Association Between the Use of Surrogate Measures in Pivotal Trials and Health Technology Assessment Decisions: A Retrospective Analysis of NICE and CADTH Reviews of Cancer Drugs

Pinto, Ashlyn; Naci, Huseyin; Neez, Emilie; Mossialos, Elías

doi:10.1016/j.jval.2019.10.010

Cited by 18 publications

(19 citation statements)

References 26 publications

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“…A prior review of regulatory submissions found that only 9% (4/43) of non-RCT submissions used an adjusted ITC. 23 In this analysis, the first case of adjusted ITC was not until 2015 (3, 7% of 2015 submissions) increasing to 29% (30) in 2019. Over the same period, use of naive ITC reduced as a proportion of all submissions between 2015 (22, 48%) and 2019 (22, 22%).…”

Section: Methodological Approaches For Ecsmentioning

confidence: 78%

“…The increasing availability of RWD and gradual acceptance by HTA and regulatory bodies has been extensively covered by other commentators. 23,[31][32][33][34] In relation to SAT-based submissions, RWD ECs may be considered more appropriate as they allow more relevant comparator cohorts to be constructed and enable the collection of more contemporary standard of care treatments than prior clinical trials data. However, we suggest that manufacturers assess other important factors when designing an EC as there is variation between HTA bodies in acceptance of RWD.…”

Section: Impact Of Ecs On Hta Decision-makingmentioning

confidence: 99%

“…20,21 In general, unanchored comparisons are less well established than anchored methods, and additional care is needed on interpretation. 12,22,23 External comparator (EC) data (also referred to as "external controls," "historical comparators," or "synthetic controls") collected from patient cohorts outside of the clinical study, or "index study" is being used more frequently to provide contextual information on a product's clinical efficacy, safety, and cost-effectiveness. Here patient selection criteria from the index study protocol are applied to the external data source (to the extent possible) so that the comparator population looks as similar as possible to the index study population.…”

Section: Introductionmentioning

confidence: 99%

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Use of External Comparators for Health Technology Assessment Submissions Based on Single-Arm Trials

et al. 2021

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Background: Single-arm trial (SAT) data is increasingly reviewed for drug approvals by regulators and Health Technology Assessment (HTA) bodies. Supplementary data in the form of external comparators (ECs) can be used to provide clinical context to support these drug evaluations. In this study we characterized HTAs for SAT-based submissions, the use of supplementary EC data and outcomes from HTA review.Methods: HTA Accelerator database was used to describe SAT-based HTA submissions with decisions (2011-2019).Results: A total of 433 SAT-based HTA submissions were identified between 2011 and 2019 with a 13-fold increase during this period. Around 65%(283/433) were in oncology or hem-oncology. Around 52%(226/433) of submissions contained some type of EC data, including prior clinical trials (24%, 104) and real-world data (RWD) (20%, 87), but 40%(175) contained no EC data. The overall acceptance rate for SAT-based submissions was 48% and with RWD EC data acceptance was 59%. In the latest 5year period (2015-2019), use of RWD ECs increased 22% as a proportion of submissions per year, whereas, prior trial ECs decreased (-14%) and use of no EC remained stable (-2%). Between 2015 to 2017 and 2018 to 2019, acceptance rate for RWD ECs increased by 20% (41% in 2015-2017 to 61% in 2018-2019) whereas prior trial EC use decreased by 10% and no EC submissions decreased 16%. Of 226 submissions using ECs, only 29%(66) used an adjusted indirect treatment comparison method.Conclusions: SAT-based submissions to HTA bodies are rapidly evolving in terms of composition and acceptance. Types of EC and methodological approach used are important determinants of positive outcomes.

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Section: Methodological Approaches For Ecsmentioning

confidence: 78%

Section: Impact Of Ecs On Hta Decision-makingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Use of External Comparators for Health Technology Assessment Submissions Based on Single-Arm Trials

et al. 2021

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“…6,7 Four previous studies have investigated the impact of surrogate endpoints on HTA decisions. Two studies focused on cancer drugs, 8,9 and 2 considered the range of technology appraisals undertaken by either the National Institute of Health and Care Excellence (NICE) in the United Kingdom or the Canadian Common Drug Review. 10,11 However, these previous studies did not assess HTA agencies' approach to validation of the surrogate endpoints or how this related to their coverage recommendation.…”

Section: Introductionmentioning

confidence: 99%

Validity of Surrogate Endpoints and Their Impact on Coverage Recommendations: A Retrospective Analysis across International Health Technology Assessment Agencies

et al. 2021

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Background Surrogate endpoints (i.e., intermediate endpoints intended to predict for patient-centered outcomes) are increasingly common. However, little is known about how surrogate evidence is handled in the context of health technology assessment (HTA). Objectives 1) To map methodologies for the validation of surrogate endpoints and 2) to determine their impact on acceptability of surrogates and coverage decisions made by HTA agencies. Methods We sought HTA reports where evaluation relied on a surrogate from 8 HTA agencies. We extracted data on the methods applied for surrogate validation. We assessed the level of agreement between agencies and fitted mixed-effects logistic regression models to test the impact of validation approaches on the agency’s acceptability of the surrogate endpoint and their coverage recommendation. Results Of the 124 included reports, 61 (49%) discussed the level of evidence to support the relationship between the surrogate and the patient-centered endpoint, 27 (22%) reported a correlation coefficient/association measure, and 40 (32%) quantified the expected effect on the patient-centered outcome. Overall, the surrogate endpoint was deemed acceptable in 49 (40%) reports ( k-coefficient 0.10, P = 0.004). Any consideration of the level of evidence was associated with accepting the surrogate endpoint as valid (odds ratio [OR], 4.60; 95% confidence interval [CI], 1.60–13.18, P = 0.005). However, we did not find strong evidence of an association between accepting the surrogate endpoint and agency coverage recommendation (OR, 0.71; 95% CI, 0.23–2.20; P = 0.55). Conclusions Handling of surrogate endpoint evidence in reports varied greatly across HTA agencies, with inconsistent consideration of the level of evidence and statistical validation. Our findings call for careful reconsideration of the issue of surrogacy and the need for harmonization of practices across international HTA agencies.

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“…While NICE and ICER represent two of the largest and most consequential HTA agencies, we know very little about how their methodologies compare or the degree to which they reach similar conclusions. Studies by Chabot and Rocchi in 2014 [6], and Pinto and colleagues in 2020 compared English and Canadian HTA for oncology drugs [7] and both studies found variation in recommendations due to differences in available policy tools to address issues of clinical uncertainty and unfavorable cost-effectiveness.…”

Section: Introductionmentioning

confidence: 99%

Cost-effectiveness of cancer drugs: Comparative analysis of the United States and England

et al. 2020

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Background: England's National Institute for Health and Care Excellence (NICE) and the US' Institute for Clinical and Economic Review (ICER) both conduct cost-effectiveness evaluations for new cancer drugs to help payers make drug coverage decisions. However, NICE and ICER assessments have been noted to reach different conclusions. We aim to better understand the degree to which their recommendations diverge and what drives these apparent differences. Methods: We compared the methods and results of publicly available cost-effectiveness evaluations performed by ICER and NICE of similarly assessed cancer drugs. Assessments were compared based on incremental cost-effectiveness ratio, comparator treatment, price, recommendation, and the design of the economic evaluation. Findings: Among 11 commonly assessed cancer drugs, ICER and NICE were in concordance for 7 evaluations and in discordance on the cost-effectiveness and coverage decisions for 4 drugs. Most new cancer drugs were not cost-effective in either the US (7/11) or England (7/11). Furthermore, NICE's capacity to negotiate price discounts and access schemes result in much lower cost per QALY valuations and more favourable recommendations than those of ICER for similarly assessed cancer drugs. Interpretations: NICE and ICER employ similar health technology assessment (HTA) methodologies and were aligned with most recommendations, finding that many new and expensive cancer drugs are cost ineffective. Growing use of ICER assessments will continue to send stronger price signals to manufacturers that cancer drugs with low value for money will be viewed less favourably by private insurers. NICE provides an important reminder of how much lower other countries pay for drugs when comparative effectiveness and valuebased pricing are integrated into public drug coverage decisions.

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Association Between the Use of Surrogate Measures in Pivotal Trials and Health Technology Assessment Decisions: A Retrospective Analysis of NICE and CADTH Reviews of Cancer Drugs

Cited by 18 publications

References 26 publications

Use of External Comparators for Health Technology Assessment Submissions Based on Single-Arm Trials

Use of External Comparators for Health Technology Assessment Submissions Based on Single-Arm Trials

Validity of Surrogate Endpoints and Their Impact on Coverage Recommendations: A Retrospective Analysis across International Health Technology Assessment Agencies

Cost-effectiveness of cancer drugs: Comparative analysis of the United States and England

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