Endpoint Adjudication Resources, Regulations & Guidelines

Adjudication-Methods-FDA

Discover the Endpoint Adjudication Charter Template (What Should Be Included?) by the Endpoint Adjudication Professional Group on Linkedin 


USE OF ADJUDICATION METHODS IN CLINICAL TRIALS

69% of the NMEs approved in the US used an adjudication method in their phase III development program whereas, in Europe, 41% of the approvals included a central review

REGULATIONS & GUIDELINES

  1. ESTABLISHMENT AND OPERATION OF CLINICAL TRIAL DATA MONITORING COMMITTEES 
    FDA Guidance for Industry

    ABSTRACT: [...] "This guidance discusses the roles, responsibilities and operating procedures of Data Monitoring Committees (DMCs) (also known as Data and Safety Monitoring Boards (DSMBs) or Data and Safety Monitoring Committees (DSMCs)) that may carry out important aspects of clinical trial monitoring. This guidance is intended to assist clinical trial sponsors in determining when a DMC may be useful for study monitoring, and how such committees should operate. We recognize that in many clinical trials the sponsor delegates some decision-making regarding the design and conduct of the trial to some other entity such as a steering committee (see Section 3.2) or contract research organization (CRO) (see 21 Code of Federal Regulations (CFR) 312.3(b)) [...]"
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  2. GUIDELINE ON DATA MONITORING COMMITTEES
    EMA Committee for Medicinal products for human use (CHMP)

    ABSTRACT: [...] This Guideline document deals with independent Data Monitoring Committees. It is intended as an overview guide to highlight the key issues involved when sponsors include data monitoring committees as part of their trial management. While confirmatory, double blind,  randomized clinical trials are in the focus of this guideline, the general principles outlined in this document also apply to other clinical trial situations [...].
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  3. STANDARD FOR CLINICAL TRIAL IMAGING ENDPOINTS - August 2011
    FDA Guidance for Industry

    ABSTRACT: [...]The purpose of this guidance is to assist sponsors in the use of endpoints that depend on the 20 results of imaging tests in clinical trials of therapeutic drugs and biological products.2 This 21 guidance focuses on the imaging standards that we regard as important when imaging is used to 22 assess a primary endpoint, or an endpoint component, in a clinical trial intended to confirm a 23 drug’s efficacy. [...].
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  4. CLINICAL TRIAL IMAGING ENDPOINT PROCESS - March 2015 - Draft Guidance (revises the previous Guidance of 2011)

    ABSTRACT: [...] The purpose of this guidance is to assist sponsors in optimizing the quality of imaging data obtained in clinical trials intended to support approval of drugs and biological products. This guidance focuses on imaging acquisition, display, archiving, and interpretation process standards that we regard as important when imaging is used to assess a trial’s primary endpoint or a component of that endpoint. [...]
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  5. DIABETES MELLITUS - EVALUATING CARDICASCULAR RISK IN NEW ANTIDIABETIC THERAPIES TO TREAT TYPE 2 DIABETES
    FDA Guidance for Industry

    ABSTRACT: [...] This guidance provides recommendations for the development of drugs and therapeutic biologics regulated within the Center for Drug Evaluation and Research at the Food and Drug Administration (FDA) for the treatment of diabetes mellitus.2 Specifically, this guidance makes recommendations about how to demonstrate that a new antidiabetic therapy to treat type 2 diabetes is not associated with an unacceptable increase in cardiovascular risk [...]
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  6. CLINICAL TRIAL ENDPOINTS FOR THE APPROVAL OF CANCER DRUGS AND BIOLOGICS
    FDA Guidance for Industry

    ABSTRACT: [...]This guidance is the first in a planned series of cancer endpoint guidances. It provides recommendations to applicants on endpoints for cancer clnical trials submitted to Food and Drug Administration (FDA) to support effectiveness claims in new drug applications (NDAs), biologic license applications (BLAs), or supplemental applications. [...] DOWNLOAD THE DOCUMENT 

 

ARTICLES & PUBLICATIONS

An Overview and Analysis Regarding the Use of Adjudication Methods in EU and US Drug Approvals

Background: Several regulatory guidelines recommend that assessments of endpoints supporting drug approval should be verifiable by applicants and the regulatory agencies to minimize the potential for bias. This becomes especially critical when assessments are not based on measurable data but are derived from the interpretation of measurements, when they require the application of complex endpoint assessments, or when a study cannot be blinded. To make such interpretation more robust, a verification of (subjective) assessments by an independent panel of experts is frequently utilized. The objective of this paper was to analyze how often adjudicated methods across efficacy and safety assessments were used in drug approvals in the European Union and United States in 2013 and early 2014.

Authors: Stephanie Krumholz-Bahner, Mimmo Garibbo, Kenneth A. Getz and Beat E. Widler.
Therapeutic Innovation & Regulatory Science
DOI: 10.1177/2168479015580382tirs.sagepub.com
tirs.sagepub.com

LINK TO DOCUMENT

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Subjective endpoints in clinical trials: the case for blinded independent central review

.... Primary efficacy and safety endpoints in clinical trials are often subjective assessments made by site personnel. For international confirmatory trials conducted over broad geographic regions and different clinical practice settings, variability in these subjective assessments can be substantial. Centralized endpoint assessment committees (EACs) offer a mechanism through which to reduce assessment bias and potentially increase assessment precision and accuracy, particularly in open-label trials. An overview of regulatory agencies' rationales for an EAC is reviewed. In addition, the two main types of EACs, the blinded independent central review, and the consensus panel are compared. Selection of endpoints for EAC evaluation and design of EAC process to maximize EAC value proposition are also discussed.

Author(s): Richard Walovitch, Bin Yao, Patrick Chokron, Helen Le, Glenn Bubley
Published: Dove Medical Press on September 2013 Volume 2013:5 - Pages 111-117

LINK TO DOCUMENT

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Blinded Independent Central Review (BICR) of The Progression-Free Survival Endpoint

.... Progression-free survival (PFS) is an endpoint of increasing use in phase III clinical trials.
[...] When PFS is considered an appropriate endpoint for a trial, care must be taken to ensure that the PFS endpoint is reliably and reproducibly measured.
Specifically, there are unique sources of bias related to PFS that must be considered. These include: evaluation-time bias, attrition bias, and reader-evaluation bias.

Author(s): OHAD AMIT, WILL BUSHNELL, LORI DODD, NANCY ROACH, DANIEL SARGENT

Published: The Oncologist 2010;15:492–495 www.TheOncologist.com

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Best Practices in the Use of Medical Imaging Techniques in Clinical trials 

[...] This task force was charged with harmonizing, and in some cases standardizing, the operating procedures that are used to analyze imags by central laboratories [...] found that a variety of imaging operation and analysis approaches are common across most medical imaging techniques and terapheutics areas [...] This report describes some of the procedures that seems essential for using medical imaging techniques to support new drug applications.

Author(s): Robert Ford, MD; P.David Mozley, MD

Published: Drug Information Journal Vol 42, pp 515-523, 2008 - 0092-8615/2008

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Observer Bias in randomized clinical trials with binary outcomes: sustematic review of trials with both blinded and non blinded outcome assessors 

[...] The randomised clinical trial is regarded as the most valid method for assessing the benefits and harms of healthcare interventions. One challenge to the validity of such trials is the tendency for assessments of outcomes to systematically deviate from the truth because of predispositions in observers, such as from hope or expectation.
[...] Thus, on average, the odds ratios based on non-blinded assessments were exaggerated by 36% compared with the odds ratios based on blinded assessments.

Author(s): Asbjørn Hróbjartsson, Ann Sofia Skou Thomsen, Frida Emanuelsson, Britta Tendal, Jørgen Hilden, Isabelle Boutron, Philippe Ravaud, Stig Brorson

Published: on BMJ 2012;344:e1119, 27 February 2012

LINK TO DOCUMENT

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