Opinions and letters of support on the qualification of novel methodologies for medicine development

The European Medicines Agency (EMA) publishes opinions on the qualification of innovative development methods and letters of support for novel methodologies that have been shown to be promising in the context of research and development into pharmaceuticals. 

The opinions are given by EMA's Committee for Medicinal Products for Human Use (CHMP) on the basis of recommendations by the Scientific Advice Working Party.

For more information and guidance on the qualification of novel methodologies, see Qualification of novel methodologies for medicine development.

Simcyp Simulator

Qualification opinion for Simcyp Simulator

Adopted Reference Number: EMADOC-1700519818-2006369

Overview of comments received on the draft qualification opinion for Simcyp Simulator

Reference Number: EMADOC-1700519818-2115746

Draft qualification opinion for Simcyp Simulator

Draft: consultation closed Consultation dates: 08/05/2025 to 19/06/2025 Reference Number: EMADOC-1700519818-2006369 Summary:

Comments should be provided using this template. The completed comments form should be sent to [e-mail] 

Annex 1 - Bayesian Analysis

Annex 2 - Description of Systems models and related parameters for the full and minimal PBPK models

Annex 3 - Simcyp Compound Summaries - Cimetidine

Annex 3 - Simcyp Compound Summaries – Fluvoxamine

Annex 3 - Simcyp Compound Summaries - Midazolam

Annex 4 - Evolution of DDI qualification matrix and substrates inhibitors

Annex 5 - DDI Qualification Matrix

Annex 6 - Substrate-Inhibitor Matrix for CYP competitive and mechanism-based inhibition of CYP1A2, CYP2C8, CYP2C9, CYP2C19, and CYP3A4/5

Annex 6 - Briefing document - Qualification of the effects of invetsigational drugs as victims or perpetrators of CYP=mediated drug interactions involving inhibition in the Simcyp Simulator

Annex 6 - SAWP discussion meeting 15 January 2025

Annex 6 - SAWP discussion meeting 10 July 2024

Annex 6 - SAWP discussion meeting 6 March 2024

Annex 6 - Preparation meeting 21 February 2023

Annex 6 - Response to EMA 18 March 2025

Annex 6 - Response to EMA 16 December 2024

Annex 6 - Response to EMA 19 February 2025 (items 1 and 5)

Annex 6 - Response to EMA 9 April 2025

Annex 6 - Response to EMA 19 February 2025 (items 2-4)

Annex 6 - CYPDDI document

Annex 6 - Additional supporting documentation – System parameters and compound files

Annex 6 - Fluvoxamine summary March 2025

Annex 6 - Response to EMA

Annex 6 - Response to EMA 21 December 2023

Annex 6 - Response to EMA 26 June 2024

Annex 6 - DDI qualification matrix

Annex 6 - V19R1 vs V20R1 version comparison

Annex 6 - V20R1 vs V21R1 version comparison

Annex 6 - V21R1 vs V22R1 version comparison

Annex 6 - V22R1 vs V23R2 version comparison

Artificial intelligence-based measurement of non-alcoholic steatohepatitis histology

Qualification opinion for artificial intelligence-based measurement of non-alcoholic steatohepatitis histology in liver biopsies to determine disease activity in NASH/MASH clinical trials

Adopted Reference Number: EMADOC-1700519818-1761332 Corr.1

Overview of comments received on the draft qualification opinion for artificial intelligence-based measurement of non-alcoholic steatohepatitis histology (AIM-NASH) tool

Draft qualification opinion for artificial intelligence-based measurement of non-alcoholic steatohepatitis histology in liver biopsies to determine disease activity in NASH/MASH clinical trials

Draft: consultation closed Consultation dates: 06/12/2024 to 24/01/2025 Reference Number: EMADOC-1700519818-1761332 Summary:

Comments should be provided using the template 'Questions and answers: Qualification of digital technology-based methodologies to support approval of medicinal products'. You can find the template here: CHMP qualification opinions

The completed comments form should be sent to [e-mail]

User manual: AIM-NASH algorithm for artificial intelligence-based measurement of non-alcoholic steatohepatitis histology

Briefing book: AI-based histologic measurement of NASH (AIM-NASH)

Written responses to first list of Issues for artificial intelligence-based measurement of non-alcoholic steatohepatitis histology (AIM-NASH) tool

Written responses to second list of Issues for artificial intelligence-based measurement of non-alcoholic steatohepatitis histology (AIM-NASH) tool

Centiloid measure of Amyloid PET to quantify brain amyloid deposition

Qualification opinion for Centiloid measure of Amyloid PET to quantify brain amyloid deposition

Adopted Reference Number: EMADOC-1700519818-1200791

Overview of comments received on draft qualification opinion for Centiloid measure of Amyloid PET to quantify brain amyloid deposition

Draft Qualification opinion for Centiloid measure of Amyloid PET to quantify brain amyloid deposition

Summary CL- Additional Analyses presented at Discussion Meeting for Centiloid measure of Amyloid PET to quantify brain amyloid deposition

Final briefing book submitted for qualification opinion on Centiloid measure of Amyloid PET to quantify brain amyloid deposition

GFR slope as a Validated Surrogate Endpoint for RCT in CKD

Qualification Opinion for GFR slope as a Validated Surrogate Endpoint for RCT in CKD

Overview of comments on draft Qualification opinion for GFR slope as a Validated Surrogate Endpoint for RCT in CKD

DRAFT qualification opinion for GFR slope as a Surrogate Endpoint in RCT for CKD

Draft Reference Number: EMA/SA/00000104642

Briefing document - GFR slope as a Surrogate Endpoint in RCT for CKD

Responses to list of issues - GFR slope as a Surrogate Endpoint in RCT for CKD

Presentation - GFR slope as a Validated Surrogate Endpoint for CKD in RCT

Stride velocity 95th centile as primary endpoint in studies in ambulatory Duchenne Muscular Dystrophy

Qualification Opinion for Stride velocity 95th centile as primary endpoint in studies in ambulatory Duchenne Muscular Dystrophy studies

Reference Number: EMADOC-1700519818-1127132

Overview of comments on draft Qualification Opinion for Stride velocity 95th centile as a primary endpoint in studies in ambulatory Duchenne Muscular Dystrophy

Draft Qualification Opinion for Stride velocity 95th centile as primary endpoint in studies in ambulatory Duchenne Muscular Dystrophy

Draft: consultation closed Consultation dates: 28/02/2023 to 10/04/2023

Responses to list of issues - Stride velocity 95th centile as primary endpoint in studies in ambulatory Duchenne Muscular Dystrophy

iBox Scoring System as a secondary efficacy endpoint in clinical trials investigating novel immunosuppressive medicines in kidney transplant patients

Qualification opinion for the iBox Scoring System as a secondary efficacy endpoint in clinical trials investigating novel immunosuppressive medicines in kidney transplant patients

Reference Number: EMADOC-1700519818-946771

Overview of comments received on Draft Qualification Opinion of the iBox Scoring System as a secondary efficacy endpoint in clinical trials investigating novel immunosuppressive medicines in kidney transplant patients

DRAFT Qualification opinion for the iBox Scoring System as a secondary efficacy endpoint in clinical trials investigating novel immunosuppressive medicines in kidney transplant patients

Reference Number: EMADOC-1700519818-946771

Qualification opinion - Appendix for Final Draft Qualification Opinion

Reference Number: EMADOC-360526170-1156137

Qualification opinion - C-PATH response to iBox Scoring System (Composite Biomarker Panel) - Second List of Issues

Qualification opinion - C-PATH response to iBox Scoring System (Composite Biomarker Panel) - List of Issues

Qualification opinion - Applicant revised briefing book for iBox Scoring System (Composite Biomarker Panel)

Reference Number: EMADOC-1700519818-946771

Use of Enroll-HD (a Huntington’s disease patient registry) as a data source and infrastructure support for post-authorisation monitoring of medical products

Qualification opinion of the use of Enroll-HD (a Huntington’s disease patient registry) as a data source and infrastructure support for post-authorisation monitoring of medical products

Adopted Reference Number: EMADOC-1700519818-828910

Submission of comments on Enroll-HD: Registry for Huntington's Disease

Draft qualification opinion for the use of Enroll-HD (a Huntington’s disease patient registry) as a data source and infrastructure support for post-authorisation monitoring of medical products

Draft: consultation closed Consultation dates: 23/02/2022 to 11/04/2022 Reference Number: EMA/SA/0000056662

Enroll-HD Registry for Huntington's Disease - Briefing Package - 1 of 2 - questions and answers and context of use

Enroll-HD Registry for Huntington's Disease - Briefing package - 2 of 2 - Supplement

Qualification Advice List of Issues: Enroll-HD Response

Reference Number: EMA/SA/0000056662

Prognostic Covariate Adjustment (PROCOVA™)

Qualification opinion for Prognostic Covariate Adjustment (PROCOVA™)

Reference Number: EMADOC-1700519818-907465

Overview of comments received for Prognostic Covariate Adjustment (PROCOVA™) with responses

Draft qualification opinion for prognostic covariate adjustment (PROCOVA™)

Draft: consultation closed Consultation dates: 22/03/2022 to 02/05/2022 Reference Number: Case No.: EMA/SA/0000059571

Briefing book

Reference Number: Version 2.0

PROCOVA™ handbook

Response to list of issues

Response to 2nd list of issues

Islet Autoantibodies (AAs) as Enrichment Biomarkers for Type 1 Diabetes (T1D) Prevention Clinical Trials

Qualification Opinion of Islet Autoantibodies (AAs) as Enrichment Biomarkers for Type 1 Diabetes (T1D) Prevention Clinical Trials

Adopted Reference Number: EMA/CHMP/SAWP/186420/2022

Overview of comments received on Draft qualification opinion on Islet Autoantibodies (AAs) with answers

Draft qualification opinion of Islet Autoantibodies (AAs) as Enrichment Biomarkers for Type 1 Diabetes (T1D) Prevention Clinical Trials

Draft: consultation closed Consultation dates: 03/11/2021 to 14/12/2021 Reference Number: EMA/580542/2021

Islet Autoantibodies (AAs) - Briefing document

Islet Autoantibodies (AAs) - Written response to the list of issues

Islet Autoantibodies (AAs) - Appendix H

IMI PREFER

Qualification opinion on IMI PREFER

Adopted Reference Number: EMADOC-1700519818-808373

Overview of comments received on draft qualification opinion on IMI PREFER

Draft qualification opinion on IMI PREFER

Draft: consultation closed Consultation dates: 15/10/2021 to 25/11/2021 Reference Number: EMADOC-1700519818-732587 Summary:

In this follow-up procedure to a previous qualification advice, IMI PREFER seek qualification for a framework (see documents in Annex provided by the applicant for qualification opinion by the CHMP) intended to provide suggestions on how patients’ perspectives could be measured through patient 11 preference studies and then incorporated into regulatory decision processes, as applicable.

Relevant considerations include what matters to patients, how much it matters, and how e.g., trade-offs between benefits and harms as well as other study object attributes of interest can be identified and 14 addressed from the patients’ perspective.

CHMP & EUnetHTA parallel Scientific Advice: Qualification of a Framework & Points to consider for method selection with methods for performing patient preference studies to inform regulatory & HTAbody medical product decision-making: Briefing document

Multiple sclerosis clinical outcome assessment (MSCOA)

Qualification opinion on Multiple sclerosis clinical outcome assessment (MSCOA)

Adopted Reference Number: EMA/CHMP/SAWP/74371/2020

Overview of comments received on 'Draft qualification opinion on Multiple Sclerosis Clinical Outcome Assessment (MSCOA) qualification opinion'

Reference Number: EMA/550514/2019

Draft qualification opinion of Multiple sclerosis clinical outcome assessment (MSCOA)

Draft: consultation closed Consultation dates: 18/06/2019 to 20/09/2019 Reference Number: EMA/CHMP/SAWP/336445/2019 Corr.1

Treatment effect measures when using recurrent event endpoints

Qualification opinion of clinically interpretable treatment effect measures based on recurrent event endpoints that allow for efficient statistical analyses

Adopted Reference Number: EMA/CHMP/SAWP/120610/2020

Overview of comments on the draft qualification opinion of clinically interpretable treatment effect measures based on recurrent event endpoints that allow for efficient statistical analyses

Reference Number: EMA/365402/2019

Draft qualification opinion of clinically interpretable treatment effect measures based on recurrent event endpoints that allow for efficient statistical analyses

Draft: consultation closed Consultation dates: 19/06/2019 to 09/10/2019 Reference Number: EMA/CHMP/SAWP/291384/2019

Qualification opinion - Treatment effect measures when using recurrent event endpoints - Applicant's submission

Qualification opinion - Treatment effect measures when using recurrent event endpoints - First list of issues

Reference Number: EMA/CHMP/SAWP/179482/2018

Qualification opinion - Treatment effect measures when using recurrent event endpoints - Applicant's responses to first list of issues

Qualification opinion - Treatment effect measures when using recurrent event endpoints - Second list of issues

Qualification opinion - Treatment effect measures when using recurrent event endpoints - Applicant's responses to second list of issues

Qualification opinion - Treatment effect measures when using recurrent event endpoints - Third list of issues

Qualification opinion - Treatment effect measures when using recurrent event endpoints - Applicant's responses to third list of issues

Qualification opinion - Treatment effect measures when using recurrent event endpoints - Fourth list of issues

Qualification opinion - Treatment effect measures when using recurrent event endpoints - Applicant's responses to fourth list of issues

eSource Direct Data Capture (DDC)

Qualification opinion on eSource Direct Data Capture (DDC)

Adopted Reference Number: EMA/CHMP/SAWP/483349/2019

Overview of comments on the draft qualification opinion on eSource Direct Data Capture (DDC)

Reference Number: EMA/179292/2019

Draft qualification opinion on eSource Direct Data Capture (DDC)

Draft: consultation closed Consultation dates: 15/11/2018 to 14/03/2019 Reference Number: EMA/282576/2018

Stride velocity 95th centile as a secondary endpoint in Duchenne Muscular Dystrophy measured by a valid and suitable wearable device

Qualification opinion on stride velocity 95th centile as a secondary endpoint in Duchenne Muscular Dystrophy measured by a valid and suitable wearable device

Adopted Reference Number: EMA/CHMP/SAWP/178058/2019

Overview of comments on 'Stride velocity 95th centile as a secondary endpoint in Duchenne Muscular Dystrophy measured by a valid and suitable wearable device' (EMA/532515/2018)

Reference Number: EMA/178057/2019

Draft qualification opinion on stride velocity 95th centile as a secondary endpoint in Duchenne Muscular Dystrophy measured by a valid and suitable wearable device

Draft: consultation closed Consultation dates: 21/09/2018 to 30/11/2018 Reference Number: EMA/CHMP/SAWP/527447/2018 Summary:

This report provides a final agreed draft Context of Use for public consultation describing where Stride Velocity measured at the ankle 95th Centile is deemed by CHMP as an appropriate endpoint in studies to support regulatory decision making on medicines for the treatment of Duchenne Muscular Dystrophy (DMD), together with CHMP's scientific consideration of the submission leading to the draft opinion. The document also includes the questions posed by the applicant and also raised by CHMP to the Applicant, and all the data provided by the applicant in support of the Application.

Cellular therapy module of the European Society for Blood & Marrow Transplantation (EBMT) Registry

Qualification opinion on Cellular therapy module of the European Society for Blood & Marrow Transplantation (EBMT) Registry

Adopted Reference Number: EMA/CHMP/SAWP/792574/2018

Overview of comments received on 'Draft qualification opinion on Cellular therapy module of the European Society for Blood & Marrow Transplantation (EBMT) Registry' (EMA/CHMP/SAWP/423488/2018)

Reference Number: EMA/618737/2018

Draft qualification opinion on Cellular therapy module of the European Society for Blood & Marrow Transplantation (EBMT) Registry

Draft: consultation closed Consultation dates: 29/06/2018 to 21/08/2018 Reference Number: EMA/CHMP/SAWP/423488/2018

The European Cystic Fibrosis Society Patient Registry (ECFSPR) and CF Pharmaco-epidemiology Studies

Qualification Opinion on The European Cystic Fibrosis Society Patient Registry (ECFSPR) and CF Pharmaco-epidemiology Studies

Adopted Reference Number: EMA/CHMP/SAWP/622564/2018

Review of comments submitted on the draft Qualification opinion - The European Cystic Fibrosis Society Patient Registry (ECFSPR)

Reference Number: EMA/482816/2018

Qualification opinion - The European Cystic Fibrosis Society Patient Registry (ECFSPR)

Draft: consultation closed Consultation dates: 09/02/2018 to 09/04/2018 Reference Number: EMA/CHMP/SAWP/802259/2017 Summary:

This report provides a draft context of use for public consultation describing where this registry is deemed by CHMP as an appropriate data source for post-authorisation studies to support regulatory decision making on medicines for the treatment of cystic fibrosis, together with CHMP's response to the questions posed by the Consortium.

Molecular neuroimaging of the dopamine transporter as biomarker to identify patients with early manifest Parkinsonism in Parkinson's disease

Qualification opinion on dopamine transporter imaging as an enrichment biomarker for Parkinson’s disease clinical trials in patients with early Parkinsonian symptoms

Adopted Reference Number: EMA/CHMP/SAWP/765041/2017 Summary:

Critical Path Global Ltd.’s Critical Path for Parkinson’s (CPP) is a multinational consortium of the Critical Path Institute supported by Parkinson’s UK and industry. This broad collaboration of pharmaceutical companies, government agencies, academic institutions, and charities aims to accelerate the development of therapies for Parkinson’s disease (PD).

Overview of comments on 'Draft qualification opinion on molecular neuroimaging of the dopamine transporter as biomarker to identify patients with early manifest Parkinsonism in Parkinson’s disease'

Reference Number: EMA/9764/2018 Summary:

Submission of comments on 'Draft qualification opinion on molecular neuroimaging of the dopamine transporter as biomarker to identify patients with early manifest Parkinsonism in Parkinson’s disease' (EMA/765041/2017)

Draft qualification opinion on molecular neuroimaging of the dopamine transporter as biomarker to identify patients with early manifest Parkinsonism in Parkinson’s disease

Draft: consultation closed Consultation dates: 24/01/2018 to 07/03/2018 Reference Number: EMA/765041/2017 Summary:

Qualification of molecular neuroimaging of the dopamine transporter as biomarker for to identify patients with early manifest Parkinsonism in Parkinson’s disease.

Plasma fibrinogen as a prognostic biomarker (drug development tool) for all-cause mortality and COPD exacerbations in COPD subjects

Qualification opinion on plasma fibrinogen as a prognostic biomarker (drug development tool) for all-cause mortality and COPD exacerbations in COPD subjects

Adopted Reference Number: EMA/CHMP/SAWP/264260/2018

Overview of comments on 'Draft qualification opinion on plasma fibrinogen as a prognostic biomarker (drug development tool) for all-cause mortality and COPD exacerbations in COPD subjects'

Reference Number: EMA/264099/2018

Draft qualification opinion on plasma fibrinogen as a prognostic biomarker (drug development tool) for all-cause mortality and COPD exacerbations in COPD subjects

Draft: consultation closed Consultation dates: 30/03/2017 to 03/05/2017 Reference Number: EMA/474186/2016 Summary:

The COPD Foundation, COPD Biomarker Qualification Consortium (CBQC) has presented the background information, proposed contexts of use, and data analyses to support their proposal for the qualification of plasma fibrinogen as a drug development tool (prognostic biomarker) to identify COPD subjects at high risk for all-cause mortality or COPD exacerbations for inclusion in interventional clinical trials. The intent is to enable trials which utilize these important endpoints to be conducted more efficiently (reduced subject numbers, reduced study costs) by study sponsors with improved confidence in the study outcomes.

Proactive in COPD

Qualification opinion on Proactive in chronic obstructive pulmonary disease (COPD)

Adopted Reference Number: EMA/CHMP/SAWP/226829/2018

Overview of comments received on "Qualification opinion on Proactive in chronic obstructive pulmonary disease (COPD)"

Reference Number: EMA/225940/2018

Draft qualification opinion on Proactive in chronic obstructive pulmonary disease (COPD)

Draft: consultation closed Consultation dates: 20/12/2017 to 29/01/2018 Reference Number: EMA/810227/2017 Summary:

Under the Innovative Medicines Initiative Joint-Undertaking (IMI-JU) framework, the public-private PROactive Consortium developed two Patient Reported Outcome (PRO) instruments to capture physical activity (PA) data in patients with Chronic Obstructive Pulmonary Disease (COPD) in clinical trial settings. One of those tools is the D-PPAC which is supposed to enable daily data collection (recall period of 1 day).

Paediatric ulcerative colitis activity index (PUCAI)

Qualification opinion on paediatric ulcerative colitis activity index (PUCAI)

Adopted Reference Number: EMA/CHMP/SAWP/801872/2015 Summary:

This is a non-invasive clinical disease activity multi-item index aimed to reflect the severity of ulcerative colitis (UC) in children. It is aimed to be discriminative (i.e. evaluating disease activity for judging study entry) and evaluative (as an outcome measure in paediatric UC with and without endoscopic assessment).

Overview of comments received on 'Qualification opinion on paediatric ulcerative colitis activity index (PUCAI)'

Reference Number: EMA/760013/2015 Summary:

Comments on 'Qualification Opinion of paediatric ulcerative colitis activity index (EMA/CHMP/SAWP/485560/2015)

Draft qualification opinion on the paediatric ulcerative colitis activity index (PUCAI)

Draft: consultation closed Consultation dates: 18/09/2015 to 26/10/2015 Reference Number: EMA/CHMP/SAWP/485560/2015 Summary:

The paediatric ulcerative colitis activity index (PUCAI) measures disease activity in pediatric ulcerative colitis (Turner D. et al., 2007). It was developed to act as an accurate non-invasive (i.e. suitable for children) reflection of endoscopic inflammatory activity and has proven to have high reliability and responsiveness to change in clinical trials. After its publication, it has also proved to be highly accurate in predicting clinical course of pediatric ulcerative colitis and hence was incorporated in international clinical algorithms for the management of acute severe ulcerative colitis and ambulatory pediatric ulcerative colitis.

Ingestible sensor system for medication adherence as biomarker for measuring patient adherence to medication in clinical trials

Qualification opinion on ingestible sensor system for medication adherence as biomarker for measuring patient adherence to medication in clinical trials

Adopted Reference Number: EMA/CHMP/SAWP/513571/2015 Summary:

Proteus® Digital Health™ Inc. (Proteus) has developed an ingestible event marker (IEM, also known as

ingestible sensor (IS)), a platform technology that can be co-formulated with active pharmaceutical

compounds into drug/device combinations, integrating measuring of medication adherence into oral

pharmacotherapy.

Draft qualification opinion on the ingestible sensor system for medication adherence as biomarker for measuring patient adherence to medication in clinical trials

Draft: consultation closed Consultation dates: 16/09/2015 to 26/10/2015 Reference Number: EMA/CHMP/SAWP/513571/2015 Summary:

Proteus Digital Health Inc. intends to have its Proteus technology approved as a ‘qualified method’ for measuring adherence to medication in clinical trials by associating relevant physiologic and behavioural parameters, such as indications of therapeutic response. The Proteus technology is an ingestible event marker, a platform technology that can be co-formulated with active pharmaceutical compounds into drug/device combinations, integrating measuring of medication adherence into oral pharmacotherapy. The ingestible event marker is approved for marketing in the European Union and the United States as a medical device.

Total kidney volume (TKV) as a prognostic biomarker for use in clinical trials evaluating patients with autosomal dominant polycystic kidney disease (ADPKD)

Qualification opinion - Total Kidney Volume (TKV) as a prognostic biomarker for use in clinical trials evaluating patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Adopted Reference Number: EMA/CHMP/SAWP/473433/2015

Overview of comments on 'Total kidney volume (TKV) as a prognostic biomarker for use in clinical trials evaluating patients with autosomal dominant polycystic kidney disease (ADPKD)'

Reference Number: EMA/733775/2015

Draft qualification opinion total kidney volume (TKV) as a prognostic biomarker for use in clinical trials evaluating patients with autosomal dominant polycystic kidney disease (ADPKD)

Draft: consultation closed Consultation dates: 22/07/2015 to 02/10/2015 Reference Number: EMA/CHMP/SAWP/473433/2015 Summary:

The Critical Path Institute’s Polycystic Kidney Disease Outcome Consortium (PKDOC) intends to qualify Total Kidney Volume (TKV) as a prognostic biomarker (i.e. predictive for the outcome with the current standard of treatment) in order to improve efficiency in conducting clinical trials. The applicant started to work with the United States Food and Drug Administration in 2010 and initiated the discussion with the European Medicines Agency in 2013. Five observational studies including long-term outcome regarding the change in TKV over time, with or without various therapeutic interventions (such as diet, blood pressure control, cytostatics etc.) have been integrated into one database according to Clinical Data Interchange Standards Consortium (CDISC) standards.

Presentation - PKD presentation of outcomes: Consortium / European Medicines Agency Scientific Advice Working Party teleconference (Third list of issues)

Summary:

Presentation of PKD outcomes consortium European Medicines Agency Scientific Advice Working Party teleconference (3rd List of issues)

Final briefing book - Qualification of total kidney volume as a prognostic biomarker for use in clinical trials evaluating patients with autosomal dominant polycystic kidney disease (ADPKD)

PKDOC response to the European Medicines Agency third list of issues - Total kidney volume as a prognostic biomarker for use in clinical trials evaluating patients with autosomal dominant polycystic kidney disease (ADPKD...

Qualification opinion list of issues - Total kidney volume (TKV) as a prognostic biomarker for use in clinical trials evaluating patients with autosomal dominant polycystic kidney disease (ADPKD)

Reference Number: EMA/CHMP/SAWP/298348/2014

Exacerbations of chronic pulmonary disease tool (EXACT), and EXACT-respiratory symptoms measure (E-RS) for evaluating treatment outcomes in clinical trials in COPD

Draft qualification opinion of qualification of exacerbations of chronic pulmonary disease tool (EXACT), and EXACT-respiratory symptoms measure (E-RS) for evaluating treatment outcomes in clinical trials in chronic pulmo...

Draft: consultation closed Consultation dates: 13/04/2015 to 25/05/2015 Reference Number: EMA/CHMP/SAWP/178465/2015 Summary:

The EXACT-PRO Initiative (EXAcerbations of Chronic Pulmonary Disease Tool – Patient-Reported Outcome) brought together clinical, research, methodology, and regulatory experts to develop a new patient-reported outcome (PRO) instrument to standardize the symptomatic assessment of exacerbations of COPD for evaluating frequency, severity, and duration of exacerbations in clinical trials of COPD (“EXACT”, 14-items PRO).

User manual E-RS (EXACT-respiratory symptoms): Applicant submission version 3.0

User manual (EXACT): Applicant submission version 7.0

In-vitro hollow fiber system model of tuberculosis (HFS-TB)

Qualification opinion on in-vitro hollow-fibre-system model of tuberculosis (HFS-TB)

Adopted Reference Number: EMA/CHMP/SAWP/47290/2015 Summary:

The CPTR initiative is a broad collaboration of pharmaceutical companies, government regulatory and multilateral agencies, academia, civil society advocates and non-government organizations that aim to accelerate the development of new, safe and highly effective TB treatment regimens with shorter therapy durations than the current standard of care. CPTR was formed through the collaboration and support of the Bill & Melinda Gates Foundation, the Global Alliance for TB Drug Development and the Critical Path Institute. The CPTR PCS-WG strives to identify, develop consensus around and build the evidence base to support potential new drug development tools (DDTs) for TB medical product development.

Draft qualification opinion on in vitro hollow-fibre-system model of tuberculosis (HFS-TB)

Draft: consultation closed Consultation dates: 18/11/2014 to 09/01/2015 Reference Number: EMA/CHMP/SAWP/381716/2014 Summary:

Approximately 10 years ago, the HFS-TB was developed by Gumbo et al. and first presented at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). Since that time, the model has been refined to become more sophisticated in its utility and application, which has expanded to include the ability to influence effective dose selection in clinical settings. The HFS-TB enables a quantitative understanding of the relationship between dynamic drug concentrations, as well as dynamic populations of drug-susceptible and drug-resistant Mycobacterium tuberculosis, over time.

Response to the European Medicines Agency list of issues - In vitro hollow-fibre-system model of tuberculosis (HFS-TB)

Dossier submitted for qualification opinion - In vitro hollow-fibre-system model of tuberculosis (HFS-TB)

Consultation dates: 18/11/2014 to 09/01/2015

Presentation for Drug Regimens Consortium (CPTR) scientific-advice meeting with the European Medicines Agency: Hollow-fiber system for tuberculosis (HFS-TB)

MCP-Mod as an efficient statistical methodology for model-based design and analysis of phase-II dose-finding studies under model uncertainty

Qualification opinion of MCP-Mod as an efficient statistical methodology for model-based design and analysis of phase-II dose-finding studies under model uncertainty

Adopted Reference Number: EMA/CHMP/SAWP/757052/2013

Overview of comments on the qualification opinion of MCP-Mod as an efficient statistical methodology for model-based design and analysis of Phase II dose finding studies under model uncertainty'

Reference Number: EMA/617236/2013

Request for CHMP Qualification Opinion - Annex 1

Request for CHMP qualification opinion response to questions dated 11 June 2013 - Annex 2

Discussion meeting for MCP-Mod qualification opinion request - Annex 3

Draft qualification opinion of MCP-Mod as an efficient statistical methodology for model-based design and analysis of phase-II dose-finding studies under model uncertainty

Draft: consultation closed Consultation dates: 15/10/2013 to 24/11/2013 Reference Number: EMA/CHMP/SAWP/592378/2013 Summary:

Estimating dose-response and selection of a dose for confirmatory Phase III trials and potential market

authorisation is among the most difficult elements of the whole development process. Dose finding

studies are commonly designed using a small number of doses and a narrow dose-range, often focused

on the upper end of the dose response relationship.

Request for CHMP qualification opinion on efficient statistical methodology for model-based design and analysis of phase-II dose-finding studies under model uncertainty

Response to the questions raised by the qualification team - CHMP qualification opinion on efficient statistical methodology for model-based design and analysis of phase-II dose-finding studies under model uncertainty

Presentation for discussion meeting on efficient statistical methodology for model-based design and analysis of phase-II dose-finding studies under model uncertainty

A novel data-driven model of disease progression and trial evaluation in mild and moderate Alzheimer's disease

Qualification opinion of a novel data-driven model of disease progression and trial evaluation in mild and moderate Alzheimer’s disease

Adopted Reference Number: EMA/CHMP/SAWP/567188/2013

Overview of comments on 'qualification opinion of a novel data-driven model of disease progression and trial evaluation in mild and moderate Alzheimer’s disease'

Reference Number: EMA/471475/2013

Draft qualification opinion of a novel data-driven model of disease progression and trial evaluation in mild and moderate Alzheimer’s disease

Draft: consultation closed Consultation dates: 19/07/2013 to 27/08/2013 Reference Number: EMA/CHMP/SAWP/420174/2013 Summary:

The work described in this submission is intended to produce a tool that provides a common quantitative basis for the evaluation of study design and analysis methodologies for clinical studies in the mild and moderate Alzheimer's-disease population, with cognition as a primary endpoint.

Alzheimer's disease novel methodologies / biomarkers for the use of cerebrospinal-fluid amyloid beta 1-42 and t-tau and / or positron-emission-tomography amyloid imaging (positive / negative) as biomarkers for enrichment

Qualification opinion of Alzheimer’s disease novel methodologies / biomarkers for the use of cerebrospinal-fluid amyloid beta 1-42 and t-tau and / or positron-emission-tomography amyloid imaging (positive / negative) as ...

Adopted Reference Number: EMA/CHMP/SAWP/893622/2011 Summary:

The European Medicines Agency’s (EMA) qualification process is a new, voluntary, scientific pathway leading to either a CHMP opinion or a Scientific Advice of novel methodologies on innovative methods or drug development tools.

Overview of comments received on 'qualification opinion of Alzheimer’s disease novel methodologies / biomarkers for the use of cerebrospinal-fluid amyloid beta 1-42 and t-tau and / or positron-emission-tomography amyloid...

Reference Number: EMA/922/2012

Qualification opinion of Alzheimer’s disease novel methodologies / biomarkers for the use of cerebrospinal-fluid amyloid beta 1-42 and t-tau signature and / or positron-emission-tomography amyloid imaging (positive / neg...

Draft: consultation closed Consultation dates: 17/11/2011 to 22/12/2011 Reference Number: EMA/CHMP/SAWP/893622/2011 Summary:

In follow-up to the positive qualification opinion on the use of cerebrospinal fluid (CSF) biomarkers in predementia Alzheimer's disease adopted on 14 April 2011 (EMA/CHMP/SAWP/102001/2011).

Qualification opinion of Alzheimer’s disease novel methodologies / biomarkers for positron-emission-tomography amyloid imaging (positive / negative) as a biomarker for enrichment, for use in regulatory clinical trials in...

Adopted Reference Number: EMA/CHMP/SAWP/892998/2011 Summary:

The European Medicines Agency’s (EMA) qualification process is a new, voluntary, scientific pathway leading to either a CHMP opinion or a Scientific Advice of novel methodologies on innovative methods or drug development tools.

Overview of comments received on 'qualification opinion of Alzheimer’s disease novel methodologies / biomarkers for positron-emission-tomography amyloid imaging (positive / negative) as a biomarker for enrichment, for us...

Reference Number: EMA/991202/2011

Qualification opinion of Alzheimer’s disease novel methodologies / biomarkers for positron-emission-tomograpy amyloid imaging (positive / negative) as a biomarker for enrichment for use in predementia Alzheimer's disease...

Draft: consultation closed Consultation dates: 17/11/2011 to 22/12/2011 Reference Number: EMA/CHMP/SAWP/892998/2011 Summary:

In follow-up to the positive qualification opinion on the use of cerebrospinal fluid (CSF) biomarkers in predementia Alzheimer's disease adopted on 14 April 2011 (EMA/CHMP/SAWP/102001/2011).

Low hippocampal volume (atrophy) by magnetic-resonance imaging for use in clinical trials for regulatory purpose in predementia stage of Alzheimer's disease

Qualification opinion of low hippocampal volume (atrophy) by magnetic-resonance imaging for use in clinical trials for regulatory purpose in predementia stage of Alzheimer’s disease

Adopted Reference Number: EMA/CHMP/SAWP/809208/2011 Legal effective date: 17/11/2011 Summary:

The European Medicines Agency’s (EMA) qualification process is a new, voluntary, scientific pathway leading to either a CHMP opinion or a Scientific Advice of novel methodologies on innovative methods or drug development tools. It includes qualification of biomarkers developed by consortia, networks, public/private partnerships, learned societies or pharmaceutical industry for a specific intended use in pharmaceutical research and development.

Overview of comments on 'qualification opinion of low hippocampal volume (atrophy) by magnetic-resonance imaging for use in clinical trials for regulatory purpose in predementia stage of Alzheimer’s disease'

Reference Number: EMA/879297/2011

Qualification opinion of low hippocampal volume (atrophy) by magnetic-resonance imaging for use in regulatory clinical trials in predementia stage of Alzheimer’s disease

Draft: consultation closed Consultation dates: 22/09/2011 to 01/11/2011 Reference Number: EMA/CHMP/SAWP/102001/2011

Novel methodologies in the predementia stage of Alzheimer's disease: cerebrospinal-fluid-related biomarkers for drugs affecting amyloid burden

Qualification opinion of novel methodologies in the predementia stage of Alzheimer’s disease: cerebrospinal-fluid-related biomarkers for drugs affecting amyloid burden

Adopted Reference Number: EMA/CHMP/SAWP/102001/2011 Legal effective date: 14/04/2011

Overview of comments received on 'qualification opinion of novel methodologies in the predementia stage of Alzheimer’s disease: cerebrospinal-fluid-related biomarkers for drugs affecting amyloid burden'

Reference Number: EMA/252172/2011

Alzheimer's disease novel methodologies / biomarkers for BMS-708163

Qualification opinion of Alzheimer’s disease novel methodologies / biomarkers for BMS-708163

Draft: consultation closed Consultation dates: 10/02/2011 to 25/03/2011 Reference Number: EMA/CHMP/SAWP/102001/2011

ILSI / HESI submission of novel renal biomarkers for toxicity

Qualification opinion ILSI / HESI submission of novel renal biomarkers for toxicity

Adopted Reference Number: EMA/CHMP/SAWP/283298/2010 Legal effective date: 21/10/2010 Summary:

The European Medicines Agency qualification process is a new, voluntary, scientific pathway leading to

either a CHMP opinion or a Scientific Advice on innovative methods or drug development tools. It

includes qualification of biomarkers developed by consortia, networks, public/private partnerships,

learned societies or pharmaceutical industry for a specific intended use in pharmaceuticals R&D.

Overview of comments on qualification opinion ILSI / HESI submission of novel renal biomarkers for toxicity

Reference Number: EMA/CHMP/SAWP/627644/2010 Legal effective date: 21/10/2010

Consultation on qualification opinion ILSI / HESI submission of novel renal biomarkers for toxicity

Draft: consultation closed Consultation dates: 18/03/2010 to 31/07/2010 Reference Number: EMA/283298/2010 Summary:

The European Medicines Agency qualification process is a new, voluntary, scientific pathway leading to either a CHMP opinion or a Scientific Advice on innovative methods or drug development tools. It includes qualification of biomarkers developed by consortia, networks, public/private partnerships, learned societies or pharmaceutical industry for a specific intended use in pharmaceuticals R&D.

Final conclusions on the pilot joint European Medicines Agency / Food and Drug Administration VXDS experience on qualification of nephrotoxicity biomarkers

Final conclusions on the pilot joint European Medicines Agency / Food and Drug Administration VXDS experience on qualification of nephrotoxicity biomarkers

Reference Number: EMEA/679719/2008 Rev. 1

Letters of support

Letter of Support for intermediate Age-Related Macular Degeneration (AMD) biomarker and novel clinical endpoint development

Reference Number: EMADOC-1700519818-1790091

Letter of support for Measurable Residual Disease (MRD) as a Surrogate Efficacy Endpoint in Clinical Studies with Acute Myeloid Leukemia

Reference Number: EMADOC-1700519818-1285629

Letter of support for Universal Immune System Simulator – Tuberculosis disease model (UISS-TB-DR)

Reference Number: EMADOC-1700519818-1207681

Letter of Support for PRE score

Reference Number: EMADOC-1700519818-1207253

Letter of support for a composite endpoint method for acceptability evaluation of oral drug formulations in the paediatric population

Letter of Support for World Federation of Hemophilia (WFH) Gene Therapy Registry (GTR)

Reference Number: EMADOC-1700519818-1173599

Letter of Support for Forskolin-Induced Swelling (FIS) Assay: Biomarker for Cystic Fibrosis Transmembrane Conductance Regulator Protein (CFTR)

Reference Number: EMADOC-1700519818-1037383

Letter of Support for TUMMY-UC – a Patient- and Observer-Reported Outcome for Paediatric Ulcerative Colitis (UC)

Reference Number: EMADOC-1700519818-1033762

Letter of support for the development of the PAH-SYMPACT Instrument for use in Pulmonary Hypertension clinical trials

Reference Number: EMADOC-1700519818-1054252

Letter of Support for the statistical adjustment on deep learning prognosis covariates obtained from histological slides

Reference Number: EMADOC-1700519818-1064889

Letter of support for Minimal Disease Activity Score (MDA) as primary outcome instrument for clinical studies in psoriatic arthritis (PsA)

Reference Number: EMADOC-1700519818-782278

Letter of Support for an Acceptability Score Test in relative acceptability testing for oral medicines in children under 12 years of age

Reference Number: EMADOC-1700519818-1066960

Letter of Support for Braintale platforms

Reference Number: EMADOC-1700519818-982447

Letter of Support of model-based clinical trial simulation platform (CTSP) for Duchenne Muscular Dystrophy

Reference Number: EMADOC-1700519818-955047

Letter of support for TREAT-NMD Core Dataset for Spinal Muscular Atrophy (SMA)

Reference Number: EMADOC-1700519818-958775

Letter of support for Neurofilament light in childhood neurological diseases

Reference Number: EMADOC-1700519818-959805

Letter of support for a Model-based Clinical Trial Simulation Platform to Optimize Design of Efficacy Evaluation Studies in Parkinson’s Disease

Reference Number: EMADOC-1700519818-955717

Letter of support for the Global Platform Study of Novel Medicines in Paediatric and Adolescent Relapsed and Refractory B-cell Non-Hodgkin Lymphoma (Glo-BNHL platform)

Reference Number: EMADOC-1700519818-746444

Letter of support for Sjögren’s Tool for Assessing Response (STAR)

Reference Number: EMADOC-1700519818-746443

Letter of support for intermediate Age-Related Macular Degeneration (AMD) biomarker and novel clinical endpoint development

Reference Number: EMADOC-1700519818-776978

Letter of Support for performing registry-based post authorisation safety studies (PASS) in Multiple Sclerosis (MS) using data of the Big MS Data Network (BMSD)

Reference Number: EMADOC-1700519818-759902

Letter of support for Master Protocol for Type 1 diabetes prevention studies in INNODIA

Reference Number: EMADOC-1700519818-703684

Letter of support for International Niemann-Pick Disease Registry (INPDR)

Reference Number: EMA/206704/2021

Letter of support for Mobilise-D digital mobility outcomes as monitoring biomarkers - Follow-up

Reference Number: EMA/CHMP/SAWP/277641/2021

Letter of support for Mobilise-D digital mobility outcomes as monitoring biomarkers

Reference Number: EMA/234828/2020

Letter of support for N170 ERP as a prognostic biomarker for adaptive social functioning and its potential to stratify study populations in people with Autism spectrum disorders (ASD) without intellectual disability

Reference Number: EMA/508140/2020

Letter of support for the VABS-II Adaptive Behavior Composite (VABS-II-ABC) score as measure of adaptive social functioning in people with Autism Spectrum Disorders (ASD) without intellectual disability

Reference Number: EMA/548136/2020

Letter of support for drug-induced renal tubular injury biomarker(s)

Reference Number: EMA/715025/2016 Summary:

On 12 August 2016 the Applicant Firalis SAS (on behalf of Safer and Faster Evidence-based Translation (SAFE-T) consortium) requested follow up qualification advice for novel biomarkers to assess DIKI pursuant to Article 57(1)(n) of Regulation (EC) 726/2004 of the European Parliament and of the Council. The procedure started during the SAWP meeting held on 30 August – 02 September 2016 and the advice was given in the framework of a joint EMA-FDA parallel advice procedure.

Letter of support for Islet autoantibodies as enrichment biomarkers for type 1 diabetes prevention studies, through a quantitative disease progression model

Reference Number: EMA/625951/2019

Letter of support for Corrected T1 (cT1)

Reference Number: EMA/274962/2019

Letter of support for Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF)

Reference Number: EMA/274960/2019

Retraction of the “Letter of support for drug -induced liver injury (DILI) biomarker” (EMA/423870/2016)

Reference Number: EMA/188045/20199

Letter of support for the development of Patient-Reported Outcomes tools for use as an endpoint in Inflammatory Bowel Disease (IBD) clinical trials

Reference Number: EMA/262838/2018

Letter of support for Model-based CT enrichment tool for CTs in aMCI

Reference Number: EMA/693969/2018

Letter of support for intermediate age related macular degeneration (AMD) biomarker and novel clinical endpoint development

Reference Number: EMA/72511/2018

Letter of support for the development of a needs-based quality of life Patient Reported Outcome (PRO) measure specific to adults with plexiform neurofibromas

Reference Number: EMA/716127/2017 Summary:

On 1 March 2017 the Applicant Galen Research Ltd requested qualification opinion for a plexiform neurofibromas quality of life scale (the PlexiQoL), as biomarker for use as a secondary endpoint in clinical studies pursuant to Article 57(1)(n) of Regulation (EC) 726/2004 of the European Parliament and of the Council.

Letter of support for glutamate dehydrogenase, a biomarker of hepatocellular liver injury

Reference Number: EMA/666090/20177

Letter of support for drug-induced vascular injury (DIVI) biomarker

Summary:

We are issuing this Letter of Support to SAFE”T and PSTC to encourage the further study of soluble biomarkers of endothelial cell injury and inflammation, and potential soluble markers of vascular smooth muscle cell injury, to monitor for drug”induced vascular injury (DIVI) in early clinical drug development.

Letter of support for molecular imaging of the dopamine transporter biomarker as an enrichment biomarker for clinical trials for early Parkinson's disease

Letter of support for Patient Data Platform for capturing patient-reported outcome measures for Dravet syndrome

Reference Number: EMA/327846/2016 Summary:

On 09 December 2015 the applicant Dravet Syndrome Foundation Spain requested qualification opinion for Patient Data Platform as an electronic tool for capturing patient reported outcomes in paediatric epilepsies, pursuant to article 57(1)(n) of regulation (EC) 726/2004 of the European Parliament and of the Council.

Letter of support for reading speed and functional reading independence (FRI) index in geographic atrophy

Reference Number: EMA/14494/2016 Summary:

On 16 February 2015 the applicant Roche Registration Ltd requested scientific advice for use of reading speed and functional reading independence (FRI) index pursuant to Article 57(1)(n) of regulation (EC) 726/2004 of the European Parliament and of the Council.

Letter of support for Leuven Postprandial Distress Scale (LPDS) as PRO in Postprandial Distress Syndrome (PDS)

Reference Number: EMA/794574/2015

Letter of support to explore EEG utility to measure deficits in social recognition in people with autism spectrum disorders (ASD) and its potential to stratify patient groups

Reference Number: EMA/794518/2015 Summary:

On 14 September 2015 the Applicant EU-AIMS Consortium (IMI) requested follow-up qualification advice for methodology EEG to be used to stratify populations of people with Autism Spectrum Disorder (ASD) pursuant to Article 57(1)(n) of Regulation (EC) 726/2004 of the European Parliament and of the Council.

Letter of support to explore MRI methodology to be used to stratify populations of people with autism spectrum disorder (ASD)

Reference Number: EMA/794542/2015 Summary:

On 14 September 2015 the Applicant EU-AIMS Consortium (IMI) requested follow-up qualification advice for MRI methodologies to be used to stratify populations of people with Autism Spectrum Disorder (ASD) pursuant to Article 57(1)(n) of Regulation (EC) 726/2004 of the European Parliament and of the Council.

Letter of support for eye tracking to be used to stratify populations of people with autism spectrum disorder (ASD)

Reference Number: EMA/794527/2015 Summary:

On 14 September 2015 the Applicant EU-AIMS Consortium (IMI) requested follow-up qualification advice for Eye-tracking methodologies to be used to stratify populations of people with Autism Spectrum Disorder (ASD) pursuant to Article 57(1)(n) of Regulation (EC) 726/2004 of the European Parliament and of the Council.

Letter of support for measures of executive function and basic emotions to be used to stratify populations of people with autism spectrum disorder (ASD) and predict clinical outcome

Reference Number: EMA/794534/2015 Summary:

On 14 September 2015 the Applicant EU-AIMS Consortium (IMI) requested follow-up qualification advice for measures of executive function and basic emotions to be used to stratify populations of people with Autism Spectrum Disorder (ASD) and predict clinical outcome pursuant to Article 57(1)(n) of Regulation (EC) 726/2004 of the European Parliament and of the Council.

Letter of support to explore clinical outcomes assessments utility to measure clinical symptoms in people with autism spectrum disorders (ASD)

Reference Number: EMA/794457/2015 Summary:

On 14 September 2015 the Applicant EU-AIMS Consortium (IMI) requested follow-up qualification advice for Clinical Outcomes Assessments to measure clinical symptoms in people with Autism Spectrum Disorder (ASD) pursuant to Article 57(1)(n) of Regulation (EC) 726/2004 of the European Parliament and of the Council.

Letter of support for skeletal muscle injury biomarkers

Reference Number: EMA/116308/2015

Letter of support for micro-aneurysm formation rate (MAFR) biomarker

Reference Number: EMA/775397/2014 Summary:

On 07 June 2013 the applicant Critical Health S.A. requested qualification of micro-aneurysm formation rate (MAFR) measured with a validated automated method, as an enrichment biomarker for studies of clinically significant macular oedema (CSMO) pursuant to Article 57(1)(n) of Regulation (EC) 726/2004 of the European Parliament and of the Council.

Letter of support for Predictive Safety Testing Consortium translational drug-induced kidney injury biomarkers

Reference Number: EMA/651243/2014

External links

• Innovative Medicines Initiative (IMI) projects and regulators
• IMI webinar on regulatory acceptance mechanisms