The Impasse on Overall Survival in Oncology Reimbursement Decision-Making: How Can We Resolve This?

Lux, Michael P.; Ciani, Oriana; Dunlop, W.; Ferris, Andrea; Friedlander, Michael

doi:10.2147/cmar.s328058

Cited by 12 publications

(14 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, evidence shows unclear correlations between surrogate endpoints and OS, which means such surrogate endpoints may not accurately predict clinical benefit ( 17 – 20 ). Scholars are divided on drugs of uncertain clinical benefit, with some opposing the positive reimbursement decisions of drugs with unclear clinical benefits ( 21 ) and others advocating that a new standard for drugs with surrogate endpoints should be established ( 22 ). Previous studies have analyzed the relevance between reimbursement decisions and clinical trial endpoints ( 23 – 28 ), the situation is not consistent across countries, while few studies have focused on the situation in China.…”

Section: Introductionmentioning

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

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

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

View full text Add to dashboard Cite

show abstract

“…This raises questions on whether regulatory or reimbursement decisions for new cancer treatments, which are mostly taken on aggregate, population level can equally benefit separate patients' groups. In practice, reimbursement decisions are often based primarily on the existence of mature OS data (10), which can overlook the preferences of specific patient groups who might benefit from the treatment in alternative, patient relevant end points. Even more so, when these end points are congruent with what patients consider to be the most significant outcome from their own viewpoint.…”

Section: Discussionmentioning

confidence: 99%

Patient preferences do matter: a discrete choice experiment conducted with breast cancer patients in six European countries, with latent class analysis

Stamuli

Corry

Foss

2023

Int J Technol Assess Health Care

View full text Add to dashboard Cite

Objectives The evolution of breast cancer (BC) treatments has resulted in tailored therapies for the different types and stages of BC. Each treatment has a profile of benefits and adverse effects which are taken into consideration when planning a treatment pathway. This study examines whether patients’ preferences are in line with what is considered important from decision makers viewpoint. Methods An online discrete choice experiment was conducted in six European countries (France, Germany, Ireland, Poland, Spain, UK) with BC patients. Six attributes were included: overall survival (OS), hyperglycemia, rash, pain, functional well-being (FWB), and out-of-pocket payment (OOP). Sixteen choice sets with two hypothetical treatments and a “No treatment” option were presented. Data were analyzed with the use of heteroscedastic conditional, mixed logistic, and latent class models. Marginal rate of substitution (MRS) were estimated for OOP versus the rest of attributes to establish the ranking of preferences for each attribute. Results Two hundred and forty-seven patients with advanced or metastatic BC and 314 with early-stage BC responded. Forty-nine percent of patients were < 44 years old and 65 percent had completed university education. The MRS of the analysis demonstrated that “severe pain” is the highest dis-preferred attribute level, followed by “severe impairment in FWB” and OS. Four classes of patients as “decision makers” were identified. Conclusions This study suggests that there is heterogeneity in treatment preferences of BC patients depending on their sociodemographic and disease-related characteristics. In combination with clinical guidelines, patient preferences can support the selection and tailoring of treatment options.

show abstract

“… 35 The aforementioned points thus contribute to the limitations of OS as an endpoint to demonstrate long-term treatment benefit. 5 While OS is an important endpoint in measuring the value of therapies and what matters to patients, with more therapies and multiple lines of therapy, it is often difficult to use OS as a clear measure of treatment effect. Therefore, further consideration should be given to other clinical endpoints that are important to health-care workers, prescribers, and patients.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, as an endpoint readily available in RWD sources, real-world TTD could be a useful measure indicative of short- and long-term benefit in aNSCLC and can be employed during reimbursement decision-making discussions, given that OS data interpretation may be limited, even with longer follow-up. 5 Previous patient-level pooled analyses of eight trials showed an overall strong correlation ( r =0.91) between TTD and PFS when studying patients with aNSCLC treated within the drug categories of EGFR-TKI, ALK-TKI, immune checkpoint inhibitors, or chemotherapy. 20 Therefore, TTD was used to evaluate real-world effectiveness in the three analytic cohorts as a proxy for PFS, which was the primary endpoint in the three selected RCTs.…”

Section: Methodsmentioning

confidence: 96%

“…In situations where trial OS data are immature, the evidence generated based on real-world data (RWD) can be helpful in addressing the uncertainty payers face related to the effectiveness of a therapy beyond the trial data. 5 Given the widespread availability of RWD, there is substantial interest in validating and comparing clinical effectiveness using RWD observed in clinical practice settings and clinical efficacy generated from randomized clinical trials (RCTs). 6 , 7 Real-world evidence (RWE) can demonstrate the short- and long-term clinical value of a drug in a clinical practice, 8 as well as help payers predict meaningful health benefit for patients underrepresented in RCTs.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Considerations for the Utility of Real-World Evidence Beyond Trial Data in Advanced NSCLC: The Case of Frontline Tyrosine Kinase Inhibitors

Gaitonde¹,

Chirikov²,

Kelkar³

et al. 2022

CMAR

View full text Add to dashboard Cite

Background To extend the discussion on the use of real-world evidence (RWE) in conveying the clinical value of treatment beyond trial data, the primary objective of this study was to assess if efficacy gains in progression-free survival (PFS) observed in randomized controlled trials (RCT) correlate with efficacy gains in the real-world setting. For this, we assessed the treatment benefit of three tyrosine kinase inhibitors (TKIs) in aNSCLC. Methods Using matched cohorts identified in the Flatiron Health database (2011–2020), we mimicked the following cohorts of TKI versus platinum-based chemotherapy (PBC) from the following trials: (1) erlotinib, EURTAC; (2) afatinib, LUX-Lung 3; and (3) crizotinib, PROFILE 1014. Time to treatment discontinuation (TTD) hazard ratio (HR) was used as a proxy for PFS HR, the primary endpoint in the selected RCTs. HRs were calculated via Cox proportional hazard models. Results Overall, 1,118 patients were included across the three RWE cohorts. Frontline TKI regimens had statistically significantly better real-world TTD than their matched PBC comparator group (HR 0.37, 95% confidence interval [CI] 0.30–0.44 for erlotinib; HR 0.42, 95% CI 0.32–0.55 for afatinib; HR 0.37, 95% CI 0.26–0.53 for crizotinib). The benefit in real-world OS was not different between TKIs and PBC patients, attributed to a high proportion of switching to subsequent therapy. Study findings of relative treatment benefit (HR) for real-world TTD and OS were deemed similar to those for PFS and OS from the pivotal RCTs. Conclusion The relative treatment effect, measured as real-world TTD HR over the long term, was similar to trial-based PFS HR, implying that the clinical benefit of aNSCLC treatments conveyed in trials translated into the clinical setting. This is important, given that OS data interpretation is limited, even with longer follow-up. Additionally, our RWE analysis endorses TTD as a relevant endpoint to measure clinical benefit.

show abstract

The Impasse on Overall Survival in Oncology Reimbursement Decision-Making: How Can We Resolve This?

Cited by 12 publications

References 65 publications

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

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

Patient preferences do matter: a discrete choice experiment conducted with breast cancer patients in six European countries, with latent class analysis

Considerations for the Utility of Real-World Evidence Beyond Trial Data in Advanced NSCLC: The Case of Frontline Tyrosine Kinase Inhibitors

Contact Info

Product

Resources

About