26 January 2017 EMA/CHMP/626873/2016 Rev 0
Work plan for the Biostatistics Working Party (BSWP) for 2017 Chairperson: Anja Schiel Status of the work plan: Adopted in January 2017
1. Meetings scheduled for 2017 Face-to-face meetings are planned for the following dates •
27-28 March 2017
•
06-07 July 2017
•
26-27 October 2017
The above mentioned dates may be modified as needed. Additional virtual meetings may be organised ad hoc to respond to time-sensitive requests on products and to progress guidelines, as required.
2. Guidelines 2.1. New EU Guidelines Action: Lead Guideline on the investigation of subgroups in confirmatory clinical trials EMA/CHMP/539146/2013 Target date
Final guideline expected to be released in Q3 2017
Comments
Comments received during the 2014 public consultation and discussed at the EMA. Working parties or SmPC Advisory Group to be consulted.
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Reflection paper on statistical methodology for the comparative assessment of quality attributes in drug development Target date
Draft reflection paper expected to be released for a 6-month public consultation in Q1 2017.
Comments
The reflection paper is developed in collaboration with the CHMP Biologics working Party (BWP), the Biosimilar Medicinal Products Working Party (BMWP), the Quality Working Party (QWP) and the Scientific Advice Working Party (SAWP). PKWP will be kept informed of the development of this RP
Action: Specialised input Guideline on the clinical development of medicinal products for the treatment of autism-spectrum disorder EMA/CHMP/40896/2013 Leading group
Central Nervous System Working Party
Target date
Final guideline to be released in Q4 2017.
Comments
Contribution to the finalisation of the guideline.
2.2. EU Guidelines under revision Action: Lead Points to consider on multiplicity issues in clinical trials CPMP/EWP/908/99 Target date
Draft guideline expected to be released for a 6-month public consultation in Q1 2017.
Comments
The current Points to Consider is being revised into a guideline. The guideline was developed in collaboration with the SAWP and the Cardiovascular Working Party (CVSWP). A training of the assessors may be organised via webinar once the guideline has been finalised.
Guideline on data monitoring committees CHMP/EWP/5872/03 Target date
Publication of a Q&A document for comments expected in Q2 2017.
Comments
The guideline was adopted in 2003. Since then there have been questions on the role and necessity for a Data Monitoring Committee (DMC) in different Phases of drug development as well as with regard to the responsibilities for implementing DMC decisions. The Q&A document would provide answers to such questions. The CVS WP and ONC WP were informed about this Q&A, and the Good Clinical Practice (GCP) Inspections Working Group (IWG) was consulted. BSWP will consider GCP IWG proposals for the revision of the guideline and for the drafting of a Q&A on adjudication committees.
Work plan for the Biostatistics Working Party (BSWP) for 2017 EMEA/CHMP/626873/2016
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Action: Specialised input Guideline on clinical investigation of medicinal products for the treatment of chronic cardiac failure (EMA/CHMP/47656/2015; replacing the Note for Guidance on clinical investigation of medicinal products for the treatment of cardiac failure [CPMP/EWP/235/95 Rev. 1]) Leading group
Cardiovascular Working Party (CVSWP)
Target date
Final guideline to be published in Q1 2017.
Comments
Public consultation for the draft guideline ended on 31st August 2016. The revised guideline was developed in collaboration with SAWP and BSWP.
Guideline on clinical investigation of medicinal products in the treatment or prevention of diabetes mellitus (CPMP/EWP/1080/00 Rev. 2) Leading group
Cardiovascular Working Party (CVSWP)
Target date
Draft guideline to be released for public consultation in Q2 2017.
Comments
Public consultation of the concept paper ended on 31st October 2016. The revised guideline was developed in collaboration with SAWP and BSWP.
Question and answer document on the development of fixed combinations of drugs belonging to different therapeutic classes in the field of cardiovascular treatment and prevention (CHMP/EWP/191583/2003) Leading group
Cardiovascular Working Party (CVSWP)
Target date
Concept paper to be released for public consultation in Q2 2017.
Comments
Revision will follow the finalisation of the Draft Guideline on clinical development of fixed combination medicinal products (EMA/CHMP/281825/2015). The concept paper will be developed in collaboration with SAWP and BSWP.
Guideline on the clinical investigation of new medicinal products for the treatment of acute coronary syndrome (EMA/CHMP/207892/2015 Rev. 1; replacing CPMP/EWP/570/98) Leading group
Cardiovascular Working Party (CVSWP)
Target date
Final guideline to be published Q3 2017
Comments
Draft guideline released for public consultation that ended on 31st October 2016. The guideline was developed in collaboration with SAWP and BSWP.
Guideline on medicinal products for the treatment of Alzheimer's disease and other dementias, CPMP/EWP/553/1995 revision 1 Leading group
Central Nervous System Working Party (CNSWP)
Target date
Final guideline to be released Q3 2017.
Work plan for the Biostatistics Working Party (BSWP) for 2017 EMEA/CHMP/626873/2016
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Comments
Contribution to the development of the revised guideline
Note for Guidance on the Evaluation of anticancer medicinal products in man CHMP/205/95 Rev. 4 Leading group
Oncology Working Party (ONCWP)
Target date
Finalised rev. 5 and concept paper on revision 6 to be published Q2 2017.
Comments
Contribution to the finalisation of the revised guideline and the drafting of the concept paper.
Revision of the addendum to the guideline on evaluation of anticancer medicinal products in man paediatric oncology (CPMP/EWP/569/02 Rev. 2) Leading group
Oncology Working Party (ONCWP)
Target date
Draft to be released for public consultation by Q2 2017.
Comments
Contribution to the development of the revised guideline. This document aims to complement the current guideline with specific regulatory requirements related to paediatric oncology.
Reflection paper on the regulatory guidance for the use of health related quality of life (HRQL) measures in the evaluation of medicinal products (CHMP/EWP/139391/2004) Leading group
Oncology Working Party (ONCWP)
Target date
Concept paper to be published by Q1 2017. Draft reflection paper to be released for public consultation by Q4 2017.
Comments
Contribution to the development of the concept paper and the revised reflection paper. Collaboration with CVS WP.
2.3. ICH Guidelines E9(R1) Addendum to statistical principles for clinical trials on choosing appropriate estimands and defining sensitivity analyses in clinical trials Target date
Step 2 is planned for 2017.
Comments
Development of a draft Addendum to ICH E9. Collaboration with E9(R1) EU members, including the E9(R1) Rapporteur who is a BSWP member.
E11(R1) Clinical investigation of medicinal products in the paediatric population Target date
Step 4 is planned in 2017.
Comments
Draft addendum was published in September 2016. Support E11 (R1) EU members from CHMP and the Paediatric Committee (PDCO) in the development of the addendum.
E17 General principles on planning/designing multi-regional clinical trials
Work plan for the Biostatistics Working Party (BSWP) for 2017 EMEA/CHMP/626873/2016
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Target date
Step 4 is planned in 2017.
Comments
Draft guideline was published in June 2016. Support finalisation of E17. Collaboration with E9(R1) EU members; one is also a BSWP member.
3. Medicinal Products-specific activities 3.1. Pre-Authorisation activities Contribution to relevant methodological and statistical aspects for the following regulatory systems. - Scientific Advice and Protocol Assistance upon request of the SAWP. - Scientific Advice for the in-depth review of quality data for similar biological medicinal products upon request of the SAWP. - Paediatric Investigational Plans upon request of PDCO. - Innovation Task Force requests upon request of EMA ITF. Comments: Contribution to briefing meetings on statistical and methodological topics with external parties (pharmaceutical companies, academia, public/private partnership or patients’ associations) through meeting preparation or participation of experts.
3.2. Evaluation and supervision activities Contribution to relevant methodological and statistical aspects of evaluation activities upon request of CHMP and other committees.
4. Input in European activities 4.1. Training for the network and knowledge building Organise one or several assessor trainings in 2017 on relevant methodology topics, such as survival analysis, interim analysis and estimands, utilising the European Union Network Training Centre technical facilities.
4.2. Interactions with learned societies and specialised organisations Meeting with Statistical Associations Organise a meeting with the European Federation of Statisticians in the Pharmaceutical Industry (EFSPI).
4.3. Other input into European activities Action: Lead Trial integrity in the presence of interim results in on-going clinical trials Target date
Draft a regulatory position by Q2 2017.
Work plan for the Biostatistics Working Party (BSWP) for 2017 EMEA/CHMP/626873/2016
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Comments
Discuss methodological issues of trial integrity when interim analysis results of an ongoing trial become available and are assessed for marketing authorisation assessments. This should consider sponsor involvement, acceptability of methods to maintain integrity such as ‘firewalls’, and publication of results, by sponsor or by regulator (in relation to EMA Policy 0070 on the publication of clinical data for medicinal products for human use). If additional guidance is proposed, BSWP will discuss whether existing guidance documents are most appropriate to include the different aspects, or if these aspects call for the development of new guidance documents. Collaboration with CVS WP. Other working parties of relevance for this subject, such as ONC WP, will be consulted.
Analysis methods to account for treatment switch for time-to-event endpoints in oncology clinical trials Target date
Draft a BSWP position for ONC WP by Q2 2017.
Comments
Continue work related to methods on treatment switch for time-to-event endpoints. Collaboration with ONC WP.
Review of CIOMS X report Target date
Review of the CIOMS X report by Q2 2017.
Comments
BSWP will review the CIOMS X report published in September 2016. Based on this review and other considerations BSWP will consider whether there is a need to write a guideline on safety assessment.
Analysis of Individual Patient Data for evaluation and surveillance of medicinal products Target date
Draft a regulatory position by Q4 2017.
Comments
Identify areas where scientific assessment can be extended to visualisation or analysis of IPD. Investigate mechanisms that can leverage current analytical capabilities in the network, and ways to develop it in the future. Collaboration with other working parties as appropriate.
Action: Specialised input Clinical aspects of biosimilarity Leading group
Biosimilar Medicinal Products Working Party (BMWP)
Target date
2017
Comments
Discussion on methodological elements related to clinical aspects of biosimilarity.
Type I error control in two-stage designs in bioequivalence studies
Work plan for the Biostatistics Working Party (BSWP) for 2017 EMEA/CHMP/626873/2016
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Leading group
Pharmacokinetics Working Party (PKWP)
Target date
Provide responses to PKWP by Q2 2017.
Comments
Finalise work related to type I error control in two-stage designs in bioequivalence studies.
Similarity of dissolution profiles (Appendix 1 of the Guideline on the investigation of bioequivalence) Leading group
Pharmacokinetics Working Party (PKWP)
Target date
Continue the discussion of the acceptability of the Mahalanobis distance and other possible similarity measures for the assessment of similarity of dissolution profiles in 2017.
Comments
This is a joint request from the CHMP Pharmacokinetics WP and the Quality WP. There might be connection to the development of the Reflection paper on statistical methodology for the comparative assessment of quality attributes in drug development mentioned above.
5. Input in International activities (beyond ICH guidelines) 5.1. Activities with other regulators Meetings with FDA Organise a meeting at each BSWP face-to-face meeting via teleconference with FDA statisticians from CDER (and if possible, CBER and CDRH) to discuss methodological issues. The objective is to foster methodological interaction on topical subjects, e.g. related to guideline development.
6. Contribution to dialogue and engagement with stakeholders and external parties 6.1. Workshops Action: Lead Expert group meeting on ICH E9(R1) Addendum to statistical principles for clinical trials on choosing appropriate estimands and defining sensitivity analyses in clinical trials Organise a workshop in Q4 2017 in relation with E9(R1) Addendum to statistical principles for clinical trials on choosing appropriate estimands and defining sensitivity analyses in clinical trials. The date of the workshop will be conditional on the time of the publication of E9(R1). This workshop will discuss the draft ICH E9(R1) Addendum, and will continue interaction with CHMP and other EMA committees started at the February 2016 internal workshop on estimands. The CVSWP is planning to contribute to this workshop.
Work plan for the Biostatistics Working Party (BSWP) for 2017 EMEA/CHMP/626873/2016
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BSWP targeted consultation on the Reflection Paper on statistical methodology for the comparative assessment of quality attributes in drug development Organise a workshop in Q3 2017 in relation with the Reflection Paper on statistical methodology for the comparative assessment of quality attributes in drug development. The date of the workshop will be conditional on the time of the publication of the Reflection Paper. This workshop will discuss comments received during the public consultation.
Action: Specialised input EMA Joint Meeting with IDeAl, iNSPiRe, ASTERIX on small populations, London, March 2017 EMA will organise a joint meeting of the European Commission-funded 7th Framework Programme projects IDeAl, iNSPiRe and ASTERIX. BSWP members will contribute in their personal capacity in the organisation of a meeting in H1 2017 at EMA to derive a joint statement on recommended statistical methodology in small population clinical trials based on the outcome of FP7 projects IDeAl, iNSPiRe and ASTERIX. This meeting is of direct relevance to BSWP work, therefore outcomes of this meeting may be discussed by BSWP. Joint EMA Symposium in the margins of the CEN-ISBS conference, Vienna, August 2017 BSWP members will contribute in their personal capacity in the organisation of a joint EMA symposium in the margins of the Conference on Biometrics & Biopharmaceutical Statistics organised by the Central European Network (CEN) and the International Society for Biopharmaceutical Statistics (ISBS) in Vienna in Q3 2017. This meeting will likely be of direct relevance to BSWP work and outcomes of this meeting may thus be discussed by BSWP.
Work plan for the Biostatistics Working Party (BSWP) for 2017 EMEA/CHMP/626873/2016
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