Obinutuzumab in Combination with Chemotherapy for the First-Line Treatment of Patients with Advanced Follicular Lymphoma: An Evidence Review Group Evaluation of the NICE Single Technology Appraisal

The National Institute for Health and Care Excellence (NICE), as part of the institute’s single technology appraisal (STA) process, invited the company that makes obinutuzumab (Roche Products Limited) to submit evidence of the clinical and cost effectiveness of the drug in combination with chemotherapy, with or without obinutuzumab as maintenance therapy for adult patients with untreated, advanced follicular lymphoma (FL) in the UK. Kleijnen Systematic Reviews Ltd (KSR), in collaboration with Erasmus University Rotterdam, was commissioned to act as the Evidence Review Group (ERG). This paper describes the company’s submission, the ERG review, and NICE’s subsequent decisions. The clinical evidence was derived from two phase III, company-sponsored, randomised, open-label studies. Most evidence on obinutuzumab was based on the GALLIUM trial that compared obinutuzumab in combination with chemotherapy as induction followed by obinutuzumab maintenance monotherapy with rituximab in combination with chemotherapy as induction followed by rituximab maintenance monotherapy in previously untreated patients with FL (grades 1–3a). Long-term clinical evidence was based on the PRIMA trial, studying the benefit of two years of rituximab maintenance after first-line treatment in patients with FL. The cost-effectiveness evidence submitted by the company relied on a partitioned survival cost-utility model, implemented in Microsoft® Excel. The base-case incremental cost-effectiveness ratio (ICER) presented in the company submission was <£20,000 per quality-adjusted life-year (QALY) gained. Although the ERG concluded that the economic model met the NICE reference case to a reasonable extent, some errors were identified and several assumptions made by the company were challenged. A new base-case scenario produced by the ERG suggested an ICER that was higher than the company base case, but still below £30,000 per QALY gained. However, some ERG scenario analyses were close to or even above the threshold. This was the case in particular for assuming a treatment effect that did not extend beyond trial follow-up. These results led to an initial negative recommendation by the appraisal committee. Subsequently, the company submitted a revised base case focu

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)

Lenalidomide with Rituximab for Previously Treated Follicular Lymphoma and Marginal Zone Lymphoma:An Evidence Review Group Perspective of a NICE Single Technology Appraisal

The National Institute for Health and Care Excellence (NICE) invited the manufacturer (Celgene) of lenalidomide (Revlimid®), as part of the Single Technology Appraisal (STA) process, to submit evidence for the clinical effectiveness and cost-effectiveness of lenalidomide in combination with rituximab (MabThera®), together referred to as R2, for the treatment of adults with treated follicular lymphoma (FL) or marginal zone lymphoma (MZL). Kleijnen Systematic Reviews Ltd, in collaboration with Maastricht University Medical Centre+, was commissioned to act as the independent Evidence Review Group (ERG). This paper summarises the company submission (CS), presents the ERG's critical review on the clinical and cost-effectiveness evidence in the CS, highlights the key methodological considerations, and describes the development of the NICE guidance by the Appraisal Committee. The CS included one relevant study, for the comparison of R2 versus rituximab monotherapy (R-mono): the AUGMENT trial. In addition, the company performed an unanchored indirect comparison of R2 versus rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) and rituximab combined with cyclophosphamide, vincristine, and prednisolone (R-CVP), using data for R2 from the AUGMENT trial and pooled data for R-CHOP/R-CVP from the Haematological Malignancy Research Network (HMRN) database. During the STA process, the company provided an addendum containing evidence on only the FL population, in line with the marketing authorisation obtained at that time, which did not include MZL. The probabilistic incremental cost-effectiveness ratios (ICERs) presented by the company were £27,768 per quality-adjusted life year (QALY) gained for R2 versus R-CHOP, £41,602 per QALY gained for R2 versus R-CVP, and £23,412 per QALY gained for R2 versus R-mono. The ERG's concerns included the validity of the unanchored comparison, the unavailability of a state transition model to verify the outcomes of the partitioned survival model, substantial uncertainty in survival curves, and potential over-estimation of utility values. The revised ERG base case resulted in ICERs ranging from £16,874 to £44,888 per QALY gained for R2 versus R-CHOP, from £23,135 to £59,810 per QALY gained for R2 versus R-CVP, and from £18,779 to £27,156 per QALY gained for R2 versus R-mono. Substantial uncertainty remained around these ranges. NICE recommended R2 within its marketing authorisation, as an option for previously treated FL (grade 1-3A) in adults, contingent on the company providing lenalidomide according to the commercial arrangement