Linda Long

The effectiveness and cost-effectiveness of erythropoiesis-stimulating agents (epoetin and darbepoetin) for treating cancer treatment-induced anaemia (including review of technology appraisal no. 142): a systematic review and economic model.

BACKGROUND Anaemia is a common side effect of cancer treatments and can lead to a reduction in quality of life. Erythropoiesis-stimulating agents (ESAs) are licensed for use in conjunction with red blood cell transfusions to improve cancer treatment-induced anaemia (CIA). OBJECTIVE To investigate the effectiveness and cost-effectiveness of ESAs in anaemia associated with cancer treatment (specifically chemotherapy). DATA SOURCES The following databases were searched from 2004 to 2013: The Cochrane Library, MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Web of Science, Cumulative Index to Nursing and Allied Health Literature, British Nursing Index, Health Management Information Consortium, Current Controlled Trials and ClinicalTrials.gov. The US Food and Drug Administration and European Medicines Agency websites were also searched. Bibliographies of included papers were scrutinised for further potentially includable studies. REVIEW METHODS The clinical effectiveness review followed principles published by the NHS Centre for Reviews and Dissemination. Randomised controlled trials (RCTs), or systematic reviews of RCTs, of ESAs (epoetin or darbepoetin) for treating people with CIA were eligible for inclusion in the review. Comparators were best supportive care, placebo or other ESAs. Anaemia- and malignancy-related outcomes, health-related quality of life (HRQoL) and adverse events (AEs) were evaluated. When appropriate, data were pooled using meta-analysis. An empirical health economic model was developed comparing ESA treatment with no ESA treatment. The model comprised two components: one evaluating short-term costs and quality-adjusted life-years (QALYs) (while patients are anaemic) and one evaluating long-term QALYs. Costs and benefits were discounted at 3.5% per annum. Probabilistic and univariate deterministic sensitivity analyses were performed. RESULTS Of 1457 titles and abstracts screened, 23 studies assessing ESAs within their licensed indication (based on start dose administered) were included in the review. None of the RCTs were completely aligned with current European Union licenses. The results suggest a clinical benefit from ESAs for anaemia-related outcomes and an improvement in HRQoL scores. The impact of ESAs on AEs and survival remains highly uncertain, although point estimates are lower, confidence intervals are wide and not statistically significant. Base-case incremental cost-effectiveness ratios (ICERs) for ESA treatment compared with no ESA treatment ranged from £ 19,429 to £ 35,018 per QALY gained, but sensitivity and scenario analyses demonstrate considerable uncertainty in these ICERs, including the possibility of overall health disbenefit. All ICERs were sensitive to survival and cost. LIMITATIONS The relative effectiveness of ESAs was not addressed; all ESAs were assumed to have equivalent efficacy. No studies were completely aligned with their European labelling beyond the starting dose evaluated. There is questionable generalisability given that the included trials were published >20 years ago and there have been many changes to chemotherapy as well as to the quality of supportive treatment. Trial quality was moderate or poor and there was considerable unexplained heterogeneity for a number of outcomes, particularly survival, and evidence of publication bias. Adjustments were not made to account for multiple testing. CONCLUSIONS ESAs could be cost-effective when used closer to licence, but there is considerable uncertainty, mainly because of unknown impacts on overall survival. STUDY REGISTRATION This study is registered as PROSPERO CRD42013005812. FUNDING The National Institute for Health Research Health Technology Assessment programme.

What is the clinical effectiveness and cost-effectiveness of conservative interventions for tendinopathy? An overview of systematic reviews of clinical effectiveness and systematic review of economic evaluations

BACKGROUND Lateral elbow tendinopathy (LET) is a common complaint causing characteristic pain in the lateral elbow and upper forearm, and tenderness of the forearm extensor muscles. It is thought to be an overuse injury and can have a major impact on the patients social and professional life. The condition is challenging to treat and prone to recurrent episodes. The average duration of a typical episode ranges from 6 to 24 months, with most (89%) reporting recovery by 1 year. OBJECTIVES This systematic review aims to summarise the evidence concerning the clinical effectiveness and cost-effectiveness of conservative interventions for LET. DATA SOURCES A comprehensive search was conducted from database inception to 2012 in a range of databases including MEDLINE, EMBASE and Cochrane Databases. METHODS AND OUTCOMES We conducted an overview of systematic reviews to summarise the current evidence concerning the clinical effectiveness and a systematic review for the cost-effectiveness of conservative interventions for LET. We identified additional randomised controlled trials (RCTs) that could contribute further evidence to existing systematic reviews. We searched MEDLINE, EMBASE, Allied and Complementary Medicine Database, Cumulative Index to Nursing and Allied Health Literature, Web of Science, The Cochrane Library and other important databases from inception to January 2013. RESULTS A total of 29 systematic reviews published since 2003 matched our inclusion criteria. These were quality appraised using the Assessment of Multiple Systematic Reviews (AMSTAR) checklist; five were considered high quality and evaluated using a Grading of Recommendations, Assessment, Development and Evaluation approach. A total of 36 RCTs were identified that were not included in a systematic review and 29 RCTs were identified that had only been evaluated in an included systematic review of intermediate/low quality. These were then mapped to existing systematic reviews where further evidence could provide updates. Two economic evaluations were identified. LIMITATIONS The summary of findings from the review was based only on high-quality evidence (scoring of > 5 AMSTAR). Other limitations were that identified RCTs were not quality appraised and dichotomous outcomes were also not considered. Economic evaluations took effectiveness estimates from trials that had small sample sizes leading to uncertainty surrounding the effect sizes reported. This, in turn, led to uncertainty of the reported cost-effectiveness and, as such, no robust recommendations could be made in this respect. CONCLUSIONS Clinical effectiveness evidence from the high-quality systematic reviews identified in this overview continues to suggest uncertainty as to the effectiveness of many conservative interventions for the treatment of LET. Although new RCT evidence has been identified with either placebo or active controls, there is uncertainty as to the size of effects reported within them because of the small sample size. Conclusions regarding cost-effectiveness are also unclear. We consider that, although updated or new systematic reviews may also be of value, the primary focus of future work should be on conducting large-scale, good-quality clinical trials using a core set of outcome measures (for defined time points) and appropriate follow-up. Subgroup analysis of existing RCT data may be beneficial to ascertain whether or not certain patient groups are more likely to respond to treatments. STUDY REGISTRATION This study is registered as PROSPERO CRD42013003593. FUNDING The National Institute for Health Research Health Technology Assessment programme.