Oncology drugs and added benefit: insights from 3 European health technology assessment agencies on the role of efficacy endpoints

Smith, Nathaniel; Fu, An-Chen; Fisher, T. Forrest; Meletiche, DM; Pawar, Vivek

doi:10.1080/13696998.2021.2009711

Cited by 7 publications

(4 citation statements)

References 18 publications

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“… 55 There are also reports that OS data are important for reimbursement from the National Institute for Health and Care Excellence. 56 , 57 These results are not significantly different from our study results in Japan. However, it is very disappointing that similar results were obtained, as Japan has a postapproval reverification system called re-examination and re-evaluation.…”

Section: Discussioncontrasting

confidence: 81%

“…In the EU, it has been reported that approximately one-third of anticancer drugs cannot complete the postmarketing requirement 5 years after approval . There are also reports that OS data are important for reimbursement from the National Institute for Health and Care Excellence . These results are not significantly different from our study results in Japan.…”

Section: Discussionmentioning

confidence: 99%

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Assessment of Surrogate End Point Trends in Clinical Trials to Approve Oncology Drugs From 2001 to 2020 in Japan

et al. 2023

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ImportanceA surrogate end point (SEP) is an end point used in clinical trials as an alternative for measuring the true clinical benefit. The use of SEPs in trials shortens their duration.ObjectivesTo investigate the use of SEPs in clinical trials to support the approval of anticancer drugs and to determine whether confirmatory studies that use overall survival (OS) as an end point are being conducted in Japan.Design, Setting, and ParticipantsIn this cross-sectional study, drug approvals and background information were obtained from publicly available information, such as the Pharmaceuticals and Medical Devices Agency website, for anticancer drugs approved in Japan from January 2001 to December 2020. Data analysis was performed from September 2021 to March 2022.Main Outcomes and MeasuresCharacteristics of approved oncology drugs in Japan, end points for pivotal clinical trials, and outcomes of confirmatory trials using OS as an end point following drug approval.ResultsThere were 299 anticancer drugs approved in Japan during the study period. Of these, 142 (47.5%) were molecular-targeted drugs, the most common of which targeted non–small cell lung cancer. There were 111 (37.1%) anticancer drugs with orphan designation. From 2001 to 2005, OS was used as an end point in 1 approval (3.6%); however, from 2006 to 2020, OS was used in 86 approvals (31.7%). Of the 212 anticancer drugs approved on the basis of SEPs, confirmatory studies with OS as the end point were conducted for only 37 approvals (17.5%); for the remaining 175 approvals, studies are under way for 35 approvals (16.5%), were waivered for 75 approvals (35.4%), and were not conducted for 65 approvals (30.7%). Furthermore, in 20 drug approvals (9.4%), the conducted confirmatory studies were not effective in determining the OS, but the drugs were approved following re-examination.Conclusions and RelevanceThe findings of this study suggest that starting from 2005, the use of OS as an end point has increased in studies supporting the approval of anticancer drugs in Japan. However, even after 2005, approximately two-thirds of these approvals were SEP based. Postmarketing surveillance studies of the true end points are necessary to validate the use of SEPs.

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Section: Discussioncontrasting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Assessment of Surrogate End Point Trends in Clinical Trials to Approve Oncology Drugs From 2001 to 2020 in Japan

et al. 2023

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“…Similar studies in other countries were examined to facilitate a qualitative comparison ( 24 , 25 ), which shown that OS (92.6%) was the most common endpoint of drug that received a positive reimbursement decision, while only 7.4% of drug chose PFS in England and France. While in Canada, the most common primary endpoints with the positive reimbursement decisions were PFS (53.9%) and OS (32.1%), and the most frequently used endpoint for drugs with negative reimbursement decisions was ORR (38.5%) ( Table 4 ).…”

Section: Discussionmentioning

confidence: 99%

Correlation between clinical trial endpoints of marketed cancer drugs and reimbursement decisions in China

Ling

Qin

Feng

et al. 2022

Front. Public Health

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ObjectiveThis study aimed to assess whether different clinical trial endpoints in pivotal trials of cancer drugs were associated with reimbursement decisions in China.Materials and methodsCancer drugs marketed before June 30th, 2021 with publicly available technical review reports for application of drug registration on Center for Drug Evaluation (CDE) website were reviewed. The trial design characteristics and relevant clinical outcomes [e.g., overall survival (OS), progression-free survival (PFS) and objective response rate (ORR)] were extracted from the technical review reports, while the reimbursement decisions were reviewed from National Healthcare Security Administration (NHSA) website. The differences in trial characteristics and clinical outcomes between drugs with positive reimbursement decisions and negative ones were compared by hypothesis test (Pearson's chi-squared test, Fisher's exact test, independent samples t-test and Mann-Whitney U test). The correlation between different clinical trial endpoints and reimbursement decisions was analyzed by multivariate logistic regression.ResultsThere were 112 cancer drug indications included in this study. Among these indications, 76 received a positive reimbursement decision, and the most common primary endpoints of them were PFS (42.1%) and ORR (30.3%). Taking PFS (OR = 7.333) and ORR (OR = 5.271) as the primary endpoints were more likely to receive a positive reimbursement decision compared with OS (P = 0.003). The proportion of drugs marketed with phase I (75.0%) and phase II (85.7%) clinical trials receiving positive reimbursement decisions are significantly higher than those marketed with phase III clinical trials (61.3%, P = 0.043). The magnitude of clinical benefit only had subtle influences (Prisk benefit − OS = 0.627, Prisk benefit − PFS = 0.087, Psurvival benefit − OS = 0.545, Psurvival benefit − PFS = 0.189) on the drug reimbursement decisions, however, the drug prices and clinical needs also made a difference on that.ConclusionThis study found that, in Chinese drug price negotiations from 2017 to 2021, policymakers have focused more on meeting clinical needs and filling therapeutical gaps in National Reimbursement Drug List (NRDL), while requirements for the selection of primary endpoints, clinical trial phases, and clinical benefits have been reduced. In the future, emphasis should be put on the use of surrogate endpoints and clinical benefits.

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“…Surrogate endpoint data were also sufficient to achieve adoption and reimbursement (11,12), but more clinically relevant and patient-related QoL endpoints have been used much more sparingly in palliative trials (13). Some authors still consider health-related QoL metrics as challenging to assess and accident-sensitive (11).…”

Section: Editorial Commentarymentioning

confidence: 99%

The value of patient reported outcomes in palliative radiotherapy: A discussion in light of current findings

Gaertner¹,

Zimmermann²,

Simone³

2023

Ann Palliat Med

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Oncology drugs and added benefit: insights from 3 European health technology assessment agencies on the role of efficacy endpoints

Cited by 7 publications

References 18 publications

Assessment of Surrogate End Point Trends in Clinical Trials to Approve Oncology Drugs From 2001 to 2020 in Japan

Assessment of Surrogate End Point Trends in Clinical Trials to Approve Oncology Drugs From 2001 to 2020 in Japan

Correlation between clinical trial endpoints of marketed cancer drugs and reimbursement decisions in China

The value of patient reported outcomes in palliative radiotherapy: A discussion in light of current findings

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