Prm80 - The Use of External Data to Better Inform Survival Extrapolations in Submissions to the National Institute for Health and Care Excellence (Nice)

Abstract

OBJECTIVES: The Weber effect, a peak in adverse event (AE) reporting of a drug at the end of second year and continuous decline thereafter, has been considered an important bias for a long time. The aim of this study was to analyze the temporal reporting patterns of fourteen drugs (approved in 2006) for ten years in FAERS database. METHODS: A retrospective analysis was executed on the fourteen drugs approved in 2006. The drugs were selected according to the following conditions. Drugs should be approved in 2006 so that the Adverse Event (AE) reports will be available for at least ten years and the drug should not have acclaimed any major safety alerts. Reports of all drugs were normalized for ease of analysis in such a way that the highest count in the reports of any of the 40 quadrants of the drug in question was considered as 100 and remaining count of reports of that particular drug was normalized accordingly. The reporting pattern were analyzed by quarterly and yearly basis. The data set for analysis was retrieved from FAERS database between 2006 and 2016. RESULTS: The analysis was performed by using 19,539 primary suspected reports associated with the fourteen drugs approved in 2006. Four different types of reporting patterns were observed on analysis according to quarterly basis, namely, transitory decline, plateau prior to the rise in AE reports resumes, Weber effect, M-type pattern. Significant Weber pattern was observed when the reports were analyzed yearly basis. CONCLUSIONS: The present analysis showed that FAERS reporting is pertinent to Weber effect. It is advisable to address Weber effect in all studies which utilize FAERS database and quantification of such effects are required as it may affect the results drawn from the database.OBJECTIVES: Immature survival data can result in higher uncertainty over longterm extrapolations, and consequently in decision-making. Such uncertainty can be reduced with the use of external data. We aimed to review the use of external data to better inform survival extrapolations in submissions to the National Institute for Health and Care Excellence (NICE). METHODS: All NICE technology appraisals (TAs) that dealt with any stage of cancer and had been completed after December 2001 were reviewed. All relevant documents available on the NICE website were reviewed with special attention to the reports developed by the independent Assessment Group (AG) or Evidence Review Group (ERG). We included TAs where external data was used to inform survival extrapolations. Then, in addition to general information about the TA, we extracted the following information: external data source (historical trial, registry data or general population mortality), methods explored in the sponsor submission, criticism and alternative scenarios proposed by AG or ERG. RESULTS: Out of 143 reviewed TAs, ten TAs reported the use of external data to quantitatively inform survival extrapolations. These TAs were in two indications: melanoma (n¼8) and chronic lymphocytic leukemia (n¼2). Most frequently, a m...

Exploring clinical and economic value of novel therapies in oncology; contemporary challenges and applications

“…Twenty studies reported survival outcomes at the 10 24 MRD sensitivity threshold, 6,11,[19][20][21][22][23][24][25]27,28,31,32,34,38,42,48,50,53,55 18 studies at the 10 25 threshold, 4,29,30,33,[36][37][38][39][40][41][43][44][45]47,49,52,54 and 5 studies at the 10 26 threshold. 7,10,40,46,57 MRD negativity was associated with improved survival across all sensitivity thresholds (P , .001 for all subgroups vs MRD positivity; Figure 5; supplemental Figure 2A-B). MRD negativity was associated with significantly improved PFS at both 10 24 (HR, 0.38; 95% CI, 0.32-0.45; P , .001; Figure 5A) and 10 25 sensitivity thresholds (HR, 0.31; 95% CI, 0.27-0.36; P , .001; Figure 5A).…”

“…By MM disease setting. Survival outcomes were reported in 25 studies in transplant-eligible patients with NDMM, 6,10,18-40 8 studies in transplant-ineligible patients with NDMM, 11,[41][42][43][44][45][46][47] and 5 studies in patients with RRMM. 31,[48][49][50] Seven studies reported PFS/OS outcomes in patients in whom the disease setting was undefined.…”

“…Three studies reported survival outcomes in patients whose MRD status was assessed by the NGF method. 7,40,46 Nine studies reported outcomes by the NGS method, 10,30,37,[43][44][45]47,49 and 8 studies assessed outcomes by the polymerase chain reaction (PCR) method. Survival outcomes were favorable in MRD-negative patients regardless of the method of MRD assessment (Figure 5; supplemental Figure 4A-B).…”

“…By depth of clinical response at the time of MRD measurement. Thirteen studies reported survival outcomes in patients whose MRD status was assessed after the achievement of CR or better, 18,21,35,36,46,52,53,55,59 and 9 studies reported outcomes in patients whose MRD status was assessed after the achievement of very good partial response (VGPR) or better. 11,24,[28][29][30]33,34,38,41 5A).…”

“…This naïve or unadjusted pooling of historical trial data was later used to support HTABs submissions for apalutamide with androgen deprivation therapy for treating high-risk nm-CRPC. (46) In the manufacturer submission, pooled historical trials OS in placebo arms were either used to qualitatively compare the parametric models' fit on the registrational trial OS versus pooled historical trials OS or quantitatively by an 'informed fits' approach.…”