Acceptance of surrogate end points in clinical trials supporting approval of drugs for cancer treatment by the Japanese regulatory agency

H. Maeda, T. Kurokawa

研究成果: Article

11 引用 (Scopus)

抄録

Background: This study investigated the historic use of different end points to support approval of drugs for cancer treatment in Japan. Patients and methods: Anticancer drugs approved between April 2001 and April 2014 were comprehensively investigated using publicly available information. Results: Before the revision of the guideline for oncology drugs in April 2006 in Japan, >80% of end points supporting approval were response rate and overall survival (OS) was not frequent. After the revision of the guideline in Japan, using OS in pivotal clinical trials applied for approval increased to more than approximately one-third of oncology drugs, although trials with an end point of response rate decreased. Regarding drugs for major cancers including non-small-cell lung cancer, gastric cancer, colorectal cancer, and breast cancer, survival was used as an end point in 44.0%, whereas surrogate end points were used in 56.0%. Exploration of potential factors for using surrogate end points other than survival carried out through determinations of odds ratios and 95% confidence intervals identified 'orphan drug designation in Japan' and 'accelerated approval by the U.S. Food and Drug Administration' as significant factors. Conclusions: The revised guideline for oncology drugs in Japan requires the results of phase 3 studies with survival as an end point at the time of new drug application at least for major cancers. The regulatory agency in Japan also accepts surrogate end points as end points supporting approval besides survival; however, the number of surrogate end points has decreased after the revision of the guideline.We consider that accepting surrogate end points in the Japanese regulatory systems is important to approve oncology drugs quickly in Japan.

元の言語English
ページ(範囲)211-216
ページ数6
ジャーナルAnnals of Oncology
26
発行部数1
DOI
出版物ステータスPublished - 2015 1 1

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Drug Approval
Japan
Biomarkers
Clinical Trials
Pharmaceutical Preparations
Survival
Neoplasms
Guidelines
Therapeutics
Stomach Neoplasms
Orphan Drug Production
Breast Neoplasms
United States Food and Drug Administration
Non-Small Cell Lung Carcinoma
Colorectal Neoplasms
Survival Rate
Odds Ratio
Confidence Intervals

ASJC Scopus subject areas

  • Oncology
  • Hematology

これを引用

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title = "Acceptance of surrogate end points in clinical trials supporting approval of drugs for cancer treatment by the Japanese regulatory agency",
abstract = "Background: This study investigated the historic use of different end points to support approval of drugs for cancer treatment in Japan. Patients and methods: Anticancer drugs approved between April 2001 and April 2014 were comprehensively investigated using publicly available information. Results: Before the revision of the guideline for oncology drugs in April 2006 in Japan, >80{\%} of end points supporting approval were response rate and overall survival (OS) was not frequent. After the revision of the guideline in Japan, using OS in pivotal clinical trials applied for approval increased to more than approximately one-third of oncology drugs, although trials with an end point of response rate decreased. Regarding drugs for major cancers including non-small-cell lung cancer, gastric cancer, colorectal cancer, and breast cancer, survival was used as an end point in 44.0{\%}, whereas surrogate end points were used in 56.0{\%}. Exploration of potential factors for using surrogate end points other than survival carried out through determinations of odds ratios and 95{\%} confidence intervals identified 'orphan drug designation in Japan' and 'accelerated approval by the U.S. Food and Drug Administration' as significant factors. Conclusions: The revised guideline for oncology drugs in Japan requires the results of phase 3 studies with survival as an end point at the time of new drug application at least for major cancers. The regulatory agency in Japan also accepts surrogate end points as end points supporting approval besides survival; however, the number of surrogate end points has decreased after the revision of the guideline.We consider that accepting surrogate end points in the Japanese regulatory systems is important to approve oncology drugs quickly in Japan.",
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N2 - Background: This study investigated the historic use of different end points to support approval of drugs for cancer treatment in Japan. Patients and methods: Anticancer drugs approved between April 2001 and April 2014 were comprehensively investigated using publicly available information. Results: Before the revision of the guideline for oncology drugs in April 2006 in Japan, >80% of end points supporting approval were response rate and overall survival (OS) was not frequent. After the revision of the guideline in Japan, using OS in pivotal clinical trials applied for approval increased to more than approximately one-third of oncology drugs, although trials with an end point of response rate decreased. Regarding drugs for major cancers including non-small-cell lung cancer, gastric cancer, colorectal cancer, and breast cancer, survival was used as an end point in 44.0%, whereas surrogate end points were used in 56.0%. Exploration of potential factors for using surrogate end points other than survival carried out through determinations of odds ratios and 95% confidence intervals identified 'orphan drug designation in Japan' and 'accelerated approval by the U.S. Food and Drug Administration' as significant factors. Conclusions: The revised guideline for oncology drugs in Japan requires the results of phase 3 studies with survival as an end point at the time of new drug application at least for major cancers. The regulatory agency in Japan also accepts surrogate end points as end points supporting approval besides survival; however, the number of surrogate end points has decreased after the revision of the guideline.We consider that accepting surrogate end points in the Japanese regulatory systems is important to approve oncology drugs quickly in Japan.

AB - Background: This study investigated the historic use of different end points to support approval of drugs for cancer treatment in Japan. Patients and methods: Anticancer drugs approved between April 2001 and April 2014 were comprehensively investigated using publicly available information. Results: Before the revision of the guideline for oncology drugs in April 2006 in Japan, >80% of end points supporting approval were response rate and overall survival (OS) was not frequent. After the revision of the guideline in Japan, using OS in pivotal clinical trials applied for approval increased to more than approximately one-third of oncology drugs, although trials with an end point of response rate decreased. Regarding drugs for major cancers including non-small-cell lung cancer, gastric cancer, colorectal cancer, and breast cancer, survival was used as an end point in 44.0%, whereas surrogate end points were used in 56.0%. Exploration of potential factors for using surrogate end points other than survival carried out through determinations of odds ratios and 95% confidence intervals identified 'orphan drug designation in Japan' and 'accelerated approval by the U.S. Food and Drug Administration' as significant factors. Conclusions: The revised guideline for oncology drugs in Japan requires the results of phase 3 studies with survival as an end point at the time of new drug application at least for major cancers. The regulatory agency in Japan also accepts surrogate end points as end points supporting approval besides survival; however, the number of surrogate end points has decreased after the revision of the guideline.We consider that accepting surrogate end points in the Japanese regulatory systems is important to approve oncology drugs quickly in Japan.

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