Tackling access and payer barriers for growth hormone therapy in Saudi Arabia: a consensus statement for the Saudi Working Group for Pediatric Endocrinology.

Prompt diagnosis and early treatment are key goals to optimize the outcomes of children with growth hormone deficiency (GHD) and attain the genetically expected adult height. Nonetheless, several barriers can hinder prompt diagnosis and treatment of GHD, including payer-related issues. In Saudi Arabia, moderate-to-severe short stature was reported in 13.1 and 11.7 % of healthy boys and girls, respectively. Several access and payer barriers can face pediatric endocrinologists during the diagnosis and treatment of GHD in Saudi Arabia. Insurance coverage policies can restrict access to diagnostic tests for GHD and recombinant human growth hormone (rhGH) due to their high costs and lack of gold-standard criteria. Some insurance policies may limit the duration of treatment with rhGH or the amount of medication covered per month. This consensus article gathered the insights of pediatric endocrinologists from Saudi Arabia to reflect the access and payer barriers to the diagnostic tests and treatment options of children with short stature. We also discussed the current payer-related challenges endocrinologists face during the investigations of children with short stature. The consensus identified potential strategies to overcome these challenges and optimize patient management.

Pediatric growth hormone treatment in Italy: A systematic review of epidemiology, quality of life, treatment adherence, and economic impact.

OBJECTIVES: This systematic review aims to describe 1) the epidemiology of the diseases indicated for treatment with growth hormone (GH) in Italy; 2) the adherence to the GH treatment in Italy and factors associated with non-adherence; 3) the economic impact of GH treatment in Italy; 4) the quality of life of patients treated with GH and their caregivers in Italy. METHODS: Systematic literature searches were performed in PubMed, Embase and Web of Science from January 2010 to March 2021. Literature selection process, data extraction and quality assessment were performed by two independent reviewers. Study protocol has been registered in PROSPERO (CRD42021240455). RESULTS: We included 25 studies in the qualitative synthesis. The estimated prevalence of growth hormone deficiency (GHD) was 1/4,000-10,000 in the general population of children; the prevalence of Short Stature HOmeoboX Containing gene deficiency (SHOX-D) was 1/1,000-2,000 in the general population of children; the birth prevalence of Turner syndrome was 1/2,500; the birth prevalence of Prader-Willi syndrome (PWS) was 1/15,000. Treatment adherence was suboptimal, with a range of non-adherent patients of 10-30%. The main reasons for suboptimal adherence were forgetfulness, being away from home, pain/discomfort caused by the injection. Economic studies reported a total cost for a complete multi-year course of GH treatment of almost 100,000 euros. A study showed that drug wastage can amount up to 15% of consumption, and that in some Italian regions there could be a considerable over- or under-prescribing. In general, patients and caregivers considered the GH treatment acceptable. There was a general satisfaction among patients with regard to social and school life and GH treatment outcomes, while there was a certain level of intolerance to GH treatment among adolescents. Studies on PWS patients and their caregivers showed a lower quality of life compared to the general population, and that social stigma persists. CONCLUSION: Growth failure conditions with approved GH treatment in Italy constitute a significant burden of disease in clinical, social, and economic terms. GH treatment is generally considered acceptable by patients and caregivers. The total cost of the GH treatment is considerable; there are margins for improving efficiency, by increasing adherence, reducing drug wastage and promoting prescriptive appropriateness.

Cost-Utility of Acromegaly Pharmacological Treatments in a French Context.

Objective: Efficacy of pharmacological treatments for acromegaly has been assessed in many clinical or real-world studies but no study was interested in economics evaluation of these treatments in France. Therefore, the objective of this study was to estimate the cost-utility of second-line pharmacological treatments in acromegaly patients. Methods: A Markov model was developed to follow a cohort of 1,000 patients for a lifetime horizon. First-generation somatostatin analogues (FGSA), pegvisomant, pasireotide and pegvisomant combined with FGSA (off label) were compared. Efficacy was defined as the normalization of insulin-like growth factor-1 (IGF-1) concentration and was obtained from pivotal trials and adjusted by a network meta-analysis. Costs data were obtained from French databases and literature. Utilities from the literature were used to estimate quality-adjusted life year (QALY). Results: The incremental cost-utility ratios (ICUR) of treatments compared to FGSA were estimated to be 562,463 € per QALY gained for pasireotide, 171,332 € per QALY gained for pegvisomant, and 186,242 € per QALY gained for pegvisomant + FGSA. Pasireotide seems to be the least cost-efficient treatment. Sensitivity analyses showed the robustness of the results. Conclusion: FGSA, pegvisomant and pegvisomant + FGSA were on the cost-effective frontier, therefore, depending on the willingness-to-pay for an additional QALY, they are the most cost-effective treatments. This medico-economic analysis highlighted the consistency of the efficiency results with the efficacy results assessed in the pivotal trials. However, most recent treatment guidelines recommend an individualized treatment strategy based on the patient and disease profile.

Economic burden of growth hormone deficiency in a US pediatric population.

BACKGROUND: Pediatric growth hormone deficiency (GHD) is a rare disorder of short stature that is currently treated with daily injections of somatropin. In addition to short stature, GHD is associated with other comorbidities such as impaired musculoskeletal development, cardiovascular disease, and decreased quality of life. OBJECTIVE: To analyze somatropin utilization, adherence, and health care costs among children with GHD who had either Medicaid or commercial health insurance. METHODS: Children (aged < 18 years) with a GHD diagnosis between January 1, 2008, and December 31, 2017, were identified in the IBM MarketScan Commercial and Medicaid databases. Patients with at least 12- and 6-month continuous enrollment pre- and postdiagnosis were eligible. Children with GHD were direct matched (1:3) to controls without GHD (or other short stature-related disorders) on age, gender, plan type, region, and race (Medicaid only). Index date was the date of the first GHD diagnosis during the selection window for GHD patients and using random assignment for controls. Patients were followed until the end of continuous database enrollment or December 31, 2018. Baseline comorbidities and medications were measured during the 12 months pre-index, whereas somatropin treatment patterns along with all-cause and GHD-related health care costs were measured during the variable follow-up period. Multivariable modeling was used to compare costs between GHD patients and controls and between somatropin-treated and -untreated GHD patients while adjusting for baseline characteristics. RESULTS: There were 6,820 Medicaid and 14,070 commercial patients with GHD who met the study inclusion criteria. Mean (SD) age at index was 9.5 (4.5) years for Medicaid patients and 11.1 (3.7) years for commercial patients. The majority of patients were male (> 65%), and mean follow-up time for all cases and controls was 3-4 years. Overall, 63.2% of Medicaid and 68.4% of commercial GHD patients were treated with somatropin at some point during follow-up. Among Medicaid GHD patients, the treatment rate was highest among White males and lowest among Black females. Adherence was low as the proportion of days covered was ≥ 80% for only 18.4% of Medicaid patients and 32.3% of commercial patients and 49.1% of treated Medicaid and 24.3% of treated commercial patients discontinued before turning age 13. After adjusting for baseline characteristics, all-cause non-somatropin annualized costs were 5.67 times higher (Δ$19,309) for Medicaid GHD patients and 5.46 times higher (Δ$12,305) for commercial GHD patients than matched non-GHD controls. Adjusted all-cause non-somatropin annualized costs were 0.59 times lower (Δ$14,416) for treated Medicaid patients and 0.69 times lower (Δ$7,650) for treated commercial patients than for untreated patients. CONCLUSIONS: Pediatric GHD presents a significant health care burden, and many patients remain untreated or undertreated. Untreated GHD was associated with higher non-somatropin health care costs than treated GHD. Strategies to optimize treatment and improve adherence may reduce the health care burden faced by these patients. DISCLOSURES: This study was funded by Ascendis Pharma, Inc. Smith and Pitukcheewanont are employed by Ascendis Pharma, Inc. Manjelievskaia, Lopez-Gonzalez, and Morrow are employed by IBM Watson Health, which received funding from Ascendis Pharma, Inc., to conduct this study. Kaplowitz is a paid consultant of Ascendis Pharma, Inc.

The Content of Pre-habilitative Interventions for Patients Undergoing Repair of Abdominal Aortic Aneurysms and Their Effect on Post-Operative Outcomes: A Systematic Review.

OBJECTIVE: Patients requiring abdominal aortic aneurysm (AAA) repair are at risk of post-operative complications due to poor pre-operative state. Pre-habilitation describes the enhancement of functional capacity and tolerance to an upcoming physiological stressor, intended to reduce those complications. The ability to provide such an intervention (physical, pharmacological, nutritional, or psychosocial) between diagnosis and surgery is a growing interest, but its role in AAA repair is unclear. This paper aimed to systematically review existing literature to better describe the effect of pre-habilitative interventions on post-operative outcomes of patients undergoing AAA repair. DATA SOURCES: EMBASE and Medline were searched from inception to October 2020. Retrieved papers, systematic reviews, and trial registries were citation tracked. REVIEW METHODS: Randomised controlled trials (RCTs) comparing post-operative outcomes for adult patients undergoing a period of pre-habilitation prior to AAA repair (open or endovascular) were eligible for inclusion. Two authors screened titles for inclusion, assessed risk of bias, and extracted data. Primary outcomes were post-operative 30 day mortality, composite endpoint of 30 day post-operative complications, hospital length of stay (LOS), and health related quality of life (HRQL) outcomes. The content of interventions was extracted and a narrative analysis of results undertaken. RESULTS: Seven RCTs with 901 patients were included (three exercise based, two pharmacological based, and two nutritional based). Risk of bias was mostly unclear or high and the clinical heterogeneity between the trials precluded data pooling for meta-analyses. The quality of intervention descriptions was highly variable. One exercise based RCT reported significantly reduced hospital LOS and another improved HRQL outcomes. Neither pharmacological nor nutritional based RCTs reported significant differences in primary outcomes. CONCLUSION: There is limited evidence to draw clinically robust conclusions about the effect of pre-habilitation on post-operative outcomes following AAA repair. Well designed RCTs, adhering to reporting standards for intervention content and trial methods, are urgently needed to establish the clinical and cost effectiveness of pre-habilitation interventions.

Effectiveness, economical and safety aspects of growth hormone (GH) therapy in growth promoting doses in patients with isolated GH deficiency after the attainment of near-final height. Is there a need to modify the criteria of therapy withdrawal?

INTRODUCTION: Apart from growth promotion, growth hormone (GH) has important metabolic effects. Patients with severe GH deficiency (GHD) should be treated with GH throughout life. Current criteria for growth promoting therapy withdrawal in Poland differ from the latest recommendations. Aim of the study To assess cost-effectiveness and safety of continuation of GH therapy in growth promoting doses in patients with isolated GHD after the attainment of near-final height (near-FH) and the incidence of persistent GHD after the therapy withdrawal. MATERIAL AND METHODS: 160 children with isolated GHD (height < 3 centile, GH peak < 10.0 µg/l), who continued GH therapy for growth promotion after the attainment of near-FH (height velocity   2.0) at near-FH and incidence of severe GHD in retesting (performed in 62 patients). RESULTS: Height gain after near-FH was 1.1 ±0.8 cm in boys and 1.0 ±0.8 in girls. Increase of height by 1.0 cm required on average 487 mg of GH (264 injections). IGF-1 concentrations at near-FH were increased in 39 patients, with no clinical side effects. None of the patients retested had GH peak   10.0 µg/l. CONCLUSIONS: There is no rationale to continue GH therapy in growth promoting doses in the patients with isolated GHD after fulfilling the criteria of near-FH.

Pharmacological Acromegaly Treatment: Cost-Utility and Value of Information Analysis.

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.

Cost-Effectiveness and Efficacy of a Novel Combination Regimen in Acromegaly: A Prospective, Randomized Trial.

CONTEXT: Combination therapy with somatostatin receptor ligand (SRL) plus pegvisomant for patients with acromegaly is recommended after a maximizing dose on monotherapy. Lower-dose combination regimens are not well studied. OBJECTIVE: To compare cost-effectiveness and efficacy of 3 lower-dose combination regimens in controlled and uncontrolled acromegaly. DESIGN AND SETTING: Prospective, randomized, open-label, parallel arm study at a tertiary referral pituitary center. PATIENTS: Adults with acromegaly regardless of response to prior SRL and biochemical control status at baseline, stratified by an SRL dose required for insulin-like growth factor (IGF)-I normalization during any 3-month period within 12 months preceding enrollment. INTERVENTION: Combination therapy for 24 to 32 weeks on arm A, high-dose SRL (lanreotide 120 mg/octreotide long-acting release [LAR] 30 mg) plus weekly pegvisomant (40-160 mg/week); arm B, low-dose SRL (lanreotide 60 mg/octreotide LAR 10 mg) plus weekly pegvisomant; or arm C, low-dose SRL plus daily pegvisomant (15-60 mg/day). MAIN OUTCOME MEASURE: Monthly treatment cost in each arm in participants completing ≥ 24 weeks of therapy. RESULTS: Sixty patients were enrolled and 52 were evaluable. Fifty of 52 (96%) demonstrated IGF-I control regardless of prior SRL responsiveness (arm A, 14/15 [93.3%]; arm B, 22/23 [95.7%]; arm C, 14/14 [100%]). Arm B was least costly (mean, $9837 ±â€…1375 per month), arm C was most expensive (mean, $22543 ±â€…11158 per month), and arm A had an intermediate cost (mean, $14261 ±â€…1645 per month). Approximately 30% of patients required pegvisomant dose uptitration. Rates of adverse events were all < 10%. CONCLUSIONS: Low-dose SRL plus weekly pegvisomant represents a novel dosing option for achieving cost-effective, optimal biochemical control in patients with uncontrolled acromegaly requiring combination therapy.

Cost-effectiveness analysis of second-line pharmacological treatment of acromegaly in Spain.

Objective: To estimate the cost-effectiveness of second-line pharmacological treatments in patients with acromegaly resistant to first-generation somatostatin analogues (FG SSA) from the Spanish National Health System (NHS) perspective.Methods: A Markov model was developed to analyze the cost-effectiveness of pegvisomant and pasireotide in FG SSA-resistant acromegaly, simulating a cohort of patients from the treatment beginning to death. Treatment with pegvisomant or pasireotide was compared to FG SSA retreatment. Efficacy data were obtained from clinical trials and utilities from the literature. Direct health costs were obtained from Spanish sources (€2018).Results: The Incremental Cost Effectiveness Ratio (ICER) of pegvisomant vs. FG SSA was €85,869/Quality-adjusted life years (QALY). The ICER of pasireotide vs. FG SSA was €551,405/QALY. The ICER was mainly driven by the incremental efficacy (4.41 QALY for pegvisomant vs. FG SSA and 0.71 QALY for pasireotide vs. FG SSA), with a slightly lower increase in costs with pegvisomant (€378,597 vs. FG SSA) than with pasireotide (€393,151 vs. FG SSA).Conclusion: The ICER of pasireotide compared to FG SSA was six times higher than the ICER of pegvisomant vs. FG SSA. Pegvisomant is a more cost-effective alternative for the treatment of acromegaly in FG SSA-resistant patients in the Spanish NHS.

Cost-effectiveness of somatostatin analogues in the treatment of acromegaly.

INTRODUCTION: Somatostatin analogues (SSAs) are the largest contributor to the direct medical cost of acromegaly management worldwide. The aim of this review was to identify and report available evidence on the cost-effectiveness of SSAs in the treatment of acromegaly. AREAS COVERED: A literature search on relevant papers published up to April 2018 was performed. A total of 22 eligible studies (10 full-text articles and 12 conference abstracts) conducted in 14 countries were included in the analysis. In majority of studies, modelling technique was the principal research method. EXPERT COMMENTARY: The results of cost-effectiveness analyses: 1) support published recommendations where SSAs are indicated as first-line medical treatment for patients with persistent disease after surgery or who are not eligible for surgery; 2) suggest that preoperative medical therapy with SSAs may be highly cost-effective in acromegalic patients with macroadenoma, in centres without optimal surgical results 3) indicate that in some countries pasireotide and pegvisomant appeared to be cost-effective or even dominant strategies in comparison to first-generation SSAs. The main limitation of economic evaluations was the lack of high-quality studies designed to directly compare various treatment strategies in acromegaly.

Valuing height: diagnosis, valuation and the case of idiopathic short stature.

This paper proposes a 'valuographic' approach to diagnosis, exploring how values and valuation practices are implicated in the contested diagnostic category of idiopathic short stature (ISS). ISS describes children who are 'abnormally' short but do not have any other detectable pathology. In the USA growth-promoting hormone therapy has been approved for ISS children, since 2003. However, no other jurisdiction has approved this treatment and the value of ISS as a diagnostic category remains disputed among healthcare professionals. Drawing on qualitative interviews with paediatric endocrinologists in the UK and the US, this study presents a historical snapshot illustrating how the problematisation of ISS as a diagnosis involved multiple registers of value including epistemic, economic and moral calculations of worth. Contestation of the diagnosis was not just about what counts but about what ought to be counted, as respondents' accounts of ISS gave differential weight to a range of types of evidence and methods of assessment. Ultimately what was at stake was not just the value of increased height for short patients, but what it meant to properly practice paediatric endocrinology. Consideration is then given to how a valuographic approach can be applied to sociological studies of diagnosis more broadly.

Cost-Conscious Growth-Promoting Treatment: When Discretion Is the Better Part of Value.

Assessing cost-effectiveness of human growth hormone (hGH) treatment to augment height is complicated by uncertainty about how best to measure its therapeutic effect. Cost-conscious growth promotion practice, however, is possible and likely an emerging practical requisite as health care payers increasingly deny the medical necessity of and restrict support for short stature treatment. The increase in denials is not surprising given the expansion and continued high cost of hGH treatment, debate about the value of such treatment, and universal need to restrain burgeoning health care costs. Renunciation of sweeping payer rejection of hGH-for-height treatment is strengthened by cost-conscious practices that (1) recommend no treatment for most short children and restrict treatment to severe, likely disabling short stature; (2) initiate hGH treatment only after evidence-based informed assent; (3) utilize alternative less costly and less invasive options when possible; (4) minimize hGH treatment duration and dosage; and (5) resist enhancement of normal adult stature. A new era of cost-conscious hGH prescribing that prompts thoughtful restraint in hGH use could help preserve hGH approval for children most in need of treatment.

Effects of financial support on treatment of adolescents with growth hormone deficiency: a retrospective study in Japan.

BACKGROUND: Treatment costs for children with growth hormone (GH) deficiency are subsidized by the government in Japan if the children meet clinical criteria, including height limits (boys: 156.4 cm; girls: 145.4 cm). However, several funding programs, such as a subsidy provided by local governments, can be used by those who exceed the height limits. In this study, we explored the impacts of financial support on GH treatment using this natural allocation. METHODS: A retrospective analysis of 696 adolescent patients (451 boys and 245 girls) who reached the height limits was conducted. Associations between financial support and continuing treatment were assessed using multiple logistic regression analyses adjusting for age, sex, height, growth velocity, bone age, and adverse effects. RESULTS: Of the 696 children in the analysis, 108 (15.5 %) were still eligible for financial support. The proportion of children who continued GH treatment was higher among those who were eligible for support than among those who were not (75.9 % vs. 52.0 %, P < 0.001). The odds ratios of financial support to continuing treatment were 4.04 (95 % confidence interval [CI]: 1.86-8.78) in boys and 1.72 (95 % CI: 0.80-3.70) in girls, after adjusting for demographic characteristics and clinical factors. CONCLUSIONS: Financial support affected decisions on treatment continuation for children with GH deficiency. Geographic variations in eligibility for financial support pose an ethical problem that needs policy attention. An appropriate balance between public spending on continuation of therapy and improved quality of life derived from it should be explored.

Cost-effectiveness analysis of preoperative treatment of acromegaly with somatostatin analogue on surgical outcome.

CONTEXT: There is no uniform standard of care for acromegaly. Due to the high costs involved, steps must be taken to ensure the cost-effective delivery of treatment. OBJECTIVE: Taking the results of an earlier meta-analysis as a starting point, this study aims to determine whether treatment with long-acting somatostatin analogue (SSA) prior to surgery improves the cost-effectiveness of the treatment of acromegaly. METHODS: The results are presented as an Incremental Cost Effectiveness Ratio (ICER) immediately after surgery, for the following year and over the next four decades. The cure rates percentage (95% CI) for the three randomized prospective controlled trials were 44.4% (34.2-54.7) and 18.2% (10.1-26.3) for preoperative treated and untreated patients respectively. The cost of pharmacological treatments was based on the number of units prescribed, dose and length of treatment. RESULTS: The mean (95% CI) ICER immediately after surgery was €17,548 (12,007-33,250). In terms of the postoperative SSA treatment, the ICER changes from positive to negative before two years after surgery. One decade after surgery the ICER per patient/year was €-9973 (-18,798; -6752) for postoperative SSA treatment and €-31,733 (-59,812; -21,483) in the case of postoperative pegvisomant treatment. CONCLUSIONS: In centres without optimal surgical results, preoperative treatment of GH-secreting pituitary macroadenomas with SSA not only shows a significant improvement in the surgical results, but is also highly cost-effective, with an ICER per patient/year one decade after surgery, of between €-9973 (-18,798; -6752) and €-31,733 (-59,812; -21,483) for SSA and pegvisomant respectively.

Three-year experience with access to nationally funded growth hormone (GH) replacement for GH-deficient adults.

OBJECTIVE: Treatment of growth hormone (GH)-deficient adults with GH has been shown to improve a range of metabolic abnormalities and enhance quality of life. However, the results of access to nationally funded treatment have not been reported. DESIGN: Retrospective case series auditing nationally funded treatment of defined GH-deficient adults in New Zealand, with carefully designed entry and exit criteria overseen by a panel of endocrinologists. PATIENTS: Applications for 201 patients were assessed and 191 approved for funded treatment over the initial 3 years since inception. The majority had GH deficiency following treatment of pituitary adenomas or tumours adjacent to the pituitary. RESULTS: After an initial 9-month treatment period using serum IGF-I measurements to adjust GH dosing, all patients reported a significant improvement in quality of life (QoL) score on the QoL-AGHDA(®) instrument (baseline (95%CI) 19 (18-21), 9 months 6 (5-7.5)), and mean serum IGF-I SD scores rose from -3 to zero. Mean waist circumference decreased significantly by 2.8 ± 0.6 cm. The mean maintenance GH dose after 9 months of treatment was 0.39 mg/day. After 3 years, 17% of patients had stopped treatment, and all of the remaining patients maintained the improvements seen at 9 months of treatment. CONCLUSION: Carefully designed access to nationally funded GH replacement in GH-deficient adults was associated with a significant improvement in quality of life over a 3-year period with mean daily GH doses lower than in the majority of previously reported studies.

The impact of real practice inappropriateness and devices' inefficiency to variability in growth hormone consumption.

INTRODUCTION: Growth hormone (GH) consumption is the object of a particular attention by regulatory bodies, due to its financial impact; nevertheless, GH treatment has been demonstrated to be cost-effective and is, therefore, usually reimbursed by public health service systems. In Italy, significant differences in GH consumption between regions have been recorded. Different appropriateness in real practice is a possible explanation, but the proportion of drug wasted due to different combinations of therapeutic regimes and types of devices used in drug administration is a complementary explanation. Aim of the study is, therefore, to determine how much of the variability in GH consumption is actually due to differences in clinical practice, and how much to waste. MATERIALS AND METHODS: A model was settled to estimate the population with indication for GH administration, separately for children, transition subjects and adults, based on both the scientific evidence available and directly collected clinical evaluations. A systematic literature search was conducted using Cochrane Library (HTA and NHSEE) databases, Medline via Ovid, Econlit via Ovid, Embase. CONCLUSION: The model applied to the Italian population showed that there was apparently unexplainable over-prescription and potential under-prescription in various regions, ranging from 20 to 40 % less than the estimated theoretical consumption to over 200 %. Wastage, at level of single device, could amount to as much as 15 % of the consumption, demonstrating that price per mg is not in general a good proxy of the cost per mg of therapy. Our estimates of the wastage shows a significant potential gap in the model assessment of the HTA bodies, as far as they do not explicitly take into account the issue of wastage and, consequently, the actual variability in local clinical practice.

Provincial disparities of growth hormone coverage for young adult survivors of paediatric brain tumours across Canada.

BACKGROUND: Young adult survivors of paediatric brain tumours (PBTs) who have been treated with radiation therapy will likely be severely growth hormone-deficient when retested at the achievement of final height. Growth hormone replacement therapy (GHRT) is administered to treat growth hormone deficiency (GHD). Public drug coverage for GHRT falls under the responsibility of provincial governments across Canada. This study sought to determine the extent of public drug coverage and cost in each Canadian province for GHRT to treat GHD during adulthood for young adult survivors of PBTs. METHODS: Data were collected from provincial government resources and drug formularies from 2012-2013 on the extent of coverage for GHRT based on a clinical case scenario representative of a young adult survivor of a PBT with childhood-onset radiation-induced GHD, the ingredient cost for GHRT and the applicable provincial public drug plan cost-sharing policies. A model was then created to simulate out-of-pocket costs incurred by a young adult male and a young adult female survivor of a PBT for one year of GHRT in each province with applicable cost-sharing arrangements and levels of low annual individual total income that best represent the majority of young adult survivors of PBTs. Out-of-pocket costs were expressed as a percentage of annual income. Comparisons were made between provinces descriptively, and variation among provinces was summarized statistically. RESULTS: Alberta, Manitoba, Ontario, Quebec, New Brunswick, and Newfoundland and Labrador provide coverage for GHD during adulthood on a case-by-case basis, while British Columbia, Saskatchewan, Nova Scotia and Prince Edward Island provide no coverage. The percentage of annual income to fund GHRT across the provinces without public coverage ranged from 14.4% to 25.5% for males and 21.5% to 38.3% for females, and with public coverage was 0.0% to 4.1% for males and 0.0% to 5.0% for females. INTERPRETATION: There are considerable out-of-pocket costs and variation in coverage provided by provincial public drug plans to fund GHRT for young adult survivors of PBTs with GHD. The implementation of a national drug formulary could potentially prevent undue financial hardship and remove disparities resulting from variations in provincial drug plans.

Regional tenders on biosimilars in Italy: an empirical analysis of awarded prices.

OBJECTIVE: The goal of the present study is to assess the awarded prices and thus the real level of competition the regional tenders referring to biosimilars in Italy achieved. METHODS: We conducted a web-based analysis to collect detailed information on regional biosimilar tenders, up to December 2012. We identified 191 lots referring to the three off-patent biologicals (somatropin, epoetin and filgrastim) mentioned in the 24 tenders that took place during the study period (2008-2012). A multiple linear regression analysis was conducted to assess the relationship between prices awarded (dependent variable) and potentially explanatory variables (base quantities, bioagent, number of competitors, purchasing region and time). RESULTS: While the price of somatropin stayed steady, those of filgrastim and epoetin dropped steeply. The mean number of competitors was lowest for somatropin and highest for filgrastim. One additional competitor was associated with about a 10% reduction in the price on average. The benefits of having many competitors did not fade with increasing numbers of companies. DISCUSSION: Our analysis confirms the theory that worthwhile savings can be generated in tenders, once the bid is designed in such a way that competition can produce its effects, i.e. allowing more than one manufacturer to tender. However, most of the Italian regional tenders on off-patent bioagents do not seem to exploit potential competition to the full.

The role of primary pharmacological therapy in acromegaly.

BACKGROUND AND OBJECTIVES: Primary pharmacological therapy may be the only viable treatment option for many patients with acromegaly, especially those presenting with advanced disease with large inoperable tumors. Long-acting somatostatin analogs are currently the first-line treatment of choice in this setting, where they provide biochemical control and reduce tumor size in a significant proportion of patients. We herein present a brief overview of the role of primary pharmacological therapy in the treatment of acromegaly within the context of Latin America and support this with a representative case study. CASE DESCRIPTION: A 20 year old male presented with clinical and biochemical evidence of acromegaly. The glucose-suppressed growth hormone (GH) was 5.3 µg/L, his insulin-like growth factor-1(IGF-1) was 3.5 times the ULN and serum prolactin greater than 4,000 µg/L. Pituitary MRI revealed a large and invasive mass, extending superiorly into the optic chiasm and laterally into the left cavernous sinus. He was treated with a combination of octreotide and cabergoline with remarkable clinical improvement, normalization of GH and IGF-1 values and striking shrinkage of the adenoma. CONCLUSION: This case illustrates how effective the pharmacological therapy of acromegaly can be and yet at the same time, raises several important issues such as the need for life-long treatment with costly medications such as the somatostatin analogs. Access to these agents may be limited in regions where resources are restricted and clinicians face challenges in order to make the most efficient use of available options.

Internet informs parents about growth hormone.

BACKGROUND: Parents' knowledge influences decisions regarding medical care for their children. METHODS: Parents of pediatric primary care patients aged 9-14 years, irrespective of height, participated in open focus groups (OFGs). Moderators asked the question, 'How do people find out about growth hormone (GH)?' Because many parents cited the Internet, the top 10 results from the Google searches of 'growth hormone children' and 'parents of children who take growth hormone' were examined. Three investigators independently performed content analysis and then reached a consensus. The results were tabulated via summary statistics. RESULTS: Eighteen websites were reviewed, most with the purpose of education (56%) and many funded by commercial sources (44%). GH treatment information varied, with 33% of the sites containing content only about US FDA-approved indications. Fifty-six percent of the sites included information about psychosocial benefits from treatment, with 44% acknowledging them as controversial. Although important to OFG participants, risks and costs were each omitted from 39% of the websites. CONCLUSION: Parents often turn to the Internet for GH-related information for their children, although its content may be incomplete and/or biased. Clinicians may want to provide parents with tools for critically evaluating Internet-based information, a list of prereviewed websites, or their own educational materials.