NICE Health Research Articles

The Use of Real-World Data for Estimating Relative Treatment Effects in NICE Health Technology Assessment Submissions: A Review

The Use of Real-World Data for Estimating Relative Treatment Effects in NICE Health Technology Assessment Submissions: A Review

MSR7 Incorporating External Data to Inform Overall Survival Extrapolation: A Review of NICE Health Technology Appraisals for Oncology Drugs

MSR7 Incorporating External Data to Inform Overall Survival Extrapolation: A Review of NICE Health Technology Appraisals for Oncology Drugs

MSR140 Current Trends in Survival Extrapolation Methods: A Review of NICE Health Technology Appraisals for Oncology Drugs

MSR140 Current Trends in Survival Extrapolation Methods: A Review of NICE Health Technology Appraisals for Oncology Drugs

PD01 Using ELISA Tests For Monitoring Response To Anti-TNFs In Rheumatoid Arthritis: Findings From A NICE Health Technology Assessment

IntroductionPatients with severe rheumatoid arthritis (RA) disease may be treated with tumor necrosis factor (TNF)-α inhibitors. However, their efficacy is reduced by the presence of anti-drug antibodies. The objective of this HTA was to conduct a systematic review to investigate the effectiveness of using enzyme-linked immunosorbent assay (ELISA) tests (Promonitor, IDKmonitor, LISA-TRACKER, RIDASCREEN, MabTrack, and Sanquin Diagnostic Services) to measure levels of the drug and anti-drug antibodies for monitoring response to TNF-α inhibitors in patients with RA.MethodsA range of bibliographic databases including MEDLINE, EMBASE and CENTRAL were searched from inception to November 2018. Studies were eligible for inclusion if they investigated ELISA tests in RA patients receiving treatment with a TNF-α inhibitor who had achieved the treatment target (remission or low disease activity [LDA]) or experienced a primary or a secondary non-response. The tests must compare with standard care where treatment decisions are based on clinical judgements and monitoring using a composite score such as the disease activity score 28 joints (DAS28). Risk of bias was assessed using the Cochrane (ROBINS-1) tool for non-randomized studies.ResultsTwo studies were included. One non-randomized controlled trial (non-RCT) compared standard care with therapeutic drug monitoring using Promonitor test kits in RA patients in remission/LDA receiving adalimumab, and a historically controlled study investigated Sanquin ELISA kits. The non-RCT study showed that there was a non-significant reduction in the risk of flare in the intervention group compared with the control group. Patients’ health-related quality of life outcomes were higher in the intervention group at all visits compared with the control group. However, this study had serious limitations because analyses were not performed using an intention-to-treat approach. The historically controlled study did not provide valid evidence on whether ELISA-based monitoring is clinically effective.ConclusionsThere is only limited, poor evidence available. There are considerable uncertainties on the effectiveness of using ELISA tests for monitoring response to TNF-α inhibitors in RA. Further controlled trials are required.

CO163 The Increasing Use of Population-Adjusted Indirect Comparisons in the NICE Health Technology Assessment (HTA) Submission Process and the Response to These Methods

The use of indirect comparisons to estimate efficacy estimates is established in the NICE HTA process. Network meta-analysis (NMA) allows a comparison to be made between interventions that have been assessed in different clinical trials where common comparators link studies. However, in cases where only single arm trials, trials with very different populations or non-linking trials are available, alternative statistical approaches such as matching-adjusted indirect comparison (MAIC) and simulated treatment comparison (STC) can be used.

P47 Understanding Evidence Requirements for Diagnostic Devices for Reimbursement and Market Access: Insights and Lessons From Review of NICE Diagnostics Assessment Reports (2011-2022)

Personalized medicine driven by diagnostics has potential to improve patient outcomes and save costs for payers. However, a significant number of diagnostics are unable to receive reimbursement coverage for market access. The objective of this analysis was to understand the evidence requirements for diagnostics based on review of NICE Health Technology Assessment (HTA) reports.

EE111 Adoption of Piecewise Modelling: A Review of Nice Health Technology Appraisals in Oncology

10 years ago, NICE DSU Technical Support Document 14 noted the underutilization of piecewise models as an alternative to fully parametric models for survival extrapolations and recommended their consideration where more flexible survival models are required. This study aimed to review the adoption of the piecewise approach in recent assessments of oncology drugs submitted to the National Institute for Health and Care Excellence (NICE).

PCN249 A Review of Consistencies in Decision-Making across Nice Health Technology Assessments of Immune Checkpoint Inhibitors

PCN249 A Review of Consistencies in Decision-Making across Nice Health Technology Assessments of Immune Checkpoint Inhibitors

PDG66 A Review of the Outcomes of NICE Health Technology Appraisal Appeals

PDG66 A Review of the Outcomes of NICE Health Technology Appraisal Appeals

P257 Real-world evidence of TNF inhibition in axial spondyloarthritis: can we generalise the results from clinical trials?

Abstract Background The development and utility of management guidelines assumes that clinical trial findings are generalisable. Seldom is data available to test this. We aimed to determine, in the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS), the proportion of patients commencing TNF inhibition (TNFi) that would/would not have been eligible for clinical trials that led to TNFi treatment guidelines, and whether treatment response differed between the trials and this real-world population. Methods Biologic-naïve spondyloarthritis patients were recruited from across Great Britain. Data was obtained from clinical records, and participants completed postal questionnaires. Participant characteristics were extracted from the placebo-controlled randomised trials in the NICE Health Technology Assessment: TNF-alpha inhibitors for ankylosing spondylitis and non-radiographic axial spondyloarthritis (TA383). Descriptive statistics were used to examine differences, including treatment response (ASAS-20), between BSRBR-AS participants who would/would not have been eligible for the clinical trials, and the trial participants. Results 816/2420 (34%) BSRBR-AS participants were commencing TNFi. They were younger (mean age 44 versus 50yrs) with shorter disease duration (15 versus 22yrs), more active disease (BASDAI 6.4 versus 4.0), and poorer function (BASFI 6.2 versus 3.8). Fourteen clinical trials were identified. Compared to trial populations, fewer BSRBR-AS participants were male (67% versus 71%; difference: -4.1% (95%CI: -7.8%, -0.4%)) and fewer were HLA-B27 positive (76% versus 82%; difference: -6.6% (-10.6%, -2.6%)). BSRBR-AS participants were 6yrs older than trial participants, with longer symptom duration. They reported similar disease activity (BASDAI: 6.4 versus 6.2; difference 0.2 (-0.3, 0.7)), although significantly poorer function (BASFI: 6.2 versus 5.1; difference 1.1 (0.5, 1.8)) and spinal mobility (BASMI: 4.2 versus 3.3; difference 1.0 (0.8, 1.1)). Only 333 (41%) of BSRBR-AS participants commencing TNFi would have been eligible for any of the relevant trials. Ten trials reported ASAS20 response criteria, and 864/1401 participants reported a positive treatment response (61.7%). Follow-up data was available for 318 (39%) BSRBR-AS participants, of whom 163 (51.3%) achieved an ASAS20 treatment response (difference: 10.4% (4.4%, 16.5%)). There was no difference in ASAS20 response between those who would/would not have been eligible for clinical trials (50% versus 52%; difference 2.0% (-9.4%, 13.4%)). Conclusion In this real-world population, although the likelihood of meeting response criteria was unrelated to factors determining trial eligibility, the proportion of patients responding to TNFi was lower than in the clinical trial literature. Could this be explained by selection bias? Although fewer BSRBR-AS participants provided follow-up data than in the clinical trials, to account for the observed difference participants lost to follow-up would have to be one-third more likely to achieve ASAS20 response than those who provided follow-up data. We believe this is unlikely. These findings have important implications for the generalisability of trial results, and also for the cost-effectiveness of TNFi agents. Disclosures G.T. Jones: Grants/research support; GTJ is/was a grant holder for research funded by Pfizer, AbbVie, UCB and Celgene., GTJ is/was involved in research that received financial support from Novartis. L.E. Dean: Grants/research support; LED is/was involved in research that received financial support from Pfizer, AbbVie, UCB and Novartis. E. Pathan: None. G.J. Macfarlane: Grants/research support; GJM is/was a grant holder for research funded by Pfizer, AbbVie, UCB and Celgene., GJM is/was involved in research that received financial support from Novartis.

PNS318 NETWORK META-ANALYSES COMBINING RANDOMIZED AND NON-RANDOMIZED EVIDENCE; A NICE HTA REVIEW

Randomized controlled trials (RCTs) are considered the most reliable sources of information for evidence synthesis in network meta-analyses (NMAs). However, interest in including non-randomized studies (NRSs) in NMAs is growing. NRSs may complement evidence provided by RCTs and they can be used to connect disconnected evidence networks of RCTs. Statistical techniques including Bayesian hierarchical models have been developed to account for potential bias from including RCTs and NRSs in NMAs. This review aims to assess NICE technology appraisals which included NMAs combining RCTs and NRSs and to evaluate how the risk of bias has been addressed in these NMAs. A NICE health technology assessment (HTA) review was conducted on submissions appraised between 2001-2019. NMAs combining both RCT and NRS evidence were included. NMAs constructed using indirect treatment comparison techniques to connect a single-arm pivotal trial with other comparators are excluded if they don’t include RCT evidence in the network. Two relevant submissions were identified. Unavailability of RCTs was the reason for including NRSs in the NMAs. The sources of NRSs were evidence from other indirect treatment comparisons and observational studies. Risk of bias for RCTs was evaluated using CRD's guidance for undertaking reviews in health care and the NICE user guide. For the NRSs evidence; no formal quality assessment was done in one submission, but the second submission used ROBINS-I tool. In both submissions, specific methodologies for adjusting the bias that is introduced by combining different study designs in NMAs were not implemented. Inclusion of RCTs and NRSs in NMAs submitted to NICE is limited and differences in the risk of bias was not well addressed in the included NMAs. Available methodologies for incorporating RCTs and NRSs in NMAs can benefit future submissions which would require combining RCT and NRS evidence in NMAs.

PMU98 UTILITY OF EARLY ACCESS TO MEDICINES SCHEME DATA FOR NICE DECISION-MAKING

The Early Access to Medicines Scheme (EAMS) gives patients with life-threatening or seriously debilitating conditions early access to new medicines prior to marketing authorisation, with the potential for real world data collection to support market access. To date, NICE appraisals of EAMS medicines have not featured EAMS data. This analysis assessed the potential benefit of EAMS data to NICE Health Technology Assessment. Published NICE guidance on EAMS medicines was reviewed to assess whether data collected during the EAMS period would have made a difference to NICE decisions, where these were not recommended, optimised (restricted in a way not mandated by the marketing authorisation) or recommended in the Cancer Drugs Fund (CDF; because more clinical evidence is needed to prove cost-effectiveness). Of the EAMS medicines appraised by NICE (n=16), 5 were recommended; 1 was not recommended because of structural issues with the model resulting in no robust cost-effectiveness estimate; 5 had optimised recommendations either to reflect how the medicine would be used in NHS clinical practice or to include a stopping rule because long-term data on treatment duration was lacking; and 5 were recommended in the CDF because of limited data on long-term survival and treatment duration. It is unlikely that EAMS data would have made a fundamental difference to the recommendations because treatment during EAMS usually reflects NHS clinical practice and it is not feasible for long-term data addressing uncertainties about treatment duration and survival to be collected during the EAMS period. It appears that EAMS data collection is unlikely to have a direct impact on overall NICE committee recommendations. However, it could provide supplementary evidence to reduce uncertainty and enable more accurate estimates of cost-effectiveness for decision making, for example by validating trial findings and modelling assumptions, or providing new data to supplement trial results.

대사증후군 예방을 위한 모바일 헬스 애플리케이션의 개인맞춤형 콘텐츠 개발

Objectives: This study aimed to develop and pilot a mobile health application, ‘NICE Health Ten’, for a tailored health behavior intervention based on intervention mapping approach and transtheoretical model to prevent metabolic syndrome for Korean adults. Methods: We applied intervention mapping approach to design development of a mobile health application. Also, transtheoretical models concepts such as stages of change, decisional balance, and self-efficacy were applied to develop contents of mobile health application. Pilot preintervention-postintervention analysis was conducted and total 68 subjects were recruited and used ‘NICE Health Ten’ once a week for 8 weeks. Results: Health status and recommendations were provided for each physiological and behavioral factor associated with metabolic syndrome by developed ‘NICE Health Ten’. According to the pilot testing, the significant changes of knowledge, decisional balance, self-efficacy, and stages of change distribution related to healthy physical activity, healthy diet, and moderate drinking were in 20s adults who used ‘NICE Health Ten’ except for decisional balance of moderate drinking. Conclusions: Metabolic syndrome can be prevented by implementing mobile health application intervention for health behavioral change. Also, Intervention Mapping is effective to design an intervention for metabolic syndrome.

Cost-effectiveness of osimertinib in the UK for advanced EGFR-T790M non-small cell lung cancer

Aim: This study presents the cost-utility analysis that was developed to inform the NICE health technology assessment of osimertinib vs platinum-based doublet chemotherapy (PDC) in patients with EGFR-T790M mutation-positive non-small cell lung cancer (NSCLC) who have progressed on epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy.Methods and materials: A partitioned survival model with three health states (progression-free, progressed disease, and death) from a UK payer perspective and over lifetime (15 years) was developed. Direct costs included disease management, treatment-related (acquisition, administration, monitoring, adverse events), and T790M testing costs. Efficacy and safety data were taken from clinical trials AURA extension and AURA2 for osimertinib and IMPRESS for PDC. An adjusted indirect treatment comparison was applied to reduce the potential bias in the non-randomized comparison. Parametric functions were utilized to extrapolate survival beyond the observed period. Health state utility values were calculated from EQ-5D data collected in the trials and valued using UK tariffs. Resource use and costs were based on published sources.Results: Osimertinib was associated with a gain of 1.541 quality-adjusted life-years (QALYs) at an incremental cost of £64,283 vs PDC (incremental cost-effectiveness ratio [ICER]: £41,705/QALY gained). Scenario analyses showed that none of the plausible scenarios produced an ICER above £44,000 per QALY gained, and probabilistic sensitivity analyses demonstrated a 63.4% probability that osimertinib will be cost-effective at a willingness-to-pay threshold of £50,000.Limitations: The analysis is subject to some level of uncertainty inherent to phase 2 single-arm data and the immaturity of the currently available survival data for osimertinib.Conclusions: Osimertinib may be considered a cost-effective treatment option compared with PDC in the second-line setting in patients with EGFR-T790M mutation-positive NSCLC from a UK payer perspective. Further data from the ongoing AURA clinical trial program will reduce the inherent uncertainty in the analysis.

Optimiser le séjour des patients atteints de pathologie psychique en médecine et chirurgie

The action research undertaken by health manager students at the Nice health manager training institution has helped to optimise the stay of patients with a mental disorder in general medical and surgical units. Based on the assessment of the training needs of caregivers working in these units, itenables the students to anticipate their future function.

Measuring Extent of Access For Nice Health Technology Assessment Decisions: Trends From 2008 to 2013.

Measuring Extent of Access For Nice Health Technology Assessment Decisions: Trends From 2008 to 2013.

Mapping to Obtain EQ-5D Utility Values for Use in NICE Health Technology Assessments

Quality-adjusted life-years (QALYs) are widely used as an outcome for the economic evaluation of health interventions. However, preference-based measures used to obtain health-related utility values to produce QALY estimates are not always included in key clinical studies. Furthermore, organizations responsible for reviewing or producing health technology assessments (HTAs) may have preferred instruments for obtaining utility estimates for QALY calculations. Where data using a preference-based measure or the preferred instrument have not been collected, it may be possible to “map” or “crosswalk” from other measures of health outcomes. The aims of this study were 1) to provide an overview of how mapping is currently used as reported in the published literature and in an HTA policy-making context, specifically at the National Institute for Health and Clinical Excellence in the United Kingdom, and 2) to comment on best current practice on the use of mapping for HTA more generally. The review of the National Institute for Health and Clinical Excellence guidance found that mapping has been used since first established but that reporting of the models used to map has been poor. Recommendations for mapping in HTA include an explicit consideration of the generalizability of the mapping function to the target sample, reporting of standard econometric and statistical tests including the degree of error in the mapping model across subsets of the range of utility values, and validation of the model(s). Mapping can provide a route for linking outcomes data collected in a trial or observational study to the specific preferred instrument for obtaining utility values. In most cases, however, it is still advantageous to directly collect data by using the preferred utility-based instrument and mapping should usually be viewed as a “second-best” solution.