J Med Ethics: first published as 10.1136/jme.6.2.58 on 1 June 1980. Downloaded from Journal of medical ethics, I980, 6, 58-6o

World Health Organisation biomedical research guidelines and the conduct of clinical trials

Withold Rudowski Institute of Haematology, Warsaw, Poland

Editor's note practice of medicine and surgery. The special groups ofAdvisory Committees for The increasing importance, recognised by WHO, appointed in the Headquarters and Regional ofprospective randomised clinical trials has led Offices of WHO, emphasised the world-wide to discussion of the needfor their careful regulation importance of standardisation, measurement and in the interests of maintaining high professional terminology in biomedical research. The most ethical standards. Ethical problems which do arise- important need at present is to identify ways of for example where biomedical research in developing providing a comprehensive assessment of the need countries is sponsored from abroad-may best be handled by specially established professional for medical and surgical research. scientific/ethical committees. Randomised clinical trials Introducdon I think that WHO has a continuing interest in The International Federation of Surgical Colleges prospective randomised clinical trials, regarding has been associated for a long time with WHO them as one of the greatest scientific advances in as a non-governmental and non-profit organisation. our time and sometimes the only logical method of Our representatives have had many chances to choosing a method of therapy or prevention. attend the World Health Assembly, the Regional Clinical trials have contributed much to the advance- Meetings of WHO and the meetings of WHO ment of therapy and play a substantial role in the Executive Board. It was interesting to note that a medical care of the sick.' The widening use of great deal of WHO discussion has been devoted to clinical trials has stimulated broad discussion andhttp://jme.bmj.com/ biomedical research. WHO's firm conviction is reflection on the subject of human rights in clinical that continued success is critically dependant upon research on humans. advances in large-scale biomedical research and For this reason WHO sponsored the XII Round their application in the community. In I978 the Table Conference of International Organisations International Conference of WHO held in Alma- of Medical Research in Lisbon on i December Ata, USSR, reaffirmed health as a fundamental 1978, under the general headline 'Medical experi- human right and a worldwide social goal. At the mentation and the protection of human rights'. on September 29, 2021 by guest. Protected copyright. same time 22 specific recommendations were During this meeting several interesting papers were adopted requiring new skills in the philosophy of presented which could be classified as follows: educational and research needs for the era of a) Statutory regulations and ethical conduct. health science up to the year 2000. b) Concepts of clinical trials, and decision making Looking at the activities of the Research Advisory in large scale comparative studies. Committees of WHO in Europe, the following c) Other values and limitations of clinical trials. five priority areas of research promotion and development can be distinguished: It has been emphasised that in clinical trials two must a) Standardisation of methods, measurements and distinct groups be considered-the general terminology in biomedical and health services public and the individuals participating in trials.2 research. The balance of interests between that of the patient b) Prevention, prophylaxis, and early detection of involved in a clinical trials and the general public certain . good may, at times, be extremely delicate. There c) Evaluation of drugs and other therapeutic and are ethical controls of various sorts emerging from diagnostic substances. the Declaration of Helsinki, I964, and the inter- national code the d) Problems of health care delivery. expressed in Tokyo Declaration of I975, through e) Economic aspects of health care. the national system of modification of clinical trials to safeguard the patients, healthy The discussion on these priorities indicates volunteers and the reputation of the profession that an important part of this programme includes and institutions in matters of clinical investigations. both biomedical and organisational aspects of the It is now generally advised to set up ethical World Health Organisation biomedical research guidelines and the conduct of clinical trials 59 J Med Ethics: first published as 10.1136/jme.6.2.58 on 1 June 1980. Downloaded from committees and to refer to them all proposed clinical Externally sponsored research research investigations. The World Medical Asso- Another problem discussed at the Lisbon CIOMS ciation's Helsinki Declaration initiated the setting- Conference was externally sponsored research.5 At up of scientific and ethical committees.3 These the present time the power resources and technical created the terminology recently used in clinical equipment of most of the developing countries may research, the scientific and medical qualifications, not be sufficient to carry on biomedical research and the experimental . The composition on their own. In these circumstances such research of the committees, their activities, of respon- is often sponsored by external agencies. This is sibility and authority were presented by Professor acceptable under the following conditions: Giertz in accordance with WHO views. To my mind more conscious efforts should be made to bring a) Strict administrative and scientific control of about some forms of unified approach at inter- the agreement on the trial by National Scientific national level. Committees. b) The topic of must be relevant I think that at this symposium it is worthwhile to the problems of the recipient country. to quote two definitions: biomedical research and c) The results of the investigations must lead experimental protocol. According to Riis3, by to advances in that particular country and must biomedical research is understood all systematic be applicable in many developing countries.5 collections of with man as the research object. This way the field covers not only basic scientific I think that WHO is looking very carefully at projects but also social, medical and epidemio- external sponsored research in developing coun- logical research. By experimental protocol is tries and recommends very strict monitoring of understood a comprehensive collection of all investigations from a scientific and ethical point of documents describing a given scientific project. view. All sponsored research in developing coun- The following items have to be included: the tries should be subject to an agreement on publica- original concept of the trial, the approach, design tion policy before the work begins.5 and planning, methods of and the The value of controlled clinical trials is well information sheet given to patients.3 known to all who apply scientific methods to Formulation of the original concept and decision clinical problems. Among others, especially among making are particularly important stages for scale non-scientists and politicians there exist, however, comparative studies. Clinical trials often determine many misunderstandings. The most common is precisely the efficacy of treatment and the value of that clinical studies are of an extremely experimental preventive regimen. These large studies 'may cost character and that assigning patients to one or http://jme.bmj.com/ millions of dollars not only in terms of financial another type of treatment protocol is completely but also in other research resources: the large randomised.' This is not true. A patient is assigned number of research facilities and personnel to undergo clinical study when, on the basis of our required.'4 As you all know, WHO has no special- best judgment, an equal possibility exists that each ised research institutions except the International of the compared methods of treatment will be of Agency Against Cancer in Lyons. WHO however advantage to the patient.' Many people express some reservations if children or prisoners are has a very close co-operation with the leading on September 29, 2021 by guest. Protected copyright. medical research centres in the world. One of them subjected to clinical trials.6 I think these doubts can is the National Institute of Health in Bethesda, be avoided by proper planning and decisions of where some principles of large scale clinical trials ethical committees considering the ethical, moral and were elaborated and implemented. At the National scientific issues. Heart, Lung and Blood Institute, Levy and Sondik Finally I would like to stress that a , developed the specialised decision process to aid which is the application of scientific methods to in the formulation, design, conduct, analysis and clinical problems is distant from everyday clinical dissemination of the results of clinical trials. The routine. Clinical trials are a continuous function: progression of clinical trials from the initiation of each stages relies on the previous one, taking advan- an idea, through planning and the conduct of tage of its results and asking new questions which the trial, to the analysis and dissemination of the arise from them. It would not be fitting to consider results can be divided into four phases. At each any clinical trial a final step because no studies in decision point a number of groups review the pro- surgery and in medicine will ever be final but will gress of the trial. According to Levy and Sondik,4 always be subject to revision and revaluation. One these decision factors fall into four major categories. should also never renounce clinical studies pre- maturely simply because another method of a) The state of science related to the trial. therapy has been introduced. Premature termination b) The feasibility of the effect. of clinical trials results in a waste of the contri- c) Potential impact of the trial on health care. butions made up to that time and devalues the d) Ethical considerations inherent in the use of potential hazards to which the patient is exposed human subjects.4-6 during the trial.' 6o Withold Rudowski J Med Ethics: first published as 10.1136/jme.6.2.58 on 1 June 1980. Downloaded from

In summary, I wish to emphasise that in planning 4Levy, R I and Sondik, E J (1978). Decision making in and conducting clinical trials we involve the planning large scale comparative studies. Annals patients. Their cornerstone of trust rests in the oftheNewYorkAcademyoj Science, 304,pp. 441-459. faith that their rights, even those unknown to them, 5Phillips, H H (1978). Externally sponsored research. will be recognised and honoured by the physician. XIIth CIOMS Round Table Conference. Medical These rights were beautifully summarised and experimentation and the human rights. Lisbon. expressed by V Peters;7 6Cooke, R E (1978). Ethical considerations in the selection and recruitment of children for research. a) the right-to seek consultation XIIth CIOMS Round Table Conference. Medical b) the right-fully to understand treatment experimentations and the human rights. Lisbon. c) the right-to know the treatment alternatives 7Peters, V (1979). Progress against cancer, 32/2, p 7. and ramifications d) the right-to help with treatment decisions. Further reading I am deeply convinced that the International Federation of Surgical Colleges is extremely sen- Barton, W L (I979). Alma-Ata: signpost to a new health sitive to these basic human rights in medical era. World health, July, pp I0-14. experimentation. Cox, K (I979). Research into clinical surgery. Manuscript prepared for the Royal Australian College of Surgeons. Sydney. Holland, I F (1979). Ethics for a clinical investigator. References American journal of medicine, 66, pp 554-555. 'Fisher, B (I978). Clinical trials and values limitations. Ramsay, P (1970). The patient as person. New Haven Cancerjournal of clinicians, a8, pp 241-246. Yale University Press p I2. 2Williams, R N (I978). Statutory regulations and ethical Robbins, F C (I978). Criteria of adequate informed conduct. XIIth CIOMS Round Table Conference. consent. XIIth CIOMS Round Table Conference. Medical experimentation and the human rights. Medical experimentation and the human rights. Lisbon. Lisbon. 3Riis, P (I978) Ethical review committees: composition, Vere, D V (1978). Selection and recruitment of healthy authority and influence. XIIth CIOMS Round subjects in research. XIIth CIOMS Round Table Table Conference. Medical experimentation and the conference. Medical experimentation and the human human rights. Lisbon. rights. Lisbon. http://jme.bmj.com/ on September 29, 2021 by guest. Protected copyright.