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.

A PowerPoint summary of“Comparing emerging ethical issues and legal

differences impacting on European clinical trials”

A framework 6 EU project “TWR” PL016621Powerpoint 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.

(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.

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

History of clinical trials1. 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.

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!

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 time3. 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

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

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.

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.

Yellow fever and healthy volunteers1. Dr Carlos Finlay believed the Aedes aegypti

mosquito carried yellow fever2. 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

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

Vulnerable populations1. 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

The Helsinki declaration1. 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

The present position in the EU1. 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

The project1. There are differences in ethics between countries,

there are also differences across disciplines2. 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

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.

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.

Utilitarianism and clinical trials1. 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.

Liberalism and pragmatism1. 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.

Ethics issues that were considered1. 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 consent:

How 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 standards:How (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 Committees:How 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 interests:How is conflict of interests perceived (e.g., social acceptance) and regulated in your country?Are conflicts of interests increasing/decreasing/remaining the same)

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.

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?

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 states6. 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 absent8. 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 states9. 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

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?

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.

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?

Economics: key points1. 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.

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?

Theology: key points1. 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

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?

Culture: key points1. 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.

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?

Technology: key points1. 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.

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.

RECOMMENDATIONS

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

Researchers1. There is a clear gulf between the demands for documentation required in

different states of the EU2. In some it is prohibitively bureaucratic and hampers, or in some cases

prevents clinical research from taking place3. 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

Ethics Committees1. 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

Policy suggestions1. Research governance should be consistent in

all EU countries2. 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

The public1. 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:

1. Successful applications to ethics committees should be made available to the public forum to allow opportunities for communication and debate

2. Documentation released should be clearly worded and capable of being understood by the general public

3. A synopsis of the results should be made available in a similar manner

3. For patients: 1. Additional measures to enhance the

'informed' part of informed consent need to be considered

2. Any documentation for patients should be written in clear language, at the relevant reading level

3. Any vested interests of those carrying out the trial need to be declared

4. Patients' rights should be protected at policy level and by law