Objectives: To conduct a cost-utility analysis comparing drug strategies involving octreotide, lanreotide, pasireotide, and pegvisomant for the treatment of patients with acromegaly who have failed surgery, from a Brazilian public payer perspective. Methods: A probabilistic cohort Markov model was developed. One-year cycles were employed. The patients started at 45 years of age and were followed lifelong. Costs, efficacy, and quality of life parameters were retrieved from the literature. A discount rate (5%) was applied to both costs and efficacy. The results were reported as costs per quality-adjusted life year (QALY), and incremental cost-effectiveness ratios (ICERs) were calculated when applicable. Scenario analyses considered alternative dosages, discount rate, tax exemption, and continued use of treatment despite lack of response. Value of information (VOI) analysis was conducted to explore uncertainty and to estimate the costs to be spent in future research. Results: Only lanreotide showed an ICER reasonable for having its use considered in clinical practice (R$ 112,138/US$ 28,389 per QALY compared to no treatment). Scenario analyses corroborated the base-case result. VOI analysis showed that much uncertainty surrounds the parameters, and future clinical research should cost less than R$ 43,230,000/US$ 10,944,304 per year. VOI also showed that almost all uncertainty that precludes an optimal strategy choice involves quality of life. Conclusions: With current information, the only strategy that can be considered cost-effective in Brazil is lanreotide treatment. No second-line treatment is recommended. Significant uncertainty of parameters impairs optimal decision-making, and this conclusion can be generalized to other countries. Future research should focus on acquiring utility data.

1.
Melmed
S
.
Acromegaly pathogenesis and treatment
.
J Clin Invest
.
2009
Nov
;
119
(
11
):
3189
202
.
[PubMed]
0021-9738
2.
Chanson
P
,
Salenave
S
,
Kamenicky
P
.
Acromegaly
.
Handb Clin Neurol
.
2014
;
124
:
197
219
.
[PubMed]
0072-9752
3.
Liu
S
,
Adelman
DT
,
Xu
Y
,
Sisco
J
,
Begelman
SM
,
Webb
SM
, et al.
Patient-centered assessment on disease burden, quality of life, and treatment satisfaction associated with acromegaly
.
J Investig Med
.
2018
Mar
;
66
(
3
):
653
60
.
[PubMed]
1081-5589
4.
Bolfi
F
,
Neves
AF
,
Boguszewski
CL
,
Nunes-Nogueira
VS
.
Mortality in acromegaly decreased in the last decade: a systematic review and meta-analysis
.
Eur J Endocrinol
.
2018
Jul
;
179
(
1
):
59
71
.
[PubMed]
0804-4643
5.
Buchfelder
M
,
Schlaffer
SM
.
The surgical treatment of acromegaly
.
Pituitary
.
2017
Feb
;
20
(
1
):
76
83
.
[PubMed]
1386-341X
6.
Vilar
L
,
Vilar
CF
,
Lyra
R
,
Lyra
R
,
Naves
LA
.
Acromegaly: clinical features at diagnosis
.
Pituitary
.
2017
Feb
;
20
(
1
):
22
32
.
[PubMed]
1386-341X
7.
Melmed
S
,
Bronstein
MD
,
Chanson
P
,
Klibanski
A
,
Casanueva
FF
,
Wass
JA
, et al.
A Consensus Statement on acromegaly therapeutic outcomes
.
Nat Rev Endocrinol
.
2018
Sep
;
14
(
9
):
552
61
.
[PubMed]
1759-5029
8.
Leonart
LP
,
Ferreira
VL
,
Tonin
FS
,
Fernandez-Llimos
F
,
Pontarolo
R
.
Medical Treatments for Acromegaly: A Systematic Review and Network Meta-Analysis
.
Value Health
.
2018
Jul
;
21
(
7
):
874
80
.
[PubMed]
1098-3015
9.
Leonart
LP
,
Borba
HH
,
Ferreira
VL
,
Riveros
BS
,
Pontarolo
R
.
Cost-effectiveness of acromegaly treatments: a systematic review
.
Pituitary
.
2018
Dec
;
21
(
6
):
642
52
.
[PubMed]
1386-341X
10.
Lavrentaki
A
,
Paluzzi
A
,
Wass
JA
,
Karavitaki
N
.
Epidemiology of acromegaly: review of population studies
.
Pituitary
.
2017
Feb
;
20
(
1
):
4
9
.
[PubMed]
1386-341X
11.
Maione
L
,
Chanson
P
.
National acromegaly registries
.
Best Pract Res Clin Endocrinol Metab
.
2019
Apr
;
33
(
2
):
101264
.
[PubMed]
1521-690X
12.
Katznelson
L
,
Laws
ER
 Jr
,
Melmed
S
,
Molitch
ME
,
Murad
MH
,
Utz
A
, et al.;
Endocrine Society
.
Acromegaly: an endocrine society clinical practice guideline
.
J Clin Endocrinol Metab
.
2014
Nov
;
99
(
11
):
3933
51
.
[PubMed]
0021-972X
13.
Brazil. Protocolo Clínico e Diretrizes Terapêuticas da Acromegalia - Ministry of Health.
2019
.
14.
Briggs
AH
,
Weinstein
MC
,
Fenwick
EA
,
Karnon
J
,
Sculpher
MJ
,
Paltiel
AD
;
ISPOR-SMDM Modeling Good Research Practices Task Force
.
Model parameter estimation and uncertainty analysis: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force Working Group-6
.
Med Decis Making
.
2012
Sep-Oct
;
32
(
5
):
722
32
.
[PubMed]
0272-989X
15.
Caro
JJ
,
Briggs
AH
,
Siebert
U
,
Kuntz
KM
;
ISPOR-SMDM Modeling Good Research Practices Task Force
.
Modeling good research practices—overview: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force-1
.
Med Decis Making
.
2012
Sep-Oct
;
32
(
5
):
667
77
.
[PubMed]
0272-989X
16.
Eddy
DM
,
Hollingworth
W
,
Caro
JJ
,
Tsevat
J
,
McDonald
KM
,
Wong
JB
;
ISPOR-SMDM Modeling Good Research Practices Task Force
.
Model transparency and validation: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force-7
.
Med Decis Making
.
2012
Sep-Oct
;
32
(
5
):
733
43
.
[PubMed]
0272-989X
17.
Roberts
M
,
Russell
LB
,
Paltiel
AD
,
Chambers
M
,
McEwan
P
,
Krahn
M
;
ISPOR-SMDM Modeling Good Research Practices Task Force
.
Conceptualizing a model: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force-2
.
Med Decis Making
.
2012
Sep-Oct
;
32
(
5
):
678
89
.
[PubMed]
0272-989X
18.
Siebert
U
,
Alagoz
O
,
Bayoumi
AM
,
Jahn
B
,
Owens
DK
,
Cohen
DJ
, et al.;
ISPOR-SMDM Modeling Good Research Practices Task Force
.
State-transition modeling: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force—3
.
Value Health
.
2012
Sep-Oct
;
15
(
6
):
812
20
.
[PubMed]
1098-3015
19.
Husereau
D
,
Drummond
M
,
Petrou
S
,
Carswell
C
,
Moher
D
,
Greenberg
D
, et al.;
CHEERS Task Force
.
Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement
.
Value Health
.
2013
Mar-Apr
;
16
(
2
):
e1
5
.
[PubMed]
1098-3015
20.
Brazil. Methodological guideline: economic evaluaton of health technologies - Ministry of Health.
2014
.
21.
IBGE
.
Brazilian life table.
2017
.
22.
IBGE
. 2016 Brazil gross domestic product per capita.
2019
.
23.
Ben-Shlomo
A
,
Melmed
S
.
Somatostatin agonists for treatment of acromegaly
.
Mol Cell Endocrinol
.
2008
May
;
286
(
1-2
):
192
8
.
[PubMed]
0303-7207
24.
Gadelha
MR
,
Bronstein
MD
,
Brue
T
,
Coculescu
M
,
Fleseriu
M
,
Guitelman
M
, et al.;
Pasireotide C2402 Study Group
.
Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, phase 3 trial
.
Lancet Diabetes Endocrinol
.
2014
Nov
;
2
(
11
):
875
84
.
[PubMed]
2213-8587
25.
Didoni
G
,
Grottol
S
,
Gasco
V
,
Battistini
M
,
Ferone
D
,
Giusti
M
, et al.
Cost-of-illness study in acromegalic patients in Italy
.
J Endocrinol Invest
.
2004
Dec
;
27
(
11
):
1034
9
.
[PubMed]
0391-4097
26.
InflationTool
. Value of 2003 Euro (Italy) today.
2019
.
27.
OECD
. "
Purchasing power parities (PPP)
" (indicator).
2019
.
28.
Briggs
A
,
Claxton
K
,
Sculpher
M
.
Decision modelling for hralth economic evaluation
.
Oxford University Press
;
2011
.
29.
IPEA
. Instituto de Pesquisa Econômica Aplicada - Taxa de câmbio comercial para venda.
2020
.
30.
Trainer
PJ
,
Ezzat
S
,
D’Souza
GA
,
Layton
G
,
Strasburger
CJ
.
A randomized, controlled, multicentre trial comparing pegvisomant alone with combination therapy of pegvisomant and long-acting octreotide in patients with acromegaly
.
Clin Endocrinol (Oxf)
.
2009
Oct
;
71
(
4
):
549
57
.
[PubMed]
0300-0664
31.
Ghigo
E
,
Biller
BM
,
Colao
A
,
Kourides
IA
,
Rajicic
N
,
Hutson
RK
, et al.
Comparison of pegvisomant and long-acting octreotide in patients with acromegaly naïve to radiation and medical therapy
.
J Endocrinol Invest
.
2009
Dec
;
32
(
11
):
924
33
.
[PubMed]
0391-4097
32.
Strong
M
,
Oakley
JE
,
Brennan
A
.
Estimating multiparameter partial expected value of perfect information from a probabilistic sensitivity analysis sample: a nonparametric regression approach
.
Med Decis Making
.
2014
Apr
;
34
(
3
):
311
26
.
[PubMed]
0272-989X
33.
Thorn
J
,
Coast
J
,
Andronis
L
.
Interpretation of the Expected Value of Perfect Information and Research Recommendations: A Systematic Review and Empirical Investigation
.
Med Decis Making
.
2016
Apr
;
36
(
3
):
285
95
.
[PubMed]
0272-989X
34.
Soarez
PC
,
Novaes
HM
.
Cost-effectiveness thresholds and the Brazilian Unified National Health System
.
Cad Saude Publica
.
2017
May
;
33
(
4
):
e00040717
.
[PubMed]
1678-4464
35.
Adalsteinsson
E
,
Toumi
M
.
Benefits of probabilistic sensitivity analysis - a review of NICE decisions
.
J Mark Access Health Policy
.
2013
Aug
;
1
(
1
):
1
.
[PubMed]
2001-6689
36.
Ollendorf
DA
,
Chapman
RH
,
Pearson
SD
.
Evaluating and Valuing Drugs for Rare Conditions: No Easy Answers
.
Value Health
.
2018
May
;
21
(
5
):
547
52
.
[PubMed]
1098-3015
37.
Gadelha
MR
,
Wildemberg
LE
,
Bronstein
MD
,
Gatto
F
,
Ferone
D
.
Somatostatin receptor ligands in the treatment of acromegaly
.
Pituitary
.
2017
Feb
;
20
(
1
):
100
8
.
[PubMed]
1386-341X
38.
Pless
J.
The history of somatostatin analogs. J Endocrinol Invest.
2005
;28(11 Suppl International):1-4.
39.
Valentim
J
,
Passos
V
,
Mataveli
F
,
Calabró
A
.
Cost-effectiveness analysis of somatostatin analogues in the treatment of acromegaly in Brazil
.
Arq Bras Endocrinol Metabol
.
2008
Dec
;
52
(
9
):
1452
60
.
[PubMed]
0004-2730
40.
Fujii
RK
,
Mould
JF
,
Fernandes
RA
,
Furlan
F
,
Manfrin
DF
.
Economic evaluation of pegvisomant for active acromegaly patients who failed available therapies in Brazil—public health care system perspective
.
Value Health
.
2012
;
15
(
4
):
A105
105
. 1098-3015
41.
Souza
CR
,
Ferreira
CN
,
Ribeiro
AP
,
Musolino
NR
.
Economic evaluation of pegvisomanto for the treatment of patients with acromegaly with an inadequate response to a maximal dose of octreotide (alone or combined) in the context of the Unified Health System
.
Brazilian Journal of Health Economics.
2014
;
6
(
2
):
8
.
42.
Moore
DJ
,
Adi
Y
,
Connock
MJ
,
Bayliss
S
.
Clinical effectiveness and cost-effectiveness of pegvisomant for the treatment of acromegaly: a systematic review and economic evaluation
.
BMC Endocr Disord
.
2009
Oct
;
9
(
1
):
20
.
[PubMed]
1472-6823
43.
Peral
C
,
Cordido
F
,
Gimeno-Ballester
V
,
Mir
N
,
Sanchez-Cenizo
L
,
Rubio-Rodriguez
D
, et al.
Cost-effectiveness analysis of second-line pharmacological treatment of acromegaly in Spain
.
Expert Rev Pharmacoecon Outcomes Res
.
2019
May
;
•••
:
1
10
.
[PubMed]
1473-7167
44.
Rowles
SV
,
Prieto
L
,
Badia
X
,
Shalet
SM
,
Webb
SM
,
Trainer
PJ
.
Quality of life (QOL) in patients with acromegaly is severely impaired: use of a novel measure of QOL: acromegaly quality of life questionnaire
.
J Clin Endocrinol Metab
.
2005
Jun
;
90
(
6
):
3337
41
.
[PubMed]
0021-972X
45.
Burström
K
,
Johannesson
M
,
Diderichsen
F
.
Swedish population health-related quality of life results using the EQ-5D
.
Qual Life Res
.
2001
;
10
(
7
):
621
35
.
[PubMed]
0962-9343
46.
Chanson
P
,
Salenave
S
.
Acromegaly
.
Orphanet J Rare Dis
.
2008
Jun
;
3
(
1
):
17
.
[PubMed]
1750-1172
47.
Banco de Preços em Saúde. Ministry of Health of Brazil. 2019.
48.
Câmara de Regulação do Mercado de Medicamentos. Brazilian Health Regulatory Agency. 2019.
49.
Sistema de Gerenciamento da Tabela de Procedimentos, Medicamentos e Órteses, Próteses e Medicamentos do Sistema Único de Saúde. Ministry of Health of Brazil. 2019.
50.
Melmed S, Casanueva FF, Klibanski A, Klibanski A, Bronstein MD, Chanson P, et al. A consensus on the diagnosis and treatment of acromegaly complications. Pituitary. 2013 Sep;16(3):294–302.
51.
IBGE. Population. 2018.
52.
Day PF, Loto MC, Glerean M, Picasso MFR, Lovazzano S, Giunta DH. Incidence and prevalence of clinically relevant pituitary adenomas: retrospective cohort study in a Health Management Organization in Buenos Aires, Argentina. Arch Endocrinol Metab. 2016 Nov-Dec;60(6):554–561.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.