scholarly journals Conditional approval of cancer drugs in Canada: accountability and impact on public funding

2019 ◽  
Vol 26 (1) ◽  
Author(s):  
S. K. Andersen ◽  
N. Penner ◽  
A. Chambers ◽  
M. E. Trudeau ◽  
K. K.W. Chan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Outcome Measures ◽  
Preliminary Data ◽  
Public Funding ◽  
Surrogate Endpoint ◽  
Cancer Drugs ◽  
Market Authorization ◽  
Oncology Review ◽  
Health Canada ◽  
Positive Recommendation

Background We examined how conditional market approval of cancer pharmaceuticals by Health Canada (hc) affects public funding recommendations by the pan-Canadian Oncology Review (pcodr). We were also interested to see how often hc conditions are enforced.Methods Health Canada and pcodr databases for 2010–2017 were analyzed for patterns in hc conditional authorization and post-authorization reviews of cancer drugs and for correlation with pcodr reimbursement recommendations.Results Between 2010 and 2017, pcodr reviewed 105 unique drug–indication pairings; 21% (n = 22) had conditional hc authorization. In all cases, conditional authorization was given on the basis of preliminary data in a surrogate endpoint and was contingent on further data showing benefit in more robust outcome measures (for example, overall survival). Of those 22 drugs, 36% did not have updated data, 36% had updated data that met hc conditions, and 27% had data that met some, but not all, conditions. During the period considered, hc never revoked conditional authorization for failure to meet conditions. None of the 22 drugs was given an unconditional positive recommendation for public reimbursement by pcodr. A conditional recommendation was given to 11 of the drugs (50%), and reimbursement was not recommended for 6 drugs (27%) because of insufficient evidence.Conclusions One fifth of the cancer drugs reviewed for public reimbursement in Canada were conditionally authorized by hc based on preliminary data. Conditional authorization was associated with a recommendation against public funding by pcodr. No drugs had their conditional market authorization revoked for failure to meet conditions, suggesting that a more robust hc reappraisal framework is needed.

COST-EFFECTIVENESS IMPACTS CANCER CARE FUNDING DECISIONS IN BRITISH COLUMBIA, CANADA, EVIDENCE FROM 1998 TO 2008

2017 ◽  
Vol 33 (4) ◽  
pp. 481-486
Author(s):  
Zahra Ismail ◽  
Stuart J. Peacock ◽  
Laurel Kovacic ◽  
Jeffrey S. Hoch
Keyword(s):  
British Columbia ◽  
Cost Effectiveness ◽  
Outcome Measures ◽  
Nonparametric Tests ◽  
Lower Probability ◽  
Economic Evidence ◽  
Cancer Drugs ◽  
Life Years ◽  
Significant Difference ◽  
The Mean

Objectives: The Priorities and Evaluation Committee (PEC) funding recommendations for new cancer drugs in British Columbia, Canada have been based on both clinical and economic evidence. The British Columbia Ministry of Health makes funding decisions. We assessed the association between cost-effectiveness of cancer drugs considered from 1998 to 2008 and the subsequent funding decisions.Methods: All proposals submitted to the PEC between 1998 and 2008 were reviewed, and the association between cost-effectiveness and funding decisions was examined by (i) using logistic regression to test the hypothesis that interventions with higher incremental cost-effectiveness ratios (ICERs) have a lower probability of receiving a positive funding decision and (ii) using parametric and nonparametric tests to determine if a statistically significant difference exists between the mean cost-effectiveness of funded versus not funded proposals. A sub-analysis was conducted to determine if the findings varied across different outcome measures.Results: Of the 149 proposals reviewed, 78 reported cost-effectiveness using various outcome measures. In the proposals that used life-years gained as the outcome (n = 22), a statistically significant difference of nearly $115,000 was observed between the mean ICERs for funded proposals ($42,006) and for unfunded proposals ($156,967). An odds ratio indicating higher ICERs have a lower probability of being funded was also found to be statistically significant (p < .05).Conclusions: Economic evidence appears to play a role in British Columbia cancer funding decisions from 1998 to 2008; other decision-making criteria may also have an important role in recommendations and subsequent funding decisions.

Re-Evaluating Disease-Free Survival as an Endpoint vs Overall Survival in Stage III Adjuvant Colon Cancer Trials

2021 ◽  
Author(s):  
Jun Yin ◽  
Mohamed E Salem ◽  
Jesse G Dixon ◽  
Zhaohui Jin ◽  
Romain Cohen ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Disease Free Survival ◽  
Surrogate Endpoint ◽  
Free Survival ◽  
A Value ◽  
Deficient Mismatch Repair ◽  
Disease Free

Abstract Background Disease-free survival with a 3-year median follow-up (3-year DFS) was validated as a surrogate for overall survival with a 5-year median follow-up (5-year OS) in adjuvant chemotherapy colon cancer (CC) trials. Recent data show further improvements in OS and survival after recurrence, in patients who received adjuvant FOLFOX. Hence, re-evaluation of the association between DFS and OS and determination of the optimal follow-up duration of OS to aid its utility in future adjuvant trials are needed. Methods Individual patient data from nine randomized studies conducted between 1998 and 2009 were included; three trials tested biologics. Trial-level surrogacy examining the correlation of treatment effect estimates of 3-year DFS with 5 to 6.5-year OS was evaluated using both linear regression (R2WLS) and Copula bivariate (R2Copula) models and reported with 95% confidence intervals (CIs). For R2, a value closer to 1 indicates a stronger correlation. Results Data from a total of 18,396 patients were analyzed (median age = 59 years; 54.0% male), with 54.1% having low-risk tumors (pT1-3 & pN1), 31.6% KRAS mutated, 12.3% BRAF mutated, and 12.4% microsatellite instability high/deficient mismatch repair tumors. Trial level correlation between 3-year DFS and 5-year OS remained strong (R2 =0.82, 95% CI = 0.67 to 0.98; R2 =0.92, 95% CI = 0.83 to 1.00) and increased as the median follow-up of OS extended. Analyses limited to trials that tested biologics showed consistent results. Conclusion Three-year DFS remains a validated surrogate endpoint for 5-year OS in adjuvant CC trials. The correlation was likely strengthened with 6 years of follow-up for OS.

Early tumor shrinkage under first-line tyrosine kinase inhibitor as a surrogate endpoint of overall survival in patients with metastatic renal cell carcinoma.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 523-523
Author(s):  
Hideaki Miyake ◽  
Ken-ichi Harada ◽  
Masato Fujisawa
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Liver Metastasis ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Surrogate Endpoint ◽  
Tumor Shrinkage ◽  
First Line ◽  
Early Tumor Shrinkage ◽  
Early Tumor

523 Background: The objective of this study was to assess the prognostic impact of early tumor shrinkage induced by first-line tyrosine kinase inhibitors (TKIs) on overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC). Methods: This study included a total of 185 consecutive Japanese patients with mRCC, consisting of 120 and 65 who were treated with sunitinib and sorafenib, respectively, for at least 3 months as first-line therapy. Prognostic outcomes in these 185 patients were retrospectively assessed focusing on the significance of tumor shrinkage at 12 weeks after the introduction of TKIs as a predictive factor of OS. Results: As the best responses to TKIs, 3, 40, 105 and 37 were judged to show a complete response, partial response, stable disease and progressive disease, respectively. The median progression-free survival (PFS) and OS in the 185 patients was 7.3 and 33.6 months, respectively. At 12 weeks after the introduction of TKIs, 9 patients reached a tumor shrinkage from -100 to -50%, 42 patients from -49 to -25%, 59 patients from -24 to 0%, and the remaining 70 patients had a gain of tumor size or new metastatic lesions. The median OS stratified according to tumor shrinkage at 12 weeks after the introduction of TKIs as shown above was 59.2, 39.1, 27.8 and 19.1 months, respectively. Univariate analysis identified the Memorial Sloan-Kettering Cancer Center (MSKCC) classification, Heng risk classification, C-reactive protein (CRP) level, lymph node metastasis, bone metastasis, liver metastasis, number of metastatic organs, histological subtype, sarcomatoid feature, PS and tumor shrinkage as significant predictors of OS. Of these significant factors, only the MSKCC classification, CRP level, liver metastasis and tumor shrinkage were shown to be independently associated with OS by multivariate analysis. Conclusions: These findings suggest that tumor shrinkage at 12 weeks after the introduction of TKIs was shown to have a significant impact on the OS in mRCC patients; therefore, early tumor shrinkage could be used as a reliable surrogate endpoint of OS in patients with mRCC receiving TKI as first-line agent.

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