Comparing emerging ethical issues and legal differences impacting on European clinical trials

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Comparing emerging ethical issues and legal
differences impacting on European clinical trials

• David L Edbrooke, Veselina Kanatova-Buchkova,
  Josef Kure, Gary H Mills, Fruzsina Molnar-Gabor,
  Maria Nastac, Daniel Sinclair, Judith
  Sinclair-Cohen, Sandy Smith, Guido Van Steendam,
  Darina Zinovieva.

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A PowerPoint summary ofComparing emerging
ethical issues and legal differences impacting on
European clinical trials

• A framework 6 EU project
• TWR PL016621
• Powerpoint compiled by Gary H Mills and MERCS
• This PowerPoint presentation is intended as a
  read through learning guide and aid to the
  project and associated areas. It is intended that
  it can be translated and adapted to the needs of
  individual researchers in the group. If you aim
  to use it as a lecture guide, you may wish to
  first summarise the points made for ease of
  presentation.

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(TWR Project PL016621)

• This qualitative study was a specific support
  action of FP6.
• Its purpose was to explore emerging ethical
  differences during the design, conduct and
  analysis of clinical trials in a representative
  section of countries in the EU, with an emphasis
  on New Member States (NMS).
• In all, almost a hundred researchers from some
  fifty institutions in twenty countries were
  recruited, for the identification and comparison
  of emerging ethical issues and legal differences
  in clinical trials

• These issues should assume greater importance
  with closer working of member states.
• Networks in relevant disciplines were formed
  across countries and new academic relationships
  were forged.
• Advisory groups were formed from experts in the
  fields of ethics, clinical practice, law, health
  economics, theology, culture and technology. A
  multi-disciplinary group of young researchers was
  also created.

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Group coordinators

• David L Edbrooke economics
• Veselina Kanatova-Buchkova law
• Josef Kure ethics
• Gary H Mills clinical practice
• Fruzsina Molnar-Gabor young people
• Maria Nastac culture
• Daniel Sinclair theology
• Judith Sinclair-Cohen report coordinator
• Sandy Smith project coordinator
• Guido Van Steendam philosophy
• Darina Zinovieva law

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History of clinical trials

1. Probably the first record of a clinical trial is
   in the bible in The Book of Daniel.
2. King Nebuchadnezzar, ordered that several youths
   be brought to his palace, to be fed and taught
   just like his own children.
3. This included Daniel, who proposed that they be
   allowed to eat "pulses" and to drink water
   instead of wine and meat.
4. After ten days they appeared healthier than the
   other children.

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Therapeutic interventions

1. The first clinical trial of a therapeutic interve
   is attributed to Ambroise Paré (1510 -1590),
2. who used egg yolk and turpentine to heal a wound.
   
3. He found that turpentine, was far more efficient
   at healing the wounds of soldiers, than the
   state-of-the-art remedy boiling oil!

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Limes and clinical controlled trials

1. In the 18th century clinical trials began to be
   used routinely to test new medical treatments.
2. Often consent not truly implemented at this time
3. James Lind used control groups, when he showed
   that citrus fruit prevents scurvy.
4. A group of sailors in the British Navy who had
   oranges and lemons added to their diet improved
   dramatically in just 6 days, in comparison with a
   group that didn't get the fruit.
5. Later replaced by cheaper limes

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Physicians testing remedies on themselves

1. Often physicians would first test potential
   remedies on themselves, or on relatives.
2. The English physician Edward Jenner developed the
   smallpox vaccine in 1789
3. he first tried inoculating his own son, who
   caught smallpox anyway.
4. Several months later, he inoculated a neighbour's
   child, who didn't get the disease

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Childbed fever

1. During the 19th Century, clinical trials became
   larger and more organised.
2. Ignaz Semmelweis (1818-1865) from Hungary,
   observed that the mortality rate of mothers from
   childbed fever was far lower among patients
   treated by midwives rather than doctors.
3. He dramatically reduced the death rate of new
   mothers by a simple experiment that started a
   hand washing policy for doctors and medical
   students.
4. And in a controlled trial using a chloride of
   lime solution, the mortality rate fell to about
   2, which was about the same level as the women
   delivered by midwives.

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Trials where case history says death without
treatment is likely

1. In France, Louis Pasteur (1822-1895) was aware of
   the ethical implications of his work.
2. He spent many years developing an antidote for
   rabies.
3. Yet he only tried it out on a nine-year-old boy,
   who had been bitten by a rabid dog, after two
   colleagues assured him that the child would
   certainly die without treatment. The boy lived.

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Yellow fever and healthy volunteers

1. Dr Carlos Finlay believed the Aedes aegypti
   mosquito carried yellow fever
2. The mosquito was carrying the disease by biting
   infected people and then when healthy people were
   bitten, they received the disease
3. However, the virus needed to incubate for 12 days
   inside the mosquito
4. Unfortunately Finlay was attempting to inoculate
   volunteers using mosquitoes that had only
   recently been infected
5. Dr Walter Reed tested this work further to
   determine the mode of transmission
6. He built two small buildings through which air
   could circulate freely to determine whether the
   disease was airborne.
7. In one building volunteers slept on the sheets of
   yellow fever patients
8. In the second building, volunteers slept next to
   infected mosquitoes, but were protected by
   screens
9. Unlike Finlay work these had been infected for a
   long period
10. Then one volunteer was directly exposed to
    infected mosquitoes
11. He was the only one to develop yellow fever
    demonstrating the link

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19th and-20th centuries placebos and
randomisation

1. There was enormous progress in Medicine during
   the 19th century.
2. Placebos were first used in the 1860s
3. Randomisation of clinical trials started later in
   the 1920s
4. Yet cures were still largely based on clinical
   observation such as the dramatic effect of
   insulin given by Banting and Best to a dying boy
5. In the 1800s and early 1900s many dangerous
   medical practices, such as bloodletting, were
   still common.
6. During the late 20th century the double blind
   randomised controlled trials became common where
   feasible

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Vulnerable populations

1. In the years before World War II many doctors,
   believed it acceptable to conduct experiments on
   vulnerable populations
2. Infants, condemned prisoners, and mentally
   handicapped people were frequently used in
   medical experiments
3. These experiments were not regarded as unethical
   at the time
4. As late as the 1950s seminal studies on the
   development of dental caries were carried out in
   institutions for the mentally handicapped in
   Sweden and Australia

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The Helsinki declaration

1. The experiments imposed on inmates of Nazi
   concentration camps during World War II led to
   the development of a strict ethical code for the
   conduct of clinical trials the Nuremburg Code
   (1947).
2. This primarily included the principle of
   voluntary consent.
3. It also stated that studies should be based on
   the results of animal experimentation, be well
   designed, be conducted by qualified personnel and
   have a degree of risk appropriate to the
   humanitarian importance of the problem to be
   solved.
4. In 1964, the World Medical Association issued the
   Helsinki Declaration which further promoted
   ethical, legal, and procedural protection for
   patients
5. Under certain circumstances, it allowed for
   experimentation on children and on those unable
   to give consent. This, for example, allowed for
   trials on patients with mental illness, and in
   paediatrics
6. Yet ethical questions surrounding clinical trials
   remain and regulation is always necessary to
   ensure a balance between medical progress and
   patient safety

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The present position in the EU

1. The expansion of Europe has lead to
   inconsistencies in European research ethics
2. The European Research Area (ERA) relies on the
   transfer of knowledge between countries
3. It is important for Europe to harmonize ethical
   standards of all its researchers
4. Such comparative research of these issues is at
   present limited
5. The challenge is to discern variations in local,
   national and international customs and practice,
   whilst developing new ways of discovering and
   understanding the emerging ethical and legal
   issues for clinical trials in Europe today
6. Failure to understand these differences could
   mean that the results of clinical trails, and
   their interpretation, could be compromised and
   biased

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The project

1. There are differences in ethics between
   countries, there are also differences across
   disciplines
2. So for this study a scientific committee of
   leading European researchers was formed to
   represent a broad spectrum of disciplines
   ethics, law, culture, clinical practice,
   theology, economics and technology
3. Intensive networking through meetings and email
   - allowed advisory groups in each of these
   disciplines to be formed across thirteen
   countries in Europe, with a particular emphasis
   on New Member States (NMS)
4. During this process it became apparent that
   citizens of New Member States, who reached
   adulthood after the fall of communism, held
   different perspectives to their older peers, so a
   further advisory group for ''young persons'' was
   set up
5. A set of questions, on the subject of clinical
   trials, was developed by the team of experts,
   which were then adapted to each of the relevant
   disciplines
6. Responses were collated via the networks to
   produce working documents for discussion and
   qualitative analysis at a meeting in the Czech
   Republic

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Three ethical approaches Communitarianism,
Utilitarianism, Liberalism.

1. This project also explored the source of ethical
   arguments and the common ethical framework
   applied to the area of clinical trials.
2. A basic comparative ethical analysis was
   undertaken using three different paradigmatic
   frameworks, namely communitarianism, liberalism,
   and utilitarianism.

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Communitarianism and clinical trials

1. One would expect that a non-extreme form of
   classical communitarianism, whether in its broad
   or narrow sense, but always focussed on the
   concept of the good of society as a whole, would
   play a vital role in these countries today.
2. However, we did not find this to be the case.
3. It seems that a form of relativist
   communitarianism i.e. the belief in the need to
   respect for individual societies, and their
   cultural, moral, and religious traditions, is
   more prevalent than classical communitarianism
   with its emphasis on the good of a single
   universal society.
4. In the context of clinical trials, for example,
   this means that the development of new therapies,
   new drugs or new medical devices for the common
   good - with a universal impact and global
   contribution - is regarded with a great deal of
   scepticism.

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Utilitarianism and clinical trials

1. It was also evident that liberal and libertarian
   views carried greater weight in ethical arguments
   regarding clinical trials than the pure
   utilitarian position
2. The classical pure utilitarian thesis i.e. the
   greatest happiness for the greatest number of
   people does not, therefore, provide support for
   participation in clinical trials in Europe.
3. Moreover, pure utilitarianism runs counter to the
   scepticism we mentioned above with regard to the
   principle of the greatest happiness, or for that
   matter benefit or profit, for the greatest
   number,
4. In the context of clinical trials, it seems,
   therefore, that popular perceptions justifying
   participation in clinical trials are not driven
   by pure utilitarian philosophy.
5. Similarly the second thesis of utilitarianism,
   about diminishing pain and the health-related
   troubles of the greatest number (the maximum good
   over the minimum pain) does not fit the rather
   skeptical expectations of the general
   availability of new medical tools developed by
   clinical trials.
6. In general the theory that the morality of any
   action is defined by its utility is not used as
   the common ethical argument in favour of clinical
   trials.

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Liberalism and pragmatism

1. The findings of the project demonstrate that the
   most popular approach to clinical trials, was
   liberalism. Liberalism is especially accepted in
   its negative form.
2. This approach respects the rights of the
   individual, but insists that the realisation of
   such rights cannot be achieved at the expense of
   the rights of another individual.
3. Thus, pure egalitarian liberalism is of less
   importance in Central and Eastern European
   countries than the libertarian approach.
4. For the libertarian approach, regulation in
   general - and particularly in the area of
   clinical trials - is often perceived as
   restrictive.
5. Similarly the need for harmonisation and
   standardisation with respect to clinical trials
   on the European or global level is not in line
   with the libertarian approach.
6. This approach, enables the maximization of profit
   for some entities involved in clinical trials,
   but does not necessarily bring profit for all
   patients, such as access to the new therapies
   that are developed.
7. We also found pragmatism to play a significant
   role. We asked why it is that so many people in
   NMS take part in clinical trials. For despite
   skepticism about the profit of the universal
   community, people in many Central and Eastern
   European countries decide to take part in
   clinical trials for pragmatic reasons they
   perceive that they will get substantially better
   medical care, by taking part, than through
   standard health care in their countries.
8. In conclusion, we perceive this pragmatic
   motivation as a challenge both on a national
   level for health care systems and on a European
   level with respect to harmonisation of ethical
   standards.

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Ethics issues that were considered

1. Are there any specific Ethical influences in your
   country, which would have an effect on the
   design, conduct and analysis of clinical trials?
2. Informed consentHow is the concept of informed
   consent perceived by patients, physicians
   (medical personel), and researchers in general?
   Describe how the principle of informed consent
   is being implemented in your country for clinical
   trials?How could the practice of informed
   consent be improved in your country?
3. Ethical standardsHow (international/European)
   ethical standards are implemented in clinical
   trials?How European standards could improve
   ethical quality of clinical trials in New Member
   and Candidate States?
4. Ethics CommitteesHow do see the current role of
   Ethics Committees?How is the responsibility to
   the community of Ethics Committee members
   perceived in your country?How could their role
   be improved?
5. Conflict of interestsHow is conflict of
   interests perceived (e.g., social acceptance) and
   regulated in your country?Are conflicts of
   interests increasing/decreasing/remaining the
   same)

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Ethics responses key points

1. Many issues were identified in a qualitative
   assessment of the ethics of clinical trials in
   NMS. The most important were found to be the
   principle of informed consent, ethical standards,
   the workings of ethics committees, conflicts of
   interest and lack of education.
2. The principle, not just the practice, of informed
   consent is more important than ever. Consent
   should be truly informed and the researcher has a
   duty to make sure that the patient understands
   the potential risks and benefits of taking part
   in a trial. Alternatives to the trial should also
   be pointed out.
3. International standards can improve the standards
   of ethics in NMS but this is a long process still
   in its infancy. Further work is needed in order
   to implement ethical principles effectively.
4. Specific emerging issues need to be identified
   for each country and there is a need for hard
   data rather than anecdotal evidence.
5. There is a need to improve the workings of
   research ethics committees. Members should have
   the relevant professional, or lay, background yet
   be free of any conflict of interest.
6. There is a need for transparency, appropriate
   training in ethics and accountability. Members of
   ethics committees need to be socially aware.
7. More public involvement is needed in the debate
   on ethical issues, so that the perceptions and
   sensitivities of ordinary people can be included
   in this process.
8. Education for the public on ethics is a necessary
   precursor to such involvement.

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Clinical Practice issues considered

1. Are there any specific Clinical Practice
   influences in your country, which would have an
   effect on the design, conduct and analysis of
   clinical trials?
2. Does the availability of provision of healthcare
   in your country and the type of provision such as
   private, state, insurance based affect the
   design, conduct and analysis of clinical trials
   or affect medical research
3. Do the hospitals support research and clinical
   trials for example by providing insurance
   protection indemnity, time, peer review,
   statistical advice and a research friendly
   atmosphere?
4. Are patients in your country generally willing to
   take part in clinical trials/medical research and
   why? Does this vary with different types of
   research or the type and severity of illness or
   the age and sex of the patient?
5. Are there any traditional or established medical
   or clinical practises or clinical organisational
   issues that affect the design, conduct and
   analysis of clinical trials or research
6. How has European law and its local national
   implementation affected the design conduct and
   analysis of clinical trials and research?

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Clinical Practice key points

1. Standards of ethics committees and procedures may
   be improving, but this is not universal and the
   process is not uniform nor is it consistently
   applied across member states. For example, in
   Latvia, ethics committee approval only covers
   drug trials. This is an astonishing inconsistency
2. Research is becoming disproportionately
   bureaucratic in some states, which-discourages
   research and impedes the success of some
   legitimate projects-diverts effort away from
   good project design - indeed some abandon
   research or go overseas-deters researchers from
   taking part in clinical research and makes them
   more likely to carry out animal or molecular
   research, where productivity is greater as
   bureaucracy is less
3. The composition of ethics committees varies
   greatly between member states. Some are
   knowledgeable and demonstrate independence others
   lack both knowledge and independence
4. Ethics committees are afforded low professional
   status if there is remuneration for members it
   is low. Yet this is an onerous and responsible
   role that should be valued by professionals and
   public
5. Commercial research, by pharmaceutical companies,
   predominates in new member states
6. There is a both a lack and decline in funding,
   time, support and facilities for independent
   scientific research. Hospital support for
   independent scientific research is declining,
   concentrating on cost versus patient turnover.
7. Private medicine is taking a greater hold on
   health care, but in this sector research is
   virtually absent
8. EU law has not produced a uniform approach to the
   adult who is unable to give consent. As a result
   research in fields such as intensive care and
   emergency medicine is impossible in some states
9. Standardised ethics forms, processes and
   documentation are needed within member states,
   and throughout the EU, in order to make the
   ethics application process less bureaucratic and
   more uniform and effective.
10. This should avoid the need for complex, different
    and multiple applications, when various
    institutions consider the same study

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Law issues that were considered

1. Are there any specific Law influences in your
   country, which would have an effect on the
   design, conduct and analysis of clinical trials?
2. Concerning clinical trials legislation how is the
   Protection of Subjects of clinical trials
   inform consent, procedures, persons with
   disability dealt with in your country
3. Does the law in your country deal with Personal
   data and its protection?
4. Does the law of your country ensure the
   Implementation of good clinical practices in the
   conduct of clinical trials on medicinal products
   for human use?
5. How does the law affect the Management of Ethics
   Committees organization of activity, financial
   organization, other problems?

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Law key points

1. The main legal principle involved in clinical
   trials is that of the patient's informed consent
   to the procedure to be carried out. In most
   countries the individual should consent to the
   trial explicitly and in written form. This is
   once he/she is acquainted with the essence of the
   procedure, the desired effect and all possible
   side effects from the trial or from any
   medication.
2. Another main legal principle that should be
   followed in the process of clinical trials is
   that the individual should be a legally capable
   person that is, a person who is able to
   understand the legal consequences of their
   actions. In most countries there is an exception
   to this principle when informed consent is given
   by a guardian or other legal representative, but
   there are also countries in which such a clinical
   trial carried out on legally incapable persons is
   forbidden.
3. In each of the countries, the main requirement of
   the administrative procedure regarding clinical
   trials, is obtaining the permission of an ethics
   committee. This committee appraises the ethical
   issues arising form a specific trial. In most
   countries the permission of the Ministry of
   Health, or head of a certain department or
   hospital is also required.
4. The question of liability in cases of death or
   damage to a person's health is legally regulated
   in each of the countries in this study. However,
   it became clear that, in some of the countries in
   question, there is a problem with enforcement.
   The application of legally prescribed penalties
   legislation is not effective and this allows for
   non-punishable actions of the medical staff
   towards the patients.

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Economic issues that were considered

1. Are there any specific Economic influences in
   your country, which would have an effect on the
   design, conduct and analysis of clinical trials?
2. Should hospitals and health care professionals
   benefit directly from undertaking clinical
   trials? How should this be done?
3. The answers suggest that the enthusiasm about
   clinical trials is inversely proportional to the
   GDP of an individual country. Is this ethical and
   how can this best be managed?
4. Should there be stringent regulation in the EC
   about management and conduct of clinical trials?
   If so what form should it take?
5. Should commercial companies have to pay a fixed
   price in all EC countries to avoid pricing to
   market?

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Economics key points

1. Patients in NMS can be eager to participate in
   clinical trials as they feel that they will gain
   access to treatment, medication, diagnostics and
   medical attention that might otherwise be
   unavailable.
2. Setting up clinical trials in NMS can be
   attractive to companies.
3. The majority of clinical trials in NMS seem to be
   drug trials sponsored by pharmaceutical
   companies.
4. A clinician's decision to conduct a trial can be
   influenced by financial incentives.
5. Remuneration for trials can be direct or indirect
   and there was some discussion as to whether the
   level of remuneration should be the same for all
   countries.
6. Participation of clinicians from NMS in clinical
   trials, can provide, prestige, continuing
   education and professional opportunities for
   researchers.
7. Patients in NMS may only be able to obtain
   certain medication if they enroll in a trial.
8. Clinicians deserve to be paid for conducting
   trials as they are carrying out work and are
   shouldering responsibility.
9. It was observed that the enthusiasm for clinical
   trials appears to be inversely proportional to
   the GDP for a country which can predispose to
   exploitation. Some creative solutions were
   proposed.
10. All felt that there should be uniform and
    effective regulation by the EC. The question was
    what form this should take and to what degree it
    could be enforced.
11. A need was identified for an international system
    for compensation for patients, in the case of an
    adverse outcome.

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Theology issues that were considered

1. Are there any specific Theological influences in
   your country, which would have an effect on the
   design, conduct and analysis of clinical trials?
2. Is the basic attitude of the religious
   establishment in your country towards clinical
   trials totally negative, entirely positive, or
   permitted within certain Limits? Please explain
   your answer.
3. What is the position of the religious
   establishment in your country on the following
   issues?(a) Clinical trials using healthy
   subjects with minimal risk(b) Clinical trials
   using healthy subjects with significant risk(c)
   Clinical trials using terminal patients which are
   designed to produce a cure(d) Clinical trials
   holding out the promise of improved quality of
   life to chronically, but not terminally ill
   patients(e) informed consent in clinical
   trials(f) The commercial aspects of clinical
   trials
4. What actual influence, if any, does established
   religion have on clinical trials, and what, if
   anything can be done in order to improve the
   dialogue between religion and science in this
   area?
5. Under which conditions, if any, is your religious
   establishment prepared to permit embryonic
   experimentation, and in particular, stem cell
   research?

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Theology key points

1. It was generally agreed that principle of running
   clinical trials was not fundamentally problematic
   from a religious perspective, provided they
   complied with the ethical safeguards laid down in
   the Declaration of Helsinki.
2. In principle there is not a religious opposition
   to the paying of subjects participating in
   clinical trials.
3. In many countries the participation of religious
   experts in medical ethics committees, is
   ubiquitous. In some countries, such participation
   is mandated by law or statutory regulations. This
   may reflect a widely held assumption that
   religious experts, by dint of their strong
   convictions, are likely to be trustworthy ethical
   watchdogs.
4. There are certain substantive areas in which
   there is strong religious opposition to research
   most notably in research involving gamete
   manipulation, embryonic tissue and stem cells.
   -It is important to emphasize that there are
   differences amongst the religions in these areas.
   -Many religious traditions have a long history
   of primary and secondary principles in these
   areas, and often employ a sophisticated casuistic
   approach in order to apply them to the case under
   discussion. Sometimes the result is unexpected.
5. It is important to develop a dialogue between
   scientists and religious experts in order that
   both disciplines are able to co-operate in a
   fruitful fashion. Scientists can help religious
   experts understand the intricacies of their
   field, and theologians can share their values and
   principles with scientists.
6. Today, there are many temptations to cut ethical
   corners, hence the need for a sense of the
   "sacred" as well as the ethical in relation to
   these issues.
7. In Europe an open and serious dialogue in an
   atmosphere that is conducive both to science and
   religion is imperative. A religious cadre,
   educated in science would help this process

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Cultural issues that were considered

• Are there any specific Cultural influences in
  your country, which would have an effect on the
  design, conduct and analysis of clinical trials?
• How much do the patients in your country agree
  with medical experiment on them?
• How much are people willing to accept medical
  experiment on sick persons either themselves,
  relatives, or close friends?
• How does the press (in your country), the media
  react generally, to experiments made by human
  beings?
• Do doctors easily recommend medicines and
  techniques insufficiently known, or with
  uncertain results?

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Culture key points

1. The meaning of culture was explored and found to
   be of a national humanistic intangible nature.
   Culture is more broadly based than Science.
2. There don't appear to be cultural influences that
   affect the design, conduct and analysis of
   clinical practice, that are country specific.
   Although there are cultural characteristics,
   common to the Czech Republic and Romania that
   emerged, such as implicit trust of patients in
   their doctors in Romania, this results in
   relatively high patient compliance for clinical
   trials.
3. The sensitivities of medical experimentation on
   individuals was discussed. It was found that
   people are more cautious with medical
   experimentation on close ones, than on
   themselves.
4. The press can be distrustful of human
   experimentation, sometimes with good reason.
5. Doctors are usually wary of recommending
   medicines and techniques that are insufficiently
   known or that have uncertain side effects on
   patients.
6. Cultural aspects are often associated with
   religious traditions.
7. More work is needed for a deeper understanding of
   cultural influences on the practice of clinical
   trials in Europe. It is hard to cover the
   differences between countries in just a few
   questions. Research involving a greater number of
   countries is needed. Such research should be
   quantitative as well as qualitative.
8. The impact of globalisation on culture cannot be
   ignored.
9. Scientists are used to the concepts of
   uncertainty and debate. However this does not fit
   well with sound bite journalism. Scientists need
   to be more aware of the limitations of the press
   and the need to prepare media-friendly
   statements. Such statements should not
   overdramatise findings and should be communicated
   in language that is clear to the non- expert.

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Technology issues that were considered

1. Are there any specific technological influences
   in your country, which would have an effect on
   the design, conduct and analysis of clinical
   trials?
2. Do new medical technologies go through a
   controlled clinical trial process before general
   use in your country?
3. Is ethical approval obtained before the use of
   newly designed medical equipment on patients?
4. Is there any exemption for locally (University or
   hospital) designed equipment (as apposed to that
   produced by a large manufacturer).
5. Are there any local (government or charitable
   bodies) grants available for the development of
   new medical equipment?

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Technology key points

1. No specific technologies were found to have an
   effect on the conduct and analysis of clinical
   trials.
2. The CE mark is accepted as the quality standard
   for technological devices.
3. In all EU countries new medical technologies go
   through a controlled clinical trial process
   before general use apart for Slovenia, where
   only a CE mark is necessary.
4. CE marking is helpful as a quality standard
   across Europe, although this is expensive and
   difficult to obtain for a new product. This makes
   local development more complicated and difficult.
   Some potential products have disappeared rather
   than go through the lengthy process.
5. In most countries ethical approval is obtained
   before the use of newly designed medical
   equipment on patients.
6. Sometimes there is exemption for locally -
   University or hospital - designed equipment, as
   opposed to that produced by a large manufacturer.
7. In almost every country there are, either
   government or public funds available for the
   development of new medical equipment, although
   competition is usually fierce.
8. It is important to facilitate European projects
   that enable citizens of NMS to gain expertise and
   access to finance to conduct clinical trials on
   medical technology.
9. Ethics requirements for the development of
   medical technologies are diverse across Europe.
   It would be helpful to have more information on
   this subject, but as change is rapid in this area
   any data collected would quickly become out of
   date.
10. The cost and complexity of obtaining patents is
    high this makes EU technology vulnerable.
11. The formation of a European Ethics Committee,
    upholding minimal, basic ethical standards could
    help harmonize standards for all states,
    especially NMS.
12. To register a technological device in Europe is
    difficult it is a much more complicated process
    than for a new drug. A standardised registration
    process is needed to facilitate full European
    economic potential and competitiveness
13. In some countries there can be a discrepancy
    between official regulations and what actually
    happens.

35
Young People's Advisory Group

1. This group considered the ethics of clinical
   trials in Europe a hot topic for debate.
2. They considered that Europeans usually take an
   individualistic approach and therefore put
   individual safety before the benefits of society
   as a whole.
3. This attitude is not helped by the media which
   generates mistrust of the medical profession.
4. In the cultural context, religion has a small but
   significant role to play in ethics.
5. Historical influences can be strong citizens of
   post communist countries perceive themselves as
   narrow-minded. This can express itself in the
   distrust of governments, conservativism and fear.
6. Apart from inter-country variations in ethics,
   there are also differences between the views of
   professionals and the perceptions of the public.
   Little value is put on these perceptions and the
   public is largely excluded from the debate.
7. Often factors that influence the agenda are
   political and economic rather than ethical.
8. There are always fresh issues emerging which
   cannot be anticipated. Laws are usually made in
   response to an ethical dilemma, rather than the
   other way round.
9. There is a need to educate health professionals
   and the public on ethical issues.

36
RECOMMENDATIONS

• Were made for the major stakeholders in clinical
  trials, namely researchers, ethics committees,
  policy makers and the public

37
Researchers

1. There is a clear gulf between the demands for
   documentation required in different states of the
   EU
2. In some it is prohibitively bureaucratic and
   hampers, or in some cases prevents clinical
   research from taking place
3. In others documentation is inadequate a
   situation that can compromise the quality of
   research as well as patients' dignity, health and
   safety.
4. To overcome this, the following investment by the
   EC should be considered
5. Basic research infrastructure to be made in all
   EU countries. This should be available,
   accessible and affordable (preferably without
   charge) to the researcher. This would for
   example, include access to academic libraries
6. National networks of experts in statistical
   analysis and clinical trail design to be made
   available in each EU country.
7. Lists of experienced researchers, willing to
   mentor less experienced colleagues in NMS, to be
   made available on an official EU website

38
Ethics Committees

1. The composition, standards and functioning of
   ethics committees vary widely between countries.
   To overcome this, the following recommendations
   should be considered
2. Guidelines for the formation and conduct of
   ethics committees in the EU. These need to be
   general enough to be applicable enough to all EU
   countries, yet flexible and sensitive to varying
   contexts and sensitivities
3. A quality assurance programme needs to be
   developed to review the structure, process and
   outcome of these committees. Such a programme
   should first be piloted in a number of
   representative member states
4. Reasonable targets need to be set for efficiency
   and effectiveness. For example, time-related
   goals for processing of applications to ethics
   committees, with an option of a fast track, under
   certain conditions
5. Members of Ethics Committees should receive
   appropriate professional training. For example,
   training and guidance of religious
   representatives of ethics committees in science,
   and vice versa guidance on religious issues for
   health professionals and lay members
6. Members of Ethics Committees should receive
   appropriate remuneration

39
Policy suggestions

1. Research governance should be consistent in all
   EU countries
2. The development of standardized and simple ethics
   committee application process for all member
   states.
3. Separate forms could be developed for different
   clinical/ research contexts eg an observational
   study looking at an anonymised database may need
   a less complicated approach to a randomized drug
   study. However not at the expense of more
   bureaucracy. These could be validated in all EU
   countries
4. A central registration/ database for all European
   clinical trials
5. An identification number to be assigned to each
   clinical trial this would be a necessary
   requirement for publication in a professional
   journal
6. Development of an international agreement on the
   running of clinical trials to include a clause
   that any misconduct abroad can be prosecuted in a
   researcher's home country
7. Issues should be approached in an
   inter-disciplinary manner to examine matters from
   all angles and garner all the relevant expertise
8. Where possible, bureaucratic elements should be
   kept to a minimum

40
The public

1. This section relates to the wider public as well
   as patients who take part in clinical trials
2. The conduct of clinical trials should be a
   transparent process. To achieve this, the
   following recommendations are made
3. Successful applications to ethics committees
   should be made available to the public forum to
   allow opportunities for communication and debate
4. Documentation released should be clearly worded
   and capable of being understood by the general
   public
5. A synopsis of the results should be made
   available in a similar manner
6. For patients
7. Additional measures to enhance the 'informed'
   part of informed consent need to be considered
8. Any documentation for patients should be written
   in clear language, at the relevant reading level
9. Any vested interests of those carrying out the
   trial need to be declared
10. Patients' rights should be protected at policy
    level and by law