Download - Disinvestment. Ana Luísa Caires de Souza
SIX YEARS OF GLARGINE FINANCED BY THE MINAS GERAIS STATE GOVERNMENT, BRAZIL: SHOULD THE
GOVERNMENT DISINVEST?
Authors:Ana Luísa Caires de SouzaFrancisco de Assis AcurcioAugusto Afonso Guerra JúniorRenata Cristina Rezende Macedo do NascimentoLeonardo Maurício Diniz
Insulin analogues: safety, efficacy and comfort
Glargine
• 2000 EMEA• 2003 ANVISA
Expectation
Administrative requests: 2,632
Expenses of Minas Gerais State Treasury with glargine grew an average of 291% per
year, reaching almost USD 6 million/2011.
BACKGROUND
Hypoglycaemic episodesComfort
Marketingstrategy
Judicialization Medicines List SES/MG/2005
Glargine expenses in Minas Gerais State, Brazil (2007-2011)
Costs: Glargine > 536% NPH
2009: Glargine and cancer
Systematic Review: Efficacy and safety of glargine in T1DM.
BACKGROUND
OBJECTIVE
To assess the efficacy and the safety of glargine in order to evaluate the pertinence of maintenance the drug on the list of SUS from Minas Gerais State in Brazil.
Search MEDLINE; Latin American and Caribbean Centre on Health Sciences Information; Cochrane Controlled Trials Databases ; National Health Service (NHS) Centre for Reviews and Dissemination.
Software Reference Manager
Keywords Portuguese, English, Spanish.
METHODS
Health Condition
T1DMGlycated hemoglobinHypoglycemiaDiabetes complications
Intervention
Glargine insulin, NPH insulin, Regular insulin, Animal NPH insulin, Recombinant NPH insulin, Animal regular insulin, Recombinant regular insulin
Study Type
Efficacy Effectiveness Cost effectiveness
Inclusion Criteria
Intervention: glargine monotherapy or combination regimens with other insulins.
Exclusion Criterias
languages other than English, Portuguese or Spanish; not performed in human; unrelated to T1DM; Not present at least one of the outcome measures of efficacy or safety.
Systematic Reviews of Clinical Trials identified in the search process were used for comparison and discussion of results.
METHODS
Titles and abstracts analysis
2 reviewers; Discordant: 3rd reviewer.
Outcomes measure blood concentration of glycated hemoglobin; measures of glucose; episodes of hypoglycemia; reduction of microvascular and macrovascular events; adverse effects.
Assessment of risk of bias Modified Jadad Scale (JADAD, 1996)
METHODS
RESULTSSchematic presentation of the articles included and excluded in the systematic review
Studies initially identified in the search: 803
Included titles: 137
Excluded titles: 666
Reasons
Not performed in humans: 9
Not related to T1DM: 108
Not presenting comparative results regarding the efficacy/ effectiveness of the studied drug: 546
Not presenting at least one of the outcome measures of efficacy and/or safety consideration: 3
Studies included in the final review: 58 Observational studies: 50
Clinical trials: 8
Excluded abstracts: 79
Reasons
Not performed in humans: 6
Not related to T1DM: 4
Not presenting comparative results regarding the efficacy/ effectiveness of the studied drug: 64
Not presenting at least one of the outcome measures of efficacy and/or safety consideration: 5
RESULTS/DISCUSSION
Mean score: 2,87 None estudy with scored 5-6 No double-blind study Conflict of interest: 7 trials
Modified Jadad Scale
ArticleRandomisatio
n
Appropriate
Randomisatio
n
Inappropriate Randomisatio
n
Blinding
Appropriate
Blinding
Dropout/
Withdrawal
Intention to Treat
Analysis
Score
Rosenstock et al., 200017 1 0 0 0 0 1 1 3Raskin et al., 200015 1 1 0 0 0 1 1 4Pieber et al., 200013 1 0 0 0 0 0 0 1Schober et al., 200218 1 0 0 0 0 1 1 3Doyle et al., 20045 1 1 0 0 0 1 1 4Chatterjee et al., 20072 1 1 0 0 0 1 0 3Chase et al., 20081 1 0 0 0 0 1 1 3White et al., 200922 1 0 0 0 0 1 0 2
RESULTS/DISCUSSION
Characteristics of the selected clinical trials
7 Glargine x NPH, 1 Glargine x Aspart , 0 Glargine x Detemir;
Median participants: 168 (<32 e >619);
Median follow-up: 4 months (1 month, 2 years);
Basal therapy: glargine 1x/day x NPH 1x or 2x/day;
Prandial component: lispro, aspart or regular.
RESULTS/DISCUSSION
Characteristics of participants and interventions in selected clinical trials
1591 participants
Gender• female: 56,7%
Age• Minimum age: 5 years• Maximum age: 80 years
Associated comorbidities were investigated but were not discussed in the selected studies.
BMI: there were no changes (Chase et al., 2008; Doyle et al., 2004; and Chatterjee et al., 2007)
RESULTS/DISCUSSION
Advantages in the reduction of hypoglycemia and Glycated Hemoglobin (HbA1c)
Article
Statistically significant advantage in the
reduction of episodes of hypoglycaemia
Statistically significant advantage in the reduction
of HbA1c
Rosenstock et al., 200017 NPH *
Raskin et al., 200015 NS NS
Pieber et al., 200013 Glargine Glargine
Schober et al., 200218 ** NS
Doyle et al., 20045 ** Aspart
Chatterjee et al., 20072 NS Glargine
Chase et al., 20081 Glargine NS
White et al., 200922 * NS
* Not assessed in the study.NS: No statistically significant advantage found.**It was not presented p-value.
RESULTS/DISCUSSION The trials did not show relevant differences in the adverse effects.
Chronic complications of diabetes, mitogenic effects attributed to glargine and other possible long-term undesirable effects;
Cost-benefit ratio of glargine does not support its use, particularly in poor countries, although it might be indicated in specific conditions when there are sufficient resources (Gill et al, 2010). In Brazil, the cost of treating with glargine is remarkably higher than that with NPH insulin;
The cost-effectiveness ratio seems to favour the use of the NPH. Manufacturer of glargine should present the Unified Health System (SUS) managers reasons justifying the higher cost of this drug, including novel evidence and more precise measurements of its cost-effectiveness and impact on quality-adjusted life years (QALYs).
The present systematic review did not find advantages of the treatment with
glargine compared to other investigated insulin formulations when glycemic
control and the frequency and the severity of episodes of hypoglycemia were
analyzed together. Furthermore, the available evidence is weak and is not enough.
For these reasons, the SUS State Manager was advised to disinvest or to
renegotiate the price of glargine with its manufacturer.
CONCLUSION
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2. Chatterjee S, Jarvis-Kay J, Rengarajan T, Lawrence IG, McNally PG, Davies MJ. Glargine versus NPH insulin: efficacy in comparison with insulin aspart in a basal bolus regimen in type 1 diabetes--the glargine and aspart study (GLASS). Diabetes Res Clin Pract. Ago. 2007; 77(2):215-222.
3. Cohen D, Carter P. How small changes led to big profits for insulin manufacturers. BMJ. 2010; 341:c7139.4. Currie CJ, Poole CD, Gale EAM. The influence of glucose-lowering therapies on cancer risk in type 2 diabetes.
Diabetologia. 2009; 52:1766-1777.5. Doyle EA, Weinzimer SA, Steffen AT, Ahern JA, Vincent M, Tamborlane WV. A randomized, prospective trial comparing
the efficacy of continuous subcutaneous insulin infusion with multiple daily injections using insulin glargine. Diabetes Care. Jul. 2004; 27(7):1554-1558.
6. Gill GV, Yudkin JS, Keen H, Beran D. The insulin dilemma in resource-limited countries. A way forward? Diabetologia. 2010.
7. Hemkens LG, Grouven U, Bender R, Günster C, Gutschmidt S, Selke G W, et al. Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study. Diabetologia. Set. 2009; 52(9): 1732–1744.
8. Institut für qualität und Wirtschaftlichkeit im Gesundheitswesen [Institute of Quality and Efficiency in Health Care]. Long-acting insulin analogues in the treatment of diabetes mellitus type 1 (2010). Http://www.iqwig.de/download/A05-01_Executive-Summary_Long-acting_insulin_analogues_in_diabetes_mellitus_type_1.pdf (Accessed Sep 2010).
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THANK YOU!
Ana Luísa [email protected]