Adaptive pathways for medicine evaluation and unmet medical need: the access v. evidence dilemma

London, 8th December 2016: The European Medicines Agency is hosting a stakeholder workshop on

adaptive pathways at its Canary Wharf London headquarters: a hot topic with around 150 delegates from healthcare, patient and consumer organisations, academia, industry and regulatory bodies.

The European Medicines Agency is organising this workshop in collaboration with the European Commission to gather views and proposals from stakeholders on the adaptive pathways approach, in light of the practical experience gained during the pilot project EMA ran between March 2014 and August 2016, and to plan the next steps in the exploration of this concept. 

The basis for considering adaptive pathways for evaluating medicines is to meet the challenges underlying how to resolve high unmet medical need with then aim of licensing products likely to have a major impact on patient morbidity and/or life expectancy.

The desire is to find ways to reduce unavoidable uncertainties as rapidly as possible for serious/rare debilitating and life-shortening illnesses. There are clear ethical and scientific challenges in using novel approaches to evaluate medicines without a decline in the quality of evidence on the effectiveness and safety of new treatments. 

Products which might be considered for use of adaptive evaluation pathways include both conventional medicines and advanced therapy medicinal products (ATMPs). ATMPs are medicinal product which involve either a gene therapy medicinal, a somatic cell therapy or a tissue engineered product [see more on ATMPs at Directive 2001/83/EC as amended by the ATMP Regulation 1394/2007].

Adaptive pathways contribute to an expanded  toolbox for evidence generation where conventional randomized controlled trials are not-appropriate or practical. Principles include using processes to allow rapid reaction to uncertainty by iterative development based on ongoing analysis of  pathway data [“rapid cycle analysis”]. As secondary end-points are welcomed, these pathways require pre-planning across the entire product life-span, including the post-marketing paths ie active monitoring and management of on-market use.

The adaptive pathway approach is dependent on earliest stage and ongoing multi-stakeholder networking, underpinned by risk management plans. 

Critical issues include

- resolving scientific trust in real world data and the need to develop mature, robust registries

- defining and prioritising unmet medical needs

- agreement on acceptable risks and benefits early access worth it (vs.

- maintaining safety standards

- ensuring that benefits outweigh risks

- avoiding unrealistic expectations

- establishing practical criteria for reimbursement, especially when secondary outcome measures form the basis for market authorization   

The next EACPT Congress is in Prague from 24th - 27th June 2017

Prague abstract deadline: 6th Feb 2017

Prague EACPT Congress registration is now open

The EACPT was founded 24 years ago and now includes as members all national organisations for clinical pharmacology in Europe, as well as organisations from further afield internationally. The EACPT aims to provide educational and scientific support for the more than 4000 individual professionals interested in clinical pharmacology and therapeutics throughout the European region, with its congresses attended by a global audience. The EACPT also advises policy makers on how the specialty can contribute to human health and wealth.

Opportunities from Big Data for safer medicines

14-15 November, 2016: The European Medicines Agency is hosting a web-casted workshop in London on identifying opportunities from "Big Data" in development and regulation of medicines. There has been such strong interest that a much larger venue is being used than available at its usual Canary Wharf centre, with perspectives from EU and USA policy makers, regulators, academia, health professionals and industry.

The EMA note: "Rapid developments in technology have led to the generation of vast volumes of data, which have the capability to transform the way the benefit-risk of medicinal products is assessed over their entire life cycle. However, it is recognised there are multiple challenges in the exploitation of these data. These range from the fundamental need to establish methods to enable the access to, integration and analysis of heterogeneous datasets to understanding the limitations in its use. Importantly, robust and transparent mechanisms to protect patient confidentiality are key to secure patient trust. It is important for the European Medicines Agency and the European Union medicines regulatory network to gather information on the latest developments in big data from the perspective of all stakeholders in order to identity how and when the multitude of data sources may contribute to medicinal product development, authorisation and post-marketing surveillance."

Some key threads and discussion points:
- the importance of the FAIR principles (data should be Findable, Accessible, Interoperable and
- Reusable)
- access for health professionals and researchers to the European Open Science Cloud
- a major EU initiative to promote data curation
- the power of the Cloud for cross-platform data sharing
- Big Data applied to precision medicine and pharmacogenomics
- bias in datasets
- Big Data and new EU General Data Protection Regulations - from May 2018, replacing Directive 95/46
- machine-learning for chemogenomics
- challenges to implementing applications to precision medicines in 'time poor' clinical practice
- OHDSI comumity - access to international health record data sources
- twitter not designed as a health app but may provide complementary insight into unexpected adverse effects of medicines to that obtained through traditional pharmacovigilance routes
- transferable learning - e.g. from use of Big Data in transport networks
- case studies in the EU and USA
- trade-offs: methods might be rapid, unbiased and accessible/usable by the inexperienced: but not all three
- challenges in the European Region to maximise learning from Big Health Data when there are 28 independent national health care systems with barriers and challenges to data-sharing

All talks are due to be made available on the EMA website for public access.

Safer medicines for children

From the EACPT Focus Meeting on How to Assess Medicines, Opatija, 6-9 October 2016. 

In this video, Donald Singer discusses with speaker Suzana Mimica Matanović evaluation of drugs in the pediatric population.

Discussants
Suzana Matanović: Assistant Professor of Clinical Pharmacology, School of Medicine, University of Osijek, Croatia and PCO alternate delegate at the European Medicines Agency.

Professor Donald Singer: member of the Executive Committee of the European Association for Clinical Pharmacology and Therapeutics and EACPT delegate on the European Medicines Agency Health Professionals Working Party.

 

The next EACPT biennial congress will be held in Prague Congress from 24th - 27th June 2017. The programme will provide an international scientific and educational forum for discussion of clinical pharmacology and therapeutics, including personalised pharmacotherapy. See more on our website. 

Anyone from anywhere in the world with a professional interest in clinical pharmacology and therapeutics can now join the EACPTas an Individual Associate member.

Membership benefits include:

* Access to videos of talks from EACPT Meetings
* Discounted registration fees for EACPT meetings
* Online access to the Official EACPT Journal - Clinical Therapeutics
* Access to the EACPT’s worldwide network of Individual Associate Members
* Active involvement in EACPT  

The EACPT was founded 24 years ago and now includes as members all national organisations for clinical pharmacology in Europe, as well as organisations from further afield internationally. The EACPT aims to provide educational and scientific support for the more than 4000 individual professionals interested in clinical pharmacology and therapeutics throughout the European region, with its congresses attended by a global audience. The EACPT also advises policy makers on how the specialty can contribute to human health and wealth.

WEB-RADR - innovative use of mobile technology and social media to monitor safety of medicines

The European Medicines Agency is today hosting an update workshop on the 3 year

Innovative Medicines Initiative WEB-RADR project, which was launched in September 2014.
 The project includes a series of work packages for partner organisations in Europe and the USA aimed at developing and evaluating use of mobile technology and social media as tools to monitor the safety of medicines.
 
Patients experiencing suspected adverse reactions to medicines can report these to their physician or pharmacist. In the UK and since 2014 throughout the European Union, patients can now also report suspected drug reactions direct to their national medicine safety authority. However reporting is inconsistent and important adverse side-effects may not be detected until a large number of patients have already been exposed to risk from a medicine.

Three countries in Europe - the UK, the Netherlands and Croatia - are now to evaluating a WEB-RADR mobile app for reporting suspected adverse drug reactions (side effects). The app allows patients and health professionals to reports suspected adverse drug reactions securely to the relevant National Medicines Regulatory Authority.

The Workshop is reporting on experience so far of app-based safety reporting, perspectives and expectations from patients and health professionals and data protection issues.

Clinical drug-drug interaction studies: methods, pitfalls and interpretation

From the EACPT Focus Meeting on How to Assess Medicines, Opatija, 6-9 October 2016. In this video, Donald Singer discusses with Janne Backman from Helsinki how to identify and minimise risk of drug-drug interactions.

Discussants
Janne Tapio Backman: Professor in Clinical Pharmacology and Individual Medicine, University of Helsinki, Finland
Professor Donald Singer: member of the Executive Committee of the EACPT and member  of the European Medicines Agency Health Professionals Working Party.

Here is a summary of the key points from Professor Backman's  talk at the EACPT Focus Meeting in Opatija: 

Drug-drug interactions can either markedly reduce or enhance the therapeutic or adverse effects of drugs by causing alterations in the pharmacokinetics or pharmacodynamics of drugs. If such interactions are not understood or accounted for in patient care, they can have harmful, even hazardous clinical consequences. 

Drug-drug interactions have been a major cause of drug withdrawals from the market. Regulatory agencies, including the European Medicines Agency (EMA) have therefore published guidance documents that are designed for the industry to guide their DDI studies during drug development. In particular, detailed scientific recommendations can be given concerning pharmacokinetic interactions, because such interactions can be mediated via mechanistic changes in absorption, distribution, metabolism and excretion of drugs. 

Specific approaches are suggested concerning cytochrome P450 enzymes (CYPs), non-CYP enzymes and membrane transporters. In addition, current guidance also recommends use of modelling approaches, such as physiologically based pharmacokinetic (PBPK) models to design and extend the interpretation of preclinical and clinical drug-drug interaction studies. For designing clinical drug-drug interactions studies, detailed preclinical in vitro and early clinical pharmacokinetic information is necessary. 

Despite detailed guidelines, there are many challenges in characterization of the interaction potential of a drug, both as a perpetrator and as a victim of the interaction. Such challenges arise from complex interaction mechanisms, eg, simultaneous involvement of transporters and drug metabolizing enzymes, autoinhibition and autoinduction of metabolism, time-dependent inhibition and involvement of major drug metabolites. 

Understanding the challenges and pitfalls of drug-drug interaction studies is thus necessary in interpretation of the results of studies. In this lecture, basic methods of clinical drug-drug interaction studies will be reviewed, with examples of potential pitfalls and basic principles of interpretation.
  
The next EACPT biennial congress will be held in Prague Congress from 24th - 27th June 2017. The programme will provide an international scientific and educational forum for discussion of clinical pharmacology and therapeutics, including personalised pharmacotherapy. See more on our website. 

Anyone from anywhere in the world with a professional interest in clinical pharmacology and therapeutics can now join the EACPT as an Individual Associate member.

Membership benefits include:

* Access to videos of talks from EACPT Meetings
* Discounted registration fees for EACPT meetings
* Online access to the Official EACPT Journal - Clinical Therapeutics
* Access to the EACPT’s worldwide network of Individual Associate Members
* Active involvement in EACPT  

The EACPT was founded 24 years ago and now includes as members all national organisations for clinical pharmacology in Europe, as well as organisations from further afield internationally. The EACPT aims to provide educational and scientific support for the more than 4000 individual professionals interested in clinical pharmacology and therapeutics throughout the European region, with its congresses attended by a global audience. The EACPT also advises policy makers on how the specialty can contribute to human health and wealth.

Pharmacovigilance: update on activities by the European Medicines Agency

The European Medicines Agency is today holding its Tenth stakeholder forum on the pharmacovigilance legislation of the European Union.  This forum brings together regulators with patients, consumers, healthcare professionals and industry, to take stock of what the EMA has achieved and what needs to be the focus over the coming years.

The programme is being broadcast live with presentations thereafter available on the EMA website.

Fergus Sweeney (EMA) & June Raine (PRAC Chair)

Key presentations include:

-  a 3-year update on pharmacovigilance activities by Dr Helen Lee from the European Commission 

- a report on SCOPE (The Strengthening Collaboration for Operating Pharmacovigilance in Europe) by Dr June Raine, head of the EMA's PRAC (Pharmacovigilance Risk Assessment Committee)

- the Impact of pharmacovigilance by Almath Spooner from the Health Products Regulatory Authority, Ireland

- the PROTECT health project involving active information-sharing by patients

- the WEB-RADR project on harnessing mobile apps and geo-tagging from Philip Tregunno from the UK MHRA - using social media as a signal detection and strengthening tool

-  actions from the EMA Risk Minimisation Measures Topic Group from Jamie Wilkinson, PGEU (Pharmaceutical Group of the European Union)

The EACPT – the European Assocation for Clinical Pharmacology and Therapeutics – has 34 member countries in the EU region and beyond, and around 800 individual members. Considering some of the recent pharmacovigilance activities important for an organisation such as the EACPT, these include:

–      the 2013 black triangle scheme which concerns an evolving list of medicines under additional monitoring, building on UK experience of this approach to pharmacovigilance. Many EACPT members are directly or indirectly involved in reporting and monitoring issues related to safety of medicines

–      The EMA-ADR database of ~6 million reports - a growing resource for recording and assessing risk from medicines

–      Robust systems regarding the supply chain are vital to ensure safe medicines including from internet pharmacies. Falsified/contaminated/counterfeit medicines must be excluded both in established and newer members of the EU. This will be one of the– key themes at the next EACPT Congress in Prague in June in 2017.

Important drivers for change over the next five years include

- transparency and impact of EMA pharmacovigilance activities

- enabling partnerships, including through active EMA working parties involving healthcare professionals, patients and consumers

- Digital Media to complement current safety systems for evaluating medicines

 

Enhanced systems are needed for evaluating Real World health data across the EU region, for example analogous to the US Sentinel model – an HMO partnership with FDA and Harvard, and large Clinical Practice databases in the UK.

These Real World health data resources are needed to support evaluating signals from social media to complement existing systems for identifying and preventing adverse drug reactions, as well as to support development of medicines for patients with rare diseases.

Effective expanding use of social media will to enhance communications on PV from the EMA to its partner organisations: and through them tp health professionals, patients and other stakeholders. Systematic heterogenous use of social media provides great opportunities to enhance efficiency of effective delivery and monitoring adoption of safety messages – some of which were aired at the EMA earlier this week – presentations from the day will be on the EMA website. 

Register for EACPT Focus Meeting in Opatija, Croatia on How to Assess Medicines 6th - 9th October

There is still time to register for the next EACPT Focus Meeting which will be held from 6th to 9th October, 2016 in partnership with the Croatian Society for Clinical Pharmacology and Therapeutics.

The theme of the meeting is “How to Assess Medicines from Research to Clinical Practice”.

There is a bursary fund of 10,000 € to support abstract presenters.

See meeting programme

Key dates

Online Meeting Registration Deadline - September 30, 2016  

 

The main objectives of this Focus Meeting are to increase awareness, knowledge and use of critical assessment pillars for medicinal products in everyday clinical practice in order to improve healthcare outcomes in affordable manner.

The meeting will include a combination of scientific podium lectures, interactive workshops and guided poster sessions covering three main pillars important for the critical assessment of medicinal products - efficacy, effectiveness, and economics (3E assessment).

There will be a dedicated session for Young Pharmacologists during the meeting. There will be an EACPT Scientific Communication Award for the best presentation by a young scientist. 

Confirmed speakers and topics

JANNE TAPIO BACKMAN (Finland): Clinical drug-drug interaction studies: methods, pitfalls and interpretation

NADA BOŽINA (Croatia): The role of pharmacogenetics in individulized treatment choices

YLVA BOTTIGER (Sweden): National model for the introduction and follow-up of new, expensive drugs in Sweden

GONZALO CALVO (Spain): Accelerated approval paths. What they do mean and what they should not mean?

SIMON MAXWELL (UK): Safe introduction of new medicines into clinical practice

KEN PATERSON (UK): Rapid Health Technology Assessment of New Medicines - Lessons from 15 Years Experience in Scotland

WORKSHOP 2: EXCELLENCE IN CLINICAL RESEARCH - CLINICAL TRIAL DESIGN

IGOR FRANCETIĆ (Croatia): Effectiveness assessment: when pharmacokinetics makes a difference / macrolide and azalide examples

MATTHIAS SCHWAB (Germany): Pharmacogenomics and drug response: future challenges

EDUARDO SPINA (Italy): Efficacy of antidepressants: issues related to bias in clinical trials

TABASSOME SIMON (France): Key points for building succesful clinical trial

SINIŠA TOMIĆ (Croatia): The Role of the National Competent Authority (NCA) in the Assessment of Medicinal Products in the National Procedure

DONALD SINGER (UK): Personalised medicine approaches for identifying effective therapies

SLOBODAN VUKIČEVIĆ (Croatia): Current challenges and hurdles in new drug development

We will be guests in the Adriatic coastal town Opatija, Croatia. Opatija lies at the centre of the Kvarner Riviera with the longest tradition of providing quality conference venues in Croatia. Opatija’s very attractive geographic location, lush green scenery and a pleasant climate (45° 20’ north latitude) were some of the main reasons for its origins and the rapid development of its tourism from the end of the 19th century.  The venue – Grand Hotel 4 Opatijska Cvijeta –  is located in the very centre of Opatija and includes four buildings that were named after Opatija’s best-known flowers. The hotel has 223 rooms. The hotel also includes the large Tamaris congress centre, which has 7 multi-functional halls and the latest congress equipment.

Anyone from anywhere in the world with a professional interest in clinical pharmacology
and therapeutics can now join the EACPT as an Individual Associate member.
Membership benefits include:

• Access to videos of talks from EACPT Meetings

• Discounted registration fees for EACPT meetings

• Online access to the Official EACPT Journal - Clinical Therapeutics

• Access to the EACPT’s worldwide network of Individual Associate Members

• Active involvement in EACPT 

The EACPT was founded 24 years ago and now includes as members all national organisations for clinical pharmacology in Europe, as well as organisations from further afield internationally. The EACPT aims to provide educational and scientific support for the more than 4000 individual professionals interested in clinical pharmacology and therapeutics throughout the European region, with its congresses attended by a global audience. The EACPT also advises policy makers on how the specialty can contribute to human health and wealth.

Digital Media for Health and the European Medicines Agency

The European Medicine Agency is today holding a Workshop on Social Media for its

Human Scientific Committees' Working Parties with Patients’ and Consumers’ Organisations (PCWP) and Healthcare Professionals’ Organisations. 

Social media is a group of electronic communication tools that have the potential to change how healthcare professionals, researchers, patients and consumers manage and share information in the digital age, including on the safe and effective use of medicines.

The Workshop opened with a keynote talk by M-K Looi, Wellcome Trust, on "Going viral: the state of play and potential of social media in 2016". This was followed by talks by S. Labbe, communications expert from the EMA and notes on experience of use of social media by the USA FDA presented by 2 FDA pharmacists – C. Chew and K Chiu.
 

The EMA Social Media topic group had previously identified areas and patterns of use of social media by PCWP and HCPWP member organisations in relation to the EMA and to their other key professional areas of interest and activity. In a new survey conducted over the summer of 2016, SWOT feedback has been obtained from health organisations currently active in use of social media and a further group of  organisations not currently active in use of social media.

An analysis of findings of the SWOT analysis will be presented and discussed followed by break-out sessions on best practice in use of social media experts. Further sessions will consider how digital information could be relevant to regulatory decision-making.  

The sessions are being recorded with presentations to be made available on the EMA website.

Submit abstracts for "How to Assess Medicines from Research to Clinical Practice": 6-9 October 2016. EACPT Focus Meeting - Opatija, Croatia.

The next EACPT Focus Meeting will be held from 6th to 9th October, 2016 in partnership with the Croatian Society for Clinical Pharmacology and Therapeutics.

The theme of the meeting is “How to Assess Medicines from Research to Clinical Practice”.

There will be a bursary fund of 10,000 € to support abstract presenters.

See meeting programme

Key dates

Abstract Submission Deadline - June 15, 2016

Early Registration Deadline - June 30, 2016

Online Meeting Registration Deadline - September 30, 2016  

 

The main objectives of this Focus Meeting are to increase awareness, knowledge and use of critical assessment pillars for medicinal products in everyday clinical practice in order to improve healthcare outcomes in affordable manner.

The meeting will include a combination of scientific podium lectures, interactive workshops and guided poster sessions covering three main pillars important for the critical assessment of medicinal products - efficacy, effectiveness, and economics (3E assessment).

There will be a dedicated session for Young Pharmacologists during the meeting. There will be an EACPT Scientific Communication Award for the best presentation by a young scientist. 

Confirmed speakers and topics

JANNE TAPIO BACKMAN (Finland): Clinical drug-drug interaction studies: methods, pitfalls and interpretation

NADA BOŽINA (Croatia): The role of pharmacogenetics in individulized treatment choices

YLVA BOTTIGER (Sweden): National model for the introduction and follow-up of new, expensive drugs in Sweden

GONZALO CALVO (Spain): Accelerated approval paths. What they do mean and what they should not mean?

SIMON MAXWELL (UK): Safe introduction of new medicines into clinical practice

KEN PATERSON (UK): Rapid Health Technology Assessment of New Medicines - Lessons from 15 Years Experience in Scotland

WORKSHOP 2: EXCELLENCE IN CLINICAL RESEARCH - CLINICAL TRIAL DESIGN

IGOR FRANCETIĆ (Croatia): Effectiveness assessment: when pharmacokinetics makes a difference / macrolide and azalide examples

MATTHIAS SCHWAB (Germany): Pharmacogenomics and drug response: future challenges

EDUARDO SPINA (Italy): Efficacy of antidepressants: issues related to bias in clinical trials

TABASSOME SIMON (France): Key points for building succesful clinical trial

SINIŠA TOMIĆ (Croatia): The Role of the National Competent Authority (NCA) in the Assessment of Medicinal Products in the National Procedure

DONALD SINGER (UK): Personalised medicine approaches for identifying effective therapies

SLOBODAN VUKIČEVIĆ (Croatia): Current challenges and hurdles in new drug development

We will be guests in the Adriatic coastal town Opatija, Croatia. Opatija lies at the centre of the Kvarner Riviera with the longest tradition of providing quality conference venues in Croatia. Opatija’s very attractive geographic location, lush green scenery and a pleasant climate (45° 20’ north latitude) were some of the main reasons for its origins and the rapid development of its tourism from the end of the 19th century.  The venue – Grand Hotel 4 Opatijska Cvijeta –  is located in the very centre of Opatija and includes four buildings that were named after Opatija’s best-known flowers. The hotel has 223 rooms. The hotel also includes the large Tamaris congress centre, which has 7 multi-functional halls and the latest congress equipment.

Anyone from anywhere in the world with a professional interest in clinical pharmacology
and therapeutics can now join the EACPT as an Individual Associate member.
Membership benefits include:

• Access to videos of talks from EACPT Meetings

• Discounted registration fees for EACPT meetings

• Online access to the Official EACPT Journal - Clinical Therapeutics

• Access to the EACPT’s worldwide network of Individual Associate Members

• Active involvement in EACPT 

The EACPT was founded 24 years ago and now includes as members all national organisations for clinical pharmacology in Europe, as well as organisations from further afield internationally. The EACPT aims to provide educational and scientific support for the more than 4000 individual professionals interested in clinical pharmacology and therapeutics throughout the European region, with its congresses attended by a global audience. The EACPT also advises policy makers on how the specialty can contribute to human health and wealth.