Clinical effectiveness and cost-effectiveness of beta-interferon and glatiramer acetate for treating multiple sclerosis: systematic review and economic evaluation.

BACKGROUND: At the time of publication of the most recent National Institute for Health and Care Excellence (NICE) guidance [technology appraisal (TA) 32] in 2002 on beta-interferon (IFN-ß) and glatiramer acetate (GA) for multiple sclerosis, there was insufficient evidence of their clinical effectiveness and cost-effectiveness. OBJECTIVES: To undertake (1) systematic reviews of the clinical effectiveness and cost-effectiveness of IFN-ß and GA in relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS) and clinically isolated syndrome (CIS) compared with best supportive care (BSC) and each other, investigating annualised relapse rate (ARR) and time to disability progression confirmed at 3 months and 6 months and (2) cost-effectiveness assessments of disease-modifying therapies (DMTs) for CIS and RRMS compared with BSC and each other. REVIEW METHODS: Searches were undertaken in January and February 2016 in databases including The Cochrane Library, MEDLINE and the Science Citation Index. We limited some database searches to specific start dates based on previous, relevant systematic reviews. Two reviewers screened titles and abstracts with recourse to a third when needed. The Cochrane tool and the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) and Philips checklists were used for appraisal. Narrative synthesis and, when possible, random-effects meta-analysis and network meta-analysis (NMA) were performed. Cost-effectiveness analysis used published literature, findings from the Department of Health's risk-sharing scheme (RSS) and expert opinion. A de novo economic model was built for CIS. The base case used updated RSS data, a NHS and Personal Social Services perspective, a 50-year time horizon, 2014/15 prices and a discount rate of 3.5%. Outcomes are reported as incremental cost-effectiveness ratios (ICERs). We undertook probabilistic sensitivity analysis. RESULTS: In total, 6420 publications were identified, of which 63 relating to 35 randomised controlled trials (RCTs) were included. In total, 86% had a high risk of bias. There was very little difference between drugs in reducing moderate or severe relapse rates in RRMS. All were beneficial compared with BSC, giving a pooled rate ratio of 0.65 [95% confidence interval (CI) 0.56 to 0.76] for ARR and a hazard ratio of 0.70 (95% CI, 0.55 to 0.87) for time to disability progression confirmed at 3 months. NMA suggested that 20 mg of GA given subcutaneously had the highest probability of being the best at reducing ARR. Three separate cost-effectiveness searches identified > 2500 publications, with 26 included studies informing the narrative synthesis and model inputs. In the base case using a modified RSS the mean incremental cost was £31,900 for pooled DMTs compared with BSC and the mean incremental quality-adjusted life-years (QALYs) were 0.943, giving an ICER of £33,800 per QALY gained for people with RRMS. In probabilistic sensitivity analysis the ICER was £34,000 per QALY gained. In sensitivity analysis, using the assessment group inputs gave an ICER of £12,800 per QALY gained for pooled DMTs compared with BSC. Pegylated IFN-ß-1 (125 µg) was the most cost-effective option of the individual DMTs compared with BSC (ICER £7000 per QALY gained); GA (20 mg) was the most cost-effective treatment for CIS (ICER £16,500 per QALY gained). LIMITATIONS: Although we built a de novo model for CIS that incorporated evidence from our systematic review of clinical effectiveness, our findings relied on a population diagnosed with CIS before implementation of the revised 2010 McDonald criteria. CONCLUSIONS: DMTs were clinically effective for RRMS and CIS but cost-effective only for CIS. Both RCT evidence and RSS data are at high risk of bias. Research priorities include comparative studies with longer follow-up and systematic review and meta-synthesis of qualitative studies. STUDY REGISTRATION: This study is registered as PROSPERO CRD42016043278. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Investigating long-term effects of cochlear implantation in single-sided deafness: a best practice model for longitudinal assessment of spatial hearing abilities and tinnitus handicap.

OBJECTIVES: To evaluate methods for measuring long-term benefits of cochlear implantation in a patient with single-sided deafness (SSD) with respect to spatial hearing and to document improved quality of life because of reduced tinnitus. PATIENT: A single adult male with profound right-sided sensorineural hearing loss and normal hearing in the left ear who underwent right-sided cochlear implantation. METHODS: The subject was evaluated at 6, 9, 12, and 18 months after implantation on speech intelligibility with specific target-masker configurations, sound localization accuracy, audiologic performance, and tinnitus handicap. Testing conditions involved the acoustic (NH) ear only, the cochlear implant (CI) ear (acoustic ear plugged), and the bilateral condition (CI+NH). Measures of spatial hearing included speech intelligibility improvement because of spatial release from masking (SRM) and sound localization. In addition, traditional measures known as "head shadow," "binaural squelch," and "binaural summation" were evaluated. RESULTS: The best indicator for improved speech intelligibility was SRM, in which both ears are activated, but the relative locations of target and masker(s) are manipulated. Measures that compare performance with a single ear to performance using bilateral auditory input indicated evidence of the ability to integrate inputs across the ears, possibly reflecting early binaural processing, with 12 months of bilateral input. Sound localization accuracy improved with addition of the implant, and a large improvement with respect to tinnitus handicap was observed. CONCLUSION: Cochlear implantation resulted in improved sound localization accuracy when compared with performance using only the NH ear, and reduced tinnitus handicap was observed with use of the implant. The use of SRM addresses some of the current limitations of traditional measures of spatial and binaural hearing, as spatial cues related to target and maskers are manipulated, rather than the ear(s) tested. Sound testing methods and calculations described here are therefore recommended for assessing performance of a larger sample size of individuals with SSD who receive a CI.