-index costs (in 2013 U.S. dollars) were compared using general linear modeling (GLM) to adjust for pre-index costs, DCSI, pre-index insulin, age, and gender. Results: Based on study criteria, 22,860 patients with MAPD coverage (17,292 sitagliptin, 4,282 saxagliptin, and 1,286 linagliptin) and 3,229 patients with commercial coverage (2,368 sitagliptin, 643 saxagliptin, and 218 linagliptin) were included. For MAPD patients, the mean age was 70-72 years, and females represented 50%-52% of patients. For commercial patients, mean age was 55-56 years, and females represented 44% of patients. Clinical indicators for patients on linagliptin showed a higher comorbidity level than sitagliptin or saxagliptin cohorts (MAPD DCSI 3.0 vs 2.4 and 2.2, P < 0.001; commercial DCSI 1.2 vs. 0.9 and 0.9, P < 0.001); a higher use of pre-index insulin (MAPD 22% vs. 15% and 14%, P < 0.001; commercial 18% vs. 11% and 10%, P = 0.003); and higher mean pre-index costs (MAPD $14,448 vs. $11,818 and $10,399, P < 0.001; commercial $13,868 vs. $9,357 and $8,223, P = 0.016). For the MAPD cohort, the unadjusted PDC was lower for linagliptin patients (67%) compared with saxagliptin (72%) or sitagliptin (72%) patients (P < 0.001). Significant differences were still seen when adjusted for covariates. Linagliptin patients were more likely to be nonpersistent (73%) than those on saxagliptin (65%) or sitagliptin (67%; P < 0.01 for adjusted and unadjusted comparisons). For the commercial population, there were no significant differences in mean PDC between the 3 groups (linagliptin 70%, saxagliptin 72%, and sitagliptin 74%; P = 0.096). Dichotomized comparisons of nonpersistence were significantly different (linagliptin 65%, saxagliptin 62%, and sitagliptin 57%; P = 0.010), although upon adjustment using a Cox proportional hazard model, no significant differences were found. When controlling for other factors, post-index adjusted health care costs were similar between the medication cohorts (MAPD: sitagliptin = $13,913, saxagliptin = $13,651, and linagliptin = $13,859; commercial: sitagliptin = $11,677, saxagliptin = $12,059, and linagliptin = $11,163; all P > 0.25). Conclusions: For MAPD and commercial populations, baseline patient demographics were similar between the 3 DPP-4 inhibitor groups, but the linagliptin group may have had more complex patients (higher pre-index costs, higher DCSI, and more use of insulin). For the MAPD population, patients on linagliptin were less adherent and persistent than patients taking sitagliptin or saxagliptin for all unadjusted and adjusted comparisons. For the commercial population, which was notably smaller, these differences were in the same direction, but not all were statistically significant. When controlling for baseline factors, 12-month post-index direct medical health care costs were similar between index DPP-4 inhibitors. Disclosures: No external funding was provided for this research. The project was done as part of internal work by Humana employees. Rascati received no compensation. None of the authors have any financial disclosures or conflicts of interests to report. Worley and Everhart are employees of Comprehensive Health Insights, a subsidiary of Humana, and Meah is an employee of Humana. Discussion of the adherence and persistence data was presented as a poster at the Academy of Managed Care Pharmacy Nexus Conference, October 2015. Cost data were presented as a poster at the International Society for Pharmacoeconomics and Outcomes Research 18th Annual European Congress, November 2015. Study concept and design were contributed by Rascati, Worley, and Meah, along with Everhart. Rascati took the lead in data collection, assisted by Meah, and data interpretation was performed by all the authors. The manuscript was written primarily by Rascati, along with Worley, Everhart, and Meah, and revised by Rascati, Everhart, and Worley, with assistance from Meah.

Cost-effectiveness of vildagliptin for people with Type 2 Diabetes Mellitus in Brazil; findings and implications

Article

Feb 2017

Introduction: Vildagliptin is an inhibitor of the enzyme dipeptidyl peptidase 4, indicated for the treatment of type 2 diabetes mellitus, combined or not with metformin. This study aims to evaluate the cost-effectiveness of vildagliptin in the Brazilian context. Areas covered: Using MEDLINE, Cochrane Library, Lilacs and CRD, six studies were selected for the economic models. This study utilised cost data in the Brazilian health system to provide the context. Expert commentary: Type 2 diabetes mellitus is an epidemic disease and represents a challenge for all health care systems. Although guidelines clearly define first-line treatment, there are several other promising treatments. Vildagliptin is one of them, resulting in a mean lifetime increase of 0.31 years compared to metformin alone and 1.19 more life years compared to other metformin combinations. Considering observational data, life years with dual vildagliptin-containing treatments were 0.37 more compared to other dual treatments. However, its high cost versus generic metformin and its unclear safety profile weakens its subsequent cost-effectiveness. Consequently, the incorporation of vildagliptin or its combination with metformin is currently not recommended for the Brazilian Health Care System. This may change as more data becomes available.

The Cost-Effectiveness of Alogliptin Versus Sulfonylurea as Add-on Therapy to Metformin in Patients with Uncontrolled Type 2 Diabetes Mellitus

Article

Full-text available

Oct 2016

Introduction: ENDURE (ClinicalTrials.gov identifier, NCT00856284), a multicenter, double-blind, active-controlled study of 2639 patients with uncontrolled type 2 diabetes mellitus (T2DM), found that metformin in combination with alogliptin (12.5 and 25 mg doses), when compared to standard add-on therapy (sulfonylurea, SU), exerted sustained antihyperglycemic effects over 2 years. This economic analysis of ENDURE aimed to quantify the relationship between increased glycemic durability and cost-effectiveness of alogliptin in the UK clinical setting, and communicate its sustained glycemic benefit in economic terms. Methods: Using baseline characteristics and treatment effects from the ENDURE trial population, between-group cost-effectiveness analyses compared the combined use of metformin and alogliptin (MET + ALO12.5/25) in patients with inadequately controlled T2DM, as an alternative to metformin and SU (MET + SU). In scenario analyses, an intragroup cost-effectiveness analysis compared MET + ALO12.5/25 with MET + SU; a between-group cost-effectiveness analysis also compared MET + ALO12.5/25 versus MET + SU within a subpopulation of patients who achieved HbA1c control (<7.5%) at 2 years on study drug. Results: Compared with baseline profiles of patients, combination therapies with alogliptin or SU were associated with improvements in length and quality of life and were cost-effective at established norms. Despite increased drug acquisition costs, alogliptin at 12.5 mg and 25 mg doses resulted in greater predicted lifetime quality-adjusted life year (QALY) gains with associated incremental cost-effectiveness ratios (ICERs) of £10,959/QALY and £7217/QALY compared to SU, respectively. Conclusion: The ENDURE trial and the present cost-effectiveness analysis found that the glycemic durability of alogliptin therapy was associated with improved long-term patient outcomes, QALY gains, and ICERs that were cost-effective when evaluated against standard threshold values. Alogliptin therefore represents a cost-effective treatment alternative to SU as add-on therapy to metformin in patients with poorly managed T2DM. Funding: Takeda Development Centre Europe Ltd.

Cost-effectiveness of dipeptidyl peptidase-4 inhibitor monotherapy in elderly type 2 diabetes patients in Thailand

Article

Full-text available

Sep 2016

Background The management of type 2 diabetes mellitus (T2DM) in elderly population poses many challenges. Dipeptidyl peptidase-4 (DPP-4) inhibitors show particular promise due to excellent tolerability profiles, low risk of hypoglycemia, and little effect on body weight. This study evaluated, from the health care system’s perspective, the long-term cost-effectiveness of DPP-4 inhibitor monotherapy vs metformin and sulfonylurea (SFU) monotherapy in Thai elderly T2DM patients. Methods The clinical efficacy was estimated from a systematic review and meta-analysis. Baseline cohort characteristics and cost parameters were obtained from published studies and hospital databases in Thailand. A validated IMS CORE Diabetes Model version 8.5 was used to project clinical and economic outcomes over a lifetime horizon using a 3% annual discount rate. Costs were expressed in 2014 Thai Baht (THB) (US dollar value). Incremental cost-effectiveness ratios were calculated. Base-case assumptions were assessed through several sensitivity analyses. Results For treating elderly T2DM patients, DPP-4 inhibitors were more expensive and less effective, ie, a dominated strategy, than the metformin monotherapy. Compared with SFU, treatment with DPP-4 inhibitors gained 0.031 more quality-adjusted life years (QALYs) at a total cost incurred over THB113,701 or US$3,449.67, resulting in an incremental cost-effectiveness ratio of THB3.63 million or US$110,133.50 per QALY. At the acceptable Thai ceiling threshold of THB160,000/QALY (US$4,854.37/QALY), DPP-4 inhibitors were not a cost-effective treatment. Conclusion DPP-4 inhibitor monotherapy is not a cost-effective treatment for elderly T2DM patients compared with metformin monotherapy and SFU monotherapy, given current resource constraints in Thailand.

Benefit of Early Add-on of Linagliptin to Insulin in Japanese Patients With Type 2 Diabetes Mellitus: Randomized-Controlled Open-Label Trial (TRUST2)

Article

Jan 2021

IntroductionThis trial was conducted to assess the long-term safety, efficacy, and benefit of early add-on of linagliptin to insulin in patients with type 2 diabetes mellitus (T2DM).Methods This trial enrolled 246 subjects. The subjects were randomized to the linagliptin group or the control group and were observed for 156 weeks. After week 16, subjects in the control group were also allowed to add linagliptin to evaluate the benefit of early add-on of linagliptin to insulin. The primary end point was a change in HbA1c from baseline to week 16. Secondary end points included fasting plasma glucose, daily insulin dose, and frequency of adverse events.ResultsHbA1c and fasting plasma glucose levels significantly decreased from baseline to week 16 in the linagliptin group compared with the control group. The significant improvement in HbA1c continued until week 52. The daily insulin dose significantly decreased in the linagliptin group compared with the control group. The frequency of hypoglycemia and adverse events was comparable in both groups.Conclusions Add-on of linagliptin to insulin was tolerated, improved glycemic control, and reduced the daily insulin dose. This study demonstrates the long-term safety, efficacy and benefit of early add-on of linagliptin to insulin in Japanese T2DM patients.

Quality of economic evaluations of ventricular assist devices: A systematic review

Article

Jun 2020

Objective Because of a lack of suitable heart donors, alternatives to transplantation are required. These alternatives can have high costs. The aim of this study was to perform a systematic review of cost-effectiveness studies of ventricular assist devices (VADs) and to assess the level of evidence of relevant studies. The purpose was not to present economic findings. Methods A systematic review was performed using four electronic databases to identify health economic evaluation studies dealing with VADs. The methodological quality and reporting quality of the studies was assessed using three different tools, the Drummond, Cooper, and CHEERS (Consolidated Health Economic Evaluation Reporting Standards) checklists. Results Of the 1,258 publications identified, thirteen articles were included in this review. Twelve studies were cost–utility analyses and one was a cost-effectiveness analysis. According to the Cooper hierarchy scale, the quality of the data used was heterogeneous. The level of evidence used for clinical effect sizes, safety data, and baseline clinical data was of poor quality. In contrast, cost data were of high quality in most studies. Quality of reporting varied between studies, with an average score of 17.4 (range 15–19) according to the CHEERS checklist. Conclusion The current study shows that the quality of clinical data used in economic evaluations of VADs is rather poor in general. This is a concern that deserves greater attention in the process of health technology assessment of medical devices.

Metformin and second- or third-generation sulphonylurea combination therapy for adults with type 2 diabetes mellitus

Article

Apr 2019

Background: The number of people with type 2 diabetes mellitus (T2DM) is increasing worldwide. The combination of metformin and sulphonylurea (M+S) is a widely used treatment. Whether M+S shows better or worse effects in comparison with other antidiabetic medications for people with T2DM is still controversial. Objectives: To assess the effects of metformin and sulphonylurea (second- or third-generation) combination therapy for adults with type 2 diabetes mellitus. Search methods: We updated the search of a recent systematic review from the Agency for Healthcare Research and Quality (AHRQ). The updated search included CENTRAL, MEDLINE, Embase, ClinicalTrials.gov and WHO ICTRP. The date of the last search was March 2018. We searched manufacturers' websites and reference lists of included trials, systematic reviews, meta-analyses and health technology assessment reports. We asked investigators of the included trials for information about additional trials. Selection criteria: We included randomised controlled trials (RCTs) randomising participants 18 years old or more with T2DM to M+S compared with metformin plus another glucose-lowering intervention or metformin monotherapy with a treatment duration of 52 weeks or more. Data collection and analysis: Two review authors read all abstracts and full-text articles and records, assessed risk of bias and extracted outcome data independently. We used a random-effects model to perform meta-analysis, and calculated risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs) for effect estimates. We assessed the certainty of the evidence using the GRADE instrument. Main results: We included 32 RCTs randomising 28,746 people. Treatment duration ranged between one to four years. We judged none of these trials as low risk of bias for all 'Risk of bias' domains. Most important events per person were all-cause and cardiovascular mortality, serious adverse events (SAE), non-fatal stroke (NFS), non-fatal myocardial infarction (MI) and microvascular complications. Most important comparisons were as follows:Five trials compared M+S (N = 1194) with metformin plus a glucagon-like peptide 1 analogue (N = 1675): all-cause mortality was 11/1057 (1%) versus 11/1537 (0.7%), risk ratio (RR) 1.15 (95% confidence interval (CI) 0.49 to 2.67); 3 trials; 2594 participants; low-certainty evidence; cardiovascular mortality 1/307 (0.3%) versus 1/302 (0.3%), low-certainty evidence; serious adverse events (SAE) 128/1057 (12.1%) versus 194/1537 (12.6%), RR 0.90 (95% CI 0.73 to 1.11); 3 trials; 2594 participants; very low-certainty evidence; non-fatal myocardial infarction (MI) 2/549 (0.4%) versus 6/1026 (0.6%), RR 0.57 (95% CI 0.12 to 2.82); 2 trials; 1575 participants; very low-certainty evidence.Nine trials compared M+S (N = 5414) with metformin plus a dipeptidyl-peptidase 4 inhibitor (N = 6346): all-cause mortality was 33/5387 (0.6%) versus 26/6307 (0.4%), RR 1.32 (95% CI 0.76 to 2.28); 9 trials; 11,694 participants; low-certainty evidence; cardiovascular mortality 11/2989 (0.4%) versus 9/3885 (0.2%), RR 1.54 (95% CI 0.63 to 3.79); 6 trials; 6874 participants; low-certainty evidence; SAE 735/5387 (13.6%) versus 779/6307 (12.4%), RR 1.07 (95% CI 0.97 to 1.18); 9 trials; 11,694 participants; very low-certainty evidence; NFS 14/2098 (0.7%) versus 8/2995 (0.3%), RR 2.21 (95% CI 0.74 to 6.58); 4 trials; 5093 participants; very low-certainty evidence; non-fatal MI 15/2989 (0.5%) versus 13/3885 (0.3%), RR 1.45 (95% CI 0.69 to 3.07); 6 trials; 6874 participants; very low-certainty evidence; one trial in 64 participants reported no microvascular complications were observed (very low-certainty evidence).Eleven trials compared M+S (N = 3626) with metformin plus a thiazolidinedione (N = 3685): all-cause mortality was 123/3300 (3.7%) versus 114/3354 (3.4%), RR 1.09 (95% CI 0.85 to 1.40); 6 trials; 6654 participants; low-certainty evidence; cardiovascular mortality 37/2946 (1.3%) versus 41/2994 (1.4%), RR 0.78 (95% CI 0.36 to 1.67); 4 trials; 5940 participants; low-certainty evidence; SAE 666/3300 (20.2%) versus 671/3354 (20%), RR 1.01 (95% CI 0.93 to 1.11); 6 trials; 6654 participants; very low-certainty evidence; NFS 20/1540 (1.3%) versus 16/1583 (1%), RR 1.29 (95% CI 0.67 to 2.47); P = 0.45; 2 trials; 3123 participants; very low-certainty evidence; non-fatal MI 25/1841 (1.4%) versus 21/1877 (1.1%), RR 1.21 (95% CI 0.68 to 2.14); P = 0.51; 3 trials; 3718 participants; very low-certainty evidence; three trials (3123 participants) reported no microvascular complications (very low-certainty evidence).Three trials compared M+S (N = 462) with metformin plus a glinide (N = 476): one person died in each intervention group (3 trials; 874 participants; low-certainty evidence); no cardiovascular mortality (2 trials; 446 participants; low-certainty evidence); SAE 34/424 (8%) versus 27/450 (6%), RR 1.68 (95% CI 0.54 to 5.21); P = 0.37; 3 trials; 874 participants; low-certainty evidence; no NFS (1 trial; 233 participants; very low-certainty evidence); non-fatal MI 2/215 (0.9%) participants in the M+S group; 2 trials; 446 participants; low-certainty evidence; no microvascular complications (1 trial; 233 participants; low-certainty evidence).Four trials compared M+S (N = 2109) with metformin plus a sodium-glucose co-transporter 2 inhibitor (N = 3032): all-cause mortality was 13/2107 (0.6%) versus 19/3027 (0.6%), RR 0.96 (95% CI 0.44 to 2.09); 4 trials; 5134 participants; very low-certainty evidence; cardiovascular mortality 4/1327 (0.3%) versus 6/2262 (0.3%), RR 1.22 (95% CI 0.33 to 4.41); 3 trials; 3589 participants; very low-certainty evidence; SAE 315/2107 (15.5%) versus 375/3027 (12.4%), RR 1.02 (95% CI 0.76 to 1.37); 4 trials; 5134 participants; very low-certainty evidence; NFS 3/919 (0.3%) versus 7/1856 (0.4%), RR 0.87 (95% CI 0.22 to 3.34); 2 trials; 2775 participants; very low-certainty evidence; non-fatal MI 7/890 (0.8%) versus 8/1374 (0.6%), RR 1.43 (95% CI 0.49 to 4.18; 2 trials); 2264 participants; very low-certainty evidence; amputation of lower extremity 1/437 (0.2%) versus 1/888 (0.1%); very low-certainty evidence.Trials reported more hypoglycaemic episodes with M+S combination compared to all other metformin-antidiabetic agent combinations. Results for M+S versus metformin monotherapy were inconclusive. There were no RCTs comparing M+S with metformin plus insulin. We identified nine ongoing trials and two trials are awaiting assessment. Together these trials will include approximately 16,631 participants. Authors' conclusions: There is inconclusive evidence whether M+S combination therapy compared with metformin plus another glucose-lowering intervention results in benefit or harm for most patient-important outcomes (mortality, SAEs, macrovascular and microvascular complications) with the exception of hypoglycaemia (more harm for M+S combination). No RCT reported on health-related quality of life.

Avaliação econômica de vildagliptina para o tratamento de pessoas vivendo com diabetes mellitus tipo 2 - perspectiva do sistema público de saúde brasileiro

Thesis

Full-text available

Mar 2017

Gustavo Laine Araújo de Oliveira

No Brasil, saúde é entendida como um direito de cidadania. Para garanti-la, o país fez adoção por um sistema universal – o Sistema Único de Saúde (SUS). Por meio deste, devem ser executadas ações de assistência terapêutica integral, incluindo a assistência farmacêutica. Uma das etapas da assistência farmacêutica é a seleção dos medicamentos. Para subsidiar a escolha, tem ganhado importância o conjunto de conceitos e métodos denominado Avaliação de Tecnologias em Saúde. Essa abordagem utiliza as evidências científicas e econômicas para subsidiar as decisões em saúde. No Brasil, cerca de 6% de todos os óbitos são atribuídos ao diabetes mellitus, sendo que 41% deles ocorrem antes dos setenta anos de idade. Dentre as pessoas vivendo com a doença, o diabetes mellitus tipo 2 (DMT2) é o tipo diagnosticado em 85% a 95% delas. No Brasil, os medicamentos considerados essenciais pelo SUS para pessoas vivendo com DMT2 são metformina, glibenclamida, gliclazida, insulina regular e insulina NPH. Pacientes com prescrição médica de medicamentos diferentes desses têm acionado o SUS judicialmente para sua obtenção. Em Minas Gerais, vildagliptina foi o hipoglicemiante oral mais adquirido para o atendimento de demandas judiciais. O objetivo deste estudo foi definir a razão custo-efetividade de vildagliptina para o tratamento de pessoas vivendo com DMT2. Estudo transversal identificou o preço médio registrado para aquisições de hipoglicemiantes orais pelo SUS. Estes preços foram comparados aos subsídios federais no programa de copagamento “Aqui Tem Farmácia Popular” e aos reembolsos de outros países com sistemas universais de saúde – Portugal, Espanha, Canadá e Reino Unido. Por meio de revisão sistemática da literatura, foram obtidos dados de eficácia e efetividade de tratamentos contendo vildagliptina e respectivos comparadores. Modelos de Markov foram utilizados na construção de coortes hipotéticas de pessoas vivendo com DMT2, para o estabelecimento da razão custo-efetividade de tratamentos contendo vildagliptina. Análise de sensibilidade probabilística foi realizada para avaliação das incertezas dos modelos, considerando disponibilidade a pagar de até o valor de um PIB per capita. O valor subsidiado pelo governo federal para cada comprimido de medicamento essencial para DMT2 pode chegar a 1023% do valor médio das aquisições do SUS por licitação. Em geral, o preço médio no SUS é inferior ao reembolsado em outros países. Por outro lado, o copagamento com recurso público no Brasil representa valores maiores que nos países estudados. A razão custo-efetividade incremental (RCEI) de vildagliptina em monoterapia comparada a metformina isolada foi de aproximadamente R$ 35 mil, considerada acima da disponibilidade a pagar no Brasil. Para a comparação entre associações com metformina, vildagliptina apresentou RCEI de cerca de R$ 8 mil. Avaliando dados de estudos observacionais, a RCEI de esquemas duplos contendo vildagliptina foi de aproximadamente R$ 15 mil. Apesar de estas duas RCEI estarem abaixo da disponibilidade a pagar estabelecida, análises de sensibilidade indicaram altas probabilidades de esses valores serem acima do PIB per capita. Assim, de acordo com as premissas deste estudo, não se recomenda a inclusão de tratamentos contendo vildagliptina na linha de cuidado do SUS para tratamento de pessoas vivendo com DMT2.

Improving postprandial hyperglycemia in patients with type 2 diabetes already on basal insulin therapy: Review of current strategies

Article

Jun 2017

A large number of patients with type 2 diabetes (T2D) on basal insulin do not reach their glycosylated hemoglobin A1c (HbA1c) goals and require additional therapy to address postprandial hyperglycemia. Guidelines from expert bodies have outlined several approaches to accomplish post-prandial glucose (PPG) control, and recent literature suggests several more. This article provides strategies for primary care physicians caring for patients with T2D who do not achieve glycemic control with basal insulin alone. Current treatment guidelines and strategies for improving PPG control will be reviewed, including the efficacy, safety, and cost effectiveness of rapid-acting insulin (RAI) analogues, premixed insulin, glucagon-like protein 1 receptor agonists, dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter-2 inhibitors, and alpha glucosidase inhibitors. Other approaches such as combinations of newer basal insulin plus RAI, and fixed-ratio combination of basal insulin and a GLP-1 receptor agonist are also described.

Cost-Effectiveness of Dipeptidyl Peptidase-4 Inhibitor Monotherapy versus Sulfonylurea Monotherapy for People with Type 2 Diabetes and Chronic Kidney Disease in Thailand

Article

Sep 2016

Objective: With a high prevalence of chronic kidney disease (CKD) in type 2 diabetes (T2DM) in Thailand, the appropriate treatment for the patients has become a major concern. This study aimed to evaluate long-term cost-effective of dipeptidyl peptidase-4 (DPP-4) inhibitor monothearpy versus sulfonylurea (SFU) monotherapy in people with T2DM and CKD. Methods: A validated IMS CORE Diabetes Model was used to estimate the long-term costs and outcomes. The efficacy parameters were identified and synthesized using a systematic review and meta-analysis. Baseline characteristics and cost parameters were obtained from published studies and hospital databases in Thailand. Costs were expressed in 2014?US Dollars. Outcomes were presented as an incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to estimate parameter uncertainty. Results: From a societal perspective, treatment with DPP-4 inhibitors yielded more quality-adjusted life years (QALYs) (0.024) at a higher cost (>66,000 Thai baht (THB) or >1,829.27 USD) per person than SFU, resulting in the ICER of 2.7 million THB/QALY (>74,833.70 USD/QALY). The cost-effectiveness results were mainly driven by differences in HbA1c reduction, hypoglycemic events, and drug acquisition cost of DPP-4 inhibitors. At the ceiling ratio of 160,000 THB/QALY (4,434.59 USD/QALY), the probability that DPP-4 inhibitors is cost-effective compared to SFU was less than 10%. Conclusions: Compared to SFU, DPP-4 inhibitor monotherapy is not a cost-effective treatment for people with T2DM and CKD in Thailand.

Economic Burden in Chinese Patients with Diabetes Mellitus Using Electronic Insurance Claims Data

Article

Full-text available

Aug 2016
PLOS ONE

Background: There is a paucity of studies that focus on the economic burden in daily care in China using electronic health data. The aim of this study is to describe the development of the economic burden of diabetic patients in a sample city in China from 2009 to 2011 using electronic data of patients' claims records. Methods: This study is a retrospective, longitudinal study in an open cohort of Chinese patients with diabetes. The patient population consisted of people living in a provincial capital city in east China, covered by the provincial urban employee basic medical insurance (UEBMI). We included any patient who had at least one explicit diabetes diagnosis or received blood glucose lowering medication in at least one registered outpatient visit or hospitalization during a calendar year in the years 2009-2011. Cross-sectional descriptions of different types of costs, prevalence of diabetic complications and related diseases, medication use were performed for each year separately and differences between three years were compared using a chi-square test or the non-parametric Kruskal-Wallis H test. Results: Our results showed an increasing trend in total medical cost (from 2,383 to 2,780 USD, p = 0.032) and diabetes related cost (from 1,655 to 1,857 USD) for those diabetic patients during the study period. The diabetes related economic burden was significantly related to the prevalence of complications and related diseases (p<0.001). The overall medication cost during diabetes related visits also increased (from 1,335 to 1,383 USD, p = 0.021). But the use pattern and cost of diabetes-related medication did not show significant changes during the study period. Conclusion: The economic burden of diabetes increased significantly in urban China. It is important to improve the prevention and treatment of diabetes to contribute to the sustainability of the Chinese health-care system.

DPP-4 inhibitor plus SGLT-2 inhibitor as combination therapy for type 2 diabetes: from rationale to clinical aspects

Article

Jul 2016

André Scheen

Introduction: Type 2 diabetes (T2D) is a complex disease with multiple defects, which generally require a combination of several pharmacological approaches to control hyperglycemia. Combining a dipeptidyl peptidase-4 inhibitor (DPP-4i) and a sodium-glucose cotransporter type 2 inhibitor (SGT2i) appears to be an attractive approach. Area covered: An extensive literature search was performed to analyze the pharmacokinetics, pharmacodynamics and clinical experience of different gliptin-gliflozin combinations. Expert opinion: There is a strong rationale for combining a DPP-4i and a SGLT2i in patients with T2D because the two drugs exert different and complementary glucose-lowering effects. Dual therapy (initial combination or stepwise approach) is more potent than either monotherapy in patients treated with diet and exercise or already treated with metformin. Combining the two pharmacological options is safe and does not induce hypoglycemia. The additional glucose-lowering effect is more marked when a gliflozin is added to a gliptin than when a gliptin is added to a gliflozin. Two fixed-dose combinations (FDCs) are already available (saxagliptin-dapagliflozin and linagliptin-empagliflozin) and others are in current development. Bioequivalence of the two compounds given as FDC tablets was demonstrated when compared with coadministration of the individual tablets. FDCs could simplify the anti-hyperglycaemic therapy and improve drug compliance.

Combination therapy of Sodium-glucose co-transporter-2 inhibitors and Dipeptidyl peptidase-4 inhibitors in type 2 diabetes: Rationale and evidences

Article

Nov 2015

No single anti-diabetic agent can correct all the patho-physiologic defects manifested in type 2 diabetes (T2DM). Therefore, multiple agents are required, for optimal glycemic control. Combination therapies, having different mechanisms of action, not only have the potential to complement their action, but may possess the properties to counter the undesired compensatory response. Recent finding suggests that sodium-glucose co-transporter-2 inhibitors (SGLT2i) increase endogenous glucose production (EGP) from liver, due to the increase in glucagon which may offset its glucose-lowering potential. In contrast, dipeptidyl peptidase-4 inhibitors (DPP4i) decrease glucagon and EGP. Especially in the light of this finding, combination therapies with SGLT2i and DPP4i are particularly appealing, and are expected to produce an additive effect. Indeed, studies find no drug-drug interaction between SGLT2i and DPP4i. Moreover, significant reduction in glycated hemoglobin also observed. This article aims to review the efficacy and safety of combination therapy of SGLT2i and DPP4i in T2DM.

The NICE cost-effectiveness threshold

Article

Full-text available

Sep 2008

The National Institute for Health and Clinical Excellence (NICE) has been using a cost-effectiveness threshold range between £20 000 and £30 000 for over 7 years. What the cost-effectiveness threshold represents, what the appropriate level is for NICE to use, and what the other factors are that NICE should consider have all been the subject of much discussion. In this article, we briefly review these questions, provide a critical assessment of NICE’s utilization of the incremental cost-effectiveness ratio (ICER) threshold to inform its guidance, and suggest ways in which NICE’s utilization of the ICER threshold could be developed to promote the efficient use of health service resources. We conclude that it is feasible and probably desirable to operate an explicit single threshold rather than the current range; the threshold should be seen as a threshold at which ‘other’ criteria beyond the ICER itself are taken into account; interventions with a large budgetary impact may need to be subject to a lower threshold as they are likely to displace more than the marginal activities; reimbursement at the threshold transfers the full value of an innovation to the manufacturer. Positive decisions above the threshold on the grounds of innovation reduce population health; the value of the threshold should be reconsidered regularly to ensure that it captures the impact of changes in efficiency and budget over time; the use of equity weights to sustain a positive recommendation when the ICER is above the threshold requires knowledge of the equity characteristics of those patients who bear the opportunity cost. Given the barriers to obtaining this knowledge and knowledge about the characteristics of typical beneficiaries of UK NHS care, caution is warranted before accepting claims from special pleaders; uncertainty in the evidence base should not be used to justify a positive recommendation when the ICER is above the threshold. The development of a programme of disinvestment guidance would enable NICE and the NHS to be more confident that the net health benefit of the Technology Appraisal Programme is positive.

Glycaemic durability with dipeptidyl peptidase-4 inhibitors in type 2 diabetes: A systematic review and meta-analysis of long-term randomised controlled trials

Article

Full-text available

Jun 2014

Objectives To evaluate glycaemic durability with dipeptidyl peptidase-4 (DPP-4) inhibitors in type 2 diabetes. Design A systematic review and meta-analysis of long-term randomised trials of DPP-4 inhibitors on haemoglobin A1c (HbA1c) was conducted. Electronic searches were carried out on the following databases: MEDLINE, EMBASE, Scopus and Web of Knowledge to December 2013. Searches were supplemented by a review of trial registries and references from identified trials. Trials were included if they lasted at least 76 weeks, and had intermediate and final assessments of HbA1c. Citations and full-text articles were screened by two reviewers. A random effect model was used to pool data. Participants Adults with type 2 diabetes. Interventions Any DPP-4 inhibitor (sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin). Outcome measures The difference between final and intermediate HbA1c assessment was the primary outcome. Results We screened 461 citations and reviewed 12 articles reporting 12 trials in 14 829 participants. All trials were of 76 weeks duration at least. The difference in HbA1c changes between final and intermediate points averaged 0.22% (95% CI 0.15% to 0.29%), with high heterogeneity (I2=91%, p<0.0001). Estimates of differences were not affected by the analysis of six extension trials (0.24%, 0.02 to 0.46), or five trials in which a DPP-4 inhibitor was added to metformin (0.24%, 0.16 to 0.32). Conclusions There is evidence that the effect of DPP-4 inhibitors on HbA1c in type 2 diabetes significantly declines during the second year of treatment. Future research should focus on the characteristics of patients that benefit most from DPP-4 inhibitors in terms of glycaemic durability.

Body-Mass Index and Mortality among Adults with Incident Type 2 Diabetes

Article

Full-text available

Jan 2014
NEW ENGL J MED

The relation between body weight and mortality among persons with type 2 diabetes remains unresolved, with some studies suggesting decreased mortality among overweight or obese persons as compared with normal-weight persons (an "obesity paradox"). We studied participants with incident diabetes from the Nurses' Health Study (8970 participants) and Health Professionals Follow-up Study (2457 participants) who were free of cardiovascular disease and cancer at the time of a diagnosis of diabetes. Body weight shortly before diagnosis and height were used to calculate the body-mass index (BMI, the weight in kilograms divided by the square of the height in meters). Multivariable Cox models were used to estimate the hazard ratios and 95% confidence intervals for mortality across BMI categories. There were 3083 deaths during a mean period of 15.8 years of follow-up. A J-shaped association was observed across BMI categories (18.5 to 22.4, 22.5 to 24.9 [reference], 25.0 to 27.4, 27.5 to 29.9, 30.0 to 34.9, and ≥35.0) for all-cause mortality (hazard ratio, 1.29 [95% confidence interval {CI}, 1.05 to 1.59]; 1.00; 1.12 [95% CI, 0.98 to 1.29]; 1.09 [95% CI, 0.94 to 1.26]; 1.24 [95% CI, 1.08 to 1.42]; and 1.33 [95% CI, 1.14 to 1.55], respectively). This relationship was linear among participants who had never smoked (hazard ratios across BMI categories: 1.12, 1.00, 1.16, 1.21, 1.36, and 1.56, respectively) but was nonlinear among participants who had ever smoked (hazard ratios across BMI categories: 1.32, 1.00, 1.09, 1.04, 1.14, and 1.21) (P=0.04 for interaction). A direct linear trend was observed among participants younger than 65 years of age at the time of a diabetes diagnosis but not among those 65 years of age or older at the time of diagnosis (P<0.001 for interaction). We observed a J-shaped association between BMI and mortality among all participants and among those who had ever smoked and a direct linear relationship among those who had never smoked. We found no evidence of lower mortality among patients with diabetes who were overweight or obese at diagnosis, as compared with their normal-weight counterparts, or of an obesity paradox. (Funded by the National Institutes of Health and the American Diabetes Association.).

Routine HIV Screening in Portugal: Clinical Impact and Cost-Effectiveness

Article

Full-text available

Dec 2013
PLOS ONE

To compare the clinical outcomes and cost-effectiveness of routine HIV screening in Portugal to the current practice of targeted and on-demand screening. We used Portuguese national clinical and economic data to conduct a model-based assessment. We compared current HIV detection practices to strategies of increasingly frequent routine HIV screening in Portuguese adults aged 18-69. We considered several subpopulations and geographic regions with varying levels of undetected HIV prevalence and incidence. Baseline inputs for the national case included undiagnosed HIV prevalence 0.16%, annual incidence 0.03%, mean population age 43 years, mean CD4 count at care initiation 292 cells/μL, 63% HIV test acceptance, 78% linkage to care, and HIV rapid test cost €6 under the proposed routine screening program. Outcomes included quality-adjusted survival, secondary HIV transmission, cost, and incremental cost-effectiveness. One-time national HIV screening increased HIV-infected survival from 164.09 quality-adjusted life months (QALMs) to 166.83 QALMs compared to current practice and had an incremental cost-effectiveness ratio (ICER) of €28,000 per quality-adjusted life year (QALY). Screening more frequently in higher-risk groups was cost-effective: for example screening annually in men who have sex with men or screening every three years in regions with higher incidence and prevalence produced ICERs of €21,000/QALY and €34,000/QALY, respectively. One-time HIV screening in the Portuguese national population will increase survival and is cost-effective by international standards. More frequent screening in higher-risk regions and subpopulations is also justified. Given Portugal's challenging economic priorities, we recommend prioritizing screening in higher-risk populations and geographic settings.

Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement

Article

Full-text available

May 2013

Economic evaluations of health interventions pose a particular challenge for reporting. There is also a need to consolidate and update existing guidelines and promote their use in a user friendly manner. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement is an attempt to consolidate and update previous health economic evaluation guidelines efforts into one current, useful reporting guidance. The primary audiences for the CHEERS statement are researchers reporting economic evaluations and the editors and peer reviewers assessing them for publication. The need for new reporting guidance was identified by a survey of medical editors. A list of possible items based on a systematic review was created. A two round, modified Delphi panel consisting of representatives from academia, clinical practice, industry, government, and the editorial community was conducted. Out of 44 candidate items, 24 items and accompanying recommendations were developed. The recommendations are contained in a user friendly, 24 item checklist. A copy of the statement, accompanying checklist, and this report can be found on the ISPOR Health Economic Evaluations Publication Guidelines Task Force website (www.ispor.org/TaskForces/EconomicPubGuidelines.asp). We hope CHEERS will lead to better reporting, and ultimately, better health decisions. To facilitate dissemination and uptake, the CHEERS statement is being co-published across 10 health economics and medical journals. We encourage other journals and groups, to endorse CHEERS. The author team plans to review the checklist for an update in five years.

Treatment of type 2 diabetes with saxagliptin: A pharmacoeconomic evaluation in Argentina

Article

Full-text available

Apr 2013

Background The increasing prevalence of diabetes and its inadequate management results in a heavy burden of the disease for the patients, the health and the productive system and the overall community. Consequently, it is necessary to have new effective drugs to treat people with diabetes to decrease such burden. DPP-4 inhibitors can help to cope with this demand, but its usage is challenged by its apparent high cost. The aim of the current study was to compare a simulated cost-effectiveness ratio of metformin (MET) plus one drug of the DPP-4 inhibitors family, saxagliptin (SAXA) or sulfonylurea (SU) treatment during a 20-year period, from the perspective of the social security system, in a cohort of people with Type 2 diabetes (T2DM) who did not attain glycosylated hemoglobin treatment target values only with MET. Methods A discrete event simulation model (Cardiff diabetes model) based on UKPDS 68 was used to simulate disease progression and to estimate the economic and health treatment consequences in people with T2DM. The clinical efficacy parameters for SAXA administration were obtained from the literature; local standard costs were considered for drug acquisition, adverse events (AEs), and micro/macrovascular complications. Costs were expressed in US dollars (2009) with an annual 3.5% discount and a 20-year time horizon. Results The SAXA + MET treated group had a lower number of non-fatal events than the SU + MET treated group. The model also predicted a lower number of fatal macrovascular events for the SAXA + MET group (149.6 vs. 152.8). The total cost of the SAXA + MET cohort was 15% higher than that of the SU + MET cohort. Treatment with SAXA + MET resulted in a higher number of quality-adjusted life years (QALYs) (9.54 vs. 9.32) and life-years gained (LYGs) (20.84 vs. 20.76) compared to those treated with SU + MET. The incremental cost per QALY and LYG gained was $7,374 and $20,490, respectively. Conclusions According to the criteria proposed by the Commission on Macroeconomics and Health, the use of the combination SAXA + MET is highly cost-effective in Argentina.

Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement

Article

Full-text available

May 2013
BJOG-INT J OBSTET GY

Consolidated Health Economic Evaluation Reporting Standards (CHEERS)—Explanation and Elaboration: A Report of the ISPOR Health Economic Evaluation Publication Guidelines Good Reporting Practices Task Force

Article

Full-text available

Mar 2013
VALUE HEALTH

Background: Economic evaluations of health interventions pose a particular challenge for reporting because substantial information must be conveyed to allow scrutiny of study findings. Despite a growth in published reports, existing reporting guidelines are not widely adopted. There is also a need to consolidate and update existing guidelines and promote their use in a user-friendly manner. A checklist is one way to help authors, editors, and peer reviewers use guidelines to improve reporting. Objective: The task force's overall goal was to provide recommendations to optimize the reporting of health economic evaluations. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement is an attempt to consolidate and update previous health economic evaluation guidelines into one current, useful reporting guidance. The CHEERS Elaboration and Explanation Report of the ISPOR Health Economic Evaluation Publication Guidelines Good Reporting Practices Task Force facilitates the use of the CHEERS statement by providing examples and explanations for each recommendation. The primary audiences for the CHEERS statement are researchers reporting economic evaluations and the editors and peer reviewers assessing them for publication. Methods: The need for new reporting guidance was identified by a survey of medical editors. Previously published checklists or guidance documents related to reporting economic evaluations were identified from a systematic review and subsequent survey of task force members. A list of possible items from these efforts was created. A two-round, modified Delphi Panel with representatives from academia, clinical practice, industry, and government, as well as the editorial community, was used to identify a minimum set of items important for reporting from the larger list. Results: Out of 44 candidate items, 24 items and accompanying recommendations were developed, with some specific recommendations for single study-based and model-based economic evaluations. The final recommendations are subdivided into six main categories: 1) title and abstract, 2) introduction, 3) methods, 4) results, 5) discussion, and 6) other. The recommendations are contained in the CHEERS statement, a user-friendly 24-item checklist. The task force report provides explanation and elaboration, as well as an example for each recommendation. The ISPOR CHEERS statement is available online via Value in Health or the ISPOR Health Economic Evaluation Publication Guidelines Good Reporting Practices - CHEERS Task Force webpage (http://www.ispor.org/TaskForces/EconomicPubGuidelines.asp). Conclusions: We hope that the ISPOR CHEERS statement and the accompanying task force report guidance will lead to more consistent and transparent reporting, and ultimately, better health decisions. To facilitate wider dissemination and uptake of this guidance, we are copublishing the CHEERS statement across 10 health economics and medical journals. We encourage other journals and groups to consider endorsing the CHEERS statement. The author team plans to review the checklist for an update in 5 years.

Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement

Article

Full-text available

Jun 2013
BMC MED

Economic evaluations of health interventions pose a particular challenge for reporting. There is also a need to consolidate and update existing guidelines and promote their use in a user friendly manner. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement is an attempt to consolidate and update previous health economic evaluation guidelines efforts into one current, useful reporting guidance. The primary audiences for the CHEERS statement are researchers reporting economic evaluations and the editors and peer reviewers assessing them for publication. The need for new reporting guidance was identified by a survey of medical editors. A list of possible items based on a systematic review was created. A two round, modified Delphi panel consisting of representatives from academia, clinical practice, industry, government, and the editorial community was conducted. Out of 44 candidate items, 24 items and accompanying recommendations were developed. The recommendations are contained in a user friendly, 24 item checklist. A copy of the statement, accompanying checklist, and this report can be found on the ISPOR Health Economic Evaluations Publication Guidelines Task Force website (http://www.ispor.org/TaskForces/EconomicPubGuidelines.asp). We hope CHEERS will lead to better reporting, and ultimately, better health decisions. To facilitate dissemination and uptake, the CHEERS statement is being co-published across 10 health economics and medical journals. We encourage other journals and groups, to endorse CHEERS. The author team plans to review the checklist for an update in five years.

Estimating the effect of sulfonylurea on HbA1c in diabetes: A systematic review and meta-analysis

Article

Full-text available

Mar 2013
DIABETOLOGIA

Aims/hypothesis: Sulfonylureas are widely prescribed glucose-lowering medications for diabetes, but the extent to which they improve glycaemia is poorly documented. This systematic review evaluates how sulfonylurea treatment affects glycaemic control. Methods: Medline, EMBASE, the Cochrane Library and clinical trials registries were searched to identify double-blinded randomised controlled trials of fixed-dose sulfonylurea monotherapy or sulfonylurea added on to other glucose-lowering treatments. The primary outcome assessed was change in HbA1c, and secondary outcomes were adverse events, insulin dose and change in body weight. Results: Thirty-one trials with a median duration of 16 weeks were included in the meta-analysis. Sulfonylurea monotherapy (nine trials) lowered HbA1c by 1.51% (17 mmol/mol) more than placebo (95% CI, 1.25, 1.78). Sulfonylureas added to oral diabetes treatment (four trials) lowered HbA1c by 1.62% (18 mmol/mol; 95% CI 1.0, 2.24) compared with the other treatment, and sulfonylurea added to insulin (17 trials) lowered HbA1c by 0.46% (6 mmol/mol; 95% CI 0.24, 0.69) and lowered insulin dose. Higher sulfonylurea doses did not reduce HbA1c more than lower doses. Sulfonylurea treatment resulted in more hypoglycaemic events (RR 2.41, 95% CI 1.41, 4.10) but did not significantly affect the number of other adverse events. Trial length, sulfonylurea type and duration of diabetes contributed to heterogeneity. Conclusions/interpretation: Sulfonylurea monotherapy lowered HbA1c level more than previously reported, and we found no evidence that increasing sulfonylurea doses resulted in lower HbA1c. HbA1c is a surrogate endpoint, and we were unable to examine long-term endpoints in these predominately short-term trials, but sulfonylureas appear to be associated with an increased risk of hypoglycaemic events.

Comparative Effectiveness of Sulfonylurea and Metformin Monotherapy on Cardiovascular Events in Type 2 Diabetes Mellitus A Cohort Study

Article

Full-text available

Nov 2012
ANN INTERN MED

The effects of sulfonylureas and metformin on outcomes of cardiovascular disease (CVD) in type 2 diabetes are not well-characterized. To compare the effects of sulfonylureas and metformin on CVD outcomes (acute myocardial infarction and stroke) or death. Retrospective cohort study. National Veterans Health Administration databases linked to Medicare files. Veterans who initiated metformin or sulfonylurea therapy for diabetes. Patients with chronic kidney disease or serious medical illness were excluded. Composite outcome of hospitalization for acute myocardial infarction or stroke, or death, adjusted for baseline demographic characteristics; medications; cholesterol, hemoglobin A1c, and serum creatinine levels; blood pressure; body mass index; health care utilization; and comorbid conditions. Among 253 690 patients initiating treatment (98 665 with sulfonylurea therapy and 155 025 with metformin therapy), crude rates of the composite outcome were 18.2 per 1000 person-years in sulfonylurea users and 10.4 per 1000 person-years in metformin users (adjusted incidence rate difference, 2.2 [95% CI, 1.4 to 3.0] more CVD events with sulfonylureas per 1000 person-years; adjusted hazard ratio [aHR], 1.21 [CI, 1.13 to 1.30]). Results were consistent for both glyburide (aHR, 1.26 [CI, 1.16 to 1.37]) and glipizide (aHR, 1.15 [CI, 1.06 to 1.26]) in subgroups by CVD history, age, body mass index, and albuminuria; in a propensity score-matched cohort analysis; and in sensitivity analyses. Most of the veterans in the study population were white men; data on women and minority groups were limited but reflective of the Veterans Health Administration population. Use of sulfonylureas compared with metformin for initial treatment of diabetes was associated with an increased hazard of CVD events or death. Agency for Healthcare Research and Quality and the U.S. Department of Health and Human Services.

Searching for a threshold not setting one

Article

Full-text available

Feb 2007
J Health Serv Res Pol

There has been much speculation about whether the National Institute for Health and Clinical Excellence (NICE) has, or ought to have, a 'threshold' ¢gure for the cost of an additional quality-adjusted life-year above which a technology will not be recommended for use. We argue that it is not constitutionally appropriate for NICE to set such a threshold, which is properly the business of parliament. Instead, the task for NICE is as a 'threshold-searcher'-to seek to identify an optimal threshold incremental cost-e¡ectiveness ratio, at the ruling rate of expenditure, that is consistent with the aim of the health service to maximize population health. This will involve the identi¢cation of technologies currently made available by the National Health Service that have incremental cost-e¡ectiveness ratios above the threshold, and alternative uses for those resources in the shape of technologies not currently provided that fall below the threshold.

Economics notes: Handling uncertainty in economic evaluation

Article

Full-text available

Jul 1999

Andrew Briggs

It is increasingly common to find the results of economic evaluations that report results in terms of cost per life year or cost per quality adjusted life year (QALY) grouped together for comparison in so called cost effectiveness league tables. It is worrying, however, that the rankings in such league tables are made on the basis of point estimates of cost effectiveness without any consideration for the inherent uncertainty involved in their calculation. Consider the figure, where the point estimates for seven different healthcare interventions are plotted in increasing order of magnitude. What is immediately apparent is that the range of uncertainty (shown by the size of the bars around the point estimates) is such that a completely different ranking than that obtained from the order of the point estimates is possible. If policymakers are to be fully informed …

Worksite mental health interventions: A systematic review of economic evaluations

Article

Full-text available

Aug 2012
OCCUP ENVIRON MED

To give an overview of the evidence on the cost-effectiveness (CE) and financial return of worksite mental health interventions. A systematic search was conducted in relevant databases. Included economic evaluations were classified into two groups based on type of intervention: (1) aimed at prevention or treatment of mental health problems among workers or (2) aimed at return to work (RTW) for workers sick-listed from mental health problems. The quality of the included economic evaluations was assessed using the Consensus Health Economic Criteria list (CHEC-list). Ten economic evaluations were included in this systematic review. All four economic evaluations on the prevention or treatment of mental health problems found a positive cost-benefit ratio, although three of these studies had low to moderate methodological quality. In five out of six economic evaluation studies on RTW interventions, no favourable CE or cost-benefit balance was found. One study of moderate methodological quality reported on a positive CE balance. Due to a limited number of economic evaluations on worksite mental health interventions of which a majority was lacking methodological quality or lacking evidence, only a tentative conclusion can be drawn from the results of this systematic review. Worksite interventions to prevent or treat mental health problems might be cost-effective, while those RTW interventions that included a full economic evaluation aimed at depressed employees do not seem to be cost-beneficial. More high-quality economic evaluation studies of effective worksite mental health interventions are needed to get more insight into the economic impact of worksite mental health interventions.

Cost-effectiveness analysis of antipsychotics in reducing schizophrenia relapses

Article

Full-text available

Apr 2012

Schizophrenia is a severe form of mental illness which is associated with significant and long-lasting health, social and financial burdens.The aim of this project is to assess the efficiency of the antipsychotics used in Spain in reducing schizophrenia relapses under the Spanish Health System perspective. A decision-analytic model was developed to explore the relative cost-effectiveness of five antipsychotic medications, amisulpride, aripiprazole, olanzapine, paliperidone Extended-Release (ER) and risperidone, compared to haloperidol, over a 1-year treatment period among people living in Spain with schizophrenia. The transition probabilities for assessed therapies were obtained from the systemic review and meta-analysis performed by National Institute for Health and Clinical Excellence (NICE). Paliperidone ER was the option that yielded more quality-adjusted life years (QALYs) gained per patient (0.7573). In addition, paliperidone ER was the least costly strategy (€3,062), followed by risperidone (€3,194), haloperidol (€3,322), olanzapine (€3,893), amisulpride (€4,247) and aripiprazole (€4,712).In the incremental cost-effectiveness (ICE) analysis of the assessed antipsychotics compared to haloperidol, paliperidone ER and risperidone were dominant options. ICE ratios for other medications were €23,621/QALY gained, €91,584/QALY gained and €94,558/QALY gained for olanzapine, amisulpride and aripiprazole, respectively. Deterministic sensitivity analysis showed that risperidone is always dominant when compared to haloperidol. Paliperidone ER is also dominant apart from the exception of the scenario with a 20% decrease in the probability of relapses. Our findings may be of interest to clinicians and others interested in outcomes and cost of mental health services among patients with schizophrenia.Paliperidone ER and risperidone were shown to be dominant therapies compared to haloperidol in Spain. It is worthwhile to highlight that schizophrenia is a highly incapacitating disease and choosing the most appropriate drug and formulation for a particular patient is crucial.The availability of more accurate local epidemiological data on schizophrenia would allow a better adaptation of the model avoiding some of the assumptions taken in our work. Future research could be focused on this.

Cost-effectiveness and budget impact of saxagliptine as additional therapy to metformin for the treatment of diabetes mellitus type 2 in the Brazilian private health system *

Article

Full-text available

Jun 2012

To compare costs and clinical benefits of three additional therapies to metformin (MF) for patients with diabetes mellitus type 2 (DM2). A discrete event simulation model was built to estimate the cost-utility ratio (cost per quality-adjusted life years [QALY]) of saxagliptine as an additional therapy to MF when compared to rosiglitazone or pioglitazone. A budget impact model (BIM) was built to simulate the economic impact of saxagliptine use in the context of the Brazilian private health system. The acquiring medication costs for the hypothetical patient group analyzed in a time frame of three years, were R$ 10,850,185, R$ 14,836,265 and R$ 14,679,099 for saxagliptine, pioglitazone and rosiglitazone, respectively. Saxagliptine showed lower costs and greater effectiveness in both comparisons, with projected savings for the first three years of R$ 3,874 and R$ 3,996, respectively. The BIM estimated cumulative savings of R$ 417,958 with the repayment of saxagliptine in three years from the perspective of a health plan with 1,000,000 covered individuals. From the perspective of private paying source, the projection is that adding saxagliptine with MF save costs when compared with the addition of rosiglitazone or pioglitazone in patients with DM2 that have not reached the HbA1c goal with metformin monotherapy. The BIM of including saxagliptine in the reimbursement lists of health plans indicated significant savings on the three-year horizon.

Health Policy and the Politics of Evidence

Article

Full-text available

Oct 2005
SOC POLICY ADMIN

National decisions on the drugs, treatments and medical devices that should be funded through public expenditure are a fundamental element of health policy. But despite a political emphasis upon evidence-based policy, the results of rigorous clinical trials and statistical modelling techniques rarely speak for themselves. So, does the pre-eminence traditionally accorded to quantitative data in the medical field underpin policy decisions on a consistent basis? Or are more subtle, less transparent characteristics of context and interaction evident in the shaping of attendant decisions? This article considers these questions by drawing on a study of decision-making in the National Institute for Health and Clinical Excellence (NICE)—an organization established by the British government in 1999 to decide whether selected health technologies should be made available throughout the National Health Service in England and Wales. In broad terms, the findings point to the primacy of arguments based on quantitatively oriented, experimentally derived data but also to a discursive hegemony of clinicians and health economists in mediating, including or debarring more qualitative, experientially based evidence. A more complex, dynamic understanding of policy governance in the field of health technology appraisal—founded on a discursive appropriation of the idea of the “common good”—goes some way to explaining the persistence of this hegemony despite an avowedly inclusive, plural approach to decision-making.

The Impact of the Pharmaceutical Pricing System on Cost-Effectiveness Results: Finnish Analysis

Article

Full-text available

Dec 2011

In Finland, the drug retail prices are determined with a regressive pharmaceutical pricing scheme (PPS) that leads to higher absolute sales margins for products with higher wholesale prices. At the same time low-priced products are sold at prices below the true costs of drug delivery. Despite these characteristics retail prices are used to represent all drug costs in health economic evaluations that are required before societal reimbursement of new drugs can be granted. We assessed the impact of PPS induced cost differences on the results of cost-utility analyses in hypothetical examples. The examples show that the Finnish PPS worsens the ICERs obtained for more expensive pharmaceuticals. The Finnish PPS is problematic when the aim is to provide Finnish patients with optimal, cost-effective treatments. In its current form, the PPS discourages innovation and comparability of results with other settings, and may prevent reimbursement of otherwise cost-effective treatments.

Searching for a threshold, not setting one: The role of the National Institute for Health and Clinical Excellence

Article

Jan 2007
J Health Serv Res Pol

There has been much speculation about whether the National Institute for Health and Clinical Excellence (NICE) has, or ought to have, a'threshold' figure for the cost of an additional quality-adjusted life-year above which a technology will not be recommended for use. We argue that it is not constitutionally appropriate for NICE to set such a threshold, which is properly the business of parliament. Instead, the task for NICE is as a 'threshold-searcher' - to seek to identify an optimal threshold incremental cost-effectiveness ratio, at the ruling rate of expenditure, that is consistent with the aim of the health service to maximize population health. This will involve the identification of technologies currently made available by the National Health Service that have incremental cost-effectiveness ratios above the threshold, and alternative uses for those resources in the shape of technologies not currently provided that fall below the threshold

Equality of what in health? Distinguishing between outcome egalitarianism and gain egalitarianism

Article

Aug 2006

When deciding how to weigh benefits to different groups, standard economic models assume that people focus on the final distribution of utility, health or whatever. Thus, an egalitarian is assumed to be egalitarian in the outcome space. But what about egalitarianism in the gains space, such that people focus instead on how equally benefits are distributed? This paper reports on a study in which members of the public were asked to rank a number of health programmes that differed in the distribution of benefits and final outcomes in ways that enabled us to distinguish between different types of egalitarianism. The results suggest that outcome egalitarianism dominates, particularly for differences in health by social class, but a sizeable minority of respondents appear to be gain egalitarians, especially when the health differences are by sex. These results have important implications for how we think about outcome-based social welfare functions in economics.

National Institute for Clinical Excellence and its value judgments

Article

Jul 2004

The National Institute for Clinical Excellence (NICE) offers health professionals in England and Wales advice on providing NHS patients with the highest attainable standards of care. NICE gives guidance on individual health technologies, the management of specific conditions, and the safety and efficacy of interventional diagnostic and therapeutic procedures. Guidance is based on the best available evidence. The evidence may not, however, be very good and is rarely complete. Those responsible for formulating the NICE’s advice therefore have to make judgments both about what is good and bad in the available science (scientific value judgments) and about what is good for society (social value judgments). In this article we focus on the scientific and social judgments forming the crux of the institute’s assessment of cost effectiveness. Scientific value judgments and those relating to clinical effectiveness are considered elsewhere.

Handling uncertainty when performing economic evaluation of healthcare interventions

Article

Jan 1999

Aims: To perform a structured review of the way in which uncertainty has been handled in economic evaluation. To assemble data on the actual distributional form and variance of healthcare costs, and to devise guidelines to improve current practice. In particular, the focus was on the handling of cost and cost-effectiveness data. Methods: The structured review was conducted at a number of different levels, reflecting the detail of the review process. At a general level, a search of the literature was undertaken to identify published economic evaluation studies that reported results in terms of cost per life-year or cost per quality-adjusted life-year values. This form of study was chosen as it is the results of these studies that are commonly grouped together and reported in cost-effectiveness league tables. Articles meeting the search criteria were reviewed using a review proforma designed to collect summary information on each study. These results were then entered as key words into a database, to allow interrogation and cross- referencing of the database by category. This overall data set was then employed to focus in on two specific areas of interest, using subsets of articles to perform more detailed reviews: All studies reporting UK results were identified from the wider group of articles. These studies were reviewed in detail, and information on the baseline cost-effectiveness results, the methods underlying those results, the range of results representing uncertainty and the number of previously published results quoted in comparison were entered into a relational database. By matching results by the methods employed using a retrospective application of a methodological 'reference case', a subset of results with improved comparability was identified, and a rank ordering of these results was then attempted. Where a range of values accompanied the baseline results, the implications of this uncertainty for the rank ordering was also examined. All studies which reported patient level cost data were identified from the overall database and reviewed in detail with respect to how they had reported the distribution and variance of healthcare costs. In addition, five available data sets of patient level cost data were examined in order to show how the healthcare costs in those data were distributed and to elucidate issues surrounding the analysis and presentation of healthcare cost differences. Economic analyses are not simply concerned with costs but also with effects, with the cost- effectiveness ratio being the outcome of interest in most economic evaluations. Unfortunately, ratio statistics pose particular problems for standard statistical methods. In this report, a review of a number of proposed methods for estimating confidence limits for cost-effectiveness ratios when patient level data are available for both cost and effectiveness is presented. Results: A total of 492 articles were found to match the search criteria, and were fully reviewed and entered into the database. Analysis of this database in terms of the method employed by analysts to handle uncertainty shows that the vast majority of studies use one-way sensitivity analysis methods only. Of some concern is that 17% of studies did not attempt any analysis to examine uncertainty, although there is weak evidence to show that this situation is improving. Of these 492 studies, 60 reported results for the UK. From these UK studies, 548 baseline cost-effectiveness results were extracted relating to 106 methodological scenarios. Application of a retrospective 'reference case' gave a single methodological scenario for each article with 333 associated baseline results. These results were converted to a common cost base year, and rank ordered to give a comprehensive 'league table' of UK results. Of the 333 results, 61 had an associated full range of values to represent uncertainty. Alternative rankings based on the high or low values from this range showed that there could be considerable disruption to the rank order based on the baseline point estimates only. The review of patient level cost data showed that 53 of the 492 studies in the database had patient level cost data and that just 15 of these had reported some measure of cost variance. Only four studies had calculated 95% confidence intervals for cost. The review of five available cost data sets showed that the cost data were not normally distributed, and in two cases showed substantial skewness. A number of methods for estimating confidence intervals for cost- effectiveness ratios have appeared in the recent literature. Examination of their statistical properties and evidence from recent Monte Carlo simulation studies suggests that many of these methods may not perform well in some circumstances. The parametric method based on Fieller's theorem and the non- parametric approach of bootstrapping produced consistently the best results, and are the preferred methods for estimating confidence intervals for cost- effectiveness ratios. However, the use of cost-effectiveness acceptability curves may provide more useful information to decision makers than standard confidence intervals. Conclusions. General recommendations: Potential guidelines arising from this review are: analysts should aim to present results using a methodological reference case in order to increase the comparability of results between studies; analysts should be aware of the potential for the incremental cost-effectiveness ratio to vary at the margin; analysts should avoid selective comparison of their results with the results from other studies; analysts should ensure that they consider the potential implications of uncertainty for the results of their analysis; interval estimates should accompany each point estimate presented; where sensitivity analysis is employed to estimate an interval, analysts should be comprehensive in their inclusion of all variables in the analysis; when reporting sensitivity analysis, analysts should be aware of the probabilistic nature of the reported range; when reporting patient level cost information, analysts should make more use of descriptive statistics; even when data are skewed, economic analyses should be based on means of distributions; when reporting statistical tests of cost differences, analysts should be aware that significance tests may be more powerful on a transformed scale but that confidence limits should be reported on the original scale; where patient level data on both cost and effect are available, the parametric approach based on Fieller's theorem or the non-parametric approach of bootstrapping should be employed to estimate a confidence interval for the cost- effectiveness ratio; sensitivity analysis has a continuing role in handling uncertainty not related to sampling variation; consideration should be given to using cost-effectiveness acceptability curves to present uncertainty in stochastic cost-effectiveness studies. Recommendations for future research: Three main areas for future research arise from this review: research into the appropriate reference case for the UK; research into the application of probabilistic sensitivity analysis methods; research into the willingness to pay for health gain and the likely value of a ceiling cost-effectiveness ratio appropriate for decision making, estimated from consumer surveys and implied through the application of cost-effectiveness databases.

The measurement of individual utility and social welfare

Article

Jan 1998

Paul Dolan

It has been suggested by a number of economists that decisions about how to allocate scarce health care resources should be informed by the cost per quality-adjusted life-years (QALYs) of the different alternatives. One of the criticisms of the QALY approach is that it is based on the measurement of individual utility; yet the values elicited are used to inform social choice. In this respect, it is argued that the QALY approach fails to take account of distributional issues that are known to be important in the context of health care. This paper addresses this issue and presents an approach grounded in microeconomic theory that is flexible enough to deal with a wide range of efficiency-equity trade-offs, while making the nature of the trade-off transparent. In addition, it is an approach that is relatively simple to investigate empirically, and the results of a preliminary study are presented as illustration of this.

US cost-effectiveness of saxagliptin in type 2 diabetes mellitus

Article

Jan 2012

Objectives: To evaluate the cost-effectiveness of saxagliptin versus sulfonylurea (glipizide) added to metformin in patients with type 2 diabetes mellitus (T2DM) from a US payer perspective. Study Design: Data from a 52-week randomized controlled trial comparing saxagliptin and glipizide in combination with metformin were used in a simulation model to estimate long-term health outcomes in a cohort of T2DM patients. Methods: Evidence from a clinical trial and other published literature were used to assess disease progression rates and associated healthcare costs. Subjects were simulated in yearly time increments, and the model estimated the 5-year and lifetime (ie, 40-year) clinical and economic outcomes, taking into account the cost and disutility associated with weight gain and hypoglycemia events. The model estimated the incidence of microvascular and macrovascular complications, diabetes-specific mortality, all-cause mortality, and costs and quality-adjusted life-years (QALYs) associated with the treatment strategies. Results: The analysis suggests that compared with glipizide plus metformin the 5-year QALY gain for saxagliptin plus metformin was 0.53 with a cost of $13,374 per QALY. At 40 years, lifetime QALY gain for saxagliptin plus metformin rose to 2.64 per patient and cost per QALY was reduced to $1052. Sensitivity analysis indicated disutility values were a key driver, whereas the impact of overall costs was more modest. Conclusions: Over a T2DM patient's lifetime, addition of saxagliptin to metformin is associated with improvement in QALYs when considering cost and disutility due to treatment side effects. Cost effectiveness is within acceptable cost-effectiveness threshold in the United States.

PDB22 Potential Budget Impact of Linagliptin in France Estimated From Current Pattern of Dipeptidyl Peptidase 4 Inhibitors Prescriptions

Article

Nov 2012

Methods for The Economic Evaluation of Health Care Programmes

Book

Jan 1997

Assessment of the Relative Effectiveness and Tolerability of Treatments of Type 2 Diabetes Mellitus: A Network Meta-analysis

Article

Aug 2014
CLIN THER

Purpose: The relative effectiveness and tolerability of treatments for type 2 diabetes mellitus (T2DM) is not well understood because few randomized, controlled trials (RCTs) have compared these treatments directly. The purpose of the present study was to evaluate the relative effectiveness and tolerability of treatments of T2DM. Methods: We performed a network meta-analysis of available RCTs with pharmacologic interventions in T2DM and compared antidiabetic drugs and combination regimens with metformin (the reference drug). Glycemic control (proportion achieving HbA1c goal) and tolerability (risk of hypoglycemia) were the primary outcomes of interest. Direct and indirect relative effects (unadjusted) were expressed as odds ratios and 95% CIs. Findings: Eight treatments (glucagon-like peptide-1 [GLP-1] agonists plus metformin, sulfonylureas plus metformin, dipeptidyl peptidase-4 [DPP-4] inhibitors] plus metformin, colesevelan plus metformin, thiazolidinediones plus metformin, meglitinides plus metformin, α-glucosidase inhibitor plus metformin, and rosiglitazone monotherapy) outperformed metformin (direct effects). Triple combinations of GLP-1, thiazolinedione, insulin, metiglinide, or sulfonylureas added to a metformin backbone improved glycemic control (indirect effects). Higher risk of hypoglycemia was noted for sulfonylureas, α-glycosidases, and metiglinides when added to metformin (direct effects). Across indirect effects, only 17% of comparisons yielded less risk of hypoglycemia (70% were worse and 13% were comparable). Implications: Our results point out the relative superiority of 2- and 3-drug combination regimens over metformin and summarize treatment effects and tolerability in a comprehensive manner, which adds to our knowledge regarding T2DM treatment options.

Economic evaluations of interventions designed to prevent mental disorders: A systematic review

Article

Jun 2014
EARLY INTERV PSYCHIA

AimThe prevention of mental disorders is a growing field and there are interventions that have been demonstrated to prevent some disorders, particularly depression, from developing. The aim of the current study is to update two existing reviews of the cost-effectiveness studies of preventive interventions for mental disorders in order to determine whether such interventions are good value-for-money.MethodsA search was undertaken in Medline, PsycInfo and Econlit. The search was limited to articles published in English covering the period from 2010 to September 2013. Inclusion criteria for the review comprised comparative economic evaluations of interventions designed to prevent mental disorders.ResultsTen new economic evaluations have been published since 2010, more than doubling the numbers of economic evaluations of preventive interventions for mental disorders published prior to 2010. Using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist, the majority of studies were of a good standard and used cost-utility frameworks.Conclusions Indicated types of interventions for the prevention of depression and anxiety appeared to be particularly good value-for-money and most of these studies were modelled evaluations. Unfortunately, many such interventions are still not routinely provided. Future trials of preventive interventions for mental disorders need to include robust economic evaluations so that the economic impact of such interventions from the individual study participant perspective can be determined.

Severe Hypoglycemia Rates and Associated Costs Among Type 2 Diabetics Starting Basal Insulin Therapy in the United States.

Article

Jun 2014

Objectives: To derive current real-world data on the rates and costs of severe hypoglycemia (SH) for people with type 2 diabetes mellitus (T2D) who have initiated basal insulin therapy and to examine differences in SH rates and costs stratified by history of prior SH events. Methods: We used a nation-wide electronic health records database that included encounter and laboratory data, as well as clinical notes, to estimate the rates and costs of SH events among adults with T2D who initiated basal insulin between 2008 and 2011. Unadjusted and regression-adjusted rates and quarterly costs were calculated for all patients as well as stratified by history of a SH event before starting basal insulin and history of a SH event during the basal insulin titration period. Results: We identified 7235 incident cases of basal insulin use among patients with T2D who did not use insulin during the previous 12 months. Regression-adjusted incidence and total event rates were 10.36 and 11.21 per 100 patient-years, respectively. A history of SH events during the pre-index baseline and post-index titration periods were statistically significantly associated with both the incidence and total event rates (p < 0.01). Regression-adjusted total healthcare and diabetes-related costs were statistically significantly (p < 0.01) higher in those quarters when a SH event occurred than in those quarters without any SH events ($3591 vs. $487 and $3311 vs. $406, respectively). A history of previous SH or SH events during the titration period were not statistically significantly associated with costs. Conclusions: These results suggest that the real-world burden of SH is high among people with T2D who start using basal insulin and that history of previous SH events, both before starting insulin and during the insulin titration period, influences future SH. These results can also provide insights into interventions that can prevent or delay SH. These results should, however, be interpreted in light of the key limitations of our study: not all SH events may have been captured or coded in the database, data on filled prescriptions were not available, and the post-titration follow-up period could have been divided into time units other than quarters (3 month blocks) resulting in potentially different conclusions. Further real-world studies on the frequency and costs of SH, using methods to identify as many SH events as possible, can allow healthcare providers to make more informed decisions on the risks and benefits of basal insulin therapy in T2D patients.

Resource allocation, social values and the QALY: A review of the debate and empirical evidence

Article

Sep 2002

David LB Schwappach

Most health economists agree that public preferences should play a major role in setting criteria for distributing scarce resources. The quality-adjusted life year (QALY) is used as a preference-based measure for the outcome of health-care activities in health economic evaluative studies. Traditionally, health economists proposed maximizing the additional health gain in terms of QALYs so as to maximize social welfare. Evidence has grown however, that neither potential health gain as a single relevant determinant of value, nor the rule of maximizing this health gain are sufficient. Concerns about fairness and equity are also important to the public in distributional decisions. This paper reviews the debate on the role and limitations of the QALY in health-care priority setting and the empirical evidence surrounding it. A framework is used to systematically explore the available data on factors considered to be important to the public in health-care resource allocation, and to investigate how these fit with the implicit value judgements inherent in the original QALY formulation. Potential sources of social value are classified into (1) factors that relate to the characteristics of patients and (2) factors related to the characteristics of the intervention's effect on patients' health. As well as these main categories, the article considers preferences for distributional rules. Recent approaches that aim to capture public preferences more comprehensively and to better reflect the value attributed to different health-care programmes in economic evaluation methods are outlined briefly.

Insulin Therapy for Type 2 Diabetes Mellitus

Article

Jun 2014
J Am Med Assoc

Importance: The incidence and prevalence of type 2 diabetes mellitus are increasing. Objective: To review currently available insulin therapy, as well as evidence on the use, application, initiation, and intensification of insulin in the outpatient setting. Evidence review: Data sources included PubMed for trials and investigations in type 2 diabetes examining insulin use from January 1998 to April 2014. Findings: The hemoglobin A1c target for most patients with type 2 diabetes is 7% but needs to be modified when there is increased risk of hypoglycemia, reduced life expectancy, extensive comorbidities, or reduced resources. Insulin therapy may be considered early or late in the disease course; adverse effects include weight gain and hypoglycemia. Basal insulin can be added to oral hypoglycemic agents (generally stopping sulfonylureas) initially, and later, prandial insulin can be added in a stepwise fashion. Insulin treatment must be individualized, and there are a number of challenges to insulin initiation and intensification. Conclusions and relevance: Insulin can help achieve ideal hemoglobin A1c goals for patients with type 2 diabetes. Barriers such as adherence, patient preferences, clinician preferences, and resource allocation must be addressed.

Potential Impact of Dipeptidyl Peptidase-4 Inhibitors on Cardiovascular Pathophysiology in Type 2 Diabetes Mellitus

Article

May 2014

Michael H Davidson

Cardiovascular (CV) disease remains the major cause of mortality and morbidity in patients with type 2 diabetes mellitus (T2DM). The pathogenesis of CV disease in T2DM is complex and multifactorial, and includes abnormalities in endothelial cells, vascular smooth muscle cells, myocardium, platelets, and the coagulation cascade. Dipeptidyl peptidase-4 (DPP-4) inhibitors are a newer class of agents that act by potentiating the action of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide. This review summarizes CV disease pathophysiology in T2DM and the potential effect of DPP-4 inhibitors on CV risk in patients with T2DM. Preclinical and small observational studies and post hoc analyses of clinical trial data suggest that DPP-4 inhibitors may have beneficial CV effects. Some effects of DPP-4 inhibitors are GLP-1 dependent, whereas others may be due to GLP-1-independent actions of DPP-4 inhibitors. Analyses of major adverse CV events occurring during clinical development of DPP-4 inhibitors found no increased risk of CV events or mortality and even a potential reduction in CV events. Two large CV outcome trials have been completed and report that saxagliptin and alogliptin did not increase or decrease adverse CV outcomes in patients with T2DM and CV disease or at high risk for adverse CV events. More patients in the saxagliptin group than in the placebo group were hospitalized for heart failure, and there was a similar numerically increased risk of hospitalization for heart failure with alogliptin; however, the risk was not significantly greater compared with placebo. Dipeptidyl peptidase-4 inhibitors may affect some of the pathologic processes involved in the increased CV risk inherent in T2DM.

Utilization of Glucose, Blood Pressure and Lipid Lowering Medications among people with type 2 diabetes in the United States 1999-2010

Article

May 2014

Background Changes in relation to drug treatment to various control targets for diabetes were studied using the National Health and Nutrition Examination Survey (NHANES) 1999-2010. Methods Data on 3094 participants aged ≥20 with diagnosed type 2 diabetes were analyzed. Use of medications for lowering glucose, blood pressure, and lipids in the past month was assessed by questionnaire. Data from two survey cycles were combined together to produce estimates for each four-year period. Results Usage of metformin increased from 34.8% to 53.8% and was the most prevalent medications during this period (P<0.001), and half of subjects taking metformin could achieve HbA1c <7.0% in 2007-2010. Dipeptidyl peptidase-4 (DPP-4) inhibitors, were used by 7.4% of participants in 2007-2010. Usage of angiotensin receptor blockers (ARB) and beta-blockers increased significantly from 7.4% to 21.4% and from 15.3% to 31.8%, respectively from 1999-2010 (P≤0.001). 64.7% of participants could attain blood pressure control by 2007-2010. Usage of statins doubled in 1999-2010 and 52.2% of subjects took statins by 2007-2010 (P<0.001). Conclusions Metformin is the first line drug for diabetes while DPP-4 inhibitors started to be used since 2007. Blood pressure control improved in 1999-2010 partly due to increased drug prescriptions. Although statins were widely used about half of the participants did not take them.

Gender Differences in Composite Control of Cardiovascular Risk Factors Among Patients with Type 2 Diabetes

Article

Apr 2014
DIABETES TECHNOL THE

Objective: Disparities in outcomes for cardiovascular disease (CVD) exist between men and women with type 2 diabetes mellitus (T2DM). We examined gender differences in composite control of cardiovascular risk factors in a sample of adults with T2DM. Subjects and methods: This was a cross-sectional study of 680 people recruited from three primary care settings. Primary outcomes were individual and composite control of CVD risk factors. Control of individual risk outcomes was defined as glycosylated hemoglobin A1c (HbA1c) level of <7%, blood pressure (BP) of <130/80 mm Hg, and low-density lipoprotein (LDL) cholesterol level of <100 mg/dL. Composite control was defined as having all three outcomes under control simultaneously. Linear and logistic regression models were used to assess differences in individual means and individual and composite outcomes control between men and women, while adjusting for relevant covariates. Results: Men made up 56% of the sample, approximately 67% were non-Hispanic black, and 78% made less than $35,000 annually. Unadjusted mean systolic BP (134 mm Hg vs. 130 mm Hg, P=0.005) and LDL cholesterol (99.7 mg/dL vs. 87.6 mg/dL, P<0.001) levels were significantly higher in women than in men. Adjusted linear regression showed mean diastolic BP (β=3.09; 95% confidence interval 0.56, 5.63) was significantly higher in women. Overall, 12.4% of the sample had composite control, and women had poorer composite control compared with men (5.9% vs. 17.3%). Adjusted logistic models showed that men were significantly more likely to have composite risk factor control (odds ratio 2.90; 95% confidence interval 1.37, 6.13) compared with women. Conclusions: In this sample of adults with T2DM, women had significantly lower composite control compared with men, when adjusting for relevant confounders. It is imperative that women are informed about CVD risk factors, educated on how to reduce them, and aggressively treated to avoid adverse outcomes. Additional research involving women is needed to explore and reduce disparities in CVD risk between men and women with T2DM.

Effect of gender on treatment outcomes in type 2 diabetes mellitus

Article

Oct 2013

To evaluate the effect of gender on clinical outcomes in people with type 2 diabetes mellitus (T2DM) receiving antidiabetes therapy. This is a pooled analysis from nine similarly designed phase 3 and 4 randomized, controlled studies evaluating insulin glargine and an active comparator (NPH insulin, insulin lispro, premixed insulin, oral antidiabetes drugs, dietary intervention) in adults with T2DM. Impact of gender on outcomes including HbA1c, fasting plasma glucose (FPG), weight-adjusted insulin dose, and hypoglycemia incidence was evaluated after 24 weeks of treatment. Overall, 1651 male and 1287 female individuals were included; 49.8% and 50.2% were treated with insulin glargine or comparators, respectively. Females receiving insulin glargine were less likely than males to achieve a glycemic target of HbA1c≤7.0% (53mmol/mol) (54.3% vs 60.8%, respectively, p=0.0162); there was no difference between females and males receiving comparators (52.7% vs 51.3%, respectively, p=0.4625). Females had significantly greater reductions in FPG (3.1mg/dL, p=0.0458), required significantly higher insulin doses (0.03IU/kg, p=0.0071), and had significantly higher annual rates of symptomatic (p<0.0001), glucose-confirmed (<50 and <70mg/dL) symptomatic (p=0.0005 and p<0.0001), and severe hypoglycemia (p=0.0020) than males. Females in this analysis had smaller reductions in HbA1c and were less likely to reach glycemic goals despite higher insulin doses and more hypoglycemic events than males. Differences in gender responses to therapy should be considered when individualizing treatment for people with T2DM.

Head-to-head comparison of dipeptidyl peptidase-IV inhibitors and sulphonylureas----A meta-analysis from randomized clinical trials.

Article

Mar 2014
DIABETES-METAB RES

Dipeptidyl peptidase-IV (DPP-4) inhibitors and sulphonylureas are two important second-line anti-diabetic agents. The objective of this research was to evaluate the efficacy and safety of DPP-4 inhibitors compared with sulphonlyureas by meta-analytic approach of available randomized studies. We searched MEDLINE, EMBASE, and the Cochrone Central Register of Controlled Trials databases up to 30 June 2013 collecting all randomized clinical trials with a treatment duration ≥ 18 weeks. Data on glycated haemoglobin(HbA1c), body weight, hypoglycemia, total adverse events and cardiovascular events were retrieved and analyzed. The analysis included 12 randomized studies comprising 10,982 patients with type 2 diabetes mellitus (T2DM). Based on meta-analysis, sulphonylureas lowered HbA1c significantly more than DPP-4 inhibitors with weighted mean difference (WMD) of 0.105(95% Confidence Interval, CI, 0.103 to 0.107). The results were consistent in trials with longer(>32 weeks) or shorter(≤32 weeks) duration; however, DPP-4 inhibitors showed greater reduction in HbA1c compared to the second generation sulphonylureas and in patients with baseline eGFR < 50 mL/min/1.73 m(2) . Patients treated with DPP-4 inhibitors are less likely to achieve HbA1c < 7% compared with sulphonylureas(Mantel-Haenszel odds ratio, MH-OR, 0.91; 95%CI 0.84 to 0.99). DPP-4 inhibitors was associated with a reduction in body weight(WMD -1.652; 95%CI -1.658 to -1.646), and lower risk of hypoglycemia(MH-OR, 0.13; 95%CI 0.11 to 0.16), total adverse events(MH-OR, 0.79; 95%CI 0.72 to 0.87) and cardiovascular events(MH-OR, 0.53; 95%CI 0.32 to 0.87) compared to sulphonylureas. Although compared to sulphonylureas, DPP-4 inhibitors is less efficacious, it demonstrates a beneficial effect on body weight, episode of hypoglycemia, and total adverse events. This article is protected by copyright. All rights reserved.

Economic Evaluation of Health Care Interventions: The biggest bang for the buck or the bigger bucks for the bang?

Article

Amiram Gafni

Administrative Behavior: A Study of Decision-Making Processes in Administrative Organization

Article

Jan 1976

Herbert A Simon

Efficacy and safety of dipeptidyl peptidase-4 inhibitors and metformin as initial combination therapy and as monotherapy in patients with type 2 diabetes mellitus: A Meta-analysis.

Article

Jun 2013
DIABETES OBES METAB

This meta-analysis was performed to provide an update on the efficacy and safety of dipeptidyl peptidase-4 (DPP-4) inhibitors and metformin as initial combination therapy and as monotherapy in patients with type 2 diabetes mellitus (T2DM). We conducted a search on MEDLINE, Embase and Cochrane Collaborative database for randomized controlled trials (RCTs) of DPP-4 inhibitors and metformin as initial combination therapy or as monotherapy monotherapy in patients with T2DM by the end of December 2012, using the key words "alogliptin," "dutogliptin," "linagliptin," "saxagliptin," "sitagliptin," and "vildagliptin," and "metformin." RCTs were selected for meta-analysis if (1) they were RCTs comparing DPP-4 inhibitors plus metformin as initial combination therapy or DPP-4 inhibitor monotherapy to metformin monotherapy, (2) duration of treatment was ≥12 weeks, and (3) reported data on HbA1c change, fasting plasma glucose (FPG) change, weight change, adverse cardiovascular (CV) events, hypoglycaemia, or gastrointestinal adverse events (AEs). A total of 8 RCTs was included. Compared with metformin monotherapy, DPP-4 inhibitors monotherapy was associated with lower reduction in HbA1c level [weighted mean differences (MD)=0.28, 95% confidence intervals (CI) (0.17, 0.40), P<0.00001], lower reduction in FPG level [MD=0.81, 95%CI(0.60, 1.02), P <0.00001], lower weight loss [MD=1.51, 95%CI(0.89, 2.13), P<0.00001], but lower risk of adverse CV events [risk ratio (RR)=0.36, 95%CI(0.15, 0.85), P=0.02], lower risk of hypoglycaemia [RR=0.44, 95%CI(0.27, 0.72), P=0.001] and lower risk of gastrointestinal AEs [RR=0.63, 95%CI(0.55, 0.70), P <0.00001]. Compared with metformin monotherapy, DPP-4 inhibitors plus metformin as initial combination therapy was associated with higher reduction in HbA1c level [MD=-0.49, 95%CI(-0.57, -0.40), P<0.00001], higher reduction in FPG level [MD=-0.80, 95%CI(-0.87, -0.74), P<0.00001], lower weight loss [MD=0.44, 95%CI(0.22, 0.67), P=0.0001]; but was not associated with a further reduction in adverse CV events [RR=0.54, 95%CI(0.25, 1.19), P=0.13], nor the higher risk of hypoglycaemia [RR=1.04, 95%CI(0.72, 1.50), P=0.82], nor the prolonged risk of gastrointestinal AEs [RR=0.98, 95%CI(0.88, 1.10), P=0.77]. DPP-4 inhibitors, which were safe and effective in controlling the blood glucose, may possibly decrease the risk of CV events in patients with T2DM. It could be a credible alternative for T2DM patients who, for some reason, cannot use metformin, or are in high risk of CV exposure. High-quality, large sample and long-term follow-up clinical trails are needed to confirm the long-term conclusions.

Health, Economics and Health Economics

Chapter

Jan 1981

Anthony John Culyer

Quality-Adjusted Life-Years Lack Quality in Pediatric Care: A Critical Review of Published Cost-Utility Studies in Child Health

Article

Nov 2004
VALUE HEALTH

Objectives. Cost-utility analysis in which health benefits are quantified in terms of quality-adjusted life-years (QALYs) has now become the standard type of cost-effectiveness analysis. These studies are potentially influential in determining the extent of funding for particular pediatric interventions, and so their methodologic quality is extremely important. The objective of this study was twofold: first, to critically appraise published cost-utility analyses of interventions in child and adolescent health care in terms of the methods used to derive QALYs and, second, to discuss unresolved methodologic issues that are pertinent to the measurement of QALYs in pediatric populations. Methods. A comprehensive search using computerized databases (including Medline, Embase, Econlit, and databases specific to economic evaluation), Web searches, and citation tracking was undertaken to identify cost-utility studies of interventions that were aimed at those who were younger than 16 years and published before April 2004. The methods of individual studies were compared with the recognized published guidelines of the US Panel on Cost-Effectiveness in Health and Medicine and the National Institute for Clinical Excellence in England and Wales, which recommend the use of a generic health state classification system (eg, Health Utility Index, EuroQol-5D), a choice-based valuation method (eg, standard gamble or time trade-off) and preferences of the general public in estimating QALYs. Studies therefore were categorized and evaluated according to the methods used to describe the health state, the valuation technique, and source of preferences. Results. Fifty-four studies were reviewed, 34 (63%) of which were published in the past 5 years. A generic health status classification instrument was used in 22 (35%) cases; the remainder developed study-specific health state descriptions or elicited preferences directly from patients or proxies. In 3 (5%) cases, sources were unclear. Preference weights were elicited using choice-based techniques in 28 (42%) cases, either as tariffs for health status classification instruments (17 cases) or by directly valuing health state descriptions or patient health (11 cases). Preferences of the general public were used in only 23 (37%) cases. Four studies aggregated QALYs for mother/child or parents/child pairs without giving any theoretical justification. Although there was an increasing tendency for studies to use generic health status classification instruments, choice-based methods, and preferences of the general public, the majority of studies still did not adhere to these standard recommendations even in the period between January 2000 and March 2004. Despite increasing standardization in the methods advocated for economic evaluation over the past 10 years, there remains extensive variation in the actual methods used by researchers to calculate QALYs for children and adolescents. It is unclear whether these results suggest poor practice or a set of positive (or reactive) choices made by analysts in a methodologically uncertain area in which specific guidance is lacking regarding how to address the complexities of pediatric outcomes within the QALY framework. Many aspects of QALY measurement in children are not yet fully developed. In particular, there is (1) a lack of appropriate health state classification instruments that take account of the dynamics of child development, (2) a lack of health state classification instruments for use in children and infants who are younger than 5 years, and (3) the need to understand fully the role of proxies for measuring and valuing child health. Additional research efforts are also required to develop methods that account for the health benefits of parents or caregivers of the child and to consider the implications of combining different forms of utility measurement in childhood and adulthood. Conclusions. Although variations from standard recommendations may be attributable to poor practice among researchers who are either unaware of these recommendations or choose not to follow them, they could equally be the result of attempts to make research more rigorous and more defensible than it might be if the standard recommendations were followed. There are 4 potential approaches to conducting cost-utility analysis in pediatric populations: (1) the explicit development of a generic instrument designed to be applicable across both child and adult populations (likely to be difficult in practice), (2) insistence on use of a generic instrument developed for adults, (3) the use of generic instruments specifically developed for children without being concerned about comparability with interventions aimed at adults, and (4) abandoning attempts to use single outcome measures that combine mortality with quality weights. In the absence of a clear way forward, it is suggested that an expert panel be convened to debate and further consider these potential solutions and recommendations for best practice and future research. In the interim, comparisons of the relative cost-effectiveness reported as cost per QALY gained across interventions for different diseases and populations should be treated with extreme caution.

The Role of Cost-Effectiveness Analysis in Health and Medicine

Article

Dec 1997
Surv Anesthesiol

The Science Of ‘Muddling Through

Article

Apr 1959

Charles E. Lindblom

Short courses, books, and articles exhort administrators to make decisions more methodically, but there has been little analysis of the decision-making process now used by public administrators. The usual process is investigated here-and generally defended against proposals for more "scientific" methods. Decisions of individual administrators, of course, must be integrated with decisions of others to form the mosaic of public policy. This integration of individual decisions has become the major concern of organization theory, and the way individuals make decisions necessarily affects the way those decisions are best meshed with others'. In addition, decision-making method relates to allocation of decision-making responsibility-who should make what decision. More "scientific" decision-making also is discussed in this issue: "Tools for Decision-Making in Resources Planning."

The use of QALYs in health service planning

Article

Oct 1989
INT J HEALTH PLAN M

There has been substantial interest in recent years, among research workers and in health service management, in the potential use of quality-adjusted life years (QALYs) as an aid to decision-making about the development of services and use of resources in health services (Gudex, 1986; Drummond, 1986). In 1986 the North Western Regional Health Authority (RHA) initiated the first large-scale attempt to use QALYs as a practical aid to planning in the National Health Service. This paper draws on the experience of the North Western RHA in examining some methodological and practical issues relating to the future of QALYs as an aid to decision-making in the Health Service.

The Uncertainty of the Past: Organizational Learning under Ambiguity

Article

May 2006
EUR J POLIT RES

Classical theories of omniscient rationality in organizational decision-making have largely been replaced by a view of limited rationality, but no similar concern has been reflected in the analysis of organizational learning. There has been a tendency to model a simple complete cycle of learning from unambiguous experience and to ignore cognitive and evaluative limits on learning in organizations. This paper examines some theoretical possibilities for assuming that individuals in organizations modify their understanding in a way that is intendedly adaptive even though faced with ambiguity about what happened, why it happened, and whether it is good. To develop a theory of learning under such conditions, we probably require ideas about information exposure, memory, and retrieval; learning incentives; belief structures; and the micro development of belief in organizations. We exhibit one example by specifying a structural theory of the relations among liking, seeing, trusting, contact, and integration in an organization. The argument is made that some understanding of factors affecting learning from experience will not only be important to the improvement of policy making in an organizational context, but also a necessary part of a theory of organizational choice.

Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin

Article

Sep 2007
DIABETES OBES METAB

Aim: To assess the efficacy and safety of a 24-week treatment with sitagliptin, a highly selective once-daily oral dipeptidyl peptidase-4 (DPP-4) inhibitor, in patients with type 2 diabetes who had inadequate glycaemic control [glycosylated haemoglobin (HbA1c) ≥7.5% and ≤10.5%] while on glimepiride alone or in combination with metformin. Methods: After a screening, diet/exercise run-in and drug wash-off period, a glimepiride ± metformin dose titration/stabilization period and a 2-week, single-blind placebo run-in, 441 patients (of ages 18–75 years) were randomized to receive the addition of sitagliptin 100 mg once daily or placebo in a 1 : 1 ratio for 24 weeks. Of these patients, 212 were on glimepiride (≥4 mg/day) monotherapy and 229 were on glimepiride (≥4 mg/day) plus metformin (≥1500 mg/day) combination therapy. Patients exceeding pre-specified glycaemic thresholds during the double-blind treatment period were provided open-label rescue therapy (pioglitazone) until study end. The primary efficacy analysis evaluated the change in HbA1c from baseline to Week 24. Secondary efficacy endpoints included fasting plasma glucose (FPG), 2-h post-meal glucose and lipid measurements. Results: Mean baseline HbA1c was 8.34% in the sitagliptin and placebo groups. After 24 weeks, sitagliptin reduced HbA1c by 0.74% (p < 0.001) relative to placebo. In the subset of patients on glimepiride plus metformin, sitagliptin reduced HbA1c by 0.89% relative to placebo, compared with a reduction of 0.57% in the subset of patients on glimepiride alone. The addition of sitagliptin reduced FPG by 20.1 mg/dl (p < 0.001) and increased homeostasis model assessment-β, a marker of β-cell function, by 12% (p < 0.05) relative to placebo. In patients who underwent a meal tolerance test (n = 134), sitagliptin decreased 2-h post-prandial glucose (PPG) by 36.1 mg/dl (p < 0.001) relative to placebo. The addition of sitagliptin was generally well tolerated, although there was a higher incidence of overall (60 vs. 47%) and drug-related adverse experiences (AEs) (15 vs. 7%) in the sitagliptin group than in the placebo group. This was largely because of a higher incidence of hypoglycaemia AEs (12 vs. 2%, respectively) in the sitagliptin group compared with the placebo group. Body weight modestly increased with sitagliptin relative to placebo (+0.8 vs. −0.4 kg; p < 0.001). Conclusions: Sitagliptin 100 mg once daily significantly improved glycaemic control and β-cell function in patients with type 2 diabetes who had inadequate glycaemic control with glimepiride or glimepiride plus metformin therapy. The addition of sitagliptin was generally well tolerated, with a modest increase in hypoglycaemia and body weight, consistent with glimepiride therapy and the observed degree of glycaemic improvement.

The Role of Economic Evidence in Canadian Oncology Reimbursement Decision‐Making: To Lambda and Beyond

Article

Jul 2008
VALUE HEALTH

Objective: The overarching question addressed in this article is: what has been the impact of economic evidence to Canadian drug reimbursement decisions; within this, has an (explicit or implicit) threshold been identified for making such decisions; and is the impact or threshold different for oncology medications? Methods: Three sequential strategies were employed: a literature search, a review of publicly available Canadian reimbursement recommendations, and a one-day key informant roundtable, held with a purposive sample of 13 individuals from across Canada to gain information not readily accessible from the public domain. Results: Despite the formal requirement for structured economic evidence, the limited public information suggests that its uptake in the Canadian decision-making process has been tentative. Implicit economic thresholds have been published in Australia and the United Kingdom, but not in Canada. Based on reviews of reimbursement recommendations, thresholds specific to oncology medications may be higher than for nononcology medications, in Canada and elsewhere. Canadian reimbursement recommendations can appear inconsistent with respect to clinical evidence, economic evidence, and nonevidentiary factors, possibly because of a lack of transparency or context-sensitive interpretations. The key informant roundtable provided reasons for the inconsistent uptake of economic evidence: panelists were divided between those who found economic information useful and supportive to decision-making, and those who did not. Panelists generally agreed on the need for publicly defensible and ethical reimbursement restrictions. They suggested the following improvements: transparency of processes and decisions, dynamic formularies that can adapt with evolving treatment practices and clinical data, broader representation of expertise on review panels, greater use of ethics to resolve conflicts arising from different perspectives, and the development of an explicit Canadian weighting system for evidence and values. Conclusions: Economic evidence has been tentatively incorporated in reimbursement decision-making in Canada. Public reasons for recommendation indicate that this evidence is used primarily with respect to the attractiveness of an incremental cost-effectiveness ratio. Oncology drugs seem to be adopted at the highest thresholds of acceptability. Yet, decision-makers expressed a need to move beyond lambda, rejecting the simplicity of the incremental cost-effectiveness ratio and considering alternative strategies to improve decision-making, including formal guidance for weighting both evidence and values.

Use of Pharmacoeconomics Information—Report of the ISPOR Task Force on Use of Pharmacoeconomic/Health Economic Information in Health‐Care Decision Making

Article

Jul 2003
VALUE HEALTH

Objectives: Despite the growing number of pharmacoeconomic (PE)/health economic (HE) studies, very little is known about their use by decision makers. The objectives of the Task Force were to ensure that the good research practices of PE/HE studies pay attention to the needs of health-care decision makers and to develop a "toolbox" for the health-care decision maker wanting to interpret and use PE/HE studies. Methods: The membership of the Task Force consisted of individuals involved in making decisions about the availability or use of medicines and researchers into the use of economic evaluations. The group communicated by E-mail and face-to-face meetings. A literature review of decision makers' attitudes toward PE/HE studies and published economic evaluation guidelines was undertaken. In addition, a focus group discussion was held with opinion leaders in managed care pharmacy. Results: The literature review identified 16 surveys of decision makers' attitudes toward PE/HE studies and 15 published guidelines that outlined reporting requirements for economic evaluations. These were reviewed and classified. Based on the published literature and comments from decision makers, seven additional reporting requirements for studies were specified. Conclusions: While the Task Force's additional reporting requirements may be helpful to decision makers, they raise a number of issues. These include the feasibility of meeting the additional requirements, whether decision makers should receive more education in economic evaluation, and whether there should be more study of health-care decision-making procedures themselves.

Economic evaluation under managed competition: Evidence from the UK

Article

Sep 1997

Although economic evaluation in health care has a long-standing tradition in the United Kingdom, very little is known about its impact on decision making, particularly following the introduction of the internal market. Since managed competition appears to be growing in popularity worldwide, the U.K. is an interesting case study, as the reforms are well underway and there have been a number of efforts to conduct and disseminate economic evaluations. In this paper the potential for using economic evaluation in health care decision making in the U.K. is discussed. Then its actual impact is assessed in two ways. First, two case studies are discussed, on heart transplantation and the use of pharmaceuticals in the management of labour in pregnancy. Second, new data from a recent survey of potential users of economic evaluations are presented, with the emphasis on exploring the reasons for the impact, or lack of impact, of economic results. It is concluded that the NHS reforms increase the potential for the use of economic evaluation. However, there is a need to increase decision makers' awareness of economic studies and to help them interpret study methodology and results. Although worries about validity of economic studies are one of the major barriers to their use, other important barriers relate to the multiple objectives being pursued, of which increased efficiency is just one, and the difficulties of freeing resources from existing services in order to divert them to more cost-effective treatments and programmes.

Maximizing health benefits vs egalitarianism: An Australian survey of health issues

Article

Nov 1995

Economists have often treated the objective of health services as being the maximization of the QALYs gained, irrespective of how the gains are distributed. In a cross section of Australians such a policy of distributive neutrality received: (a) very little support when health benefits to young people compete with health benefits to the elderly; (b) only moderate support when those who can become a little better compete with those who can become much better; (c) only moderate support when smokers compete with non smokers; (d) some support when young children compete with newborns; and (e) wide spread support when parents of dependent children compete with people without children. Overall, the views of the study population were strongly egalitarian. A policy of health benefit maximization received very limited support when the consequence is a loss of equity and access to services for the elderly and for people with a limited potential for improving their health.

Cost Effectiveness of Dipeptidyl Peptidase-4 Inhibitors for Type 2 Diabetes

Abstract

No full-text available

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