Introduction
Acromegaly is a rare disease caused by hypersecretion of growth hormone (GH) in most cases from the pituitary adenoma, and subsequently production of insulin-like growth factor 1 (IGF-I) in peripheral tissues, leading to typical features of acromegaly. The therapeutic options are neurosurgery, medical treatment, and radiotherapy. When the disease is not cured or controlled, it reduces life expectancy by almost 10 years, causing disabilities, complications, and a decrease in quality of life [1–3]. Premature mortality in acromegaly is mainly due to cardiovascular complications, respiratory system diseases, and increased risk of various neoplasms [3–6]. The necessity for life-long treatment of acromegaly-associated comorbidities and complications influences the total costs of acromegaly patients’ management [7–8].
The pharmacoeconomic analysis covers all real costs of medical services. There are medical costs directly related to the therapeutic process: costs of medications and medical procedures (surgery, radiotherapy, imaging, laboratory analyses, medical consultations). Direct non-medical costs cover expenses of transportation, special diet, or additional nursery. Indirect costs include financial consequences of the disease (reduced employment, disability pension, or premature retirement). There are also non-measurable costs connected with pain or distress, usually causing a low quality of life [9].
Modern, comprehensive diagnostic and therapeutic methods are expensive, but they can help to restore the expected survival of patients and improve their quality of life [2, 6]. Analysis of the costs of acromegaly management is crucial for the diagnostic and therapeutic projects from the individual patient view as for the settlements of management standards for the whole population of patients.
The aim of the study was to assess the real costs of management of patients with acromegaly from one academic centre with regard to the current activity of the disease.
Material and methods
Material
Retrospective analysis was carried out based on 303 records taken from the archive of the University Clinical Hospital (known before as Independent Public Clinical Hospital No. 1). Data included a total of 124 consecutive patients with confirmed acromegaly, of whom 74 were women (59.7%) and 50 were men (40.3%), hospitalised in the Clinic of Endocrinology, Diabetes, and Isotope Therapy (present name Clinic of Endocrinology and Internal Medicine) within the period 2011-2016. The patients were divided into 4 groups: cured patients (ACUR), patients controlled by medical therapy (ACON), patients not controlled — with active disease (AACT), and de novo patients with recently diagnosed acromegaly, before any treatment (ANOV). The analysis did not include patients in whom acromegaly was not confirmed by the end of the study. We assessed the groups in terms of age, age at diagnosis, and duration of disease since diagnosis. The basic characteristics of patient groups is given in Table 1.
|
|
Group |
Whole group (n = 124) |
|||
|
ACUR (n = 39) |
ACON (n = 17) |
AACT (n = 56) |
ANOV (n = 12) |
||
|
Sex |
|||||
|
Men |
11 |
8 |
24 |
7 |
50 |
|
Women |
28 |
9 |
32 |
5 |
74 |
|
Age [years] |
|||||
|
Mean ± SD |
54.00 ± 14.68 |
56.88 ± 14.16 |
56.55 ± 15.06 |
52.50 ± 11.84 |
55.40 ± 14.40 p = 0.75 |
|
Min |
21 |
35 |
27 |
35 |
21 |
|
Max |
81 |
82 |
86 |
72 |
86 |
|
Age at diagnosis [years] |
|||||
|
Mean ± SD |
42.72 ± 15.32 |
41.53 ± 15.59 |
42.25 ± 14.09 |
48.92 ± 11.49 |
42.94 ± 14.39 p=0.45 |
|
Min |
16 |
23 |
18 |
32 |
16 |
|
Max |
73 |
75 |
74 |
69 |
75 |
|
Disease duration [years] |
|||||
|
Mean ± SD |
14.15 ± 9.41 |
17.35 ± 9.03 |
16.73 ± 11.15 |
6.75 ± 2.99 |
15.04 ± 10.13 p=0.01 |
|
Min |
4 |
5 |
5 |
3 |
3 |
|
Max |
41 |
38 |
50 |
13 |
50 |
Patients were divided according to criteria proposed by the Endocrine Society (2014), in which well controlled patients had normal serum IGF-I concentrations for age and sex, and random serum GH < 1.0 μg/L during medical therapy [10]. Patients cured by successful neurosurgery did not require adjuvant medical therapy, their IGF-I concentrations were normal, and they had GH < 1.0 μg/L after oral glucose load [10]. When hormonal normalisation failed, those patients were assigned to the group with active disease.
Methods
Costs of hospitalisations
The calculation of costs related to patient hospitalisation in the clinic was based on the system of Homogeneous Patient Groups (Polish abbreviation JGP) established and valued by the National Health Fund (Polish abbreviation NFZ). The version from 30 December 2016 was used to perform the analysis (Annex 1 to Ordinance No. 129/2016/DSOZ of the President of the NFZ). The obtained point values were multiplied by the average point price in PLN determined on the basis of the agreement between the Hospital and the NFZ for 2016. The cost of hospitalisation included the costs of the patient’s stay in the hospital, the costs of medical advice, diagnostic and laboratory tests, and the costs of pharmacotherapy. The above cost was variable if a patient with acromegaly had at least one hormonal test performed, or the daily rhythm of hormone secretion was assessed during a stay that lasted no longer than 14 days (group K53). If the stay was longer, its cost increased by PLN 208.00 for each additional day. However, if no diagnostic test was performed during hospitalisation, the stay was valued at PLN 2132.00 (group K16).
Costs of neurosurgical procedures
The JGP system was used to calculate the costs of neurosurgical procedures. The calculations included both partial removal of the pituitary gland using a transsphenoidal approach (procedure code 07.62) and a transfrontal approach (procedure code 07.613), which belong to group A11 in the JGP system. The NFZ values this group, which takes into account both the cost of the surgical procedure and the perioperative hospital stay, are 297 points (PLN 15,444.00). The price of one point for the procedure in 2016 was PLN 52.00.
Costs of radiotherapy
The costs of radiotherapy were divided into stereotactic radiotherapy, which is now used as standard, and conventional radiotherapy, which is now rarely used in the treatment of acromegaly. Due to the difficulties in determining the exact method of settling the procedure, an arithmetic mean was calculated for various subtypes of these procedures. The average cost of stereotactic radiotherapy was estimated at 316.33 points, or PLN 16,449.33, and the average cost of conventional radiotherapy was 146 points (PLN 7592.00).
Imaging and endoscopic examinations (MRI, CT, ultrasound, densitometry, gastroscopy, colonoscopy)
To calculate the costs of diagnostic tests, the data included in Annex 1B of Order No. 62/2016/dsoz of the President of the NFZ were used, and from which the cost of magnetic resonance imaging (MRI) of the pituitary gland included in the procedure “MR: examination of another anatomical area without and with contrast enhancement” was estimated at 58.56 points, or PLN 545.00. In the case of an MRI examination of 2 different areas, the “MR: examination of 2 other anatomical areas without and with contrast enhancement” procedure was used for calculations, which was valued at 102.76 points, i.e. PLN 955.00. The cost of computed tomography (CT) of the head with contrast was estimated by the NFZ at 30 points, which corresponds to PLN 264.00. The cost of performing a CT scan of another area (neck, chest, abdomen, pelvis, limbs) is 45 points (PLN 396.00) for one area, and 65 points (PLN 571.00) for 2 or more areas. During diagnostics, one patient required somatostatin receptor scintigraphy performed at another facility, the cost of which was estimated at the hospital at PLN 5150.00 and is the average commercial price of this test from 2 Nuclear Medicine Departments.
The costs of ultrasound examinations were estimated by the NFZ only in outpatient health care at PLN 64.40 for ultrasound of the thyroid or abdominal cavity (group W12) and at PLN 92 for echocardiography (group W17). Densitometry using two-energy X-ray absorptiometry (DXA) in one location was valued at 7 points (PLN 64.40).
Some patients required planned endoscopic diagnostics. During the diagnosis, the costs of gastroscopy and colonoscopy with biopsy were taken into account, which was valued by the NFZ at 20 and 40 points, respectively, which corresponds to PLN 152.00 and PLN 304.00.
The costs of additional treatments
Information about previous surgical procedures was obtained from the anamnesis and patients medical records. The JGP system was used to calculate the costs of procedures. In some cases, it was not possible to obtain accurate information about the scope of the procedure or the final method of billing for the procedure. In these cases, the final cost was obtained by calculating the arithmetic average of the costs of procedures related to a given organ or type of procedure, but differing in scope (e.g. total/partial, major/comprehensive/radical). In the case of cholecystectomy, the cost depended on age, and in patients < 65 years of age it was 60 points, and in patients over 65 years of age it was 70 points, which corresponds to PLN 3120.00 and PLN 3640.00, respectively. In the case of biliary prosthesis, the cost is 160 points, i.e. PLN 8320.00. The average cost of thyroidectomy and parathyroidectomy was 73 points, or PLN 3796.00. The average cost of hip replacement was calculated at 150.36 points (PLN 7818.46), and the cost of knee joint replacement at 161.00 points (PLN 8372.00). The cost of adrenalectomy was estimated by the NFZ at 130 points, i.e. PLN 6760.00. The average costs of vaginectomy and hysterectomy due to cancer were 170.5 points and 229.5 points, respectively, i.e. PLN 8866.00 and PLN 11,934.00. Ovary removal was valued at 68 points, i.e. PLN 3536.00. The public payer valued nephrectomy at 152 points (PLN 7904.00). The average cost of mastectomy due to a tumour was estimated at 115.67 points (PLN 6014.67). The cost of nephrectomy is 152 points, or PLN 7904.00. The cost of removing a salivary gland tumour is 134 points. (PLN 6968.00). The valvuloplasty procedure was valued at 473 points, which corresponded to PLN 24,596.00. The cost of carpal tunnel surgery is 25 points (PLN 1300.00).
The costs of pharmacological treatment of acromegaly
When calculating the costs of pharmacological treatment of acromegaly, the costs of somatostatin analogues (SSAs) and dopamine agonists were taken into account. Long-acting first-generation SSAs (lanreotide and octreotide) are reimbursed in Poland for the treatment of acromegaly. To calculate these costs, the data included in the list of reimbursed drugs from Appendix 1 to the Announcement of the Minister of Health on 28 December 2016, were used. The type of drug and the dose were obtained from patient information cards. Based on the medical anamnesis, information was obtained about the therapy used before hospitalisation, and based on medical recommendations, the therapy to be used until the next stay at the clinic. Taking into account that changing the dose was usually preceded by hospitalisation to perform the necessary examinations and tests, it was assumed that the patient would continue to take the treatment recommended after hospitalisation until the next stay. On this basis, information was obtained about the monthly and annual cost of SSA treatment for each patient.
The costs of pharmacological treatment of acromegaly complications
Information about the medications used by patients was obtained from interviews and medical records. In the case of the use of reimbursed drugs, data from the list of reimbursed drugs from the Announcement of the Minister of Health on 28 December were used. In the case of drugs that are not reimbursed, prices were obtained in the period 2016–2017 from the Drug Index published by the Medycyna Praktyczna (Practical Medicine) portal. On this basis, the monthly and then annual treatment costs were calculated. The currency exchange rate according to the National Bank of Poland on 1 December 2016 was 1 EUR = PLN 4.462; USD 1 = PLN 4.198.
Statistical analysis
Using descriptive statistical methods, basic data were prepared and divided into groups: ACUR, ACON, AACT, ANOV. Data analyses were performed using the R statistical environment version 3.6.2 and additional packages dedicated to specific types of data analyses and visualisations. For each variable or group of variables, first, a basic statistical description was performed, including the calculation of the skewness of the distribution. Due to the high skewness of most of the analysed distributions and the occurrence of outliers, it was decided that non-parametric statistical analyses would be used to answer the research questions. Comparisons of mean values of variables between groups of patients were performed using the Kruskal-Wallis (KW) test based on rank sums and the chi-square statistic. The effect size for the KW test was the eta-squared statistic calculated from the test statistic of the KW test. The eta-squared statistic is conventionally interpreted as indicating a small effect for values in the range 0.01-0.06, a moderate effect for values in the range 0.06-0.14, and a large effect for values in the range 0.14-1. If the statistical significance of the KW test was noted, pairwise comparisons were performed between individual groups of patients using the Mann-Whitney (MW) test. P values for these analyses were corrected using Holm’s correction for multiple comparisons. The r statistic was used as a measure of the strength of the effect for this test, and it was assumed that absolute values in the range 0.1-0.3 indicate a small effect, values in the range 0.3-0.5 indicate a moderate effect, and values in the range 0.5-1 indicate a large effect. Analysis of relationships between continuous variables were based on Spearman’s rho coefficient due to the non-linear but monotonic nature of some relationships and the occurrence of observations that deviate significantly from the centre of bivariate distributions. Variable distributions were visualised using boxplots. The extremes show the 25th and 75th percentiles (i.e. interquartile range, IQR), while the bold line inside the box indicates the median. Additionally, black points with vertical lines are superimposed on the boxes, which indicate the means and the corresponding 95% confidence interval. Relationships between variables were presented using scatterplots, where one point represents one pair of observations. Statistical tests were considered significant for p values ≤ 0.05.
Results
The study included 124 patients - 74 women (59.7%) and 50 men (40.3%) - diagnosed with acromegaly. The mean age of the entire study population was 55.40 ± 14.39 years: 57.04 ± 14.99 years for women and 52.98 ± 13.4 years for men. The average age at diagnosis was 42.94 ± 14.38 years. The average duration of the disease was 16.73 ± 6.75 years. Detailed characteristics of the patient groups are presented in Table 1.
In 4 patients, acromegaly coexisted with multiple endocrine neoplasia syndrome (MEN), including as a component of MEN 1 syndrome in 3 patients, and with McCune-Albright syndrome in one patient. Two patients with active acromegaly during the study period were treated with pasireotide as part of a clinical trial. One patient took oral octreotide as part of a clinical trial. Therapy combining a somatostatin analogue and a dopamine agonist was used by 2 patients with active acromegaly. Five patients with acromegaly did not agree to surgical treatment.
The total costs of acromegaly management
The total costs of acromegaly management are shown in Table 2. They were highest in the ACON group, and the next was the AACT group. Comparative analysis revealed the lower costs in the ACUR group, less than in groups ACON and AACT (p = 0.00, p = 0.00, respectively). These costs were lower in the ANOV group than in groups ACON and AACT (p = 0.00, p = 0.00, respectively).
|
Group |
Mean |
SD |
Median |
Min |
Max |
|
ACUR |
39,378.40 |
57,261.80 |
24,065.80 |
2,175.39 |
257,686.00 |
|
ACON |
193,852.00 |
118,470.00 |
149,950.00 |
62,174.20 |
404,078.00 |
|
AACT |
145,068.00 |
103,003.00 |
106,681.00 |
3709.34 |
455,726.00 |
|
ANOV |
6308.76 |
2704.72 |
4761.11 |
4341.00 |
13,077.65 |
|
Entire group |
105,086.70 |
108,264.40 |
66,016.60 |
2175.39 |
455,726.20 |
The total costs of the SSA treatment in patients with acromegaly are shown in Table 3. They are highest in the ACON group, the next is the AACT group. The costs of SSA were lower in the ACUR group than in the ACON and AACT groups (p = 0.00, p = 0.00, respectively).
|
Group |
Mean |
SD |
Median |
Min |
Max |
|
ACUR |
23,690.80 |
52,199.60 |
0 |
0 |
242,229.00 |
|
ACON |
177,551.00 |
114,707.00 |
121,049.00 |
60,042.20 |
391,313.00 |
|
AACT |
127,727.00 |
96,628.10 |
90,066.30 |
0 |
409,869.00 |
|
ANOV |
– |
– |
– |
– |
– |
|
Entire group |
99,062.51 |
103,970.50 |
62,096.65 |
0 |
409,869.00 |
The total costs of neurosurgical treatment in patients with acromegaly are shown in Table 4. They are highest in the ACUR group, the next is the AACT group. The costs were lower in the ACON group than in the ACUR group (p = 0.00).
|
Group |
Mean |
SD |
Median |
Min |
Max |
|
ACUR |
7920.00 |
8585.56 |
0 |
0 |
30,888.00 |
|
ACON |
1816.94 |
5129.04 |
0 |
0 |
15,444.00 |
|
AACT |
5239.93 |
7378.40 |
0 |
0 |
15,444.00 |
|
ANOV |
– |
– |
– |
– |
– |
|
Entire group |
5653.61 |
7755.47 |
0 |
0 |
30,888.00 |
The mean total cost of neurosurgeries in entire group was PLN 17,374.50 ± 10,182.38, and it was similar among the subgroups of patients. The mean total costs of radiotherapy were highest in the AACT group (PLN 3163.00 ± 7440.96), the next in the ACON group (PLN 893.18 ±2251.35), and then the ACUR group (PLN 194.67 ± 1215.69); the differences were not statistically significant.
The costs per year of acromegaly management
Analysis of mean costs of hospitalisation per year is shown in Table 5. They were highest in the ANOV group in comparison to groups ACON, ACUR, and AACT (p = 0.002, p = 0.045, p = 0.045, respectively).
|
Group |
Mean |
SD |
Median |
Min |
Max |
|
ACUR |
3410.22 |
1247.23 |
3614.00 |
2132.00 |
7592.00 |
|
ACON |
2950.49 |
834.98 |
2964.00 |
2132.00 |
4662.67 |
|
AACT |
3295.61 |
1027.84 |
3280.33 |
2132.00 |
5928.00 |
|
ANOV |
4606.33 |
1522.11 |
3796.00 |
3796.00 |
7592.00 |
|
Entire group |
3411.19 |
1194.00 |
3480.10 |
2132.00 |
7592.00 |
Mean costs per year of SSA treatment were highest in the groups AACT (PLN 56,678.4 ± 25,352.7) and ACON (PLN 54,811.6 ± 15,734.6) in comparison to the ACUR group (PLN 8103.23 ± 13,756.7; p < 0.01, for both). Mean costs per year of diagnostic procedures were highest in the ANOV group (PLN 949.33 ± 1.42) than in remaining groups (PLN 335.9–440.54). Mean costs per year of additional surgical procedures were highest in the ACON group (PLN 883.94 ± 1675.36); the lowest were in the ACUR group (PLN 80.00 ± 348.59; p = 0.024). Mean costs per year of additional therapies covered by NFZ were PLN 423.12 ± 699.5 5 in entire group; they were highest in the AACT group (PLN 573.22 ± 906.13) and lowest in the ANOV group (PLN 120.42 ± 156.47; p = 0.066). The mean costs per year of additional therapies covered by patients themselves were PLN 488.42 ± 473.84 for the entire group, they were highest in group AACT (614.19 ± 521.31), but the differences were not statistically significant.
Analysis of the mean costs per year of acromegaly management is shown in Table 6. They were highest in the AACT group, higher than in groups ACUR and ANOV (p < 0.001, for both). The next expensive was the ACON group, the costs were higher than in groups ACUR and ANOV (p < 0.001, p < 0.009, respectively).
|
Group |
Mean |
SD |
Median |
Min |
Max |
|
ACUR |
16,781.10 |
16,432.70 |
12,353.80 |
2175.40 |
64,421.40 |
|
ACON |
60,098.20 |
16,072.90 |
63,272.60 |
32,472.70 |
89,472.10 |
|
AACT |
64,861.20 |
24,744.60 |
65,864.00 |
3709.30 |
122,761.30 |
|
ANOV |
6308.76 |
2704.72 |
4761.11 |
4341.00 |
13,077.65 |
|
Entire group |
43,419.90 |
31,600.60 |
45,575.30 |
2175.40 |
122,761.30 |
Discussion
The high costs of acromegaly treatment result in a significant economic burden for both the patient, his/her family, and society as a whole. The presented data indicate a spotty distribution of acromegaly management costs. There are great differences between therapy, diagnostics, and hospitalisation costs. The greatest impact on the overall costs is medical therapy, while other costs burden the health service system to a lesser extent. For example, according to Lesen et al., in 2013 in Sweden, the total annual cost of treating a patient was EUR 12,000 [11]. In the treatment of acromegaly, as well as other diseases, direct costs are the most significant component of treatment expenses. Few publications allow the estimation of the amount of these expenses. In the above mentioned paper, the share of direct costs was approximately 77% of all costs incurred, i.e. EUR 9200 per patient [11].
In the present study mean hospitalisation costs were highest in de novo patients, and the lowest in well controlled patients. This was caused by a wide variety of diagnostics and preparation for neurosurgery in de novo patients. On the other hand, regular, often yearly, hospitalisations influence the costs in other groups. The reason for the lowest costs in patients controlled by medical therapy is that medical therapy with SSA is carried out on an out-patient basis, the costs of therapy do not influence the hospitalisation costs. Ribeiro-Oliveira et al. showed higher costs per year of hospitalisation of acromegaly patients in comparison with the general population (USD 8646 vs. 739, respectively) [12]. Didoni et al. presented higher hospitalisation costs of well controlled patients than those with active disease [13]. Kamusheva et al. reported that occurrence of other diseases in patients with acromegaly was connected with a longer hospitalisation period and higher costs [14]. Additionally, the presence of diabetes, musculoskeletal disorders, or sleep apnea in acromegaly patients increased the probability of hospitalisation 1.5–2-fold, and the coincidence of cardiovascular diseases as much as 3-fold [15].
In our analysis, the costs of neurosurgeries were highest in cured patients and lowest in controlled patients. The cured patients underwent at least one successful surgery, but many of them had more operations. The controlled patients usually had one non-successful operation. In Italy, the costs of neurosurgeries were on average EUR 7019 (EUR 7019–21,056) [16], and in China USD 7243 [17]. Radiotherapy costs were shown in the group of patients with active disease (PLN 1174.95) only. For comparison, those costs in China were on average USD 4092 [17].
The costs of medical therapy included mainly the costs of SSA. They were administered on an outpatient basis with reimbursement of the health service system. In our study, total SSA costs were lowest in patients cured by neurosurgery. SSA therapy was administered to them only preoperatively, according to Polish Society of Endocrinology recommendations [18]. Patients from other groups received SSA for a longer time, causing higher treatment costs. For comparison, the mean cost per year of medical therapy in China was USD 8040 [17]; in Sweden EUR 13,500 [11]; and in Spain EUR 13,000 [19]. Patients with the uncontrolled disease despite medical therapy caused higher costs than well controlled ones (USD 10,140 vs. 6162) [17]. A study by an Italian team led by Cocchiara, conducted on a group of 73 patients, showed that the average annual cost of pharmacological treatment was EUR 4927 for therapy with first-generation SSA (octreotide, lanreotide). The average cost of treatment with pegvisomant was EUR 9161 [16]. Placzek et al. analysed data from the HealthCore integrated research database of 757 acromegaly patients with private insurance in the United States. They showed that the total annual cost of treatment is USD 10,903, of which USD 4757 are the costs of surgical and pharmacological treatment [20]. In a Swedish study pharmacological treatment alone (mainly SSA and pegvisomant) accounted for over 48% of all expenses, which corresponds to EUR 5800 per patient [11]. In Bulgaria the monthly cost of medical therapy covered by the public payer was EUR 784.59, and EUR 195.94 by the patient [14]. Seven years follow-up of 134 patients from Italy showed costs per year of EUR 7968.41 in well controlled patients and EUR 12,533.02 in uncontrolled patients [13].
In our study the costs of diagnostic procedures were highest in the controlled patients. It is caused by the necessity for regular follow-up, especially in patients on chronic SSA therapy. Those costs were estimated in Sweden at EUR 600 [11]; in Italy EUR 82.57 for uncontrolled patients and EUR 67.31 for controlled patients [13].
The costs of additional surgeries were highest in well controlled patients and lowest in cured patients. This could be influenced by the frequent need for cholecystectomy in patients on chronic SSA therapy. The costs of acromegaly complication pharmacotherapy were highest in the patients with active disease; interestingly, in our data costs per year covered by patients themselves were slightly greater than costs covered by the health service system (PLN 488 vs. 423). Ribeiro-Oliveira et al. reported yearly costs of acromegaly complication medical therapy at USD 1917 in the USA, versus those costs in patients without acromegaly at USD 1253 [12]. Whittington et al. analysed the costs of acromegaly complications: diabetes, hypertension, colon cancer, hypopituitarism, and sleep apnoea. Their cost per year for patients with well controlled acromegaly was USD 4774 but USD 18,925 for active acromegaly. They performed simulation indicated additional life-long costs of acromegaly complication therapy of USD 192,000 in well controlled patients, but USD 285,000 in uncontrolled patients (active disease) [8]. Data from the USA report that patients with acromegaly required more frequent therapy with antibiotics (70.0% vs. 55.6%), analgesics (56.3% vs. 38.1%); psychiatric medication (42.6% vs. 24.8%) and sex hormones (37.3% vs. 12.7%). Eighty-five per cent of acromegaly patients had at least 3 additional medications prescribed [7].
The assessment of indirect costs of disease is not often given in publications due to the difficulty in obtaining reliable data and the large variety of parameters taken into account in the calculation. Lesen et al. assessed indirect costs based on the number of days spent at home due to temporary disability caused by acromegaly and its complications and lost income due to the patient’s premature death. The indirect costs of acromegaly in the Swedish population were 23% of all costs (EUR 2700 per patient) [11]. Liu et al. demonstrated, based on surveys completed by acromegaly patients in the USA, that the total indirect costs of acromegaly can be as high as USD 25,145 per patient per year. Including costs related to absence from work amounted to USD 6702 per person, costs due to job loss — USD 6106, and costs related to total inability to work caused by acromegaly and its complications — an average of USD 10,653 per year [21]. Yuen performed a retrospective analysis of data from medical and employment databases in the USA. The data obtained from 47 patients with acromegaly were compared with a control group of 940 patients. It was shown that the total costs of therapy were significantly higher in the group of patients with acromegaly than in the control group. Direct medical costs accounted for 79.8% of the costs. In the group of patients with acromegaly, indirect costs related to short-term and long-term incapacity for work were also higher than in patients without acromegaly [22]. We have not analysed indirect costs in our patients, but the number of acromegaly complications and accompanying disorders presented in them is high and additionally influences the total costs of acromegaly management [23, 24]. Data supporting our observation of many acromegaly comorbidities and complications were also published by other authors [25, 26].
There are other differences due to insurance availability and local specificity. In China, the mean cost per year of management of patients with acromegaly was USD 11,013, including the cost of medical therapy — 67%, neurosurgery — 29%, and radiotherapy — 4% of the costs. In China the insurance covers only 47% of the total costs causing patient expenses of USD 5814 per year [17]. Yuen et al. showed 10-fold higher costs of medical care of American patients with acromegaly than other patients (USD 34,454 vs. 3497). The costs of medication comprised 25% of costs in both groups, but patients with acromegaly paid 88.9% more than others did. The average cost of medical therapy of acromegaly was USD 9925 and reflected 20.5% of all costs covered by patients [22]. A retrospective analysis of 160 patients with acromegaly caused by pituitary macroadenoma showed that pre-surgical SSA treatment led to better surgical results, longer life expectancy, and a decrease in the costs [27]. Pre-surgical SSA administration has been recommended in Poland since 2007 [1, 18]. Previously, Orlewska et al. carried out a prospective study on a group of 139 Polish patients treated for acromegaly with lanreotide autogel. The total direct annual treatment costs per patient were estimated at PLN 50,692 (about EUR 12,000). Ninety-seven per cent of the costs were pharmacological treatment. Other direct costs, not connected to pharmacotherapy, included: outpatient care (49%), hospitalisation (23%), diagnostic tests (20%), and laboratory tests (8%) [28]. In the latter study no subgroups of patients were analysed.
Based on our results, one can state that from a pharmacoeconomic point of view, the most important is radical, successful neurosurgery leading to disease cure. This is also important and beneficial from a medical point of view, reducing possible complications and comorbidities. Neurosurgery failure results in a need for life-long and expensive medical therapy or radiotherapy encumbered by possible side effects and complications. Knowledge of the high medical and social costs of acromegaly should encourage us to seek early diagnosis of acromegaly resulting in efficacious treatment and lowering the costs covered by patients and society.
Acknowledgements
Ipsen reviewed this manuscript for scientific accuracy but had no input into the content.
Ethics statement
Study approved by the local Bioethics Committee.
Author contributions
Presented in the Authors statement file.
Conflict of interest
Authors got a sponsorship from Ipsen (travel grants, lectures fees, research grants).
Funding
This study was sponsored under a grant from Ipsen. Ipsen had no input into the study design, analysis, or interpretation of results.
