Guidelines for clinical evaluation of anti‐cancer drugs

Abstract

Clinical studies intended for regulatory approval must demonstrate the clinical benefits of the drug in a target population. Clinical development of a drug proceeds by stepwise clinical studies; after safety and pharmacokinetics are evaluated and the recommended dosage and administration are determined, efficacy and safety are evaluated in an exploratory manner, and finally clinical benefits are compared with conventional standard therapies. Guidelines for the clinical evaluation of anti‐cancer drugs in Japan were established in 1991 and amended in 2006 after molecular‐targeted drugs were introduced. Recent progress in the development of drugs acting on the immune system and cancer genomic medicine targeting rare but important molecular subtypes have altered the strategy for development of anti‐cancer drugs. It is often difficult to conduct a confirmatory randomized controlled study using overall survival as the primary endpoint in rare molecular subtypes, and the primary evaluation of the efficacy of some drugs and subsequent approval is based on the tumor response. As conducting clinical studies for rare subtypes solely within Japan is difficult, drug development needs to be conducted within a global study. However, this requires robust monitoring to detect possible ethnic differences in pharmacokinetics and drug efficacy. Development using the conditional approval system for drugs enforced in 2020 may be considered, when clinical utility is evaluated based on surrogate endpoints. Because of these changes, we have revised the guidelines for the clinical evaluation of anti‐cancer drugs in Japan. To promote global development of anti‐cancer drugs involving Japan, the guidelines have been translated into English.

DNA Damage Clustering after Ionizing Radiation and Consequences in the Processing of Chromatin Breaks

“…This high death toll has necessitated the development of effective therapies. Indeed, a variety of therapies have been developed and successfully applied in the clinic, resulting in improved patient quality of life and cures for some malignancies [ 1 ]. Notably, radiotherapy remains an integral part of most cancer treatment regimens.…”

A Comparison of Post-marketing Measures Imposed by Regulatory Agencies to Confirm the Tissue-Agnostic Approach

“…There is currently limited guidance available on the data requirements to confirm a tissue-agnostic indication in the post-marketing setting. In the guideline of the PMDA it is recommended that high quality data, including data from cancer types not evaluated in the clinical trials, is required after marketing authorization ( 9 ). For future applications, a global strategy toward the generation of data in the post-marketing setting may be of interest, dependent on emerging insights from the current approaches.…”

“…As there are currently few tissue-agnostic approvals, regulatory experience is limited. The EMA and PMDA have issued guidance documents that include information on master protocol designs and the registration of medicinal products for tissue-agnostic indications ( 8 , 9 ). Another relevant document is the FDA guidance for industry on developing targeted therapies in low-frequency molecular subsets of a disease ( 10 ).…”

Identification of Novel Modalities Through Bibliometric Analysis for Timely Development of Regulatory Guidance: A Case Study of T Cell Immunity

“…Instead, the management of immune-related adverse events, which are distinct from those of conventional cytotoxic and molecular-targeted drugs, has drawn attention, as discussed ( 44 , 45 ). Recent progress in the development of immunotherapy has altered the strategy for developing anti-cancer drugs, necessitating revision of the guideline for these clinical evaluations in Japan ( 102 ).…”