Durvalumab for the Treatment of Locally Advanced, Unresectable, Stage III Non-Small Cell Lung Cancer:An Evidence Review Group Perspective of a NICE Single Technology Appraisal

As part of the Single Technology Appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer (AstraZeneca) of durvalumab (IMFINZI(TM)) to submit evidence for the clinical and cost effectiveness of durvalumab for the treatment of patients with locally advanced, unresectable, stage III non-small cell lung cancer whose tumours express programmed death-ligand 1 (PD-L1) on >= 1% of tumour cells and whose disease has not progressed after platinum-based chemoradiation therapy. 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 a systematic review that identified one randomised controlled trial, comparing durvalumab with SoC. Participants with tumours expressing PD-L1 on >= 1% of tumour cells accounted for approximately 40% of the total participants. In this subgroup, a benefit in progression-free survival (PFS) [hazard ratio (HR) 0.44, 95% confidence interval (CI) 0.31-0.63] and overall survival (HR 0.54, 95% CI 0.35-0.81) was reported. Adverse events were comparable between both treatments, but more serious adverse events were reported for durvalumab (64/213 [30%] vs. 18/90 [20%]). The ERG's concerns regarding the economic analysis included a likely overestimation of PFS for the durvalumab arm, the choice of timepoint for treatment waning, as well as the way treatment waning was incorporated in the model, and potential overestimation of utility values without applying an age- or treatment-related decrement. The revised ERG base-case resulted in a deterministic incremental cost-effectiveness ratio of 50,238 pound per quality-adjusted life-year gained, with substantial remaining uncertainty. NICE recommended durvalumab as an option for use within the Cancer Drugs Fund only in a subpopulation (concurrent platinum-based chemoradiation therapy) with a commercially managed access agreement in place

Adherence to Highly Active Antiretroviral Treatment in HIV-Infected Rwandan Women

Scale-up of highly active antiretroviral treatment therapy (HAART) programs in Rwanda has been highly successful but data on adherence is limited. We examined HAART adherence in a large cohort of HIV+ Rwandan women.The Rwanda Women's Interassociation Study Assessment (RWISA) was a prospective cohort study that assessed effectiveness and toxicity of ART. We analyzed patient data 12±3 months after HAART initiation to determine adherence rates in HIV+ women who had initiated HAART.Of the 710 HIV+ women at baseline, 490 (87.2%) initiated HAART. Of these, 6 (1.2%) died within 12 months, 15 others (3.0%) discontinued the study and 80 others (19.0%) remained in RWISA but did not have a post-HAART initiation visit that fell within the 12±3 month time points leaving 389 subjects for analysis. Of these 389, 15 women stopped their medications without being advised to do so by their doctors. Of the remaining 374 persons who reported current HAART use 354 completed the adherence assessment. All women, 354/354, reported 100% adherence to HAART at the post-HAART visit. The high self-reported level of adherence is supported by changes in laboratory measures that are influenced by HAART. The median (interquartile range) CD4 cell count measured within 6 months prior to HAART initiation was 185 (128, 253) compared to 264 (182, 380) cells/mm(3) at the post-HAART visit. Similarly, the median (interquartile range) MCV within 6 months prior to HAART initiation was 88 (83, 93) fL compared to 104 (98, 110) fL at the 12±3 month visit.Self-reported adherence to antiretroviral treatment 12±3 months after initiating therapy was 100% in this cohort of HIV-infected Rwandan women. Future studies should explore country-specific factors that may be contributing to high levels of adherence to HAART in this population

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)