BMI trajectories after primary school-based lifestyle intervention: Unravelling an uncertain future. A mixed methods study.

This mixed methods study aimed to examine plausible body mass index (BMI) trajectories after exposure to a primary school-based lifestyle intervention to aid in estimating the long-term intervention benefits. BMI trajectories for children at control schools (mean 7.6 years of age) were modelled until 20 years of age through extrapolating trial evidence (N = 1647). A reference scenario assumed that the observed 2-year effects of the 'Healthy Primary Schools of the Future' (HPSF) and 'Physical Activity Schools' (PAS) were fully maintained over time. This was modelled by applying the observed 2-year BMI effects until 20 years of age. Expert opinions on likely trends in effect maintenance after the 2-year intervention period were elicited qualitatively and quantitatively, and were used for developing alternative scenarios. Expert elicitation revealed three scenarios: (a) a constant exposure-effect and an uncontrolled environment with effect decay scenario, (b) a household multiplier and an uncontrolled environment with effect decay scenario, and (c) a household multiplier and maintainer scenario. The relative effect of HPSF at 20 years of age was -0.21 kg/m2 under the reference scenario, and varied from -0.04 kg/m2 (a) to -0.06 kg/m2 (b), and -0.50 kg/m2 (c). For PAS, the relative effect was -0.17 kg/m2 under the reference scenario, and varied from -0.04 kg/m2 (a, b), to -0.21 kg/m2 (c). The mixed methods approach proved to be useful in modelling plausible BMI trajectories and specifying uncertainty on effect maintenance. Further observations until adulthood could reduce the uncertainty around future benefits. This trial was retrospectively registered at Clinicaltrials.gov (NCT02800616).

Fluocinolone Acetonide Intravitreal Implant for Treating Recurrent Non-infectious Uveitis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

The National Institute for Health and Care Excellence (NICE) invited Alimera Sciences, the company manufacturing fluocinolone acetonide intravitreal implant (FAc) 0.19 mg (tradename ILUVIEN®), to submit evidence on the clinical and cost-effectiveness of FAc for treating recurrent non-infectious uveitis. Kleijnen Systematic Reviews Ltd, in collaboration with Maastricht University Medical Centre + , was commissioned to act as the independent Evidence Review Group (ERG). This paper contains a summary of the clinical and cost-effectiveness evidence submitted by the company, the ERG's critique on the submitted evidence, and the guidance issued by the NICE Appraisal Committee (AC). The company submission (CS) was mainly informed by the PSV-FAI-001 trial in which FAc was compared with (limited) current practice [(L)CP], which was not considered to be representative of UK clinical practice by the ERG. There was no comparison of FAc to any treatment listed in the final scope, and especially to the dexamethasone intravitreal implant (dexamethasone), which was considered to be a relevant comparator by the AC. The primary outcome of the PSV-FAI-001 was recurrence of uveitis in the treated eye. Most of the events for the primary outcome were imputed during the PSV-FAI-001 trial, which probably led to an overestimation of the number of recurrences of disease, and a biased estimate of the relative effectiveness of FAc versus (L)CP. Finally, the place of FAc in the treatment pathway was not clearly defined by the company. Substantial uncertainty surrounded the cost-effectiveness results due to the shortcomings of the clinical evidence. Additionally, the quality of life of patients was not measured during the PSV-FAI-001 trial and long-term effectiveness data of FAc were lacking. The ERG adjusted several issues identified in the CS and added dexamethasone as a comparator in the decision analytic model. The ERG presented multiple analyses as base-cases because several elements of the assessment remained uncertain. The fully incremental ERG results ranged from dexamethasone (extendedly) dominating FAc (when assuming a hazard ratio of 1 or 0.7 for dexamethasone versus FAc) to an incremental cost-effectiveness ratio (ICER) of £30,153 per quality-adjusted life-year (QALY) gained for FAc versus (L)CP [when assuming a hazard ratio of 0.456 for dexamethasone versus (L)CP]. The ICER of FAc versus (L)CP ranged from £12,325 to £30,153 per QALY gained. After a second AC meeting where alternative company scenarios comparing FAc with dexamethasone were considered by the AC, the AC concluded that "the results of the company's analyses ranged from the fluocinolone acetonide implant being dominant (that is, it was more effective and costs less), to an ICER of £29,461 per QALY gained, and most of the ICERs were below £20,000 per QALY gained". Therefore, the AC recommended FAc as a cost-effective use of National Health Service (NHS) resources for treating recurrent non-infectious uveitis affecting the posterior segment of the eye in the final TA590 guidance (published July 2019).

Comparison of EQ-5D and SF-36 in untreated patients with symptoms of intermittent claudication.

AIM: To compare health-related quality of life (HRQoL) descriptions and utility scores in newly diagnosed peripheral arterial disease (PAD) patients, using two most widely used instruments, EuroQol 5D (EQ-5D) and Medical Outcome Study 36-item Short-Form Health Status Survey (SF-36). METHODS: Patients' self-assessment of HRQoL was measured by the Dutch versions of the EQ-5D and SF-36 in the 204 patients. RESULTS: Mean utility scores ranged from 0.675 for Short-Form Six-Dimension, 0.648 for the EQ-5D UK tariff and 0.715 for the Dutch EQ-5D tariff. A moderate correlation between the utility scores was found due to different valuation techniques of these instruments. CONCLUSION: Both instruments have clinical validity for use in the PAD and can be used alongside each other to provide a holistic assessment of the HRQoL. Before using these two instruments interchangeably for utility score calculations and healthcare resource allocation, a thorough sensitivity analysis is necessary to explore the robustness of the value argument based on these utility scores.

Ixekizumab for Treating Moderate-to-Severe Plaque Psoriasis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

The National Institute for Health and Care Excellence invited Eli Lilly and Company Ltd, the company manufacturing ixekizumab (tradename Taltz®), to submit evidence for the clinical and cost effectiveness of ixekizumab. Ixekizumab was compared with tumour necrosis factor-α inhibitors (etanercept, infliximab, adalimumab), ustekinumab, secukinumab, best supportive care and, if non-biological treatment or phototherapy is suitable, also compared with systemic non-biological therapies and phototherapy with ultraviolet B radiation for adults with moderate-to-severe plaque psoriasis. Kleijnen Systematic Reviews Ltd, in collaboration with Maastricht University Medical Center, was commissioned as the independent Evidence Review Group. This article presents a summary of the company submission, the Evidence Review Group report and the development of the National Institute for Health and Care Excellence guidance for the use of this drug in England and Wales by the Appraisal Committee. The Evidence Review Group produced a critical review of the clinical and cost effectiveness of ixekizumab based on the company submission. The company submission presented three randomised controlled trials identified in a systematic review. All randomised controlled trials were phase III, multicentre placebo-controlled trials including 3866 participants with moderate-to-severe psoriasis. Two trials also included an active comparator (etanercept). All randomised controlled trials showed statistically significant increases in two primary outcomes, static Physician Global Assessment (0,1) and improvement of 75% from baseline in the Psoriasis Area and Severity Index. Ixekizumab was generally well tolerated in the randomised controlled trials, with similar discontinuation rates because of adverse events as placebo or etanercept. The most frequent adverse events of special interest were infections and injection-site reactions. The company submission also included a network meta-analysis of relevant comparators. The Evidence Review Group highlighted some issues regarding the systematic review process and an issue with the generalisability of the findings in that the trials failed to include patients with moderate psoriasis according to a widely used definition. This issue was considered by the Appraisal Committee and the population was deemed generalisable to patients in England and Wales. Based on the network meta-analysis, the Appraisal Committee concluded that ixekizumab was more clinically effective than adalimumab and ustekinumab, and agreed it was likely that ixekizumab was similarly effective compared with secukinumab and infliximab while tolerability was similar to other biological treatments approved for treating psoriasis. The Evidence Review Group's critical assessment of the company's economic evaluation highlighted a number of concerns, including (1) the use of relative outcomes such as Psoriasis Area and Severity Index response to model the cost effectiveness; (2) the exclusion of the consequences of adverse events; (3) the assumption of no utility gain in the induction phase; (4) equal annual discontinuation rates for all treatments; (5) the selection of treatment sequences for consideration in the analyses and; (6) the transparency of the Visual Basic for Applications code used to develop the model. Although some of these issues were adjusted in the Evidence Review Group base case, the Evidence Review Group could not estimate the impact of all of these issues, and thus acknowledges that there are still uncertainties concerning the cost-effectiveness evidence. In the Evidence Review Group base-case incremental analysis, the treatment sequence incorporating ixekizumab in the second line has an incremental cost-effectiveness ratio of £25,532 per quality-adjusted life-year gained vs. the etanercept sequence. Ixekizumab in the first-line sequence has an incremental cost-effectiveness ratio of £39,129 per quality-adjusted life-year gained compared with the treatment sequence incorporating ixekizumab in the second line. Consistent with its conclusion regarding clinical effectiveness, the Appraisal Committee concluded that the cost effectiveness of ixekizumab for treating moderate-to-severe plaque psoriasis was similar to that of other biological treatments, already recommended in previous National Institute for Health and Care Excellence guidance. The committee concluded that the incremental cost-effectiveness ratio was within the range that could be considered a cost-effective use of National Health Service resources.

Cost-effectiveness analysis of sacral neuromodulation and botulinum toxin A treatment for patients with idiopathic overactive bladder.

UNLABELLED: Study Type - Therapy (economic analysis). LEVEL OF EVIDENCE: 1b. OBJECTIVE: To assess and compare the costs and effects value of either starting with sacral neuromodulation (SNM) or botulinum toxin A (BTX) treatment in patients with refractory idiopathic overactive bladder from a societal perspective. MATERIALS AND METHODS: An economic model comparing SNM with BTX was developed. A clinical relevant effect (i.e. success) was defined as 50% or greater reduction in incontinence episodes or urgency frequency symptoms. Information on the clinical effectiveness of the two treatments and on the course of the disease with the two treatments were based primarily on published literature and, when required, on expert opinion. Both treatments were assumed to be performed under general anaesthesia and, for SNM treatment, first-stage tined lead test was used. All costs were based on national data from the year 2008. Analyses from the societal perspective were conducted for a 5-year duration. Costs were discounted at 4% and effects at 1.5%. In addition, different modelling scenarios were used to see determine any changes in the results obtained. RESULTS: Starting with SNM resulted in a higher quality adjusted life year (QALY) gain (difference of 0.23) and a higher cost (difference of €6428) compared to starting with BTX. The corresponding incremental cost-effectiveness ratio was €27,991/QALY. The probability of this ratio being cost effective (e.g. under €40,000/QALY) is 88%. SNM starts to be cost-effective after 4 years. SNM was not cost-effective in some other scenarios, such as when BTX was conducted under local anaesthesia or when peripheral nerve evaluation or bilateral testing was used for SNM. CONCLUSIONS: Starting with SNM, treatment is cost-effective after 5 years compared to BTX. However, in some scenarios, such as the use of local anaesthesia for BTX treatment and SNM peripheral nerve evaluation or bilateral test, SNM was not cost-effective.