Medical Care |

Medical Care

##SEVER##

/e/efgcp.eu1.html

Efgcp

The Newsletter of the European Forum for Good Clinical Practice
‘Where Science and Ethics Meet'
Medicines for elderly people
New guidelines forethical research New guidelines call for
Dates for your diary ethical research in and
New look and logo for elderly people
Stuttgart hosts experttraining 20th anniversary
A history of the EFGCP
Joseph Hoet Lecture
Clinical trials are ill
Annual Conference 2013
Ethical dimensions of
emerging technologies
The EFGCP's Geriatric Medicines Working Marie Vetel and François Hirsch to present Party (GMWP) has published ethical a first draft based on the European guidelines on medical research for and with Medicines Agency paediatrics guideline, older people. The guidelines, the fruit of with the aim of fostering ethical research more than three years of intensive work, in this neglected area.
can be found on the EFGCP website, The overall principles and key elements www.efgcp.eu, and a shorter version was of this guidance were further discussed and published in the May edition of The Journal revised by the GMWP in the following of Nutrition, Health and Aging.
years and presented at the European This document is based on several Medicines Agency's workshop on workshops organised by the EFGCP Medicines for Older People, held in GMWP. Three years ago, it invited Jean- London in March 2012. Following public consultation, the of their conditions and treatment. Medicines GMWP received many thoughtful comments used by older people should be of high from academia, investigators, regulators, quality, appropriately researched and patients advocacy groups and the evaluated throughout their life cycles. The look – and
pharmaceutical industry, and met twice to population included should be representative review and incorporate as many comments as of the future consumers of the tested drugs." possible into the final text. The group has The guidance covers definitions of both shared the text with all those who had geriatric and vulnerable patients, informed contributed or reviewed the draft to inform consent from older and vulnerable logo – for
them and seek their permission to mention participants, and the role of ethics committees in ensuring that research is adapted to yield the EFGCP
"Older people experience a higher appropriate outcomes for the elderly incidence of disease-related morbidities, take more medicines with multiple medication The working party hopes that its regimes and account for more adverse drug guidance will be taken up by regulators and others to become firm official guidelines – counterparts," says the guidance. "Thus, it is thus contributing to improving the quality of important to conduct more research and clinical research in this population.
clinical trials in this patient population to Laurence Hugonot, Co-Chairman,
further the understanding and management Geriatric Medicines Working Party
Twenty years of commitment to GCPand to the organisation of successfulevents leave their mark. Over time, our EFGCP Workshop on image had become outdated and Indemnity schemes for clinical trials:
"rigid" – and not representative of what a societal obligatiom?
7th DIA/EFGCP/EMA Paediatrics Medicines for EFGCP really is: an organisation that November 2013 (date to be confirmed), get things moving! Brussels, Belgium. 24 & 25 September, Hilton London This is why, without radically Docklands Riverside Hotel, London, UK changing everything, we decided to EFGCP Annual Conference 2014 on refresh our logo to convey a younger, EFGCP Regional Workshop on Benefits and risks of research: How
more modern and dynamic image. Our Turkey – a clinical role model for
do we redress the imbalance?
colours are brighter, our typography is 28 & 29 January 2014, Brussels, Belgium softer. The whole logotype has been Autumn 2013 (date to be confirmed), "cleaned" for a bigger impact. But our Istanbul, Turkey. Jointly organised by the For details of all meetings, see www.efgcp.eu, or mission and values remain unchanged.
University of Istanbul and the EFGCP. And, as we are conscious that a good communication doesn't comewithout cost, we have invested in theso-called "permanent media" – free andvisibility-bearing, they are designed tobe all around us: letterheads, businesscards, PowerPoint, brochures, and thewebsite.
Our new website will soon see the light. We have tried to build ourwebsite so as to keep our members atthe heart of the strategy, offering theman access to new functionalities formore interaction between them as wellas with the Board and the EFGCPWorking Parties.
Putting all this in place has been an enormous team effort, and one that we hope will equip the EFGCP to go forward into the future.
Stuttgart hosts expert training for RECs
The European Forum for Good Clinical
experienced and expert members need to Practice held its fourth workshop on support new members who shouldn't be training for research ethics committees expected to have detailed knowledge when (RECs) in Stuttgart on Wednesday 20th March 2013, generously hosted by the When considering members' and RECs' training needs we need to consider Its aims were to develop the report from realistically what we expect of the new the third workshop, provide delegates with member and what we expect of the access to experts experienced in training, committee as a whole. The former's needs practical examples of training and an might be deemed "basic" skills, the latter opportunity to contribute to a training "the advanced skills" more likely to be met syllabus for ethics committees. Training on by more experienced members. Members proposed EU regulations on Clinical Trials need to share, to pool, their knowledge, of Medicinal Products was also included not exploit it and "wear their experience or on the agenda. 19 representatives from 11 expertise lightly". countries attended. We need to consider assessment from Procedural differences emerged early in the inception of any analysis. "Assessment the day, but once they were identified it drives learning"; it always has and probably was possible to establish shared principles always will. Consequently any design must and build a common structure for ethics incorporate, or offer the participants committee training that accommodated Fountain at the Neues Schloss, Stuttgart. opportunities for fair and valid (self ) and respected these differences. assessment. How this might be mandated For new REC members training needs beyond simple "ethical knowledge".
or monitored would be a local decision. to address the question "What is it like to The most important voices must be Finally it was recognised that nothing be a committee member and what do I those of new members but we should can replace the expert teacher and the need to now?" Any programme must be include contributions from experienced trainer needs training and for new founded on the understanding that the task members, REC officers as well as those members a mentor such as a fellow of RECs is a practical one, to evaluate and charged with oversight of ethical review committee members, asked to support deliver an opinion on research proposals systems. It was recognised that any them in early meetings, can play a vital submitted to them. It must be pragmatic, induction programme would be just a start.
providing instruction in knowledge, skills Learning continues after any formal early For a full report of the workshop, and personal attributes that help REC courses so REC meetings need to be including details of the four "quadrants" members review research competently and uncritical arenas in which new members' addressed during the day, please email consistently – to do their job. It must go confidence is enhanced. Chairs, officers, Hugh Davies
Interactive training for inspections
Following the success of its one-day authorisation – in today's inspection course in London on 19 November landscape inspections can occur at any 2012 on training for inspections, time with and without a particular event EFGCP's Audit Working Party is now to trigger them. Especially in Europe, offering the course to individuals and health authorities conduct inspections as organisations such as universities and part of their routine oversight activity. So clinical staff need to understand The interactive course is aimed at what is required during an inspection, clinical trial centre staff such as and how to prepare for and follow-up investigators, co-investigators, study on an inspection. It is also important to nurses and coordinators and anyone understand and apply new trends such involved in the conduct of clinical trials as the concept of a risk-based approach of any phase and design, sponsored by that is becoming the reference for commercial or academic institutions. Inspections are no longer linked to a For a sample agenda and details of submission by a sponsor to health how to apply for a course, email authorities to obtain a marketing Patients' Academy takes shape
For anyone who has followed the progress of EUPATI, the European Patients' Academy on Therapeutic
Innovation, from its early beginnings the project's first full conference with a 183 participants, held in Rome
on 19 April 2013, was a revelation. Newsletter Editor Peter Wrobel reports.

Barely two years ago the idea of EUPATIwas a mere gleam in the eye, an idea floatedin discussion in the PatientPartner project.
Patients, so the idea went, need training andeducation to enable them to play a full partin the medicines research and development(R&D) process. The notion was simple and,once stated, obvious. But equally obvious,and immediately understood, was that tobring this simple idea to reality would beinherently and perhaps impossibly complex.
The Rome conference, held just 14 months after the launch of EUPATI, showed just how far the idea had developed. More than 180 delegates from 28 countries were there to hear about the plans under way for three clear areas of training and education: a certificate level course that by 2017 will produce 100 EUPATI Director Jan Geissler (left) on the platform with David Haerry from consortium patient experts drawn from across Europe; partner and patient organisation European AIDS Treatment Group. less detailed online education for 10,000patient representatives; and an Internet scrutinised, and where decisions on access of teaching them will prove more of a library with information for anyone with an will be made.
challenge – as will selecting 100 people interest in medicines R&D – hundreds of So the Patients' Academy is more than from across Europe. Even translation into thousands of people, perhaps millions.
a desirable aim: it is both crucial and urgent.
the chosen languages poses problems when, Delegates heard a series of presentations And as delegates heard, a number of hard for example, there just isn't a term for outlining the vision of the project and a decisions have had to be made to move the "randomisation" in some languages. The number of talks from people around Europe project forward. Lacking the resources to audience learned why ethical oversight and who have been implementing innovative replicate the project in every EU country transparency are fundamental to the practices in patient partnership.
and every EU language , EUPATI has had EUPATI project and how these concepts are to restrict itself in order to make the applied in practice. So-called "soft" ‘Window of opportunity'
Patients' Academy a practical possibility. communications skills are also crucial if The certificate-level course will be partnerships between patients, researchers, The atmosphere was positive, and for good English only; online education and the industry and regulators are to be as fruitful reason. As several speakers said, there is Internet library will be developed in the as possible.
now a "window of opportunity" for seven most frequently spoken languages in An overarching concern is sustainability.
effective patient involvement in medicines Europe – English, German, Spanish, Polish, The project is funded by the European R&D. All stakeholders understand the huge French, Italian and Russian (widely spoken benefits that can flow to them, from early by older people in central and eastern Initiative, but only to 2017. By then the research discussions, to better trial designs, Europe). The lynchpin of the project, the European Patients' Academy must have more meaningful patient involvement in National Platforms which will do the work established sufficient roots to carry on, HTA and regulatory processes, and in their own countries, will be established in along with ways of ensuring that the ultimately a quicker stream of properly 12 countries only.
courses and information it offers continue tested and adapted innovative medicines. There were few illusions about the scale to be relevant and up-to-date. But going by But along with the opportunity comes of the task. More work is needed on the conference in Rome, that seems to be a the threat that there may be too few presenting the projects aims and its value challenge that many will relish.
properly trained patients to take advantage also to lay patients. The broad outlines of of the seats that it is hoped will be available the content of courses and material have A full report of the conference is
at the tables where trials are designed and been established, but finding the right way available at www.patientsacademy.eu.
20th Anniversary of the EFGCP
A history of the European
Forum for Good Clinical Practice
Jean-Pierre Tassignon and Olga Kubar present a review of the activities and leadership of the EFGCP, going back
over two decades.

This is a review of the first 20 years of the if data quality could be ensured across all headquartered in Brussels. The IDF is an European Forum for Good Clinical Practice participating countries. Bringing the clinical umbrella organisation of 200 national (EFGCP). The EFGCP is a not-for-profit research establishment in emergent diabetes associations in over 160 countries.
think tank open to all stakeholders in countries up to speed with Good Clinical From this unique position and his clinical research. Members are natural as Practice (GCP) was critical, as well as innumerable trips to all countries in the well as legal persons who wish to debate in world, Prof. Hoet understood clearly that a multidisciplinary mode real life issues at the clinical research community was the interface between science and ethics globalising very quickly under the pressure concerning the practice of clinical research. of patient associations fighting for new In the late 1980s, just before the EFGCP was created, clinical research was Globalisation of clinical research would internationalising at great speed. The newly only survive if all stakeholders would adopt one set of quality standards. organisations (CROs) of the early 1980s Dr. Jean-Pierre Tassignon, also based in were developing into multinationals.
Brussels, was Executive Vice President of Headquartered mostly in the USA, where the largest clinical CRO in Europe at the clinical research was – and still is today – time (G.H. Besselaar Associates, Inc., the most prolific, the largest pharmaceutical Princeton, USA, now part of Covance, Inc.), companies and CROs were busy trying to running many multinational clinical trials in accommodate an increasing number of all age groups and indications with many clinical trials of increasing sample sizes, and experimental drugs, in particular the first they needed more clinical sites every year.
new biotech wonder-drugs erythropoietin Europe experienced an overflow of and granulocyte-colony stimulating factor transatlantic trials. (rhG-CSF). Given the size of its clinical The AIDS epidemic accelerated the operations and network of offices in internationalisation of the clinical research Europe, this CRO was the principal industry, as the mega-trials required to test The first edition of EFGCP News. customer of the EERC, meeting quasi the efficacy and safety of zidovudine, the first active drug in this indication, forced In 1991, Europe was planning to create The two started brainstorming about the sponsors and CROs to look for the European Medicines Agency. It was time need for a neutral place where professional investigators in countries which "emerged" for closer cooperation among all those organisations involved in clinical trials, as new clinical trial regions after North involved in clinical research.
including from the regulatory authorities and America and Western Europe: South Africa, even patient associations, would meet and Brazil, Australia, and major cities in Asia, The Foundation Years (1991-1993)
debate how to translate our moral, scientific such as Hong-Kong. It was necessary to and technical responsibilities into daily spread the trials globally and "go where the In Brussels, Prof. Joseph J. Hoet was Vice- practice in so many countries. An invitation patients are". Once established, the clinical Chairman of the European Ethics Review letter was co-signed proposing to establish research professionals opened permanent Committee (EERC), the first multinational the EFGCP. Representatives from 25 offices locally and investigators of all ethics committee in Europe. It was the only organisations involved in clinical research in specialties could participate in clinical trials. ethics committee to review transnational Europe met at a hotel at Brussels airport in Europe was also integrating fast. In clinical trial protocols and it enjoyed a de 1989, Germany re-united, and it was clear facto reciprocity status with the ethics This assembly of pharmaceutical that with the collapse of the Warsaw Pact in review systems of various Member States. companies, CROs, IT companies, the 1991, a lot of former communist countries Parallel to his research and teaching EERC, the United Kingdom Medical would open to clinical research associated responsibilities at the Catholic University of Research Council and the Wellcome with drug development. The multin
ational
Louvain, Prof. Hoet was also President of Foundation, nominated a Foundation multicentre clinical trial would only survive the International Diabetes Federation (IDF), Working Group under the chairmanship of ››
the EFGCP office and staff, are listed in atable in an annexe, which is available from theoffice (please email secretariat@efgcp.eu). Ofcourse, the success of the EFGCP is to a largeextent due to the invaluable directinvolvement of active members and thegenerous support from external private andpublic sponsors.
As can be judged from Figure 1, the EFGCP activities progressed in three phases.
Putting the fundamentals in place
(1993-1997)

Dr. David Langford was the first elected chair Figure 1. Cumulative number of meetings organised and co-organised by the EFGCP by year. in 1993. Wellcome plc promoted him toMedical Director Europe in the following ›› Alfred Pauls, Head of Information Systems at
Medicines and Geriatric Medicines Working year, and he stepped down after having given Schering AG. After intense consultations and Parties. The most recent EFGCP-EGAN a very strong impulse to the newly born meetings in 1992, encouraged by the result (European Genetics Alliance Network) co-led EFGCP: the first Annual Conference, the first of a needs assessment in a multistakeholder Patients' Roadmap to Treatment Working issue of EFGCP News, the first working parties conference at the European Parliament, the Party reflects the absolute necessity of nominated. His successor was Gérard Marsat, EFGCP held its constitutional assembly in including patient representatives into a very Director of Regulatory Compliance – GCP at May 1993, hosted by the European close partnership with clinical research SmithKlineBeecham in the UK. He chaired Organisation for Research and Treatment of the EFGCP until 1998. The working parties produce a constant This is the period during which the flow of position papers, guidelines, EFGCP's Working Parties became very active international workshops, large conferences and published EFGCP's first consensus papers and training courses concerning hot issues in and guidelines like "Minimal standards for In just over 20 years, the EFGCP has created their respective specialties. A Science and research ethics committees", became an productive working parties, which, together Ethics Council chaired by Prof. Françoise associate member of World Health with its board, have organised an impressive Meunier, Director General of the EORTC, number of 150 open, multidisciplinary gives general direction to the working parties. International Organisations for Medical meetings for all stakeholders of clinical While deliberately focusing the activities Sciences), and embarked on an intense research, in Europe and well beyond. It has on Europe, the EFGCP was gradually able to cooperation with the newly formed Forum produced many authoritative position papers. reach out to partner organisations on all for Ethics Committees in the CIS (FECCIS).
The board kept for itself the organisation continents. The EFGCP promoted the Already in 1991, a postgraduate course of an annual conference, the publication of development of GCP in the CIS, India, in pharmaceutical medicine was being set up the EFGCP News and the running of the China, Africa and Latin America. Of course, at the Free University of Brussels, called EFGCP as an organisation, which since 2005 given their closeness to Europe, most efforts PHARMED, and many members of the has had permanent staff in offices located in concentrated on the CIS countries. Activities EFGCP became lecturers on the course. To the European district of Brussels. The first ranged from setting up conferences locally to this day, this partnership has held firmly. annual conference was organised in 1993. sending delegates to lecture at national events, From 1994, the EFGCP invited Between 2009 and 2011, the EFGCP or hosting delegations visiting the EFGCP in representatives from patient associations to transferred its annual conference outside attend its events as lecturers, session chairs and Brussels; however, feedback from EFGCP With its neutral, multilateral setup, the facilitators of breakout groups. members and financial considerations led to EFGCP became involved in joint projects In 1991, the Soviet Union transformed the board's decision to hold the annual under the EU Framework Programmes (FP).
into the Russian Federation, opening up a vast The EFGCP was awarded FP grants in six region stretching from Eastern Europe to Identification of problems and solution projects and Innovative Medicines Initiative Central Asia and Siberia for clinical research finding by collaboration of all stakeholder (IMI) grants in two.
activities. On the borders of Russia, the groups in working parties was essential to the Nordic Council on Medicines, which working model of the EFGCP. amplification of meetings driven by the federates the interests of Sweden, Norway, Some working parties were dismantled EFGCP, usually in partnership with other Denmark and Finland, plus the Baltic States, after having completed their missions, but organisations in Europe and well beyond.
perceived the opportunity, and called upon most are still very active, in particular the The leaders who drove the development the EFGCP to help train investigators and Ethics, the Education and the Audit Working of the EFGCP on the board of directors, on members of the newly formed Ethics Parties, which were created in 1993, as well the working parties, on the EU-funded Committees in Russia and the Baltic States in as the more recently established Children's consortia, and those who were in charge of the new GCP standards. Changing gear (1998-2004)
Dr Roger Bickerstaffe, at the time Vice-President Pharmaceutical Commu-nications, Solvay Pharmaceuticals, wasEFGCP chair during this period. Figure 1indicates that, in this period, the EFGCPkicked off as a strong organiser ofinternational meetings. It hired its first staff,and this gave it the power needed to projectits expertise to all corners of the world. In 2000, Prof. Olga Kubar, at the time chairperson of FECCIS and based at thePasteur Institute in St Petersburg, Russia,joined the EFGCP Board to mark theimportance of the contribution of CIScountries to European clinical research. Thecountries of Europe plus Russia and the CIScountries host a population of 1 billion. The WHO was also very much concerned with capacity building inemergent countries, i.e. countries adopting Early EFGCP activity. Picture taken at the Falstaff restaurant, near the Brussels Bourse, during clinical trials under the new international the 4th Applied Clinical Trials European Conference & Seminar, organised with strong standards in clinical research. The EFGCP support from the EFGCP, on 21 and 22 April 1997 in Brussels. Pictured, clockwise from the delegated lecturers at training events in back, with their titles at the time: Mr. Nigel Dent, Member of the EFGCP Board and Scientific Africa, Latin America and Asia.
Consultant; Dr. Ingrid Klingmann, VP Business Development, Corning Besselaar Europe, The fine-tuning of the new position Brussels; Mrs. Susan Besnard, Member of the EFGCP Board and CEO, Besnard Associates, regarding the use of placebos in clinical Brussels; Prof. Joseph Hoet, Ethics Officer on the EFGCP Board and Director, WHO trials written in the revised World Medical Collaborating Centre, Université Catholique de Louvain; a lady from World Courier; Dr. Jean- Association Declaration of Helsinki of Pierre Tassignon, Member of the EFGCP Board and Lecturer, Université Libre de Bruxelles, 2002 required EFGCP action.
CEO Tassignon & Partners; Prof. Alexander Rudakov, Director, National Institute for Preclinical In the EU, the new Clinical Trials and Clinical Drug Evaluation, Moscow; Mrs. Elena Barmanova, Russian Research Centre for Directive (CTD) of 2001 would change the Drugs Evaluation and State Control, Moscow; Hoet, Klingmann and Tassignon were on the way clinical trials were regulated. The conference programme as lecturers. EFGCP entered into a closer cooperationwith the European institutions and addressed AG, became chairman in 2005 and was development. This developed the concepts matters related to the actual implementation succeeded in 2010 by Dr Ingrid taken up by the IMI project EUPATI of the CTD, starting from 2004, the year the Klingmann, President of Pharmaplex bvba. CTD became applicable in the whole of the In this period, the EFGCP kept pace Therapeutic Innovation), in which the Union, including ten new Member States with the vigorous trend set at the end of the EFGCP also plays a leading role. Since mainly in Central Europe. previous period. The EFGCP was 2010 the EFGCP has been involved in the In 2003, the EFGCP added a new particularly successful in joining or leading IMI-PharmaTrain project, with Klingmann dimension to its pool of interests as it joined EU-funded consortia. A very important being the Deputy Coordinator and Leader EuroSOCAP (European Standards on FP7-funded project was ICREL, led by the of the Work Package on Ethics. An Confidentiality and Privacy in Healthcare EFGCP, which measured the impact of the important outcome of this project is not Among Vulnerable Patient Populations), a Clinical Trials Directive on clinical research only the harmonisation and advancing of consortium seeking EU funding under the in Europe. As a consequence of the project master courses in pharmaceutical medicine Framework Programme. results the consortium initiated the but also the development of a concept Hence, the EFGCP reached the full "Roadmap Initiative for Clinical Research for comprehensive and harmonised scope of activities in 2004, including the in Europe", leading to a series of workshops investigator training in Europe. Financial first successes in obtaining EU Framework on areas of particular concerns in the audits by the European Commission in Programme grants.
current legislation. Their outcome strongly some of the projects underscored the influenced the European Commission's trustworthiness of the EFGCP as a The EFGCP enters the Ivy League
current draft proposal for a Clinical Trial of EU-funded consortia (2005-to
Another important project was the The efficiency of the EFGCP increased FP7-funded "PatientPartner" project, set up tremendously after it entered its own offices Dr Jean-Pierre Tassignon, President of to identify strategies on enabling patients to in the European district of Brussels in 2005.
Crossover Clinical Research Infrastructures become true partners in medicines Staff increased gradually to three FTEs. The ››
important activity for the EFGCP. The2011 annual conference was dedicated tothis topic, and a very successful trainingcourse, "GCP for the experiencedinvestigator", is regularly held at theEORTC, different European universityhospitals and clinical trial sites. An"Inspection Preparation" training coursewas recently developed by the AuditWorking Party, and further trainingprogrammes as well as a professionalisationof the training function is currently underdevelopment by the Education WorkingParty. The elaboration of a systematicapproach to training of ethics committeemembers by the Ethics Working Party hasbeen ongoing since 2007.
The EFGCP has always stressed theimportance of personal commitment of itsmembers in the working parties, on the Annual conference, Brussels, 2007: Frank Wells directs discussion. board and on the Science and EthicsCouncil. It is within the EFGCP structure ›› EFGCP website received a facelift in 2007,
Indian Forum for Good Clinical Practice that multistakeholder consensus ripens and and is currently being refreshed with new and the visit to Brussels in 2005 of a is pragmatically formulated. delegation from the Chinese State Food and It is vital to continue to reach out to Initially, only individual members were Drug Agency and the Shanghai Municipal partner organisations outside the EFGCP recruited as members of the EFGCP. They FDA to discuss systems of ethics review in and to open up the discussion to as many came mainly from the pharmaceutical Europe, visit Phase I units and meet with stakeholders as possible. A successful industry, contract research organisations, example is the ongoing collaboration with ethics committees, regulatory authorities, The Ethics Working Party published DIA in organising the Annual Paediatric academia, healthcare institutions and The Procedure for the Ethical Review of investigator networks, suppliers of IT Protocols for Clinical Research Projects in Europe In this way, the EFGCP fulfills its systems and equipment, and any other and Beyond, coordinated, regularly updated mission of helping all stakeholders in professional groups involved in clinical and expanded by Dr. Frank Wells, clinical research to cope with their research. From 2008, corporations, comparing the ethics review processes in respective responsibilities when they engage healthcare institutions, associations of the various European countries and beyond, in research on human beings. participants in clinical research and patient which became one of EFGCP's star advocates were admitted as members as publications. With his leading involvement increasingly complicated and fraught with in a global initiative for research integrity, risks. By and large, it is practised for the Partnerships with patient and patient- Wells enabled the EFGCP's Ethics Working advancement of medicine and in the public led organisations intensified. Between 2007 Party to have ongoing involvement in this interest. We trust the EFGCP will continue and 2011, the EFGCP was able to host the highly relevant area on an international to arrange for all stakeholders to consult secretariat of the European Platform for each other incessantly about the way each is Patient Organisations, Science and Industry The EFGCP's Audit Working Party has supposed to discharge his responsibilities in (EPPOSI) in Brussels. Regarding the CIS, developed a number of highly appreciated the framework of the clinical trial protocol this period is characterized by training guidelines such as The Role of the Quality for the protection of each consenting organised by FECCIS with delegates from Assurance Unit. In close collaboration with the EFGCP in Russia, the Ukraine, the EMA, the Children's Medicines and the Kazakhstan, Azerbaijan, Kyrgyzstan, Ethics Working Parties supported the Jean-Pierre Tassignon is a former
Armenia and Moldova. These meetings development of the EMA's guideline on Chairman of the EFGCP; Olga Kubar
were always supported by the local ministry ethical consideration in paediatric trials, and is a member of the EFGCP Board.
of health, the medicines agency, the national recently the Geriatric Medicines Working Members of the EFGCP Board, Chairs
ethics committee and academia. Ties were Party completed their guidelines on ethical of Working Parties and EFGCP
also strengthened in Asia, especially with considerations in geriatric trials. delegates to other bodies, along with
China, India and Thailand. It is worthwhile Since 2010 training of all stakeholders senior managers, are available at
to single out the co-foundation of the in clinical research became an increasingly Annual Conference 2013: the Joseph Hoet Lecture
Clinical trials are ill
Silvio Garattini from the Mario Negri Institute for Pharmacological Research, Italy, used the Joseph Hoet Lecture
to attack what he called the widespread misuse of clinical trials.

Randomised clinical trials are still the bestway of establishing the efficacy of anykind of treatment on a basis of evidence,regardless of the technology or type oftreatment, said Silvio Garattini. Wherethere is true uncertainty, any other kind oftrial will be dangerous and may exposepatients to avoidable risk but, on the otherhand, deciding not to treat can deprivepatients of possible benefits. However, hesaid, clinical trials are ill. And like for anyillness, it is important to establish how todiagnose the sickness, and then see howit can be prevented or treated.
The diagnosis of any disease is based on recognition of specific symptoms. Herewe are dealing with a multifactorial illness.
The first symptom is the abuse of placebo.
According to the Helsinki Declaration, the efficacy of a new drug must be challenged against the best available treatment and not helped by favourable research conditions, such as comparison with a Garattini led off with a couple of examples, one being a trial for a new drug,fingolimod, to treat multiple sclerosis.
Silvio Garattini receives the Joseph Hoet Medal from EFGCP Chairman Ingrid Klingmann. Given that we know there are drugsavailable, like interferon beta 1a and 1b or they accept the opposite and conclude that – while the adverse reactions become glatiramer, that have been shown to the new drug is not inferior. Usually in evident under clinical practice.
reduce relapses by about a third, one order to establish non-inferiority you set One justification given for non- would expect them to be used as a the "delta", the margin within which you inferiority trials is that they may enable an comparator for any new multiple sclerosis agree that a new drug is no worse than the investigator to show whether drug drugs – but not so. Fingolimod was control, said Garattini. Enlarge the delta, adherence improves. But Garattini said compared against placebo (as were drugs and everything becomes non-inferior. that if this were the case, then "better in other trials mentioned by Garattini – "Are there specific reasons for allowing compliance should lead to better results, a non-inferiority approach?" he asked. "It not a ‘not worse' outcome".
teriflunomide, laquinimod. "I submit to seems illogical to use such a design. One Other justifications put forward for you that the patients given placebo have reason advanced is that not all patients these trials include testing for non-inferior been damaged," he said. "I calculated a respond to a given treatment, so another efficacy when accompanied by greater total of 591 relapses which would have treatment is better than nothing. But in safety. This would be reasonable, said been avoided with a proper comparator." reality the proper design is to select Garattini, if the safety issues at stake have A second symptom of illness is the use patients who are not sensitive to a given comparable clinical importance. But in of non-inferiority trials. In these trials, drug and to see if the new drug is such cases, it is better to test the investigators test the null hypothesis that a effective." In such cases it is appropriate to superiority of two treatments, rather than new drug is worse than an active control.
use a placebo. Furthermore, clinical trials use a placebo. Furthermore, clinical trials When they can reject the null hypothesis, are designed to establish beneficial effects are designed to establish beneficial effects ››
›› while the adverse reactions are more likely
authorisation by regulators.
to become evident under clinical practice.
Fourth, Garattini called the use of Before 1999 there was just one non- surrogate endpoints for drug approval inferiority trial a year. After 2007 that rose "unethical", especially when there are to more than 100, said Garattini, adding, already products approved after trials "The quality of these trials is usually not involving hard endpoints – for example, very good." Specifically, only 24 per cent new statins, anti-diabetics and anti- explained how the non-inferiority margin was selected. And there have been many So we need a change in European other criticisms in the literature.
legislation. Today a drug can be approved if Garattini's third symptom was the use of it shows quality, efficacy and safety. But we surrogate endpoints. These are thought to need to add three more words: "therapeutic be a simple way of looking at something added value", said Garattini. "If we don't important, he said. "But this is not always have that we will have continued use of the case. Drugs don't act on a single target, placebo and many useless me-too drugs".
they have lots of actions, and some may Another key part of the treatment must counteract their benefit on a surrogate be the "abolition of confidentiality".
endpoint." He gave a striking example, Reasons for secrecy are mostly put forward rimonabant, an anti-obesity drug that was by industry: to remunerate development accepted on the basis of a number of costs; to avoid disclosing data that could surrogate endpoints. But when studies were give competitors an advantage; and because done on "hard outcomes" such as death or any lowering of profits could in the end strokes or myocardial infarction there was Silvio Garattini – the sickness in clinical trials reduce investment in research. no difference from a placebo, and it had needs "quick-acting therapy". Against this, Garattini advanced the many side effects – which is why it was reasons for transparency. Most trials include comparison with existing drugs, no realistic public money, he noted, and patients take Similarly, the drug nesiritide was doses and treatment schedules, and part free of charge. More than that, in most approved in 2001 for heart failure on the inadequate toxicological testing. He European countries the drug market is basis of surrogate endpoints. Ten years later, complained that opposition to the use of prosperous because it is guaranteed by a large study published in the New England animals can hamper thorough animal national health services. "Secrecy may be Journal of Medicine found that drug did not justifiable in relation to the production of affect mortality or the need for hospital re- the active principles," he said, "but there is no real reason for confidentiality for preclinical and clinical findings." This sickness in clinical trials requires Garattini's final prescription is the "quick-acting therapy". First, we should promotion of independent randomised introduce the requirement of added value: clinical trials. He cited American professor "How can we stop these things happening," new drugs must add to what is already Marc Rodwin, who said that drug asked Garattini. The first step is to do systematic reviews or meta-analysis – to Next, we have to fix the misuse of compromises their impartial assessment of challenge the question asked in the study placebo. And here, said Garattini, we have a their drugs' benefits and risks, and that before doing it. The second way is to problem with the Helsinki Declaration on biased evaluation can corrupt public register protocols so observers can establish the ethics of human experimentation. The knowledge of drugs, leading to unsafe the relation between the protocol registered first part of Article 32, stating that placebo and/or ineffective drugs and hampering and what is later reported in a publication.
may be used where there is no proven rational prescribing by physicians. "It is a His third way is to give access to raw data – intervention, is very clear. The problem very strong statement," said Garattini. "But which is "unfortunately quite uncommon", comes in the second part, which has been it's realistic." Unfortunately, independent altered to say that placebo can be used when academically driven clinical trials have "too Also important, and we don't talk too it does not subject the patient to any risk of many bureaucratic requirements", which much about it, is that more preclinical work serious or irreversible harm – which is too have raised their costs and driven down is often needed, said Garattini, adding that open, he said, noting that the European their numbers.
many drugs go into clinical use without any clinical research network ECRIN has "We need therefore to introduce a new real evidence of efficacy in preclinical trials.
proposed amendments to the Declaration element in the clinical trials necessary to get "Most of the anti-tumour drugs that go to deleting "serious or irreversible".
approval for a new drug," concluded clinical trials today have relatively little Third, non-inferiority trials should not Garattini. "One proposal is that we need two effect in animals. We know that the rates of be considered an option by the scientific pivotal trials to support marketing response are insignificant when carried over community, which he said bears heavy authorisation: one sponsor-driven, one to the clinical level." Often there is no responsibility in this, and should not be independent. I hope such proposals will be confirmation in several animal species, no accepted as a basis for marketing supported in the future." Annual Conference 2013
Ethical dimensions of emerging
technologies
Like it or not, the new electronic landscape is taking shape in front of our eyes, and its potential effect on
the ethics of clinical trials sparked two days of intense and lively discussion at the annual conference, held
this year in Brussels. Newsletter Editor Peter Wrobel reports.

As EFGCP Chairman Ingrid Klingmannsaid when opening this year's annualconference, the Forum has a track recordof picking up topics not approached byanyone else in a similar way. In the past,that has made for landmark conferencesthat have led to major initiatives in thefield. So how would this year's meetingfare, with its concentration on technology'simpacts on clinical research? The topic drew around 100 people to the Belgian Academy of Sciences at theend of January. As Klingmann promised, itwas not supposed to be a "techy"conference, but it's also true that many oreven most of the delegates were unsure atthe outset about what the topic actuallymeant – in terms of both ethical andoperational considerations.
By the end, though, delegates had been presented with a rich array ofpossibilities, successes, failures andchallenges. Above all, as Hugh Davies fromthe NHS Health Research Authority,United Kingdom, said in his overallsumming up, the new electronic landscapeis here, a reality. The status quo is no longeran option. There are e-successes and e-failures, he said, and it's our job to researchit as a healthcare intervention. In this, wemay need to "restrain the enthusiast", hewarned – and that may not make uspopular.
The conference began with two sessions laying out the scope of e-health.
Also called, variously, mHealth, connectedhealth and cybermedicine, e-health focuseson the use of information andcommunications to inform decisions andactions by professional staff and by the EFGCP Chairman Ingrid Klingmann opens the annual conference. public at large.
Discussion was kicked off by Jeremy Wyatt, professor of health informatics at intervention; and the ways in which e- the University of Leeds, United Kingdom.
health might support clinical research. His Presentations given at the conference
He picked out three challenges for clinical last challenge, though, opened up entirely may be seen by delegates and EFGCP
research. The first two were perhaps more new prospects – citizen science, or patients members at www.efgcp.eu
expected: the need to study e-health as an using the new methods to conduct their ››
"persuasive" and control groups. Thereason, Wyatt speculated, might be that"serious people use other sources as well tohelp their decision-making".
So all is not necessarily rosy in this brave new world. Worryingly, the impactof telehealth on mortality in heart failureappears to vary enormously, with sometrials showing increased mortality. Clearly,more research is needed here. Wyattwarned, too, that the Internet had beenshown to involve a whole catalogue ofadverse effects over the years.
Moving to the challenge of using new technologies to support standard clinicalresearch, Wyatt picked out a range ofpossibilities. These included onlinerecruitment, online consent, emailed SMSreminders, remote monitoring, onlineadverse reaction reports, and so on. But hewarned, too, of potential confounders inusing e-health to capture data.
Changes on the way
His third challenge, health citizen science,graphically illustrated the scale of thechanges on the way. Over a quarter ofAmericans, he said, have tracked their ownhealth data online, and there are now a"huge number" of health social networkingsites. One of these, PatientsLikeMe, hasalready conducted a trial into the use oflithium in patients with ALS (motorneurone disease). The trial – "one of thefirst examples of a really genuine citizenstudy in which patients decided on anddesigned the study" – showed nodifference in progression, and promptedlater randomised clinical trials.
In the new world, said Wyatt, a group of people could meet up via FaceBook, Patient voice: Jan Geissler from EUPATI, the European Patients' Academy on Therapeutic decide on a question, define their own Innovation, lays out the challenges. eligibility criteria, randomise themselves,obtain drugs from online pharmacies, ›› own clinical research.
triage queries from deaf people turned out measure and record end-points, collaborate Wyatt took delegates through a variety to be time-consuming and marred by a on data analysis and publish online. Where of positive and less positive experiences high rate of false positives, and the project does that leave Good Clinical Practice, he with e-health. In one, patients in the was abandoned.
Netherlands had uploaded their own Among the range of interactive and Citizen science has "real pros and photographs of their own (non- plainer "vanilla" websites, Wyatt looked at cons", he said. On the plus side, it promises pigmented) skin conditions along with a trial of "persuasive technology" – using faster, wider reach in recruitment, filling in a form. A randomised trial then computers to change what we think and enthusiasm and real patient-related looked to see whether this reduced the do – in relation to organ transplant. One outcome measures. The results are likely to need for outpatient referrals. And indeed, it site sought to encourage people to sign up be rapid and focused, and to be adopted turned out that nearly a third of visits to to donate their organs; a second site was quickly. It is also less expensive, and can dermatology clinics could have been much plainer (and with an intentionally ask new questions. avoided. On the other hand, an NHS broken link). Yet the trial recorded the But there are some cons. These include, Direct attempt to use instant messaging to same sign-up rate for organ donation in the for example, reliability, bias and the risk of Will the regulation be fit for e-purpose?
proposed Regulation "doesn't actually tools such as iPhones. And would all the stop us doing the sorts of trials we are patients understand the need to capture all thinking about," he said. But on the other relevant safety data? (On the other hand, hand, "It could be a lot more supportive." safety reporting may actually be enhanced The proposed Regulation places a "huge if data are being entered electronically in emphasis" on pragmatic interpretation by regulators and ethics committees, he noted Then take the situation of an – and his real concern was that there is investigator sitting in Brussels, using the simply no consistent approach to Internet to recruit patients from all over pragmatism among regulators and ethics Europe via Skype. What approval is committees across Europe. needed, and where – where the Moving to detail, Sykes identified investigator is sitting, or where the potential problems with just about every patients are? "Europe is not ready yet for fundamental aspect of a clinical trial – pan-European approval," he said.
starting with investigators and subjects. If, Sykes referred to Pfizer's US-based for example, treating physicians are more virtual trial. The company considered closely involved with a trial (by taking holding it in Europe, but backed off. "One blood pressure readings and uploading regulator said we couldn't do it because them into a trial database), have they now informed consent needs to be done as become investigators and will they now all close to face-to-face as possible," he said.
He acknowledged that doing consent by Pragmatism would – or should – suggest Skype, for example, might not reveal any Concerns: Pfizer's Nick Sykes expressed no, but non-pragmatic views might prevail.
off-camera coercion. There are potential worries about the lack of a consistent Likewise, what about trials that workarounds, such as involving the approach to pragmatism across Europe. involve patients becoming more active, treating physician, but they are not doing their own monitoring and without their own problems.
While the real world of research is uploading their own data? Or using After indicating other problematic accelerating the use of new technologies, Facebook for patients to run their own policy makers are finalising the details of trials? Would they start to be treated as requirements), Sykes put forward his the European Commission's proposed investigators? Would they need to see the solution. Rather than make wholesale Clinical Trial Regulation. That regulation protocol as well? Sykes queried whether changes to the proposal – there are too will come into effect towards the end of the current definition of a research many unknowns at the moment – he the current decade, and as Nick Sykes "subject" is fit for e-purpose. called for a provision for regular review to from Pfizer said, will have to support Sykes also wondered whether ensure that the Regulation continues to clinical research in Europe into the late reviewers might seek to limit the role of support new approaches to clinical trials.
2020s or even 2030s. Will it be fit for patients on the grounds that the data they The Commission was initially reluctant to purpose – for e-purpose, that is? contribute might be of variable reliability do this, but recently Sykes professed to Sykes was not sure. Certainly, the – or seek extensive validation for input having seen a "glimmer of hope".
contamination. But there is "real potential plenary sessions. the Internet. For Orri, the key issue is to for us the triallist community to engage Second, Michael Bretschneider from use e-health to enable what he calls the with patient-led studies to overcome some UCB Biosciences, Germany, asked how to "engaged patient" – one who takes an of these problems," said Wyatt, calling on prevent citizen scientists from doing harm active part in their health and in clinical clinical researchers to help people to with their own trials. One of the founding research. Hinting at the possibilities, he incorporate the literature and theory into principles of the Internet, said Wyatt, is talked about an app from Philips that uses their questions.
that we don't censor it: "We would have to a computer's webcam to image the colour In the short period for discussion, two argue quite hard and long to say we of a patient's face and, through that, to questions emerged. First, John Warden should stop patient-initiated studies." He determine pulse rate. Patients, he said, are from Hull York Medical School, United added, "We would arguably suggest doing lots of things online: "We want to Kingdom, raised concerns about obtaining monitoring and advice, but clearly those benefit from that, do it in a more organised consent online. It is right to raise this as an trials don't need to be registered and can't way, and do it in clinical trials." issue, said Wyatt, and the conference For physicians, e-health opens up the returned to the topic later several times, Next up was Miguel Orri from Pfizer, possibility of handing over the "heavy both in workshop discussion and in which has conducted clinical trials over lifting" to investigators in specialised trial ››
›› centres, leaving them time to provide
effective support. He even suggested full-time investigators, which would lead notjust to economies of scale but also moremeaningful and profitable work for theinvestigators.
The more you engage patients, said Orri, the more they are willing – and thebetter your data. And though there arerisks with electronic tools, there arebenefits as well: you know when data arefilled in, and the quality is better. "You alsoget real-time safety data – you don't haveto wait for the doctor to come back fortheir next visit, and then for the monitorto come in after that." As Pfizer sees it, the most annoying thing in trials is when patients drop out. Ithappens frequently, and it is expensive andbad for data. The hope here is thatengaged patients are more likely not todrop out.
Orri explained how in a trial on overactive bladders Pfizer recruited patientsover the Web, consented them remotely,then sent them a mobile phone and thestudy drug. It was, he said, the first USFDA-approved trial to be run completelyremotely.
"The only thing I regret is that I didn't write down the number of times I was told‘You can't do that'," said Orri. And heclaimed that doing informed consentremotely, aided by a video, written material Michael Bone, immediate past chair of the UK's Association of Research Ethics Committees, make and a test, can be a "vast improvement" ontraditional face-to-face approaches. he had to have a bone marrow transplant, Many doctors, too, use Wiki and YouTube. But the trial was not without its went on the Internet, learned about a new What Geissler called "Googled health" hurdles. Pfizer had a "good system" for drug coming up, and emailed a doctor in is a reality, with unblinding of randomised verifying the identity of patients, but they Germany. "Half an hour later I got a reply trials on the Internet a reality ten years ago.
found it off-putting. "We made the system and information about a new Phase 2 People don't want to wait until they die so complicated that we made it almost trial." Today that therapy is the gold before they find out which arm of a trial impossible for the patient to go in, and we standard for the condition.
they are on.
didn't recruit enough," he said. "We had Whatever reservations there might be "You can't keep a walled garden over 45,000 patients on the website, but about the Internet, life without it is far around medical information. You can't we only completed eighteen." from perfect. Geissler quoted figures ensure that only quality controlled showing that the average patient–doctor information gets on a website," said Patients – enabled or
consultation in Germany lasts just 9.1 Geissler. "The only way to deal with bad minutes. Combine that with the language information is to get good information barrier posed by medical and legal online." No, he said: the e-patient is Then it was time for the view from a terminology, and getting information to empowered, not overwhelmed. And the patient – delivered in gripping manner by patients becomes almost a "mission Jan Geissler, from Patvocates and EUPATI.
impossible". For Geissler, the Internet is the underutilised resource in healthcare.
"Usually I don't talk too much about In the second plenary session, myself, but I will today," he said. "The Doctors say their patients are not on delegates got down to some of the basics reason I am standing here today is because the Internet. But that's a myth, said of e-health in clinical trials: remote of the Internet." Geissler, citing a Eurobarometer study of recruitment of patients and remote Geissler has been an e-patient for 15 countries showing that almost all consenting, as well as a look at the twelve years, since he was diagnosed with patients have access to online information, infrastructure required in the new models. leukaemia. He described how he was told the elderly often via friends and relatives.
It began with remote recruitment, and make a charge for referring patients, but technologies might improve the consent will only refer if patients explicitly opt in to that service. Patients are referred to the The problems with the traditional sponsor blinded; if the sponsor wants the informed consent process are well known, patient, the information then goes and have been aired at previous EFGCP unblended to the trial investigator.
and other conferences. For Mascalzoni, the TrialReach faces ethical issues every idea of "dynamic consent" has a lot to offer.
day, said Graiver. These include the She described it as a range of approaches transparency of the business model – and IT tools put together in one making clear to patients the differences conceptual framework to enhance consent between a commercial and a non- and put the patient at the centre of decision commercial model. Other issues relate to control over data, reliability of the service, With dynamic consent, patients can and privacy.
determine their degree of control over "It's a delicate situation, interacting personal information and the use of samples over time. They can, for example, information going to sponsors and choose how much information they need.
investigators," admitted Graiver. "And we Mascalzoni talked about the model of do it for profit." He stressed that consent information "on demand", with TrialReach does not recruit patients, nor short, medium and full versions, enrol them. "We help connect patients with depending on the level of trust and the trials. If we got paid for enrolling patients individual's requirement for information.
that would be a little more tricky, ethically," "Different people want to know different things," she said. "That's a reality." The company neither gives medical Dynamic consent also allows patients advice nor endorses or recommends trials.
to set their own level of participation and It aims to provide clear information. "We communication preferences (such as never tell or even suggest to patients that frequency). A variety of aids can help to by participating in a trial they will get any overcome language barriers or problems benefit or receive any medication," said with people's capacity to absorb information. "The point is, really, we can TrialReach's experience with ethics do things the old way, but also use the new committees is "not always a happy one", channels to enhance participation and es his point in discussion. said Graiver, citing different responses from engagement." It's about helping to build a different ethics committees receiving consent culture "supported by all the a presentation by Pablo Graiver of the identical submissions. "In general there is means we can use".
possibilities and pitfalls that clearly raised some mistrust between traditional ethics Describing in detail a project involving many questions, even if there was no time committees and new technologies. And it's dynamic consent in South Tirol, immediately after his talk to discuss them.
mutual. We need more time to strengthen Mascalzoni stressed that IT "won't and Graiver represents TrialReach, a UK-based shouldn't" completely replace human for-profit company that makes its living by The company always advises sponsors contact. But the new model takes things finding patients for clinical trials.
to include information about specific further, allowing patients to change their payments, where they exist, "because the ideas over time, and re-consent if a study Inclusive or exclusive?
patient needs to know", he said. Most changes significantly. sponsors are happy to do this, but Importantly, the model seems to be For neither the first nor the last time in the ultimately it is up to them. However, some good for research, even though at the conference, Graiver addressed how ethics committees tell it not to mention any outset scientists had been concerned that inclusive (or exclusive) Internet-based allowing clickable options not to share services are. The reality, he said, is that To ethics committees that ask about data, for example, would lead to problems.
where the company operates, more than patients without Internet access, he The results from the South Tirol showed, 80 per cent of the population has some responds that some "won't be able to read for example, that 99 per cent of patients kind of connection to the Internet. But, he or buy a newspaper". Overregulation can were happy to share their data. added, the technologies should be a be as harmful as underregulation, he said.
In fact, the benefits for research seem complement to healthcare and not replace Patient rights must be safeguarded, but to be impressive. Online tools can be patients suffer from this "lengthy and designed to ensure conformity with legal The business model is straightforward: sometimes not very rational process".
and ethical requirements both globally and for the patients, everything is free. The Then it was the turn of Deborah nationally. Recruitment is easier and company charges sponsors to set up Mascalzoni from the Institute of Genetic cheaper. And greater accountability leads accounts and load up trials online. It will Medicine, Italy, to examine how new to better science, Mascalzoni said. How do ethics committees respond to semantics – data with meaning; integration quality in the new world. The morning dynamic consent? Favourably, she said, at with Web apps; BYOD – bring your own began with auditing and monitoring, least as far as the ethical board in her own device – people want to use their own introduced by Paul Strickland of Strickland region is concerned. She also cited the UK devices to connect to big systems; big data QA, United Kingdom. – "data warehouses", potential goldmines While stressing that electronic, remote, Revocation) toolset, saying that EnCoRe for researchers; mobility – access on the auditing will not necessarily replace accreditation leads to greater confidence move; and cloud computing.
face-to-face contact, Strickland saw on the part of ethics committees.
One key lesson is the need for new "ground-breaking" opportunities. He The session was wrapped up by Pascal standards so that new systems can run on envisaged auditors and monitors sitting in Ruyskart, head of IT at the European multiple platforms. The EORTC faced that their offices, accessing electronic medical Organisation for Research and Treatment challenge for images, for example by records remotely and determining whether of Cancer (EORTC), Belgium, who gave building a new imaging platform. there is a problem. "There are some an overview of the enabling technologies Opening up new data sources brings downsides, and it needs cautions, but the required for all these new clinical trial its own issues. These include not just the benefits could be absolutely huge," he said models, and an indication of some of the technical ability to handle a variety of file – including running statistical analysis on problems involved.
formats and to guarantee confidentiality, incoming data to spot trends that might The EORTC knows more than most but also ways of accessing anonymised not yet be a problem but which might about the new world of the Web, covering ("de-identified") patients if necessary. indicate issues in sites such as delays in as it does 180,000 databases, 650 studies entering data.
and 370 institutions using the same data- Intelligent data collection
Among his concerns, Strickland capture technologies – and all using one mentioned the "sixth sense" that auditors single system. Out of this experience, It is hard to predict where we will be in often feel they have that enables them to Ruyskart drew a number of conclusions, 2020, said Ruyskart, but when you look at pick up anomalies, though there is no both technical and policy-related.
what can be done, he suggested targeting science about it. Remote working might For Ruyskart, it all revolves around new data sources, building big data impede that sixth sense. It also tells you Web 3.0. If Web 1.0 was basically pages warehouses and adopting open standards.
nothing about the crucial interactions and links and Web 2.0 added forums and Combine these with Web 2.0 and 3.0 apps between investigators, study nurses and so social networking, Web 3.0 is another leap and cloud computing, and it should allow on – "all the people at the sharp end of forward. While it is not clear exactly what the transition from merely turning paper clinical trials making the whole thing come shape Web 3.0 will take, it will revolve records into electronic records, to around a number of key concepts. These intelligent electronic data collection.
On a more technical level, Strickland include: universality, the need to be able to When delegates reassembled on Day foresaw the need to ensure that access to run on any platform; accessibility (of data); Two, the focus switched to ensuring an electronic medical record is only to the From conference to…Vaudeville!
On the evening of 29 January, delegates
opportunity to network while finding out To celebrate its 20th anniversary, the were invited to take part in the Annual more about typical and cultural landmarks EFGCP was delighted to invite Conference social event – a very special of the hosting city. conference participants to a cocktailreception hosted by the City of Brussels atthe beautiful Town Hall on the famousGrand Place. The cocktails were precededby a privileged guided visit of thebuilding's historic rooms, which areusually not open to public. Participants then walked to dinner at the Vaudeville Theatre, located in thesumptuous Queen's Gallery. The elegantVaudeville Theatre has a legendary placein Brussels life and its collective memory.
It was inaugurated in 1884 and is nowlisted as a historic monument. In this artistic environment, dinner could only end on stage, with theapparition of a great birthday cakeapplauded by all. The show will now goon in 2014… Fanny Senez
E-care and research in war-torn Somalia
Latifa Ayada from Médecins SansFrontières (MSF), Luxembourg, enthralledthe conference with a gripping accountfrom one of the front lines of paediatriccare – war-torn Somalia. Ayada reportedon an observational study looking into theimpact of telemedicine on the quality ofcare.
The study took place in a 100-bed hospital in the Galdugud region of thecountry whose clinical staff generally hadpoor background education, coupled witha lack of continuing training and on-sitesupervision. Faced with this, MSF broughtin telemedicine to support clinical care. MSF started with paediatric care, as this was the area with the highestmortality in the hospital. In practice, thatmeant a mobile camera device and amicrophone in the hospital, connected toa computer in Nairobi, in neighbouringKenya, staffed by a senior paediatrician.
Latifa Ayada (right) had the conference's The idea, said Ayada, was to "export full attention with an enthralling expertise, not experts".
presentation on telemedicine and The results from the trial cover around paediatric care in Somalia. 4,000 admissions, of which 9 per centwere referred to telemedicine. In 64 per Telemedicine, said Ayada, did not just cent of cases this resulted in significant improve the quality of clinical care, it also changes to case management – and the enhanced the clinical capacity of the children in 25 per cent of the referred Somali doctors. And it brought a sense of cases had life-threatening conditions solidarity and proximity with distant missed by the Somali doctors. Overall there was a 30 per cent reduction in It was, said Hugh Davies, a brilliant adverse outcomes.
presentation. He commented that large A striking observation was that by the numbers of enthusiasts in the developed end of a year of telemedicine, only 20 per world are developing expensive gadgets cent of convulsions cases, for example, for the "worried well", so he was delighted to see MSF using telemedicine in this way.
appropriate record, not a password that Clearly, an entirely "virtual" study – pressure readings but the date and time gives access to all a patient's data.
such as that described by Miguel Orri from when taken and recorded. For an auditor, How would risk-adapted monitoring Pfizer earlier in the conference – can work.
information indicating a delay between – the current buzzword – integrate with Strickland noted that most of the concern making readings and entering them might the new approaches? The crucial thing, seemed to be coming from the quality raise a number of questions. said Strickland, is to identify at the outset assurance community, rather than from the Metrics don't tell you everything, and – when the concepts and protocols are regulators. What is important is not so Strickland emphasised that you still have being defined – the data that are critical to much the technology, but how the to find out what's going on. At their best, the study. Much will depend on the technology is used.
metrics can suggest to auditors where they attitude of the regulators. On a positive One area with considerable potential is should be looking. But when safety is one note, the UK's MHRA says it is the enhanced use of metrics. Metrics, of of the main criteria of a study it is not good conceivable that there will even be studies course, are not new, but Strickland thought enough to look at individual readings: "In where there is no on-site monitoring, that we could learn more about what's most cases there is no alternative to reading though that will depend on the level of actually happening. Electronic records will the whole record," said Strickland, warning tell you, for example, not just blood against a "check-list" mentality.
Outside old, inside state of the art: the Belgian Academy of Sciences, the venue for the EFGCP's 20th anniversary conference. Like other speakers, Strickland stressed with controls so that if something goes optimists who might run away with the that new technologies don't alter the basic wrong we learn about it in real time, and idea that the Internet will solve everything.
principles of good practice. Above all, not at the end of the trial." Yes, parents can find their way onto the "Consider what you are doing before you The ability to monitor large amounts of Internet and lay their hands on the latest do it…time to think saves time later on." data electronically will have spin-off academic papers, but these are likely to be advantages for ethical behaviour. Most true in English. And despite what they say, most Risks of misconduct?
misconduct is about bad decisions, not bad GPs in Germany, for example, do not read people. People make a mistake, then cover English (even though they say they do). So Are fraud and misconduct more likely to it up. "If we tell people we are monitoring today's patients may indeed be better ››emerge in the virtual world – or will the
patterns, that in itself is protective," said informed than their doctor – but still fall new technologies make it easier to detect Widler. "Knowledge about oversight drives down at the communications barrier.
them? That was the question addressed by Beat Widler, a clinical QA and risk In the end, we will have to re-invent the management expert from Switzerland.
way we monitor and audit, digging at data Widler identified as a key problem the that otherwise we cannot obtain. And The final presentation at the conference absence of face-to-face communication.
critical to the successful deployment of the looked to the next generation. Are young There is plenty of research, he said, to show new technologies will be the sharing of people "digital natives" born into the that people are quite prepared to cheat a QRM data from different trials. Virtual is Internet, such that they will take easily to machine or even a person with whom they not necessarily riskier, said Widler, but with health interventions online? Or to put it communicate remotely, but not a person a caveat: as long as we do not forget the another way, can we confidently expect that sitting in front of them.
human factor. We will still need inves- the figure of 80 per cent of people using Who would start cheating in a trial? To tigators, auditors and monitors…people on the Internet will inevitably increase as the the old list of usual suspects – investigators, the ground. But we will also have real new generations replace the old? CROs, sponsors – Widler added the new opportunities provided that we start sharing In the event, the talk by Ellen J.
possibility of the cheating patient. Patients, our tools and our best practices.
Helsper, from the London School of he said, might have more incentive to Economics and Political Science, United misbehave, especially in countries where Kingdom, will not have encouraged anyone access to clinical treatment is not taken for with the fond hope that things are bound granted. "As a patient I might have a vested For Klaus Rose of Klausrose Consulting, to get better. Basing herself on a raft of interest to stay in the trial, so I won't, for Switzerland, a major advantage of the new research, Helsper called the idea of the example, say I have chest pain, because I technologies is that they help parents of digital native "a myth". Yes, if you want to know I will be dropped out of the trial." children with rare diseases to get together.
reach children you can probably reach them And how can we be sure that the Rose has not only had a long career in the online. But that is not true for all children consenting person is really the subject pharmaceutical industry, he is also the everywhere, and national differences are entering the trial? parent of a child with Sturge Weber On the other hand, technologies can syndrome, a very rare condition involving We think children are confident online, help reduce the risk of misconduct, and capillary malformations of skin and the said Helsper, but where the Internet make it easier to detect. For Widler, the coatings of the brain and eyes.
becomes complicated for adults, it tends to opportunities revolve around the concept The only treatment on offer is for the get complicated for children as well. Only of "quality by design" and the use of quality symptoms, which vary greatly from child half of young people know how to change risk management technologies. The to child. But at least now, with email and their privacy settings, for example. And important thing is to be much clearer about global communication, parents can find Helsper said it was clear from the research what really matters, and monitor that each other and get together to talk. More that those children who are most vulnerable closely. "We don't need to get everything than this, they can take part in the scientific offline are the most likely to have low levels right, but we need to agree what is a of skill online. Even among young people, tolerable error." Immediacy can help, too, But Rose also had a note of caution for those who are disadvantaged are less likely EFGCP Annual Conference 2013
In depth: workshop
reports
The heart of any EFGCP Annual Conference is to be found in its
workshops, where delegates can get to grips with issues in depth. This

year eight workshops dealt with issues as varied as the difference
between traditional and Internet-based research, and how to really

to be Internet users.
involve the public in e-research.
This brought Helsper to the concept of duty of care in public health. For a largesection of the population there is seamlessintegration between life offline and online:for them the Internet is the first port of callwhen they want health information. Butthis is not true for everyone, especiallypeople with low incomes and theunemployed. In designing services predominantly for online delivery we might be missing out onthose most vulnerable, she warned. Forcingservices online does not mean that thosewho need them most will find them – andwhen they do access the platform thevulnerable get a lot less from it.
More broadly, Hugh Davies noted in his summing up that there were manyissues on which there was no consensus.
That keeps ethicists in business, he said, andhe is one himself. But more seriously hecalled for continuing open discussion, Workshop 1: Traditional and Internet
to novel transactions, including how we rather than argument and disagreement. research: are the ethical issues
identify, control and store data, and better We need to consider the views of those different? Chair: Heather Sampson,
understanding of risks and benefits. who actually participate in research, and Toronto East General Hospital,
Are the risks the same, or is it just collect, learn from and disseminate good perception of the risk? We need to practice. Read and learn, he said; use With the Internet affecting almost all kinds understand what those new risks are and guidance and codes of practice; seek of research, what happens to the ethical catalogue them. The overall feeling of the evidence; and marshal the moral arguments obligations of researchers? Rapporteur Effy workshop was that we need practical with care. Start with "I", but finish with Vayena, Institute of Biomedical Ethics, applications and best practice guidelines to University of Zurich, Switzerland, said that address the new risks and new issues, For Davies, the message from all the while there was no absolute consensus, the utilising the new technologies.
workshops was the centrality of trust, workshop tended to think that the ethical though it is very difficult to measure.
principles remain the same. But there are Workshop 2: Recruitment and new
"Given the power of modern computing to some new ethical considerations, and we technologies. Chair: Bobby James,
collect and link data, the inevitable distance need to find new ways of dealing with them in e-research between researcher and – supported by a healthy scepticism about Patients increasingly expect to be able to find participant and evident differing views, the how to deal with the novel. information about trials online, outside of trust of public, patients and patient groups Discussion ranged far and wide, taking the traditional dialogue they would have is going to be vital," he said. in the issue of trust –what it is, how to with their doctor, said rapporteur Denis Trust is easily lost and hard won, maintain it, what it means in the world of Costello from EURORDIS, Spain. So the warned Davies. And if they lose it, e- big data – and the (to many unfamiliar) workshop started from the paradigm that researchers will find their work, and any concept of the "e-me", the way we are when engagement is key, and that unless possible advances from it, seriously we go online. ("Most of us now like the technology solves a real problem it's term," noted Vayena.) People have to adapt "nothing but a gadget". "We dwelt a lot on the future," said information sheet and forgo the interview.
exceptions so far – the UK NHS has used Costello. Workshop delegates felt that in Many preferred the option of an e- one system, for example.
this future GPs would be more involved in information sheet plus a paper version There was much discussion about referring patients. That in turn needs trust during the interview section – but it was patients directly providing the data, noted between GPs and primary investigators, not a really clear view, said Fortwengel.
rapporteur Josef Glasa, Slovak Medical also raising questions about how the University, Slovakia. This development is regulatory framework might look when we Workshop 4: Privacy, confidentiality
seen as useful and promising, despite issues are asking GPs to play such a role.
electronic
of reliability and privacy. But we need to There was much discussion about the preserve face-to-face interaction as well. websites and platforms that exist to Michael Bone, Consultant Physician,
The EFGCP must be vigilant, and facilitate recruitment, and whether they are involve itself as much as possible in patient-friendly. The Internet website Some workshop delegates were surprised initiatives to harmonise, integrate and clinicaltrials.gov, said Costello, is clearly not, that TrialReach had been invited to present develop standards. There should be no prompting an interchange about the relative in the morning (see page 15), given the compromises on quality. benefits of public solutions (slow) and ethos of the EFGCP, said rapporteur Petra Some criticised ethics committees for private ones (quicker, but with concerns Knupfer, Landesärztekammer Baden- being too rigid, demanding and variable – Württemberg, Germany. It is not acceptable they should "adapt to the e-trend", be on comment from the floor: every study to encourage patients by promising them the Internet, accept e-submissions and so should have a website that explains the trial payments for participation, she said. on. Glasa noted "not many voices" from to patients.
More widely, data security in most ethics committees to counterbalance the clinical research is "hackable". What we Workshop 3: Consent and new
need is anonymisation, which is not the One clear opportunity is in rare technologies. Chair: Heather Draper,
same as coding. In this regard, the first line diseases. Where trials need many centres University of Birmingham, United
of defence is not coding but the firewall, worldwide, the Internet might enable which should only allow logging in from things that were impossible before. Other The workshop started with a case study on specified IP addresses, not from home or opportunities include improving the a patient information sheet e-form from elsewhere. Physicians should only be able process of informed consent by e-tools that Birmingham that used a three-level to access their own patients. And, thought approach, from simple to detailed, leaving the workshop, the Cloud is not data secure.
it to patients to decide which level to use.
Data warehousing, mining, fusion and Workshop 6: Preparing for the
In the event, said rapporteur Gerhard future: training needs analysis:
Fortwengel, of the University for Applied information aggregated from multiple researchers and research ethics
Sciences and Arts, Hanover, Germany, very sources, and have a negative impact on committees and reviewers. Chair:
few went to the detailed level, and users privacy. Subjects rarely know what Clinical
spent an average of 57 seconds accessing company has their information or how it information. Almost 60 per cent accessed will be used. Yet it seems that patients are Center – CRP Santé, Luxembourg
no information but still expressed an often less concerned on privacy than are the The workshop started with three questions: interest in taking part. Oddly, ethics committees, and that the least What training needs can we identify for the concerned are academic researchers.
future environment? What are the priorities understanding from those who didn't read Is it a moral imperative to share your for training in emerging e-clinical the patient information as from those who data? The workshop preferred individual technologies? And how should it be rights above social need: patients have a So should participants be allowed to right to privacy and not to share. But they Rapporteur Gerald van Roey from the choose not to get information before have a right to have their data exploited.
European Centre for Clinical Research consenting? Most at the workshop felt it is One conclusion is that we must be Training, Belgium, said the group quickly up to the patient, and a matter of trust transparent with patients and tell them it is came back to the results of the EFGCP's between patient and doctor. Others said very difficult to ensure 100 per cent 2011 conference on training: no one researchers are entitled to have informed security. But if we are too focused on should have to do the same training twice patients – one researcher would exclude privacy we will just block research.
– we should either accept each other's patients who weren't informed.
training, or train at a pan-European level "Verbal information is important: this Workshop 5: Conducting clinical
(though adapted to uneven national levels ran like a red line through the whole trials on the Internet. Chair: Ingrid
discussion," said Fortwengel, stressing the Klingmann, Pharmaplex, Belgium
Investigators, study nurses, pharmacists importance of face-to-face discussion with Clinical trials with strong e-tools are and monitors should be fully trained in a doctor. Ethics committees should already under way, but there are still no what new systems might mean for a study.
probably give greater emphasis to the standards for electronic patient records in Patients, too: we cannot rule technophobic consent interview than to the written Europe, despite progress with interfaces patients out of future trials. All training information, thought the group. and harmonisation. Healthcare providers should recognise that some people are We cannot rely only on an e- are still reluctant, with only a few resistant to new IT.
nationally or internationally, with a basicset and add-ons, enhanced by continuoustraining, and requirements for periodiccourses. It should start face-to-face, usinge-learning modules as refreshers or add-ons. Records should show on a specificlevel the training someone has taken,especially on e-tools.
Who will pay for training? Hospitals and ethics committees often lack thebudget. Industry would like to pay for goodtrainers, but as yet there is nowhere forindustry to fund this kind of training. A final recommendation was that ethics committees might soon need an IT expertjust to advise on how these tools affectclinical studies.
Workshop 7: How should ethics
committees review e-research? A
discussion using an example of e-

distressing stories. been classified, and the community has research, Sharptalk. Chair: Tobit
Whether researchers and research been positive. Amy Carton stressed that this Emmens, Exeter Medical School,
subjects participating in Internet discussions was not an NHS cost-cutting exercise.
United Kingdom
need added protection will depend on the "We're just looking to accelerate cancer The workshop examined experience from end-of-study arrangements and on the research," she said. a UK project called Sharptalk looking at study risk. But in the end it comes down to Carton's presentation of the project discussion groups for young people who what is practical: if someone posts on the generated many questions from the self-harm, which received ethics approval Internet that they will self-harm, what can workshop, said rapporteur Maja Conkic the second time round, after changes in Advancement of Clinical Research of An important message was do not Workshop 8: REALLY involving the
Serbia. These covered: the idea of the public assume that the ethics committee will know public in research using new
as co-producers of science; opportunities to everything. Healthcare for young people technologies: Citizen Science. Chair:
extend citizen science to other countries; can be very different from adult healthcare Amy Carton, Cancer Research UK
validating and publishing the associated and may require different research. So, Discussion began with a report on a project evidence; and incorporation into current make sure you represent the voice of those called Citizen Science. Still in its research ethical processes.
involved – "lived experience" as rapporteur phase, the project aims to engage the public "Who should have access to the data Hugh Davies from the UK Health Research in academic research – in this case, the outputs?" asked Conkic. "Should it be Authority relayed it. It helps to give log-ons analysis of tissue slides. published?" There were also concerns about to ethics committee members so they can Cancer research generates immense commercialisation and privacy. And see for themselves what the e-research numbers of slides to be analysed. Current informed consent procedures might need algorithms are not good enough for Among the issues considered was computers to do this, so we need human The workshop reacted positively, remote consent. Not only are there different intuition and the human eye. But with concluding that citizen scientists could run national laws relating to consenting pathologists overwhelmed by the amount and control both data analysis and data children, but also possible differences of data it can take months for these slides to collection. There was talk of broadening between what is legal and what is ethical.
be evaluated.
out from cancer to cardiovascular disease A key issue was deception online: In the project, a cooperation between and endocrinology. Internet research and deception don't mix.
the Citizen Science Alliance and Cancer "This is a world first," said Carton, "and Deception is hard to guard against because Research UK, a team of scientists and we didn't start with an evidence base." That debriefing is not easy online, so if the developers created a Web interface for the prompted Jeremy Wyatt, from the scientific validity or safety could be public to analyse real-life cancer data, University of Leeds, UK, to observe the jeopardised by subjects who mislead, then scoring slides for the intensity and amount need to understand what brings Internet research is probably not of staining. The hypothesis being tested is participants in and what helps them to appropriate. Ethical considerations in trials that citizen scientists pathology scoring is make informed judgements or provide data.
such as Sharptalk might suggest the need as accurate as scoring by pathologists. He identified a "real opportunity" for to provide care for the researchers So far more than 60,000 people have research, including randomised trials, on themselves, who were hearing, remotely, visited the site, and half million images have the methods of citizen science. The EFGCP News
The EFGCP Board
The EFGCP News is an open forum for
Ingrid Klingmann, Chairman of the Anna Chioti, Board Member discussion and information on practices
Board & Co-Chairman, EGAN-EFGCP and developments relating to Good
Patients' Roadmap to Treatment Nicky Dodsworth, Chairman, Education Clinical Practice. Comments, letters,
contributions and general input are
welcome.
Michael Bone, Vice-Chairman Jozef Glasa, Board Member Correspondence and items of interest Yves Geysels, Treasurer & Membership Laurence Hugonot, Board Member & should be addressed to Co-Chairman, Geriatric Medicines The Editor: Peter Wrobel
Clarity in Science Communication Florian von Raison, Secretary & Co- 11 Fulready Road Chairman, Geriatric Medicines Working Fabien Peuvrelle, Board Member London E10 6DT, UK Tel +44 780 317 6319 Ysbrand Poortman, Board Member, Fax +44 870 130 5680 Hugh Davies, Ethics Officer & Chairman, Patients' Rights & Duties Officer & Co- Ethics Working Party Chairman, EGAN-EFGCP Patients' Roadmap to Treatment Working Party Copyright: EFGCP 2013 All rights
Olga Kubar, Education Officer reserved. No part of this publication may Klaus Rose, Chairman, Children's be copied, transmitted or reproduced in Helen Cadiou, Board Member Medicines Working Party any way without the written permission Alfredo Cesario, Board Member Paul Strickland, Chairman, Audit Disclaimer: While the Editor and EFGCP
Kim Champion, Board Member try to ensure the accuracy of information Gerald Van Roey, Board Member presented here, no responsibility can be accepted for subsequent use of the information. The views expressed here are those of individuals and not The EFGCP acknowledges the support of its Corporate & Institutional Members:
necessarily those of the organisations by which they are employed. Corporate Silver Members
The EFGCP Secretariat
Fanny Senez, Chief Operating Officer Ingrid Heyne, Project Coordinator and EUPATI Network Manager Association of ResearchEthics Committees Pascale Leblon, Communication and ACRP Belgian Chapter Membership Coordinator EFGCP Secretariat Square de Meeûs Rue de l'Industrie, 4 BE-1000 Brussels, Belgium

Source: http://www.efgcp.eu/Downloads/EFGCP%20News%20Summer%202013%20F.pdf

pafmj.org2

Original Article Effect of Pioglitazone HDL Levels of Type-2 Diabetics Pak Armed Forces Med J 2016; 66(2):212-15 EFFECT OF PIOGLITAZONE ON SERUM HIGH DENSITY LIPOPROTEIN (HDL) LEVELS OF TYPE-2 DIABETICS Muhammad Zohaib Iqbal, Raheel Iftikhar*, Khurshid Muhammad Combined Military Hospital Multan Pakistan, *Pakistan Armed Forces Base Samunigli Quetta Pakistan

tdi.dartmouth.edu

Annals of Internal Medicine The Effectiveness of a Primer to Help People Understand RiskTwo Randomized Trials in Distinct Populations Steven Woloshin, MD, MS; Lisa M. Schwartz, MD, MS; and H. Gilbert Welch, MD, MPH Background: People need basic data interpretation skills to under- point validated scores (interest and confidence in interpreting med-