IFAPP NEWS
Int J Pharm Med 2003; 17 (2): 79-97 1364-9027/03/0002-0079/$30.00/0 © Adis Data Information BV 2003. All rights reserved.
President’s Letter Dear Presidents, Dear IFAPP delegates, This message will focus on two issues: the 6th EMEA/IFAPP Conference, and the 13th International Conference in Pharmaceutical Medicine. As you may have heard, the EMEA/IFAPP conference was a success: we sold out all places! I am grateful to you for supporting this event: indeed having a success is useful to IFAPP for several reasons. First, our scientific reputation is growing higher and higher: EMEA and other bodies identify in IFAPP an important scientific partner; and they will be pleased to jointly organise other events. Secondly, our finances have a significant benefit from this success, and we can invest our money in important activities (such as the upgrading of the website, the educational grants, the inspections to the postgraduate courses in pharmaceutical medicine, and so on). I am also pleased of this success, because we had delegates from 18 countries: 13 in Europe (Austria, Belgium, Croatia, France, Germany, Greece, Ireland, Iceland, Italy, Netherlands, UK, Sweden, Switzerland) and five outside Europe (Canada, USA, Argentina, Japan, Israel). This means
that somebody in these countries will talk about the merits of IFAPP. A report of the conference appears in this issue of IFAPP News. The work to prepare a successful 13th International Conference in Pharmaceutical Medicine is in progress, and from the meeting of the scientific committee in Geneva on 2 April, it is hoped now to finalise the programme. It is also hoped that the second announcement for the conference will appear in September. As usual, finances are under rigid control, and limited funds are available to invite speakers from Regulatory Agencies and from Academia. In this respect, let me make to all of you a proposal; that your National Association supports one speaker from your country. By doing so, you’ll get two important results: to consolidate a good scientific relationship with your guest speaker, and to help the finance of the Conference. Try to consider this one as an opportunity! Best personal regards, Domenico Criscuolo
News From Member Associations France (AMIPS) At the end of the year 2002, we switched from AMIP (Association of Pharmaceutical Physicians) to AMIPS (Association of Physicians for Health Products). This change aims to broaden the scope of our activities and to increase our membership. The new Association was announced on the occasion of our 30th anniversary.
This was also an opportunity to release a special issue of our Journal, AMIPS-Info. This issue extended to 160 pages, thanks to our Editorial Advisory Board recently set up under the presidency of Professor Huriet. Our Spring Annual Meeting will take place on the 13th of May. We have taken advantage of this unusual date to initiate a
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new formula of afternoon workshops. These sessions will be based on selected communications on the general theme of ‘innovative logistics and methodologies in health products’ investigations’. A new database has been set up by a group conducted by Dr Agnès Bouvet and has dramatically improved our internal administrative workload. Dr Marc Pierredon, Delegate to IFAPP
The Quality Assurance group will have the annual meeting in June, with a course on Good Laboratory Practice (GLP), and then plenary sessions on GLP and Good Clinical Practice (GCP); the Biotechnology group, in collaboration with the University of Milan, has planned monthly Seminars in Chemotherapy, mainly addressed to University students and researchers; the Biometrics group has in progress regular meetings on selected topics. To conclude, let me say that SSFA is maintaining its mandate to be recognised as a Scientific Association providing a rich variety of training and scientific opportunities. Dr Domenico Criscuolo, President, IFAPP
Italy (SSFA) The Italian Association, SSFA, is focusing its attention mainly on the training of professionals who join the pharmaceutical industry, and who later move on to different responsibilities. The educational programme proposed by SSFA is of a high level, regularly updated and enriched with new proposals. For instance, in the year 2003 we will launch two new courses, which will complete and strengthen those already available. Here is the summary of courses available: • Basic course for Clinical Research Associates (CRAs): this is a 5-day residential course that provides basic information for CRAs. • Advanced Course on Clinical Development: this is a 3-day course, catering for people with some years of experience in the industry, and wishing to have more knowledge of the system. • Basic Course in Project Management: this is a 3-day course, in collaboration with Bocconi Business School, aimed at giving basic information about project and people management. • Advanced Course in Project Management: this is a 2-day course, in collaboration with Bocconi Business School, aimed at providing a better insight on special issues (new). • Course on Leadership: this is a 3-day course, in collaboration with Bocconi Business School, and will give pragmatic suggestions on how to deal with critical situations when a friendly but rigid approach is required, both within the company and with external people (new). Additional training has started with some research institutions, both in Milan and Rome, to teach young physicians on the key issues to becoming a Good Clinical Investigator. Finally, thanks to a new law, since last year also in Italy, general practitioners (GPs) can join Phase III and IV clinical trials: several training sessions have been organised, in order to give GPs never previously exposed to our scenario the basics of Clinical Development. All these activities are being organised by the Pharmaceutical Medicine Working Group of SSFA: other working groups are also active in meetings and symposia. © Adis Data Information BV 2003. All rights reserved.
USA (AAPP) The American Academy of Pharmaceutical Physicians (AAPP) Investigator Certification
On 26 October, 2002, the AAPP Board of Trustees approved the implementation of an AAPP certification programme for physician investigators. Each physician who successfully completes the exam will become a Certified Physician Investigator (CPI). The first test administration is targeted for November 2003, in conjunction with AAPP’s 10th Annual Meeting Celebration in Miami, Florida. More information on this most important programme is coming soon. Please check AAPP’s website at www.aapp.org for updates. Informed Consent Booklet
AAPP is proud to announce the publication of ‘So, You’re Considering Participating in a Clinical Trial…’. This booklet is designed to introduce people to the clinical trial process, to help them understand the important role that study participants play in that process and to help people know exactly what participation may involve – including the possible risks. This booklet is an excellent source of information for everyone, including families or friends, considering participating in a clinical trial – whether it is for therapeutic drugs, procedures or devices. More information on the booklet, including how to order free copies, can be found on AAPP’s website at www.aapp.org. Annual Meeting
AAPP is proud to announce its 10th Anniversary celebration being held 6–8 November 2003 in Miami, Florida. AAPP is the only US membership organisation solely comprising physicians who work in the discovery, development and safe use of medical products. AAPP, through its educational ofInt J Pharm Med 2003; 17 (2)
IFAPP News
ferings, including annual meetings, is dedicated to fostering the education and professional competence of all pharmaceutical medicine professions, assisting pharmaceutical physicians in maintaining and enhancing their skills and knowledge, and providing a forum for the exchange of information on current issues which impact on pharmaceutical medicine. AAPP’s 10th Annual Meeting, The New Climate of Drug Development, is a vital conference for all professionals involved in all aspects of drug development, clinical research, regulatory affairs, marketing, and risk management. For additional programme information, please visit www.aapp.org or contact Heidi Bergs, AAPP’s Education Programs Coordinator, at (919) 3551003 or
[email protected]. GCP Programme
AAPP’s Education Foundation held the first 2003 Good Clinical Practices (GCPs) Course for Industry-Sponsored Clinical Trials 8–9 February in Las Vegas, Nevada. The attendance for this seminar more than doubled from the first seminar held in 2002, and was an enormous success. The remaining dates and locations for 2003 are: 31 May–1 June in Montreal, Quebec; 13–14 September in Kansas City, Mis-
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souri; 8–9 November in Miami, Florida (in conjunction with AAPP’s 10th Annual Meeting); and 6–7 December in Atlanta, Georgia. All of the GCP seminars offer a maximum of 11 hours in category 1 CME credit toward the AMA Physicians’ Recognition Award. More information, including a detailed schedule and online registration form, can be found on our website at www.aapp.org.
Come Visit Us!
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AAPP will be exhibiting at three conferences in 2003: 5–9 April at the Association of Clinical Research Professionals (ACRP) Annual Meeting in Philadelphia, Pennsylvania (Booth #720); 31 May–3 June at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois (Booth #2824); 15–19 June at the Drug Information Association (DIA) Annual Meeting in San Antonio, Texas (Booth #1079). Dr Christopher Allen AAPP Vice President, International Relations President Elect IFAP
Sixth EMEA-IFAPP Conference ‘Working Together’. Meeting report: Biotech Products: Current Issues and Comparability Challenges of immunogenicity and comparability set biotechnology products apart from non-biotech medicines. This was recognised by Domenico Criscuolo, IFAPP President, who in opening the 6th EMEA-IFAPP Conference in London on 21 February, said that this was the EMEA and IFAPP ‘working together’ for all those involved in bringing biotech products to market, to help ensure such products are clinically useful, reliable, and well tolerated. Daniel Brasseur, CPMP Chairman, in his opening remarks, reminded the meeting that “we live in a world of risks and threats” and that balancing benefits and risks is sometimes difficult. In this new world of biotech, not all the answers are yet available and industry and regulators need to work together in collaboration and cooperation, defining new terms, such as ‘bio-similar’ and redefining old ones, like ‘generic’. © Adis Data Information BV 2003. All rights reserved.
Background For readers who may be less than familiar with IFAPP, the International Federation of Associations of Pharmaceutical Physicians represents 26 national Member Associations across five continents with some 6000 pharmaceutical physicians. IFAPP’s task is to represent its Member Associations to promote the role and education of pharmaceutical physicians working in pharmaceutical medicine. IFAPP recognises that the European Agency for the Evaluation of Medicinal Products (EMEA) has a significant standing in the worldwide context of regulatory agencies. Six years ago, IFAPP and the EMEA decided to put together an annual meeting on an appropriate scientific topic of mutual interest in order to share experiences. Biotechnology is new, opening up many opportunities. It has attracted considerable academic and pharmaceutical industry inInt J Pharm Med 2003; 17 (2)
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terest, with many of the small biotechnology companies suddenly finding themselves receiving major financial support from their bigger pharmaceutical counterparts. However, unlike the nonbiotech drugs with which we have become familiar, the biotech products being generated and put into commercial R&D pipelines have challenged both the scientist and regulator at nearly every stage of their progress. Not surprisingly, places for this meeting were at a premium. The capacity audience, of about 120 people, was gathered from 15 countries and spanned medical, scientific, commercial, and regulatory interests. Next year, early registration is recommended to avoid the unfortunate position of the organisers having to decline applicants!
Morning Session: Scientific Aspects – ‘The New Scenario of Biotech Products’ Chairs: Pekka Kurki (EMEA) and Jane Barrett (IFAPP) Jean-Hugh Trouvin (CPMP, BWP, Afssaps, France) set the scene by defining what we mean by a biotech product, as an r-DNA derived mixture of large and complex protein or glycoprotein isoforms. Unlike a non-biotech product, a biotech product is not a single entity. As a result, the manufacturing process both defines the product and is critical to the quality, safety and efficacy – all of which become intimately bound together. Process changes can occur in a number of situations: scale up of production, modification of the manufacturing process, and multi-site manufacturing. Purity and stability changes make it impossible to predict what is a minor or major change, and the analytical tools available have limitations. Interpreting the data is difficult, as Jean-Hugh demonstrated with examples, indeed “You cannot measure everything”. Production changes made at or after Phase I studies make matters even more difficult, especially to answer what seems to be a simple question: “Is the new product going to have the same efficacy and safety profile as the previous one?”. Orla Nolan (EMEA and IMB) tackled the regulatory problem of comparability, saying, “It is a matter of overlapping disciplines”. However, there is also a need to decide on common definitions of terms. For example, ‘product’ means different things in different specialties. Comparability programmes need to be an integral part of the manufacturing process – so that you can be assured that the product on the shelf is the same as that in the clinical trials. Moreover, it is not a matter of ticking boxes but building up a credible database. Assumptions cannot be made at any stage, and Orla gave the example of how impurities or new © Adis Data Information BV 2003. All rights reserved.
excipients can affect subtle changes in the product’s protein folding, with changes in efficacy. Whilst antibody production has limited animal testing in the past, humanised immune systems in mice opens up a new avenue for screening. Proteomics also offers advantages, somewhat offset by the time and cost to set up in each case and the large, complex data-sets produced. Clinical studies to establish comparability of products are, of course, definitive but time consuming, costly and not always ethically justifiable. Non-clinical technology is emerging that will be critical to the success of biotech products. Barbara van Zwieten-Boot (EMEA) looked at clinical implications within a regulatory framework. With a brief summary of the CPMP guidance available to date, we heard again the recurring theme of “what does similar mean?” when referring to biotech products, since “…at the moment it must be judged by regulators on a ‘case by case’ basis”. ‘Essentially similar’ is not a term that can be used here. The decision not to undertake clinical trials to establish the similarity of two products must be carefully justified. Surrogate endpoints may sit uneasily with regulators but might be very appropriate here, provided the relation to the clinical effect is known. Unless justified, efficacy must be demonstrated for all indications separately. Alternative manufacturing processes are a source of unease, especially in distinguishing products from the same manufacturer that are on the market at the same time. Post-marketing safety data may need to be ongoing to profile similar products. Cindy Wong (MPA) explored the minefield of immunogenicity and illustrated this with several examples, observing that “all biotechnology-derived proteins are (potentially) immunogenic”. This may translate to increased or decreased efficacy, hypersensitivity reactions, neutralising antibodies against the therapeutic protein or even cross-neutralisation of endogenous proteins, or autoimmunity. Immunogenicity is unpredictable but experience is being gained of the risk factors. Since the consequences of immunogenicity can be problematic and can only be clarified in clinical trials, it is not surprising that some promising products fall at the immunity hurdle early in human studies. Anthony Dayan, a ‘retired’ toxicologist and self-confessed “serial joiner of advisory committees”, gave a refreshingly iconoclastic review of non-clinical comparability testing. He challenged the readiness of investigators, manufacturers, and regulators to tackle the issues at hand. With a pocketful of suggestions but no remedies, Anthony set up a series of arguments based on Cochran’s postulates of ‘efficiency and efficacy’ to question the relevance of non-clinical testing, the cost, and the wastage of animals. Creeping acceptance can inappropriately establish some data as a requirement. Time can be lost and drug Int J Pharm Med 2003; 17 (2)
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wasted from the clinical development programme with the increasing requirements for pre-clinical toxicity testing. Regulatory agencies need to collaborate on their requirements. Otherwise, with an excessive burden of possibly irrelevant experiments and techniques of unproven value, comparability of biotech products is “a monster that can get out of control”. All is not so difficult. Jonathan James (European Team Physician, Eli Lilly) gave a detailed review of his own clinical development programme of activated protein C in moderating the outcomes of severe sepsis. Apart from needing to establish immunogenicity safety and problems in some countries, for example France, of using a protein as a placebo, he said that the clinical trial design to demonstrate safety and efficacy of a biotechnology product should not differ greatly from that of a small molecule to treat the same disease condition. Discussion
Question time raised some challenges for the panel: “Where does a company get advice to establish similarity of biotech products?” The response was that each case will be judged on its own merits and there will be some variation between regulatory groups. “Can a bio-generic exist?” “Probably not” was the answer. A similar product could be licensed, but extreme care needs to be taken with a biotech product copying a non-biotech in the same indication. Immunogenicity for the biotech may necessitate postmarketing safety surveillance. Afternoon Session: The International Dimension – ‘Comparability of Biotech Products from Different Manufactures’ Chairs: Gerfried Nell (IFAPP) and Jean-Hugh Trouvin (EMEA) Pierrette Zorzi-Morre (EMEA) emphasised that comparability should be a step-by-step approach. The manufacturer should provide assurances that an appropriate set of analytical methods have been selected and validated to assess comparability before and after change. Pierrette established a hierarchy of strategies related to impacts on the production process, batch consistency, stability etc. The ultimate aim is to establish the need, or otherwise, for bridging preclinical and clinical studies. The European Union (EU) guideline and the International Conference on Harmonisation (ICH) guideline on biotech comparability have some differences. The sign-off for the non-clinical and clinical expert input to the ICH guideline is anticipated in November 2003. © Adis Data Information BV 2003. All rights reserved.
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Mark Smith (Development Projects Manager, Eli Lilly) examined the issue of in vitro comparability. Key to this is the retention of a reference product (which should be well defined at a sub-molecular level, as well as its consistency and stability characteristics). A comparability strategy needs to be in place early in the R&D programme. Modifications to the production process should be expected to: improve yield, decrease variability, improve safety, or to increase volume to meet market needs. An alternative or additional manufacturing site is always a possibility. Having examined the design and performance of in vitro comparability programmes, Mark’s final message echoed that of all the previous speakers – that biologics often have ambiguities in their structure-activity relationship, and this relationship does not provide a confident link to efficacy or safety. Jay Siegel is a former Director in the FDA. He shared his experience of the problems of biotechnology comparability, giving several examples. “Difficulties exist in producing a consistent product”. Scale up of production and new manufacturing sites can easily introduce changes to a biotech product. Differences may have unknown clinical significance. “No amount of physicochemical testing can fully characterise a biological”. Many molecules will have multiple active regions, including the impurities. Changes at any step of manufacture, from the master cell bank protein to the end product (including its dedicated delivery device) pose potential or actual changes to the efficacy and safety in the patient. Even the glue in the syringe! It is not surprising, then, that US generic law does not apply to biologics. Yasuhiro Hashimoto (Medibic Inc, Japan) described the ‘big changes’ in his local market. The figures speak for themselves. Japan had ten university-orientated start-up biotech companies in 1998 (compared with 279 in the US). This grew to 333 in 2002, mainly due to a considerable government commitment, led by the Prime Minister. It required changes in the regulations to allow university professors to set up and run such companies and retain intellectual property. Today, Japan has world-leading, novel gene amplification methods. However, challenges remain; from the practical problem of finding research office space around busy centres of excellence, for example in Tokyo, to communicating Japanese biotech capabilities to the rest of the world. Watch this space!
Discussion
Again, questions to the panel were testing. The issue of changing the master cell bank seemed (by definition) to label the product as ‘not similar’ within the EU but not necessarily in the US. This may reflect different experiences between the regulatory groups and the definitions used. Int J Pharm Med 2003; 17 (2)
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A degree of inconsistency was injected when the issue of vaccines was raised. These products would seem to violate many of the rules for biotech products. Innovation is inevitable, and so what happens when a product is submitted for regulatory approval that is superior to its reference product? Will comparative clinical studies be inevitable? How could you name and brand such an innovation in order to distinguish it from its predecessor? How can a case-by-case approach be standardised by regulators? With the need for confidentiality, transparency of process may not be possible. All agreed that guidelines need to be developed for a case-by-case review process. Conclusion This was a well-attended, lively meeting of minds. All those in the room had a common interest – how to make and market
predicable biotech products with the minimum of fuss and the maximum of safety for the benefit of patients. Increasing the number and/or complexity of tests that can be done per seis not acceptable. It adds to the duration and costs of research without necessarily benefiting the ultimate target – the patient. More data does not necessarily mean better data. Jean-Hugh Trouvin concluded that we are all on a learning curve with biotechnology. Collaboration is needed between regulators and industry to ensure the right tools are used in the evaluation process.
Michael Atkins President Elect, The Royal Society of Medicine Section for Pharmaceutical Medicine and Research, London, UK
The Council For Education in Pharmaceutical Medicine (CEPM): Activities and Achievements 2001–2003 When the International Federation of Associations of Pharmaceutical Physicians (IFAPP) created the Council for Education in Pharmaceutical Medicine in 2001, the Council was given five major objectives: 1. To assist IFAPP’s national Member Associations to establish appropriate educational and training programmes in pharmaceutical medicine. 2. To support the development of structured continuing medical education (CME)/continuing professional development (CPD) programmes in pharmaceutical medicine. 3. To contribute to the harmonisation of the existing Postgraduate Courses in Pharmaceutical Medicine. 4. To promote the mutual recognition of equivalent educational qualifications and CME/CPD requirements between countries. 5. To stimulate the recognition of Pharmaceutical Medicine as a distinct medical specialty. How did the Council address these objectives? On Objective 1, the Council felt that a national Member Association who wanted to establish a training programme in their country would benefit from the existence of an elaborated version of the IFAPP Syllabus for Pharmaceutical Medicine. A small working group established for each of the 12 sections of the syllabus a list of ‘desirable’ topics, as well as a list of ‘essential’ topics. Essential topics are those subjects that must be covered in the educational © Adis Data Information BV 2003. All rights reserved.
programme to allow its accreditation by IFAPP. The two lists were integrated in a document issued by the CEPM on 28 January entitled ‘Programme for Education in Pharmaceutical Medicine’. This document is available on the IFAPP website in the CEPM section. Hard copies can be obtained upon request. On Objective 2, the Council is stimulating the establishment of structured CME/CPD programmes in all countries where postgraduate courses in pharmaceutical medicine exist. So far, only the UK and Belgium are running programmes where the participants have to keep a diary of the collected credits and where these diaries are reviewed at regular intervals by a central body. This system of structured CME/CPD programmes was set up by the Faculty of Pharmaceutical Medicine and adopted by the Belgian College of Pharmaceutical Medicine. Documentation on the method of follow-up of the diaries can be obtained upon request. On Objective 3 (the harmonisation of the postgraduate courses), the Council has worked in four phases: 1. The first phase consisted in the identification, on a worldwide basis, of the existing postgraduate courses in pharmaceutical medicine. 2. In the second phase, a questionnaire was developed and sent to the organisers of the various courses in order to collect details on the organisation of the courses, their content, the conditions Int J Pharm Med 2003; 17 (2)
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for admission and the techniques of examination of the candidates. 3. In the third phase, data were collected from 11 Universities in Europe and three in Central and South America and integrated in a database which is now available on the IFAPP website. 4. Phase four consisted in the drafting of a ‘Plan of Action’. As the 14 existing postgraduate courses were created in isolation (i.e. without the assistance of a central coordinating body, although on the basis of a common syllabus), variations in the content of the courses has to be expected. The Council felt that in order to detect important omissions or major deviations from the syllabus, visits to the sites of the courses were indispensable. Consequently, the Council established a list of evaluators (one for each course) who should examine the documentation on each postgraduate course, meet the Course Director and evaluate whether the content of the programme and the technique of examination of the students are of a standard allowing accreditation of the course by IFAPP and mutual recognition of the diplomas between Universities. The Council also established a list of facilitators (one for each course) who should be pharmaceutical physicians close to the course to be examined and whose task it will be to ‘facilitate’ the work of the evaluator by serving as an intermediary between the evaluator and the course organisers. Their names will be agreed between the Council and the local Member Association. The evaluators will be members of the Council, but belonging to another country than the facilitator (i.e. different from the country where the course to be examined is located). It was decided to initiate the process in Europe first. A letter was sent to the Presidents of the eight national Member Associations concerned (Belgium, France, Germany, Portugal, Spain, Sweden, Switzerland, UK) in order to inform them about the project and to request their support and assistance, as well as their approval of the names of the facilitators and evaluators selected for the course(s) on their territory. The ‘Plan of Action’ states that the document mentioned under ‘Objective 1’ (Programme for Education in Pharmaceutical Medicine) and the ‘template’ (see next paragraph) will be used to evaluate the adequacy of the content of the courses. Insufficiencies will be identified and should be corrected before accreditation by IFAPP can be considered. It was decided to use the postgraduate courses at the Universities of Surrey and Brussels to test the system during the second quarter of 2003 and to complete the review process in Europe by the end of 2004. Finally, the Council drafted a ‘template’ for the evaluation of the existing postgraduate courses leading to a diploma in pharmaceutical medicine. This template is now available and will be used by the evaluators to test the standards of the courses and examinations. The visits to the sites will also provide an oppor© Adis Data Information BV 2003. All rights reserved.
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tunity for keeping up to date the CEPM database on postgraduate courses in pharmaceutical medicine. All the activities described under Objectives 1–3 are expected to contribute to reaching Objectives 4 and 5. When the courses are harmonised, mutual recognition will hopefully be forthcoming. Further, the Council will favour the establishment of CME/CPD programmes as close as possible to that operating in the UK. There is no doubt that the existence of IFAPP accreditation and of mutual recognition, between Universities and IFAPP, of diplomas in pharmaceutical medicine, as well as that of structured CME/CPD programmes, will promote the recognition of pharmaceutical medicine as a distinct medical specialty in the countries concerned. To achieve all this, the Council will need the full support of the whole IFAPP organisation (i.e. its Executive Committee and its national Member Associations), but also the continued enthusiasm and dedication of the members of the Council. For further information, please contact: The IFAPP Secretariat: Attention: Mrs Caroline van Bruggen, Rendementsweg 24 E-I, NL-3641 SL Mijdrecht, The Netherlands. E-mail:
[email protected] The Chairman of the CEPM: Dr Herman Lahon, 1bis, Quai aux Fleurs, F-75004 Paris, France. E-mail:
[email protected] The IFAPP website: http://www.ifapp.org Members of the Council for Education in Pharmaceutical Medicine Dr Hector Arenoso, Argentina Dr Kurt Bestehorn, Germany Dr Rob Creek, Australia Dr Anthony Chan, Ireland Dr Fergal Donnelly, European Commission Dr Ebbe Englev, Denmark Dr Anthony Fox, USA Dr Luciano Fuccella, Italy Dr Stewart Geary, Japan Dr Charles Kim, Korea Dr Peter Kleist, Switzerland Dr Kees Kraaij, The Netherlands Prof. Pierre Lafolie, Sweden Dr Herman Lahon, Belgium Dr Juan Lahuerta, Spain Dr Ewa Lindenstroem, Denmark Dr Joâo Massud Filho, Brazil Dr Ahmad Atif Mirza, Pakistan Prof. Gerfried Nell, Austria Dr Ana Maria Nogueira, Portugal Dr Robert Paul, Finland Int J Pharm Med 2003; 17 (2)
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Prof. Peter Stonier, UK Dr Akiyoshi Uchiyama, Japan
Dr Daniel Vasmant, France Dr Paulus Wijanto, Indonesia
IFAPP Grants In the year 2002, the International Federation of Associations of Pharmaceutical Physicians (IFAPP) decided to award four grants of 5000 euros each to young pharmaceutical physicians who agreed to register on one of the Postgraduate Courses in Pharmaceutical Medicine and to obtain a diploma in this discipline. Two grants had to be allocated to pharmaceutical physicians originating from countries with a national Member Association of IFAPP and to two pharmaceutical physicians originating from countries where no such national association existed. This information was widely advertised inside and outside Europe. Candidates had to submit a dossier including a completed application form, a covering letter explaining their professional goals in pharmaceutical medicine and how a grant would enable them to achieve those, a detailed CV and certified copies of their major diplomas. IFAPP’s Executive Committee delegated to its Council for Education in Pharmaceutical Medicine (CEPM) the task of reviewing the dossiers submitted by the candidates and to make a recommendation to the Executive Committee. Sixteen submissions were received in total. Upon receipt of the recommendation of the CEPM, the Executive Committee decided to award the grants to the following pharmaceutical physicians: Dr John Lee, Swedish nationality, 35 years, medical degree obtained in 1993 from the Medical School at the Karolinska In-
stitute (Stockholm), joined the pharmaceutical industry in 1995, currently Global Drug Safety Physician at AstraZeneca (Sweden) since September 1999. Dr Tatyana Maltseva, Ukrainian nationality, 31 years, medical degree obtained in 1995 from the Ukrainian State Medical University (Kiev), specialist in dermato-venerology, joined the pharmaceutical industry in 1999, currently CRA at Quintiles since August 2002. Dr Tomas Skacel, Czech nationality, 33 years, medical degree obtained in 1995 from the Palacky University (Olomouc, Czech Republic), specialist is haemato-oncology, joined the pharmaceutical industry in 1998, currently Area Clinical Research Physician at Eli Lilly since January 2000. Dr Syed Tajamul Hussain, Pakistanee nationality, 39 years, medical degree obtained in 1987 from the University of Karachi (Pakistan), joined the pharmaceutical industry in 1995, currently Assistant Medical Director at Abbott Laboratories (Pakistan) since April 2001. We wish these successful candidates great success in their studies and a brilliant career in pharmaceutical medicine.
Dr Herman Lahon Chairman, CEPM
International Code of Ethical Conduct for Pharmaceutical Physicians First edition published April 2003 This code was written by Drs Alexander L. (Sander) Becker (Australia), Jane Barrett (UK) Johan De Botha (South Africa), Johan Brun (Sweden), David Cairds (Germany), Roberto Carlesi (Italy), Luis Collia (Argentina), Maqbool Jafary (Pakistan), Gerard Nahler (Austria), Antti Jekunen (Finland), Francis de © Adis Data Information BV 2003. All rights reserved.
Halleux (Belgium), Ludger Beuhrmann (Germany) and Alan Duton (USA).
Preamble Medical ethics have been governing human behaviour as far back as 460–357BC. However, as science becomes more innovaInt J Pharm Med 2003; 17 (2)
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tive and medical research processes more creative, the ethical boundaries that limited “what was considered possible” are now being challenged by scientific endeavour using rational justifications that often go beyond common sense. The revised Declaration of Helsinki, the EU Clinical Trial Directive, and the Washington Post ‘Body-hunters’ series from December 2000, are just a few of the controversial ‘ethical’ issues that inevitably opens the pharmaceutical industry to ever increasing public scrutiny. Dialogue amongst patients, investigators, institutions, sponsors and the media, – ‘60 minutes’ and ‘Larry King’ highlights the need for transparency and guidance on how pharmaceutical physicians as ‘the conscience and guardians’ of pharmaceutical ethics can proactively manage these situations responsibly, well before they become major issues. An International Working Party was established in September 2001 to advise the International Federation of Associations of Pharmaceutical Physicians (IFAPP) on how to manage this complex area. It recognised that there are ethical issues that are of particular relevance to pharmaceutical physicians and believes that it has a responsibility to define and publish standards to which pharmaceutical physicians and others can refer. This code deals principally with those ethical issues that might face a pharmaceutical physician, whether he or she is practising within a company, a contract research organisation, as an independent consultant, in an academic department, a regulatory authority or elsewhere, and seeks to offer guidance and support. It is intended to be a living document, to be regularly reviewed and updated as issues arise or are solved. There is a need for an International Ethics Network of Pharmaceutical Physicians working on such issues, taking into account the progress achieved within therapeutics, the work already achieved by others in the field of bio-ethics and the texts already published. Pharmaceutical physicians are essential members of the teams working throughout the life-cycle of a therapeutic intervention, from the discovery research phase, through pre-clinical and clinical testing, licensing, launching, post-marketing studies and surveillance, through to its eventual demise whether on grounds of relative safety and efficacy or commercial nonviability. Being members of a team, there is an understandable tendency for pharmaceutical physicians to develop a strong interest in an intervention with which they have had a long or close association. Despite this, pharmaceutical physicians should recognise their ethical responsibility and stand aside from product loyalty when assessing factors affecting the product itself. They must remain aware at all times that the ultimate interests of both patients and their own employers are best served by an objective scientific attitude. The IFAPP recognises that this may place a © Adis Data Information BV 2003. All rights reserved.
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practising pharmaceutical physician in a position, which demands considerable determination. Ethics plays a vital role in enabling pharmaceutical physicians to situate their professional lives with their personal, communal, philosophical and religious lives. All clinical development activities and medical support services must therefore be provided by appropriately trained individuals working to agreed standards in adequately staffed departments with clear responsibilities and the authority to take necessary decisions. Accreditation of pharmaceutical physicians is an essential element of the demonstration of appropriate training in pharmaceutical medicine. As in all branches of medicine, accreditation should not be seen as a single event but as subject to re-validation, as this becomes available. Further, medical ethics does not yet feature prominently in the syllabuses of all medical schools throughout the world, yet it is increasingly recognised as important. It follows that training in Ethics in Pharmaceutical Medicine is itself important for all pharmaceutical physicians, health professionals, research ethics committee members and others involved in the research and development of therapeutic agents. The IFAPP recommends that this should feature in the various training courses provided for individuals seeking recognition as pharmaceutical physicians. By this means, the achievement of professional excellence can be fostered and self-identity and professional aspirations supported. Pharmaceutical medicine is a discipline that involves the discovery, development, evaluation, registration, monitoring and ethical marketing of medicinal products, medical devices and diagnostics. However, the users of healthcare products are not necessarily aware of the costs and complexities involved in the development and registration of a therapeutic intervention, and of the issues possibly arising throughout its subsequent existence. Pharmaceutical physicians have a responsibility to raise awareness and understanding of the different pressures and constraints governing healthcare products. Member nations are invited to review this document, and provide feedback. Please address your comments to the Working Party: c/o IFAPP secretariat, Rendementsweg 24 E-I, 3641 SL Mijdrecht, The Netherlands. Tel: +31 297 285144; fax: +31 297 256046; e-mail:
[email protected]; website: www.ifapp.org.
The Code Explained This International Code of Ethical Conduct for pharmaceutical physicians has been drafted making the fundamental assumption that pharmaceutical medicine and pharmaceutical physicians across the globe embrace the following core values in the ethical discharge of their duties: the values of Duty of Care (Good Int J Pharm Med 2003; 17 (2)
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Clinical Practice), Competence and Diligence, Impartiality, Probity, and Integrity and Accountability in the Workplace. The Structure of the proposed Code names and introduces the Core Value, then lists specific areas of ethical concern for pharmaceutical physicians. The hope is that the Code, following worldwide consultation, will be both relevant and universal, and be adopted in most parts of the world. Similarly, it may stimulate those countries that have not yet adopted a Code of Ethical Conduct to consider such an approach. Only in this way can standards and values in pharmaceutical medicine become universally accepted. However, it would be presumptuous to believe that acceptance of this Code could supersede the national sovereignty rights of any nation; however, at best it could be highly influential, and a model worth considering. Duty of Care
Good Clinical Practice
Pharmaceutical physicians are required by the nature of their job to keep themselves abreast of scientific advances that will have a major impact on the development of the new medicines of the future. A registered medical practitioner with appropriate special training should be in overall control of any research involving human subjects. This must include training in medical ethics and up to date best practices. Specific areas of ethical concern for pharmaceutical physicians: • ensuring that they remain well informed about current scientific and medical knowledge in the areas of therapeutics in which they work; • maintaining the high standards required by national and international regulations; • assimilating constructive feedback from management, internal review committees, ethics committees and the regulatory authorities; • designing clinical research programmes and protocols in areas of medical need according to regulatory requirements, national and international codes of practice, and the declaration of Helsinki; • ensuring that they fulfil their obligations in clarifying, evaluating and reporting adverse events, whether they come from research protocols, spontaneous reports or as part of a formal surveillance programme; • ensuring that documents submitted to the regulatory authorities accurately reflect the data that have been gathered in the development process; © Adis Data Information BV 2003. All rights reserved.
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ensuring that relevant data are made available for publication and that articles submitted to journals accurately reflect the data on which they are based; passing of accurate and verifiable information to the company’s sales department; teaching, training, appraising and assessing of other members of the medical department. Medical Integrity
Research involving the use of people as study subjects may be justified under certain circumstances but only after careful consideration of the risks and benefits involved. The health and well being of each such study subject is of paramount importance and relegates all other considerations to being of lesser importance. People volunteering to be study subjects, both healthy volunteers and patient volunteers, are required to give written informed consent after receiving sufficient and properly witnessed explanations of any potential risks and benefits involved. Particular care must be shown when studies include patients who are not volunteers and cannot give consent for themselves, whether due to their age (children) or lack of capacity (the unconscious or mentally incompetent, for example). Financial compensation should be appropriate without constituting exploitation, coercion or bribery, and should have been discussed with the ethical review committee. Specific areas of guidance for pharmaceutical physicians: • clarifying whether or not the company will provide continuation of support and interventions once a patient’s involvement ends and the mechanism by which this will occur; • ensuring that in the provision of disease management packages any conflict between competing interests is minimised, for example where the treatment of choice may be a therapeutic agent produced by a competitor; • ensuring that the best interests of individual patients always prevail over those of the employer; • utilising individual clinical judgement over management guidelines where it can be demonstrated that an alternative course of action is more appropriate for an individual patient; • ensuring that information is provided in accordance with the principles of evidence-based medicine to optimise the acceptability of products for which they are responsible, but within appropriate clinical management guidelines; • resisting the use of therapeutic interventions outside of clinical management guidelines without conducting appropriate clinical trials and/or obtaining the necessary regulatory clearance; • reviewing local guidelines with regard to the payment of patients in clinical trials, and ensuring that local ethical committees/institutional review boards are informed and consulted; Int J Pharm Med 2003; 17 (2)
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ensuring that patients are not inappropriately induced to take part in clinical studies; respecting their duty of care regarding the use of unlicenced or unproven interventions, regardless of the source; assuming responsibility for any patients under their care, whilst the providers of the interventions carry responsibility for the quality of whatever they supply; ensuring that patient information leaflets are clear and can be understood by the end user.
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Competence and Diligence
providing research ethics committees with all relevant information to enable them to make a considered judgement on the ethics of any given research protocol; ensuring that payments for studies, details of the recipients, and potential conflicts of interest, are totally transparent and revealed to research ethics committees; ensuring that policies that safeguard the interests of research subjects, in terms of indemnity and compensation, are clearly in place; remembering their duty to apply standards of scientific rigour and provision of quality information wherever they may be working, be it in research, production or marketing.
General Issues in Clinical Research Studies of Human Pharmacology
Intentions to perform research on humans must be carefully thought through. The person in overall control must ensure that the scientific approach is current and the methodology is good, the motivation is clear, the processes are unambiguous, and sufficient data exist to judge the safety and effectiveness of interventions proposed. Specific areas of ethical concern for pharmaceutical physicians: • ensuring that the study site chosen for a study, the chief investigator at the site and the entire support staff should be appropriately equipped and trained to properly care for each study subject participating; • remembering that it is unethical to change from an effective treatment to a trial medication unless there are sound scientific reasons for doing so, approval is obtained from a research ethics committee, the appropriate explanation is given to any trial subject and consent obtained; • ensuring that scientific and ethical standards are constantly upheld; • selecting appropriate investigators prior to the start of a clinical trial, and ensuring that they are trained to recognisably appropriate levels; • making a clear statement of the sponsors’ policy with regard to the handling of suspect data; • resisting undue pressure on any investigator in order to meet deadlines; • familiarising themselves, and staff, of the policy and standard operating procedure in place relating to the management of suspected fraud, and demonstrating commitment to implementing the policy if occasion demands; • ensuring that sufficient data are generated to allow the safe and effective use of a therapeutic intervention; • ensuring that studies are designed primarily to demonstrate the properties of the therapeutic agent under study rather than those of any comparators; • ensuring that studies involve placebos only when it is ethically appropriate to do so; © Adis Data Information BV 2003. All rights reserved.
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Specific areas of ethical concern: providing non-patient volunteers recruited into human pharmacology or phase I studies with summaries of all-important and relevant findings on the therapeutic interventions; ensuring that volunteers recruited from among employees of the sponsoring body, or among students, are not exploited, coerced or inappropriately remunerated; ensuring no conflict of interest between those who design studies, including human pharmacology or Phase I studies, and the teams responsible for their implementation; obtaining independent ethics committee approval for all clinical studies.
Studies of Therapeutic Use and Post-Marketing Surveillance
Once a therapeutic intervention has reached the stage where it is available for use, pharmaceutical physicians have an ethical responsibility to ensure that any studies they design, whether as observational post-marketing surveillance studies or as therapeutic use trials, will provide information regarding appropriate use in real life situations. Specific areas of ethical concern: • ensuring that no marketing exercise ever masquerades as a scientific study, be it a clinical trial or an observational postmarketing surveillance study; • paying due regard to the need for guidance on hypothesis generation and confirmation for such studies; • ensuring that the handling of observational databases and extracting of interpretations from them be of the highest standard; • contacting the sponsor of a study if, despite the approval that will have been given by a relevant research ethics committee, a pharmaceutical physician comes across a potentially unethical study being conducted by another person. Int J Pharm Med 2003; 17 (2)
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Special and Vulnerable Patient Groups
This group includes children, the elderly, the mentally incompetent, the mortally ill, the unconscious, the disadvantaged, and prisoners etc. These groups should not be deliberately excluded from clinical studies as to do so may cause them and others in their condition more harm. But if they are to be included then very special circumstances apply and should be followed carefully. If such people are the intended beneficiaries of the interventions under study, sufficient must be known about the interventions to make a risk versus benefit judgement possible. This usually means that data from prior work on adults able to give informed consent will have been completed and is available for review. Children
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Specific areas of ethical concern: ensuring that the local ethical position regarding the use of children in research projects is clearly understood; ensuring that where a therapeutic agent is not intended for use in children then paediatric studies are not conducted. Special Risk Groups
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Specific areas of ethical concern: ensuring that the local ethical position regarding the use of special risk groups (e.g. the elderly, the mentally incompetent, those with terminal or vital disease, those who are socially or economically disadvantaged, or any condition or circumstance where informed consent may not be obtained easily) is clearly understood; clearly understanding the local ethical position regarding non-therapeutic trials without direct benefit to the patients involved (e.g. those with hepatic or renal impairment). Research in Less Developed Countries
The locally prevailing social attitudes must be seriously considered when contemplating studies using volunteers from less developed and developing areas of the world. Judgements of what is appropriate will vary according to social, ethical, economical and governmental factors, which are local and not necessarily international. The principles of beneficence and respect for human dignity prevail everywhere. Specific areas of ethical concern: • ensuring that special care is taken to obtain local independent ethical review and approval, where the approval of an institutional review board in a developed country is not sufficient or relevant; • taking particular note of the ethnic, social, public health and economic conditions prevailing in the country concerned when any form of clinical research is being considered; • the use of placebo controls in conditions where such controls would not be acceptable in the developed world. © Adis Data Information BV 2003. All rights reserved.
Orphan Indications and/or Medicines
A particular ethical dilemma arises with regard to orphan indications and to orphan therapeutic interventions, i.e. where too few patients have a disease for a treatment to be fully investigated in the usual way. There are some rare conditions for which it is clear that there will never be a viable commercial return on investment. In such circumstances, the intervention may also not be assessable using the normal criteria. Specific areas of ethical concern: • making limited information available to others about orphan conditions, such that they can give advice to patients or their families; • making ethical decisions that it may be better to recommend an orphan intervention than to deny anyone who might benefit from it; • making information available to the owners of the relevant therapeutic agents on the need for orphan medicines and their availability. Benefit-Risk Assessments
If a pharmaceutical physician is not certain about all aspects of the status of a clinical research programme, even in the light of acceptable efficacy or safety, it is appropriate to delay making a decision on its future progress until any doubts have been resolved. Making an inappropriate decision before such doubts are resolved is unethical. Thus, both when assessing the outcome of a clinical trial programme and when reviewing the safety profile after marketing, pharmaceutical physicians must actively fulfil their scientific and ethical responsibilities. Specific areas of ethical concern: • making forthright ethical decisions where the relative evidence of efficacy is less than acceptable or where there is an unexpectedly high incidence of adverse reactions; • ensuring that adequate systems are in place to ensure the timely capture and analysis of relevant data upon which a decision to withdraw or modify an intervention might be based; • balancing the potential benefit of a trial to a larger number of patients against the possible harm done to a smaller number; • ensuring, in the case of a withdrawal of any therapeutic intervention, that as much relevant information as possible is made available to enable the clinical care of patients who are affected by the withdrawal to continue with the minimum of disturbance; • appreciating that the evidence available to formulate a benefit-risk assessment increases with time as use of the new intervention increases, and utilising such information to reduce the time taken to achieve an optimum assessment of a benefit-risk profile. Int J Pharm Med 2003; 17 (2)
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Awareness of Innovation
There are new technologies of which pharmaceutical physicians should be aware, such as pharmacogenetics and pharmacogenomics, which are used for selecting and classifying patients. In the design of research protocols using such tools, pharmaceutical physicians should be vigilant in protecting patient rights. Specific areas of ethical concern: • understanding and respecting local regulations and conventions governing the collection, management and specific analysis of clinical data for which consent may not necessarily have been given (pharmacoepidemiology); • ensuring the maintenance of high ethical standards and fulfilment of all legal requirements when using electronic clinical data management; • maintaining awareness of controversial and new therapeutic approaches in the wider context of the practice of medicine where ethical issues arise, e.g. the sampling and use of human body products (including organs, tissues, fluids or gametes), in-vitro fertilization or other methods of medically assisted procreation where medicinal products may be involved, prenatal diagnosis, certain aspects of contraception and abortion, and the interface with medical devices and delivery mechanisms; • the long-term storage of blood taken for genetic testing, and the consequences to the patients and their families of results from tests performed in the future.
Impartiality Studies are performed to increase knowledge in some way, and this knowledge should be shared with the wider world. Study findings should be communicated, whatever the outcome, for the benefit of the community at large. Communications on clinical studies must be a correct representation of all the findings, allowing others in their turn to give well-balanced advice to patients and their families.
Provision of Information
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Specific areas of ethical concern: ensuring that information provided to doctors, pharmacists, patients and members of the public is appropriate and accurate; ensuring that patient information is detailed enough to satisfy legal and regulatory requirements, but which is not so detailed that it affects the confidence of a patient or their family in the product and therefore negatively affects compliance; ensuring that products can be used appropriately in the target countries for which they are intended; recognising that summaries of product characteristics exist not only to fulfil legal requirements, but also to help physicians to use products safely and correctly. Information to Healthcare Professionals
Doctors are increasingly being encouraged to practice medicine based on all the available evidence in an attempt to improve further the quality of healthcare. Pharmaceutical physicians have a particular ethical responsibility to ensure that all the evidence on which doctors should make their decisions is freely available. It is well recognised that doctors sometimes prescribe medicines for indications or in dosage regimens that are not in accordance with the terms of the product’s marketing authorisation. Although there can be no question of promotion of interventions for such ‘off label’ use, nor should this be encouraged, relevant information, which is on file, should be provided on request to physicians and pharmacists. Specific areas of ethical concern: • ensuring that data to support marketing position statements should be of the same high quality, and conform to the same scientific criteria, regardless of whether they are published or unpublished; • encouraging the provision of all information known about an intervention to those entitled to it, regardless of whether or not this information has been published. Information to Patients
Promotion
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Specific areas of ethical concern: ensuring that any promotional material or activity does not contravene the advertising regulations and codes of practice of the countries concerned; ensuring that pharmaceutical physicians do not allow claims to be made which they consider unjustified; assuming the responsibility to ensure that market research and promotional research activities are not perceived as scientific research projects.
© Adis Data Information BV 2003. All rights reserved.
There is increasing freedom in the provision of information and the encouragement given to patients to seek as much information as they wish. This should certainly be permitted, but not so that it undermines the confidence of patients in the advice and treatment given by their own doctors. Specific areas of ethical concern: • ensuring that there is a clear understanding of the difference between providing clear information to patients, and the offering of advice, which should come from their personal physician; Int J Pharm Med 2003; 17 (2)
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ensuring that patient information is detailed enough to satisfy legal and regulatory requirements, but which is not so detailed that it affects the confidence of a patient or their family in the product and therefore negatively affects compliance; ensure that information intended for patients is appropriately directed and suitably written so patients and their families are able to make an informed decision about their treatment and medication. Information to the Media
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Specific areas of ethical concern: ensuring that expectations are not inappropriately raised as a result of the release of media briefings; reviewing briefings about potential therapeutic interventions provided to financial analysts or to the media; drawing to the attention of the authorities the distribution of any medicine, for example via the Internet and websites, which bypasses national legislation.
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Research Accountability
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Specific areas of ethical concern: ensuring that final study reports accurately reflect the clinical data and that any publication that flows from the data is wholly consistent with the report; maintaining the principle that all relevant reports should lead to a publication and not be persuaded by the argument that adverse data will have a negative impact on the finances of the company; ensuring that all studies performed are analysed and have a report written, however brief, as not to do so means that valuable data will be lost and patients will have been potentially put at risk for no benefit to themselves or others. This information should, wherever possible, lead to publication; ensuring that advertising and promotional material is both legal and ethical; balancing the need to make promotional material interesting and attractive against the need for scientific and medical accuracy;
© Adis Data Information BV 2003. All rights reserved.
Specific areas of ethical concern: refusal to accept gifts or hospitality designed to influence professional judgement; compensation for carrying out a clinical trial must be commensurate with the work required and not structured in such a way as to encourage coercive behaviour; declaration of financial interests in dealings with professional colleagues, the editors of scientific journals and the general public; payments for any reasons, to both volunteers and those performing the study must be transparent and known to the review body, as must any potentially conflicting interests; arrangements for product liability, indemnity and compensation in the event of anyone suffering damage must be clear, both to review boards and potential study subjects. Integrity and Accountability in the Workplace
Accurate Reporting
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Specific areas of ethical concern: designing clinical research protocols to answer genuine scientific questions and not to be promotional tools; implementing a clinical research protocol only after the approval of an independent research ethics committee; protecting subjects as a priority over scientific interest in all research protocols. Financial and Commercial Dealings
Probity Pharmaceutical physicians usually work for a commercially driven operation. They must, therefore, be extra vigilant that their decisions and practices are not in any way influenced by any personal financial gain. Each of the many players involved in planning, sponsoring and performing such studies must spontaneously declare potential conflicts of interest that might influence the making of balanced, unbiased judgements of what is best for study subjects.
ensuring that the commercial interest of a company is never allowed to take precedence over the requirement to report all safety data and adverse drug reactions to the authorities.
Propriety
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Specific areas of ethical concern: ensuring that colleagues are always treated fairly and are not discriminated against in any way; ensuring that a colleagues’ lifestyle, culture, beliefs, colour, gender, sexuality, or age does not prejudice a professional relationship with them; ensuring that subjects’ trust in the care or treatment they receive, or in the judgment of those treating them, is not undermined by the malicious or unfounded criticisms of colleagues. Teamwork
Multi-disciplinary teams increasingly provide pharmaceutical research. Working in a team does not change personal accountability for professional conduct and the care provided. Int J Pharm Med 2003; 17 (2)
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Specific areas of ethical concern: respect of skills and contributions of colleagues; effective communication with colleagues within and outside the team; participation in regular reviews and audits of the standards and performance of the team; willingness to deal openly and supportively with problems in the performance, conduct or health of team members.
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Leadership
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Specific areas of ethical concern: ensuring that medical team members meet the appropriate standards of conduct and care;
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addressing any problems that might prevent colleagues from other professions following guidance from their own regulatory bodies; ensuring that all team members understand their personal and collective responsibility for the safety of patients, and for openly and honestly recording and discussing problems; arranging for the provision of physician availability at all times; regularly reviewing and auditing of the standards and performance of the team and addressing any deficiencies; ensuring that systems are in place for dealing supportively with problems in the performance, conduct or health of team members.
IFAPP Directory IFAPP Secretariat
Argentina
Caroline van Bruggen, IFAPP secretariat, Rendementsweg 24 E-I, 3641 SL Mijdrecht, The Netherlands Tel.: +31 297 285144, Fax: +31 297 256046 E-mail:
[email protected]
Asociación de Médicos Asesores de la Industria Farmacéutica Argentina (AMAIFA) Website: www.amaifa.intranets.com President: Dr Alicia Arabehety AstraZeneca, Argerich 536, 1706 Haedo - Buenos Aires, Argentina Tel.: +54 11 4443 1538 E-mail:
[email protected] Delegate: Dr Luis Francisco Collia Parke-Davis / Gym, Sanabria 2353, 1417AZE Buenos Aires, Argentina Tel.: +54 11 4379 4300 ext1290, Fax: +54 11 4379 4290 E-mail:
[email protected]
Executive Committee Dr Domenico Criscuolo, President (Italy) Dr Johanna Schenk, Past-President (Germany) Dr Chris Allen, President Elect (USA) Dr Juan Lahuerta, Honorary Secretary (Spain) Dr Herman Lahon, Treasurer (Belgium)
Standing Members
Australia
Dr Mirela Barbu (Switzerland) Dr Jane Barrett (United Kingdom) Dr Luis Collia (Argentina) Dr Kees Kraaij (The Netherlands) Dr John Lee (Sweden) Dr Sidney Marques (Brazil) Dr Dimitris Michailidis (Greece) Dr Gerfried Nell (Austria) Dr Marc Pierredon (France) Dr Victoria Vázquez (Mexico) Dr Takashi Yohkaichiya (Japan)
Australian Pharmaceutical Physicians Association (APPA) Website: www.appa.net.au President: Dr Simon Fisher Bristol-Myers Squibb Pharmaceuticals, 556 Princes Highway, Noble Park, Victoria 3174, Australia Tel.: +61 3 9213 4085, Fax: +61 3 9701 1508 E-mail:
[email protected] Delegate: Dr Sander Becker, Consultant in Pharmaceutical Medicine PO Box 318, Rose Bay, NSW 2029, Australia Tel.: +61 2 9343 4067, Fax: +61 2 9343 4068
© Adis Data Information BV 2003. All rights reserved.
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E-mail:
[email protected] Austria Gesellschaft für Pharmazeutische Medizine (GPM) Website: www.gpmed.at President: Prof. Gerfried Nell Delegate: Prof. Gerfried Nell Novartis Pharma GmbH, Brunner Strasse 59, 1235 Wien, Austria Tel.: +43 1 866 57706, Fax: +43 1 866 57713 E-mail:
[email protected]
E-mail:
[email protected] Website: www.dadlnet.dk/fas/open/erhvervsforeninger/ole/ole.htm President: Dr Mogens Westergaard, Senior Medical Adviser Pfizer Denmark, Lautrupvang 8, 2750 Ballerup, Denmark Tel.: +45 44 20 12 18, Fax: +45 44 20 11 14 Mobile: +45 29 20 32 18 E-mail:
[email protected] Delegate: Dr Lena Ejbye Schmidt Spadille Clinical Trials Aps, Jernbanegade 34 C, DK-3480 Fredensborg, Denmark Tel.: +45 45 48 41 00, Fax: +45 48 48 42 00 E-mail:
[email protected]
Belgium Belgian Association of Pharmaceutical Physicians (ABEMEP, BEVEFA, BAPP) Website: www.abemep-bevefa.be President: Dr Monique Podoor Pharmakon Sarl, A. Stesselstraat 9, B-3012 Wilsele, Belgium Tel.: +32 16 89 70 30, Fax: +32 16 89 70 29 E-mail:
[email protected] Delegate: Dr Herman Lahon 1bis, Quai aux Fleurs, F-75004 Paris, France Tel.: +33 1 43 29 37 24, Fax: +33 1 43 29 37 24 E-mail:
[email protected]
Finland Finnish Association of Pharmaceutical Physicians (SuLL/FiAPP) President: Dr Timo Muhonen Bristol-Myers Squibb Finland, Metsänneidonkuja 8, FIN-02130 Espoo, Finland Tel.: +358 40 500 9845 E-mail:
[email protected] Delegate: Dr Juha-Pekka Heikkilä Aventis Pharma Oy, Huopalahdentie 24, 00351 Helsinki, FIN-00350 Finland Tel.: +358 0201 200 340, Fax: +358 0201 200 496 E-mail:
[email protected]
Brazil Sociedade Brasileira de Medicina Farmacêutica (SBMF) Rua Pamplona 788, sala 32, CEP 01405-001 São Paulo São Paulo, Brazil Tel.: +55 11 253 2848, Fax: +55 11 253 2848 President: Dr Sidney P. Marques Delegate: Dr Sidney P. Marques AstraZeneca do Brasil, Rod. Raposo Tavares, km 26,9, 06714-025 Cotia-SP, Brazil Tel.: +55 11 4613 1270, Fax: +55 11 4702 2481 E-mail:
[email protected] Denmark Danish Association of Pharmaceutical Physicians (OLE/DAPP) Trondhjemsgade 9, DK-2100 Copenhagen O, Denmark Tel.: +45 3544 8500, Fax: +45 3544 8585 © Adis Data Information BV 2003. All rights reserved.
France Association des Médecins de l’Industrie Pharmaceutique (AMIP) avenue André Morizet 83, F-92100 Boulogne, France Tel.: +33 1 4603 0345, Fax: +33 1 4603 0202 E-mail:
[email protected] Website: www.amip.asso.fr President: Dr Guy Campion Novartis Pharma, 2.4 rue Lionel Terray, 92500 RueilMalmaison, France Tel.: +33 1 55 47 6058, Fax: +33 1 55 47 6439 E-mail:
[email protected] Delegate: Dr Marc Pierredon Intervenance, Rue Beranger 10, F-92100 Boulogne, France Tel.: +33 1 4603 8575 E-mail:
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Germany
Ireland
Deutsche Gesellschaft für Pharmazeutische Medizin, DGPharMed, Olschewskibogen 7, D-80935 München, Germany Tel.: +49 89 354 99 823; Fax: +49 89 354 99 825 E-mail:
[email protected] Website: www.dgpharmed.de President: Dr Michael Herschel GlaxoSmithKline GmbH & Co. KG, Leopoldstrasse 175, D-80804 München, Germany Tel.: +49 89 36044 588, Fax: +49 89 36044 677 E-mail:
[email protected] Delegate: Dr Johanna Schenk Omnicare Clinical Research GmbH, Am Kronberger Hang 4, D-65824 Schwalbach/Taunus, Germany Tel.: +49 6196 602 150, Fax: +49 6196 602 155 E-mail:
[email protected]
Association of Pharmaceutical Physicians of Ireland (APPI) President: Dr Declan O’Callaghan Delegate: Dr Declan O’Callaghan Bristol-Myers Squibb, Watery Lane, Swords, Co. Dublin, Ireland Tel.: +353 1 813 9111, Fax: +353 1 813 9112 E-mail:
[email protected]
Greece Hellenic Society of Pharmaceutical Medicine (ELEFI) 23 Meandou Street, GR-115-28 Athens, Greece Tel.: +30 210 721 1845, Fax: +30 210 722 6100 Website: www.elefi.netfirms.com President: Dr Dimitris Michailidis Delegate: Dr Dimitris Michailidis The Athens Medical Society, Katsibiri Street 63, 15561 Athens, Greece Tel.: +30 6944 510 554, Fax: +30 210 685 4055 E-mail:
[email protected] Indonesia Indonesian Pharmaceutical Phsysicians Association (PEDFI/IPPA) President: Dr Hanna Santoso PT Bristol-Myers Squibb Indonesia, Wisma Tamara 10th Floor, J1 Jend Sudirma Jakarta 12920, Indonesia Tel.: +62 21 520 6727 or 520, Fax: +62 21 520 6735 E-mail:
[email protected] Delegate: Dr Paulus Wijanto Sanofi-Synthelabo Combiphar Menara Rajawali 17th Floor Jl. Mega Kuningan Lot #5.1, Kawasan Mega Kuningan / Jakarta 12950, Indonesia Tel.: +61 21 5761428, Fax: +61 21 5761425 E-mail:
[email protected] © Adis Data Information BV 2003. All rights reserved.
Italy Società di Scienze Farmacologiche Applicate (SSFA) Viale Abruzzi 32, I-20131 Milan, Italy Tel.: +39 02 295 36444, Fax: +39 02 295 20179 E-mail:
[email protected] Website: www.ssfa.it President: Dr Francesco De Tomasi Wyeth Pharmaceuticals, Via Nettunense 90, 04011 Aprilia (Latina), Italy Tel.: +39 6 927 15287, Fax: +39 6 927 08237 E-mail:
[email protected] Delegate: Dr Domenico Criscuolo CRC, Via Winckelmann 2, 20146 Milano, Italy Tel.: +39 02 4895 8768 ext. 104, Fax: +39 02 4895 8776 Mobile: +39 388 9479922 E-mail:
[email protected] Japan Japanese Association of Pharmaceutical Medicine (JAPhMed) Website: www.japhmed.org President: Dr Takashi Yohkaichiya Delegate: Dr Takashi Yohkaichiya Senior VP and chief Medical Officer, SNBL, Ltd, Toho Twin Tower Building, 6th Fl., 1-5-2- Yurakucho, Chiyoda-ku, Tokyo 100-0006, Japan Tel.: +81 3 3500 5045 ext. 810, Fax: +81 3 3500 5046 E-mail:
[email protected] Korea Korean Society of Pharmaceutical Medicine (KSPM) President: Dr Woo ick Jang Int J Pharm Med 2003; 17 (2)
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Lilly Korea Ltd, 7th FI., Shin An Bldg., 943-19, Daechi-Dong, Kangnam-Ku, Seoul, 135-280, Korea Tel.: +82 2 3459 2661, Fax: +82 2 3453 0919 E-mail:
[email protected] Delegate: Dr Myung Hoon Kim Aventis, Korea E-mail:
[email protected] Mexico Mexican Pharmaceutical Physicians Association (AMEIFAC/MPPA) Website: www.ameifac.org.mx President Dr Felipe Rodríguez-Davison Novartis Farmacéutica S.A. de C.V., Calzada de Tlalpan 1779, 04120 México City, Mexico Tel.: +52 55 5420 8771, Fax: +52 55 5689 6178 E-mail:
[email protected] Delegate: Dr Victoria Vazquez E-mail:
[email protected] Netherlands The Netherlands Association of Pharmaceutical Physicians (NAPP) Rendementsweg 24 E-I, 3641 SL Mijdrecht, The Netherlands Tel. +31 297 281121, Fax: +31 297 256046 E-mail:
[email protected] Website: www.nvfg.nl President: Dr Paul van Meurs Novella Research, Weerdsingel O.Z. 19, 3514 AB Utrecht, The Netherlands Tel.: +31 302724315, Fax: +31302724740 E-mail:
[email protected] Delegate: Dr Kees J. Kraaij Eli Lilly Nederland B.V., Grootslag 110, 3991 RA Houten, The Netherlands Tel.: +31 30 602 5847, Fax: +31 30 602 5842 E-mail:
[email protected] Pakistan Pakistan Association of Pharmaceutical Physicians (PAPP) President: Dr Maqbool H. Jafary Delegate: Dr Maqbool H. Jafary © Adis Data Information BV 2003. All rights reserved.
Novartis Medical Centre for Asia-Pacific, West Wharf 15, 74000 Karachi, Pakistan Tel.: +92 21 231 0384, Fax: +92 21 231 0339 E-mail:
[email protected] Portugal Associação dos Médicos Portugueses da Indústria Farmacêutica (AMPIF) Apartado 165 / Abrunheira, P-2711-901 Sintra, Portugal Tel.: +351 21 432 9648, Fax: +351 21 915 1930 E-mail:
[email protected] Website: www.ampif.pt President: Dr Ana Maria Nogueira Schering-Plough Farma, Lda, Apartado 28 / Casal do Colaride / Agualva, 2735-954 Cacém, Portugal Tel.: +351 214339320, Fax: +351 214339385 E-mail:
[email protected] Delegate: Dr Pedro Freitas Datamédica, Rua Garcia de Orta 70 2nd Dto., 1200-680 Lisboa, Portugal Tel.: +351 21 395 5268, Fax: +351 21 396 6276 E-mail:
[email protected] Serbia Serbian Association of Pharmaceutical Physicians (SFM) Srpsko lekarsko drustvo / Djordja Washingtona 19, YU-11000 Belgrade President: Prof. Dr Mlan Stanulovic E-mail:
[email protected] South Africa South African Association of Pharmaceutical Physicians (SAAPP) President: Dr David Veenhuyzen Delegate: Dr David Veenhuyzen Bayer, P.O. Box 198, 1600 Isando / Johannesburg, South Africa Tel.: +27 11 921 5064, Fax: +27 11 921 5075 E-mail:
[email protected] Spain Association de Mediciana de la Industria Farmaceutica Espanola (AMIFE) Edicomplet, c/ Capitan Haya 60, E-28020 Madrid, Spain Int J Pharm Med 2003; 17 (2)
IFAPP News
Tel.: +34 91 749 9517 Website: www.amife.org President: Dr Manuel Martín AstraZeneca, Serrano Galvache 56, E 28033 Madrid, Spain Tel.: +34 91 3101 91 00, Fax: + 34 91 301 91 55 E-mail:
[email protected] Delegate: Dr Juan Lahuerta Dal-Ré GlaxoSmithKline, Parque Tecnológico de Madrid, C/Severo Ochoa, 2, 28760 Tres Cantos (Madrid), Spain Tel.: +34 91 807 5789, Fax: +34 91 807 5943 Mobile: +34 616962350 E-mail:
[email protected] /
[email protected] Sweden Swedisch Association of Physicians in the Pharmaceutical Industry (LILF/SAPP) President: Dr Viveka Aberg Pfizer AB, Box 501, 183 25 TÄBY, Sweden Tel.: +46 519 06 307, Fax: +46 519 06 212 E-mail:
[email protected] Delegate: Dr John Lee AstraZeneca R&D SÖDERTÄLJE, S-15185 Södertälje, Sweden Tel.: +46 8 553 258 68, Fax: +46 8 553 258 68 E-mail:
[email protected] Switzerland Swiss society of Pharmaceutical Medicine (SGPM/SSPM) Website: www.sgpm.ch President: Dr Michael Wagener Eli Lilly Suisse SA, Post Box 580, CH-1214 Vernier GE, Switzerland E-mail:
[email protected] Delegate: Dr Mirela Barbu, Eli Lilly Suisse SA, Post Box 580, CH-1214 Vernier GE, Switzerland
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Tel.: +41 22 306 0403, Fax: + 41 22 306 0472 E-mail:
[email protected] United Kingdom British Association of Pharmaceutical Physicians (BrAPP) Royal Station Court/ Station Road Twyford, RG 10 9NF Reading, United Kingdom Tel.: +44 118 934 1943, Fax: +44 118 932 0981 E-mail:
[email protected] Website: www.brapp.org.uk President: Dr David Blowers David Blowers Associates Ltd, 4 Harrogate Road / Caversham / Reading, Berkshire RG4 7PN, United Kingdom Tel.: +44 118 948 3282, Fax: +44 118 946 2118 E-mail:
[email protected] Delegate: Dr Jane Barrett The Barrett Consultancy, 2 Falcon Way, Wokingham Berkshire RG41 3HD, United Kingdom Tel.: +44 118 962 7501 E-mail:
[email protected] United States of America American Academy of Pharmaceutical Physicians (AAPP) Apex Professional Park / Pemberton Hill Road 1031 Suite 101, Apex, NC 27502, USA Tel.: +1 919 355 1000, Fax: +1 919 355 1010 E-mail:
[email protected] Website: www.aapp.org President: Hans de Haan E-mail:
[email protected] Delegate: Dr Christopher Allen Merck & Co., Inc., One Merck Drive, PO Box 100, Whitehouse Station / Dept. WS3C-90, NJ 08889-0100, USA Tel.: +1 908 423 3935, Fax: +1 908 423 2470 E-mail:
[email protected]
Int J Pharm Med 2003; 17 (2)
