The work carried out by ICH under the Efficacy heading is concerned with the design, conduct, safety and reporting of clinical trials.  It also covers novel types of medicines derived from biotechnological processes and the use of pharmacogenetics/ pharmacogenomics techniques to produce better targeted medicines.
Zip file with all Efficacy Guidelines in Word format

  • E1 Clinical Safety for Drugs used in Long-Term Treatment

    Code Document Title Previously coded
  • E2A - E2F Pharmacovigilance

    Code Document Title Previously coded
    • Finalised Guideline:
      October 1994

      Description:

      The tripartite harmonised ICH Guideline was finalised under Step 4 in October 1994. This document gives standard definitions and terminology for key aspects of clinical safety reporting. It also gives guidance on mechanisms for handling expedited (rapid) reporting of adverse drug reactions in the investigational phase of drug development.

      Implementation:

      Step 5

      EU:

      Adopted by CPMP, November 1994, issued as CPMP/ICH/377/95

      MHLW:

      Adopted March 95, PAB/PCD Notification No. 227

      FDA:

      Published in the Federal Register, 1 March 1995, Vol. 60, No. 40, p. 11284-11287

    • Description:

      ICH E2B EWG was re-formed to conduct a revision of E2B(R2) Guideline in 2003 and in May 2005 a revised Guideline, E2B(R3), was released for public consultation. The ICH Steering Committee had taken a key decision that technical specifications should no longer be developed solely within ICH, but should be created in collaboration with Standards Development Organisations (SDOs) to enable wider inter-operability across the regulatory and healthcare communities. ICH E2B(R3) was the first topic harmonized under the new process. An Implementation Guide for E2B(R3) data elements and message specification was developed by the E2B EWG, which uses the ISO/HL7 27953-2 ICSR message exchange standard developed by the SDOs, and E2B(R3) reached Step 4 in November 2012. Following minor editorial updates the IG was published in July 2013.

      Implementation:

      Step 5

      EU:

      Adopted by CHMP, July 2013, issued as EMA/CHMP/ICH/287/1995

      MHLW:

      Adopted 8 July 2013, PFSB/ELD Notification No. 070805 & PFSB/SD Notification No. 070801

      FDA:

      Published in the Federal Register, 21 February 2014, Vol. 79, No. 35, p. 9908-9

    • Description:

      In July 2013, the ICH Steering Committee endorsed the establishment of the IWG on E2B(R3) to assist with the implementation of the E2B(R3) Implementation Guide (published in July 2013) and help facilitate transition from E2B(R2) to E2B(R3). Included in its tasks is support for the use of constrained ISO IDMP terminologies in ICSRs, as well as maintenance of technical documents related to E2B(R3).

      Status:

      Step 1

    • Finalised Guideline:
      November 2012

      Description:

      The tripartite core harmonised ICH Guideline was finalised under Step 4 in November 1996. This document gives guidance on the format and content of safety updates, which need to be provided at intervals to regulatory authorities after products have been marketed. The Guideline is intended to ensure that the worldwide safety experience is provided to authorities at defined times after marketing with maximum efficiency and avoiding duplication of effort.

      Based on the comments made by the members of the Expert Working Group on CIOMS V recommendations and the PhRMA-EFPIA working document, an addendum has been finalised and reached Step 4 in February 2003 (R1).

      The revised (R2) Guideline reached Step 4 of the ICH process in November 2012.

      The purpose of this Guideline’s revision is to ensure that the periodic safety update reports for marketed drugs have the role of being periodic benefit-risk evaluation reports by covering: Safety evaluation, evaluation of all relevant available information accessible to marketing authorisation holders (MAHs) and benefit-risk evaluation.

      Implementation:

      Step 5

      EU:

      Adopted by CHMP, December 2012, issued as EMA/CHMP/ICH/544553/1998

      MHLW:

      Adopted 17 May 2013, PFSB/ELD Notification No. 0517-1

      FDA:

      To be notified

    • Description:

      In November 2012, the ICH Steering Committee endorsed the establishment of the IWG on E2C(R2) to assist with the implementation of the new revision (R2) of the E2C Guideline finalised under Step 4 of the ICH Process in November 2012. This revision to E2C has introduced new concepts and principles linked to an evolution of the traditional PSUR from an interval safety report to cumulative benefit-risk report and with a change in focus from individual case reports to more aggregate data evaluation.

      This supplementary Questions and Answers document finalised under Step 4 in March 2014 intends to clarify key issues.

      Status:

      Step 5

      EU:

      To be notified

      MHLW:

      Adopted 25 August 2014

      FDA:

      To be notified

    • Finalised Guideline:
      November 2003

      Description:

      The tripartite harmonised ICH Guideline was finalised under Step 4 in November 2003. This document provides a standardised procedure for post-approval safety data management including expedited reporting to relevant authority. The definitions of the terms and concept specific to post-approval phase are also provided. E2A definitions in clinical safety data management was maintained in this document as post-approval safety data management, such as seriousness definition. The practices of the data management were standardised in such cases obtained from consumers, literatures, internets which are all specific to post-approval data management. Good case management practice was focused and recommended for expedited reporting with clear definitions.

      Implementation:

      Step 5

      EU:

      Adopted by CPMP, 20 November 2003, issued as CPMP/ICH/3945/03

      MHLW:

      Adopted 28 March 2005, PFSB/SD Notification No. 0328007

      FDA:

      Published in the Federal Register, 15 September 2003, Vol. 68, No. 178, p. 53983-4

    • Finalised Guideline:
      November 2004

      Description:

      The tripartite harmonised ICH Guideline was finalised under Step 4 in November 2004. This Guideline is intended to aid in planning pharmacovigilance activities, especially in preparation for the early postmarketing period of a new drug (in this Guideline, the term "drug" denotes chemical entities, biotechnology-derived products, and vaccines). The main focus of this Guideline is on a Safety Specification and Pharmacovigilance Plan that might be submitted at the time of licence application.

      Implementation:

      Step 5

      EU:

      Adopted by CHMP, 1 December 2004, issued as CPMP/ICH/5716/03. Coming into operation in June 2005

      MHLW:

      Adopted 16 September 2005, PFSB/ELD Notification No. 0916001 & PFSB/SD Notification No. 0916001

      FDA:

      Published in the Federal Register, 1 April 2005, Vol. 70, No. 62, p. 16827-16828

    • Description:

      The tripartite harmonised ICH Guideline was finalised under Step 4 in August 2010.
      The main focus of the DSUR is data from interventional clinical trials (referred to in this document as "clinical trials") of investigational drugs including biologicals, with or without a marketing approval, whether conducted by commercial or non-commercial sponsors.

      Following the completion of the E2F Step 4 Guideline, the E2F EWG developed DSUR Examples for commercial and non-commercial sponsors to help with the use of the E2F Guideline. It should be noted that these documents are only examples and therefore did not go through the formal ICH Step Process.

      Implementation:

      Step 5

      EU:

      Adopted by CHMP, September 2010, issued as EMA/CHMP/ICH/309348/2008

      MHLW:

      Adopted 28 December 2012, PFSB/SD Notification 1228-1

      FDA:

      Published in the Federal Register, 23 August 2011, Vol. 76, No. 163, p. 52667-8

  • E3 Clinical Study Reports

    Code Document Title Previously coded
    • Finalised Guideline:
      November 1995

      Description:

      The tripartite harmonised ICH Guideline was finalised under Step 4 in November 1995. This document describes the format and content of a study report that will be acceptable in all three ICH regions. It consists of a core report suitable for all submissions and appendices that need to be available but will not be submitted in all cases.

      Implementation:

      Step 5

      EU:

      Adopted by CPMP, December 1995, issued as CPMP/ICH/137/95

      MHLW:

      Adopted May 1996, PAB/PCD Notification No. 335

      FDA:

      Published in the Federal Register, 17 July 1996, Vol. 61, p. 37320

    • Finalised Q&As:
      July 2012

      Description:

      Since reaching Step 4 and publication within the ICH regions, experiences by all parties with the implementation of the E3 Guideline have resulted in the need for some clarification. This supplementary Questions and Answers document intends to clarify key issues.

      In July 2012, minor typographical errors were corrected in the Answer to Question 6 and the document was renamed R1.

      Implementation:

      Step 5

      EU:

      Transmission to CHMP and release for information, July 2012, issued as EMA/CHMP/ICH/435606/2012

      MHLW:

      Adopted 18 October 2012, PFSB/ELD Administrative Notice

      FDA:

      Posted on FDA website on 25 January 2013

  • E4 Dose-Response Studies

    Code Document Title Previously coded
    • Finalised Guideline:
      March 1994

      Description:

      The tripartite harmonised ICH Guideline was finalised under Step 4 in March 1994. This document gives recommendations on the design and conduct of studies to assess the relationship between doses, blood levels and clinical response throughout the clinical development of a new drug.

      Implementation:

      Step 5

      EU:

      Adopted by CPMP, May 1994, issued as CPMP/ICH/378/95

      MHLW:

      Adopted July 1994, PAB/PCD Notification No. 494

      FDA:

      Published in the Federal Register, 9 November 1994, Vol. 59, No. 216, p. 55972-55976

  • E5 Ethnic Factors

    Code Document Title Previously coded
    • Finalised Guideline:
      February 1998

      Description:

      The tripartite harmonised ICH Guideline was finalised under Step 4 in February 1998. This document addresses the intrinsic characteristics of the drug recipient and extrinsic characteristics associated with environment and culture that could affect the results of clinical studies carried out in regions and describes the concept of the "bridging study" that a new region may request to determine whether data from another region are applicable to its population.

      Implementation:

      Step 5

      EU:

      Adopted by CPMP, March 1998, issued as CPMP/ICH/289/95

      MHLW:

      Adopted August 1998, PMSB/ELD Notification No. 672, PMSB Notification No. 739

      FDA:

      Published in the Federal Register, 10 June 1998, Vol. 63, No. 111, p. 31790

    • Finalised Q&As:
      June 2006

      Description:

      Since reaching Step 4 and publication within the ICH regions, experiences by all parties with the implementation of the E5 Guideline have resulted in the need for some clarification. This supplementary Questions and Answers document intends to clarify key issues.

      Implementation:

      Step 5

      EU:

      Adopted by CPMP, 20 November 2003, issued as CPMP/ICH/5746/03

      MHLW:

      Adopted 5 October 2006, PFSB/ELD Notification

      FDA:

      Posted on FDA website 28 September 2006

  • E6 Good Clinical Practice

    Code Document Title Previously coded
    • Finalised Guideline:
      May 1996

      Description:

      The tripartite harmonised ICH Guideline was finalised under Step 4 in May 1996. This Good Clinical Practices document describes the responsibilities and expectations of all participants in the conduct of clinical trials, including investigators, monitors, sponsors and IRBs. GCPs cover aspects of monitoring, reporting and archiving of clinical trials and incorporating addenda on the Essential Documents and on the Investigator's Brochure which had been agreed earlier through the ICH process.

      Implementation:

      Step 5

      EU:

      Adopted by CPMP, July 1996, issued as CPMP/ICH/135/95/Step5, Explanatory Note and Comments to the above, issued as CPMP/768/97

      MHLW:

      Adopted March 1997, PAB Notification No. 430, MHLW Ordinance No. 28

      FDA:

      Published in the Federal Register, 9 May 1997, Vol. 62, No. 90, p. 25691-25709

    • Description:

      This topic was endorsed by the ICH Steering Committee in June 2014.

       

      Since the adoption of the ICH E6(R1) Guideline on Good Clinical Practice (GCP) in 1996, clinical trials have evolved substantially, with increases in globalisation, study complexity, and technological capabilities.  To keep pace with the scale and complexity of clinical trials and to ensure appropriate use of technology it was agreed that the approach to GCP should be modernised to enable implementation of innovative approaches to clinical trial design, management, oversight, conduct, documentation, and reporting that will better ensure human subject protection and data quality.

       

      Modernising ICH E6 by supplementing it with additional recommendations will facilitate broad and consistent international implementation of new methodologies. 

       

  • E7 Clinical Trials in Geriatric Population

    Code Document Title Previously coded
    • Finalised Guideline:
      June 1993

      Description:

      The tripartite harmonised ICH Guideline was finalised under Step 4 in June 1993. This document provides recommendations on the special considerations which apply in the design and conduct of clinical trials of medicines that are likely to have significant use in the elderly.

      Implementation:

      Step 5

      EU:

      Adopted by CPMP, September 1993, issued as CPMP/ICH/379/95

      MHLW:

      Adopted December 1993, PAB/NDD Notification No. 104

      FDA:

      Published in the Federal Register, 2 August 1994, Vol.59, No. 102, p. 39398-39400

    • Finalised Q&As:
      July 2010

      Description:

      Since reaching Step 4 and publication within the ICH regions, experiences by all parties with the implementation of the E7 Guideline have resulted in the need for some clarification. This supplementary Questions and Answers document intends to clarify key issues.

      Implementation:

      Step 5

      EU:

      Transmission to CHMP and released for information in July 2010 as EMA/CHMP/ICH/604661/2009

      MHLW:

      Adopted 17 September 2010, PFSB/ELD Notification

      FDA:

      Published in the Federal Register, 21 February 2012, Vol. 77, No. 34, p. 9948-9

  • E8 General Considerations for Clinical Trials

    Code Document Title Previously coded
    • Finalised Guideline:
      July 1997

      Description:

      The tripartite harmonised ICH Guideline was finalised under Step 4 in July 1997. This document sets out the general scientific principles for the conduct, performance and control of clinical trials. The Guideline addresses a wide range of subjects in the design and execution of clinical trials.

      Implementation:

      Step 5

      EU:

      Adopted by CPMP, September 1997, issued as CPMP/ICH/291/95

      MHLW:

      Adopted April 1998, PMSB/ELD Notification No. 380

      FDA:

      Published in the Federal Register, 17 December 1997, Vol. 62, No. 242, p. 66113

  • E9 Statistical Principles for Clinical Trials

    Code Document Title Previously coded
    • Finalised Guideline:
      February 1998

      Description:

      The harmonised tripartite Guideline was finalised under Step 4 in February 1998. This biostatistical Guideline describes essential considerations on the design and analysis of clinical trials, especially the "confirmatory" (hypothesis-testing) trials that are the basis for demonstrating effectiveness.

      Implementation:

      Step 5

      EU:

      Adopted by CPMP, March 1998, issued as CPMP/ICH/363/96

      MHLW:

      Adopted November 1998, PMBS/ELD Notification No. 1047

      FDA:

      Published in the Federal Register, 16 September 1998, Vol. 63, No. 179, p. 49583

  • E10 Choice of Control Group in Clinical Trials

    Code Document Title Previously coded
    • Finalised Guideline:
      July 2000

      Description:

      The harmonised tripartite Guideline was finalised under Step 4 in July 2000. This document addresses the choice of control groups in clinical trials considering the ethical and inferential properties and limitations of different kinds of control groups. It points out the assay sensitivity problem in active control equivalence / non-inferiority trials that limits the usefulness of trial design in many circumstances.

      Implementation:

      Step 5

      EU:

      Adopted by CPMP, July 2000, issued as CPMP/ICH/364/96

      MHLW:

      Adopted 27 February 2001, PMSB/ELD Notification No. 136

      FDA:

      Published in the Federal Register, 14 May 2001, Vol. 66, No. 93, p. 24390-91

  • E11 Clinical Trials in Pediatric Population

    Code Document Title Previously coded
    • Finalised Guideline:
      July 2000

      Description:

      The harmonised tripartite Guideline was finalised under Step 4 in July 2000. This document addresses the conduct of clinical trials of medicines in pediatric populations. This document will facilitate the development of safe and effective use of medicinal product in pediatrics.

       

      Implementation:

      Step 5

      EU:

      Adopted by CPMP, July 2000, issued as CPMP/ICH/2711/99

      MHLW:

      Adopted 15 December 2000, PMSB/ELD Notification No. 1334

      FDA:

      Published in the Federal Register, 12 April 2000, Vol. 65, No. 71, p. 19777-81

    • Description:

      This topic was endorsed by the ICH Steering Committee in August 2014.

       

      Since the adoption of the ICH E11 Guideline on Clinical Investigation of Medicinal Products in the Pediatric Populationin 2000, pediatric drug development has been enhanced by advancements in several areas of general adult drug development. Targeted scientific and technical issues relevant to pediatric populations, regulatory requirements for pediatric study plans, and infrastructures for undertaking complex trials in pediatric patient populations has been considerably advanced in the last decade, without a parallel development of harmonised guidance in these areas. This Addendum is proposed to address new scientific and technical knowledge advances in pediatric drug development.

  • E12 Clinical Evaluation by Therapeutic Category

    Code Document Title Previously coded
    • Finalised Document:
      March 2000

      Description:

      This therapeutic area document considers the Clinical Evaluation of New Antihypertensive Drugs. It provides a set of "Principles" on which there is general agreement among all three ICH regions covering endpoints and trial designs. Since there are a few differences in the requirements of the three regions that have not been harmonised, this document should be considered an "ICH Principle Document" rather than an "ICH Guideline". It will not be subject to the usual procedures leading to a fully harmonised document.

      Implementation:

      Step 5

      EU:

      Released for information, June 2000, issued as CPMP/ICH/541/00

      MHLW:

      Released for consultation, 29 May 2000, PMSB/ELD Notification No. 738

      FDA:

      Released for consultation, 9 August 2000, published in the Federal Register, Vol. 65, No. 154, p. 48720-21

  • E14 Clinical Evaluation

    Code Document Title Previously coded
    • Finalised Guideline:
      May 2005

      Description:

      The harmonised tripartite Guideline was finalised under Step 4 in May 2005. This document provides recommendations to sponsors concerning the design, conduct, analysis, and interpretation of clinical studies to assess the potential of a drug to delay cardiac repolarisation.
      This assessment should include testing the effects of new agents on the QT/QTc interval as well as the collection of cardiovascular adverse events. The investigational approach used for a particular drug should be individualised, depending on the pharmacodynamic, pharmacokinetic, and safety characteristics of the product, as well as on its proposed clinical use.
      The assessment of the effects of drugs on cardiac repolarisation is the subject of active investigation. When additional data (non-clinical and clinical) are accumulated in the future, this document may be reevaluated and revised.

      Implementation:

      Step 5

      EU:

      Adopted by CHMP, May 2005, issued as CHMP/ICH/2/04

      MHLW:

      Adopted 23 October 2009, PFSB/ELD Notification No. 1023-1

      FDA:

      Published in the Federal Register, 20 October 2005, Vol. 70, No. 202, p. 61134-35

    • Description:

      Since reaching Step 4 and publication within the ICH regions, experiences by all parties with the implementation of the E14 Guideline have resulted in the need for some clarification. The Questions and Answers developed by the E14 Implementation Working Group (IWG) are intended to facilitate the implementation of the E14 Guideline by clarifying key issues.

      The document with the first set of Q&As was finalised under Step 4 in June 2008.

      In April 2012, a second set of Q&As was developed and approved by the Steering Committee for integration in the Q&A document (E14 Q&As (R1)).

      In March 2014, a third set of Q&As was developed and approved by the Steering Committee for integration in the Q&A document (E14 Q&As (R2)).

      Implementation:

      Step 5

      EU:

      To be notified

      MHLW:

      To be notified

      FDA:

      To be notified

  • E15 Definitions in Pharmacogenetics / Pharmacogenomics

    Code Document Title Previously coded
    • Finalised Guideline:
      November 2007

      Description:

      The harmonised tripartite Guideline was finalised under Step 4 in November 2007. This Guideline contains definitions of key terms in the discipline of pharmacogenomics and pharmacogenetics, namely genomic biomarkers, pharmacogenomics, pharmacogenetics and genomic data and sample coding categories. The validation and qualification processes for genomic biomarkers, evidence for their intended use and acceptance criteria across ICH regions are outside of the scope of this guideline. As new scientific knowledge in the discipline of pharmacogenomics and pharmacogenetics emerges, the current guidance will be reviewed and expanded if appropriate.

      Implementation:

      Step 5

      EU:

      Approved by CHMP in November 2007, issued as EMEA/CHMP/ICH/437986/2006

      MHLW:

      Adopted 9 January 2008, PFSB/ELD Notification No. 0109013 & PFSB/SD Notification No. 0109002

      FDA:

      Published in the Federal Register, 8 April 2008, Vol. 73, No. 68, p. 19074-76

  • E16 Qualification of Genomic Biomarkers

    Code Document Title Previously coded
  • E17 Multi-Regional Clinical Trials

    Code Document Title Previously coded
    • Description:

      This topic was endorsed by the ICH Steering Committee in June 2014.

       

      This new guidance is proposed to provide guidance on general principles on planning/designing Multi-Regional Clinical Trial (MRCT).

      Drug development has been globalised and MRCT for regulatory submission has widely been conducted in ICH regions and beyond. Regulatory agencies are currently facing some challenges in evaluating data from MRCTs for drug approval and it was deemed necessary to developed a harmonised international Guideline to promote conducting MRCT appropriately, especially focusing on scientific issues in planning/designing MRCTs. This new Guideline will complement the guidance on MRCTs provided in ICH E5(R1) Guideline and facilitate MRCT data acceptance by multiple regulatory agencies.

  • E18 Genomic Sampling Methodologies

    Code Document Title Previously coded
    • Description:

      This topic was endorsed by the ICH Steering Committee in June 2014.

       

      This new guidance is proposed to provide guidance on genomic sample collection to evaluate efficacy and safety of a drug for regulatory approval. In the past years, genomic information has been increasingly included in drug label relevant for the benefit/risk evaluation of a drug. To accumulate such data during drug development and throughout the product life cycle, genomic samples should be collected in clinical trials and other studies following a certain methodology and be stored for certain periods. It has been reported that collection rate of such samples is still low in many ICH regions and it has been deemed necessary to harmonise the guidance that was already published independently by the different ICH regulatory authorities.

      Although ICH E15 Guideline describes definition of sample coding, there is currently no harmonised ICH Guideline on genomic samples collection in clinical trials or other studies.

      Harmonisation across regions on this topic will maximise the information gathered from the studies for e.g., sample collection and analysis (including ethical considerations) and facilitate implementation of pharmacogenomics for the benefit of all stakeholders.

  • Cross-cutting Topics

    Code Document Title Previously coded