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

  title={Acceptance of surrogate end points in clinical trials supporting approval of drugs for cancer treatment by the Japanese regulatory agency.},
  author={Hideki Maeda and Tatsuo Kurokawa},
  journal={Annals of oncology : official journal of the European Society for Medical Oncology},
  volume={26 1},
  • H. Maeda, T. Kurokawa
  • Published 2015
  • Medicine
  • Annals of oncology : official journal of the European Society for Medical Oncology
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… 

Figures and Tables from this paper

Recent trends for drug lag in clinical development of oncology drugs in Japan: does the oncology drug lag still exist in Japan?
From 2001 to 2014, molecularly targeted drugs emerged as the predominant oncology drug, and the method of development has changed from full development in Japan or bridging strategy to global simultaneous development by Japan’s taking part in global clinical trials.
Surrogate end points for overall survival
The pledge for accepting surrogate end points in the Japanese regulatory to approve oncology drugs quickly in Japan could have been more balanced as the risk of error or of not clinically relevant benefit despite statistically significant surrogate end point cannot be ignored.
Reforms of regulatory pathways for approval of new antineoplastic drugs in Japan from 2004 to 2019 and accompanying changes in pivotal clinical trial designs
The number of indications in oncology approved by the PMDA has been increasing over the past 16 years, alongside changes in regulatory pathways, and this continues to increase.
Identification of approval conditions for orphan drugs for neurological disorders by the Japanese regulatory agency
A review of the Japanese regulatory environment for orphan drug approval in the neurological field is provided by assessing the characteristics of clinical trials for orphan drugs indicated for neurological diseases in Japan.
Unique characteristics of regulatory approval and pivotal studies of orphan anticancer drugs in Japan
It is demonstrated that orphan anticancer drugs in Japan have unique characteristics compared to non-orphan drugs: shorter regulatory review and pivotal studies frequently using phase II, non-randomized, or non-controlled designs and response rate as a primary endpoint, with fewer patients.
Regulatory review time for approval of oncology drugs in Japan between 2001 and 2014. Considerations of changes, factors that affect review time, and difference with the United States
It was found that the factors related to a use of overseas data and expedited program for accelerating the reviews influenced the direction of shortening the review time, and regulatory authorities in Japan need to keep making efforts to reduce thereview time further and eliminate the reviewTime lag with the United States.
Relationships between developmental strategies for additional indications and price revisions for anticancer drugs in Japan
The strategy for additional indications was found to affect the occurrence/non-occurrence of NHI price revisions, which was significantly related to the achievement of additional indications and compound type.
The Landscape of Clinical Trials Evaluating the Theranostic Role of PET Imaging in Oncology: Insights from an Analysis of Database
Concerns are raised that clinical trials evaluating PET imaging in oncology are not receiving the attention or efforts necessary to generate high-quality evidence and advancing the clinical application of PET imaging will require a concerted effort to improve the quality of trials.
Searching for potential surrogate endpoints of overall survival in clinical trials for patients with prostate cancer
The purpose of this study was to investigate the correlation between overall survival (OS) and other clinical outcomes in patients with prostate cancer. Further, we conducted subgroup analysis in the
Characteristics of clinical trials in rare vs. common diseases: A register-based Latvian study
It is confirmed that clinical trials in rare diseases vary from those in non-rare conditions, with notable differences in enrollment, randomization, masking, and the use of active comparators.


Oncology drug development and approval of systemic anticancer therapy by the U.S. Food and Drug Administration.
Approval of oncology agents is occurring in increasingly more challenging settings, suggesting gaps between eventual practice and development in potentially suboptimal indications.
Accelerated approval of oncology products: the food and drug administration experience.
We reviewed the regulatory history of the accelerated approval process and the US Food and Drug Administration (FDA) experience with accelerated approval of oncology products from its initiation in
In the end what matters most? A review of clinical endpoints in advanced breast cancer.
There is substantial discordance among the design and conduct of clinical trials, FDA drug approval, and the current view of OS as the ultimate measure of clinical benefit in MBC, leading to an urgent need to reassess standards for clinical benefit.
Use of multiple endpoints and approval paths depicts a decade of FDA oncology drug approvals.
This research describes the degree of regulatory flexibility that the U.S. Food and Drug Administration and drug sponsors have used over the past decade in the development of new treatments for cancer.
Characteristics of clinical trials to support approval of orphan vs nonorphan drugs for cancer.
Compared with pivotal trials used to approve nonorphan cancer drugs, pivotal trials for recently approved orphan drugs for cancer were more likely to be smaller and to use nonrandomized, unblinded trial designs and surrogate end points to assess efficacy.
When are "positive" clinical trials in oncology truly positive?
The approval of a new drug for cancer treatment by the regulatory authorities, such as the United States Food and Drug Administration or European Medicines Agency, is usually based on the positive
Use of Meta-Analysis for the Validation of Surrogate Endpoints and Biomarkers in Cancer Trials
This article discusses statistical approaches to the validation of surrogate biomarkers and endpoints. One approach that has been successfully used in oncology consists of estimating associations at
Differences in maximum tolerated doses and approval doses of molecularly targeted oncology drug between Japan and Western countries
This work compared the maximum tolerated dose (MTD) of the 21 molecularly targeted drugs in the Japanese with that in the western people and found that the MTD was determined lower in theJapanese than that inThe western people.
Progression-free survival as a surrogate for overall survival in advanced/recurrent gastric cancer trials: a meta-analysis.
Treatment effects on PFS and on OS were only moderately correlated, and the validity of PFS as a surrogate endpoint for OS in advanced/recurrent gastric cancer could not be confirmed.