Key regulatory guidance relevant to adaptive designs, master protocols, and innovative trial methodology.
Resources
For IDSWG-authored guidance documents and white papers, see the Publications page.
FDA Guidance
FDA, November 2019
Adaptive Designs for Clinical Trials of Drugs and Biologics
Core FDA guidance on pre-specified adaptations, alpha control, and operational integrity in adaptive trials.
Download PDFFDA, June 2026 New
Master Protocols for Drug and Biological Product Development (Revised Draft)
Revised draft guidance issued June 24, 2026, replacing the December 2023 draft. Provides updated recommendations on the design, conduct, analysis, and regulatory submission of trials run under a master protocol, and adds a new section on evaluating drug effects across multiple diseases or disease subtypes in basket trials. Also details communication expectations between master protocol sponsors, drug sponsors, and the FDA, and expands guidance on informed consent. Open for comment through August 24, 2026. Docket: FDA-2023-D-5259.
Federal Register noticeFDA, December 2023
Decentralized Clinical Trials for Drugs, Biological Products, and Devices
Final guidance on remote assessments, local healthcare providers, and digital data collection in decentralized trials.
FDA guidance portalFDA, January 2025
Considerations for the Design and Conduct of Externally Controlled Trials
Guidance on using real-world data as a control arm, with particular relevance for rare diseases and pediatric populations.
FDA guidance portalFDA, January 2026 New
Use of Bayesian Methodology in Clinical Trials of Drug and Biological Products (Draft)
Landmark draft guidance covering Bayesian approaches to primary inference in pivotal trials, adaptive designs, rare disease trials, and incorporation of external data including real-world evidence. Covers pre-specification requirements, prior selection, success criteria, and simulation. Open for public comment; comments due March 13, 2026. Docket: FDA-2025-D-3217.
Federal Register noticeFDA, February 2026 New
Plausible Mechanism Framework for Individualized Therapies Targeting Specific Genetic Conditions (Draft)
Draft guidance establishing a framework for approval of highly individualized therapies (genome editing, RNA-based) for ultra-rare diseases where conventional randomized trials are not feasible. Describes conditions for meeting the substantial evidence of effectiveness standard via mechanistic evidence. Notes master protocols as a design option for evaluating multiple variants under a single application. Open for comment; comments due April 27, 2026. Docket: FDA-2026-D-1256.
Federal Register noticeEMA Guidance
EMA, March 2021
Guideline on Adaptive Designs in Clinical Trials
EMA guidance on adaptive methodology, Type I error control, and regulatory interaction for EU development programs.
EMA websiteEMA, 2022
Reflection Paper on Use of Real-World Data in Regulatory Decision-Making
EMA framework for when and how real-world data can support marketing authorization applications.
EMA websiteICH Guidelines
ICH, November 2019
E9(R1): Estimands and Sensitivity Analysis
The international standard for defining the target of estimation in clinical trials. Applies across FDA, EMA, and PMDA regions.
ICH websiteICH, 2024
E20: Adaptive Clinical Trials (Draft)
New ICH guideline harmonizing regulatory expectations for adaptive designs across international regions.
ICH websitePartner Organizations
Sponsor Organization
DahShu
The nonprofit organization sponsoring the IDSWG. DahShu hosts an annual Data Science Symposium and supports multiple scientific working groups advancing data science in drug development and healthcare.
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