Clinical effectiveness and cost-effectiveness of pegvisomant for the treatment of acromegaly: a systematic review and economic evaluation

Background: Acromegaly, an orphan disease usually caused by a benign pituitary tumour, is characterised by hyper-secretion of growth hormone (GH) and insulin-like growth factor I (IGF-1). It is associated with reduced life expectancy, cardiovascular problems, a variety of insidiously progressing detrimental symptoms and metabolic malfunction. Treatments include surgery, radiotherapy and pharmacotherapy. Pegvisomant (PEG) is a genetically engineered GH analogue licensed as a third or fourth line option when other treatments have failed to normalise IGF-1 levels. Methods: Evidence about effectiveness and cost-effectiveness of PEG was systematically reviewed. Data were extracted from published studies and used for a narrative synthesis of evidence. A decision analytical economic model was identified and modified to assess the cost-effectiveness of PEG. Results: One RCT and 17 non-randomised studies were reviewed for effectiveness. PEG substantially reduced and rapidly normalised IGF-1 levels in the majority of patients, approximately doubled GH levels, and improved some of the signs and symptoms of the disease. Tumour size was unaffected at least in the short term. PEG had a generally safe adverse event profile but a few patients were withdrawn from treatment because of raised liver enzymes. An economic model was identified and adapted to estimate the lower limit for the cost-effectiveness of PEG treatment versus standard care. Over a 20 year time horizon the incremental cost-effectiveness ratio was pound81,000/QALY and pound212,000/LYG. To reduce this to pound30K/QALY would require a reduction in drug cost by about one third. Conclusion: PEG is highly effective for improving patients' IGF-1 level. Signs and symptoms of disease improve but evidence is lacking about long term effects on improved signs and symptoms of disease, quality of life, patient compliance and safety. Economic evaluation indicated that if current standards (UK) for determining cost-effectiveness of therapies were to be applied to PEG it would be considered not to represent good value for money

Clinical effectiveness and cost-effectiveness of issuing longer versus shorter duration (3-month vs. 28-day) prescriptions in patients with chronic conditions: systematic review and economic modelling.

BACKGROUND: To reduce expenditure on, and wastage of, drugs, some commissioners have encouraged general practitioners to issue shorter prescriptions, typically 28 days in length; however, the evidence base for this recommendation is uncertain. OBJECTIVE: To evaluate the evidence of the clinical effectiveness and cost-effectiveness of shorter versus longer prescriptions for people with stable chronic conditions treated in primary care. DESIGN/DATA SOURCES: The design of the study comprised three elements. First, a systematic review comparing 28-day prescriptions with longer prescriptions in patients with chronic conditions treated in primary care, evaluating any relevant clinical outcomes, adherence to treatment, costs and cost-effectiveness. Databases searched included MEDLINE (PubMed), EMBASE, Cumulative Index to Nursing and Allied Health Literature, Web of Science and Cochrane Central Register of Controlled Trials. Searches were from database inception to October 2015 (updated search to June 2016 in PubMed). Second, a cost analysis of medication wastage associated with < 60-day and ≥ 60-day prescriptions for five patient cohorts over an 11-year period from the Clinical Practice Research Datalink. Third, a decision model adapting three existing models to predict costs and effects of differing adherence levels associated with 28-day versus 3-month prescriptions in three clinical scenarios. REVIEW METHODS: In the systematic review, from 15,257 unique citations, 54 full-text papers were reviewed and 16 studies were included, five of which were abstracts and one of which was an extended conference abstract. None was a randomised controlled trial: 11 were retrospective cohort studies, three were cross-sectional surveys and two were cost studies. No information on health outcomes was available. RESULTS: An exploratory meta-analysis based on six retrospective cohort studies suggested that lower adherence was associated with 28-day prescriptions (standardised mean difference -0.45, 95% confidence interval -0.65 to -0.26). The cost analysis showed that a statistically significant increase in medication waste was associated with longer prescription lengths. However, when accounting for dispensing fees and prescriber time, longer prescriptions were found to be cost saving compared with shorter prescriptions. Prescriber time was the largest component of the calculated cost savings to the NHS. The decision modelling suggested that, in all three clinical scenarios, longer prescription lengths were associated with lower costs and higher quality-adjusted life-years. LIMITATIONS: The available evidence was found to be at a moderate to serious risk of bias. All of the studies were conducted in the USA, which was a cause for concern in terms of generalisability to the UK. No evidence of the direct impact of prescription length on health outcomes was found. The cost study could investigate prescriptions issued only; it could not assess patient adherence to those prescriptions. Additionally, the cost study was based on products issued only and did not account for underlying patient diagnoses. A lack of good-quality evidence affected our decision modelling strategy. CONCLUSIONS: Although the quality of the evidence was poor, this study found that longer prescriptions may be less costly overall, and may be associated with better adherence than 28-day prescriptions in patients with chronic conditions being treated in primary care. FUTURE WORK: There is a need to more reliably evaluate the impact of differing prescription lengths on adherence, on patient health outcomes and on total costs to the NHS. The priority should be to identify patients with particular conditions or characteristics who should receive shorter or longer prescriptions. To determine the need for any further research, an expected value of perfect information analysis should be performed. STUDY REGISTRATION: This study is registered as PROSPERO CRD42015027042. FUNDING: The National Institute for Health Research Health Technology Assessment programme