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

H. Maeda, T. Kurokawa

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)211-216
Number of pages6
JournalAnnals of Oncology
Volume26
Issue number1
DOIs
Publication statusPublished - 2015 Jan 1

Fingerprint

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

Keywords

  • Drugs for cancer treatment
  • Japan
  • Oncology drugs
  • PMDA
  • Surrogate end point
  • Survival

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

Acceptance of surrogate end points in clinical trials supporting approval of drugs for cancer treatment by the Japanese regulatory agency. / Maeda, H.; Kurokawa, T.

In: Annals of Oncology, Vol. 26, No. 1, 01.01.2015, p. 211-216.

Research output: Contribution to journalArticle

@article{ca2af3896a134995afce1a1c7d4e2de9,
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.",
keywords = "Drugs for cancer treatment, Japan, Oncology drugs, PMDA, Surrogate end point, Survival",
author = "H. Maeda and T. Kurokawa",
year = "2015",
month = "1",
day = "1",
doi = "10.1093/annonc/mdu500",
language = "English",
volume = "26",
pages = "211--216",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "Oxford University Press",
number = "1",

}

TY - JOUR

T1 - Acceptance of surrogate end points in clinical trials supporting approval of drugs for cancer treatment by the Japanese regulatory agency

AU - Maeda, H.

AU - Kurokawa, T.

PY - 2015/1/1

Y1 - 2015/1/1

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.

KW - Drugs for cancer treatment

KW - Japan

KW - Oncology drugs

KW - PMDA

KW - Surrogate end point

KW - Survival

UR - http://www.scopus.com/inward/record.url?scp=84922489159&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84922489159&partnerID=8YFLogxK

U2 - 10.1093/annonc/mdu500

DO - 10.1093/annonc/mdu500

M3 - Article

VL - 26

SP - 211

EP - 216

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 1

ER -