ETHICAL GUIDELINES IN BIOMEDICAL RESEARCH

1. ETHICAL GUIDELINES IN BIOMEDICAL RESEARCH FACULTY OF MEDICINE PADJADJARAN UNIVERSITY BANDUNG 2009

2. What is RESEARCH ?

3. A PROCESS & ARRANGEMENT OF STEPS WHICH ARE PLANNED AND SYSTEMATIC, • TO OBTAIN AN ANSWER TO A CERTAIN QUESTION

4. STEPS : • IDENTIFICATION, SELECTION & DETERMINATION AND FORMULATION OF A PROBLEM 2. LITERATURE STUDY 3. FORMULATION OF HYPOTHESIS 4. IDENTIFICATION/CLASSIFICATION/ DESCRIPTION OF VARIABLES OPERATIONALLY 5. SELECTION OF DATA AS THE INSTRUMENTS OF DEDUCTION PROCESS 6. ARRANGEMENT OF THE RESEARCH DESIGN 7. SAMPLE DETERMINATION 8. DATA COLLECTION 9. DATA ANALYSIS 10. INTERPRETATION OF ANALYSIS RESULTS 11. REPORTING

5. RESEARCH DESIGN • HISTORICAL RESEARCH • DESCRIPTIVE RESEARCH • DEVELOPMENTAL RESEARCH • CASE STUDY AND FIELD RESEARCH • CORRELATIONAL RESEARCH • CAUSAL-COMPARATIVE RESEARCH • EXPERIMENTAL RESEARCH

6. HISTORICAL RESEARCH GOAL : TO RECONSTRUCT THE PAST CHARACTERISTICS : SYSTEMATIC & OBJECTIVE Expl. STUDY ABOUT CHINESE TRADITIONAL MEDICINE IN PRACTICE IN THE PAST AND ITS CURRENT RELEVANCY

7. DESCRIPTIVE RESEARCH GOAL : TO DESCRIBE SOME DATA / FACTS Expl : A SURVEY IN A CERTAIN AREA ABOUT THE NEED OF EDUCATION

8. DEVELOPMENTAL RESEARCH GOAL : TO STUDY THE PATTERN AND SEQUENCE OF GROWTH OR ALTERATION AS A FUNCTION OF TIME Expl : LONGITUDINAL STUDY ABOUT CHILDREN’S GROWTH IN SOME DIFFERENT PHASES

9. CASE STUDY AND FIELD RESEARCH : GOAL ; TO STUDY THE RECENT CONDITION AND ITS BACKGROUND AND THE INTERACTION WITH ITS ENVIRONMENT OF A CERTAIN SOCIAL UNIT Expl : STUDY OF THE COGNITIVE DEVELOPMENT IN CHILDREN

10. CORRELATIONAL RESEARCH GOAL : TO SEARCH, THE EXTENT TO WHICH THE VARIABLES IN A CERTAIN FACTOR HAVE SOME RELATIONSHIPS WITH OTHER VARIABLES IN THE OTHER FACTORS BASED ON A COEFFICIENT OF CORRELATION. Expl : A STUDY ABOUT THE CORRELATION BETWEEN I.Q. SCORE AND LEARNING ACHIEVEMENT INDEX

11. CAUSAL-COMPARATIVE RESEARCH GOAL : TO STUDY THE POSSIBILITY OF A CAUSAL - COMPARATIVE RELATIONSHIP BASED ON THE RESULT OF THE STUDY TO RE-STUDY THE FACTORS WHICH COULD BE THE CAUSE OF THE PHENOMENON Expl : STUDY ABOUT THE CHARACTERISTICS OF GOOD TEACHERS, USING THE HISTORY OF THEIR ACHIEVEMENT

12. EXPERIMENTAL RESEARCH GOAL : TO STUDY THE POSSIBILITY OF CAUSAL COMPARATIVE CORRELATIONS GIVES CERTAIN TREATMENT CONDITIONS TO ONE OR MORE EXPERIMENTAL GROUPS COMPARES ITS RESULT WITH ONE OR MORE OTHER UNTREATED GROUPS

13. Expl :. USING A DISCUSSION METHOD (TREATMENT) TO SHOW THE EFFICACY OF THAT METHOD (ACHIEVENT INDEX)

14. WHY SHOULD WE LEARN ETHIC IN BIOMEDICAL RESEARCH ?

15. PERSONS WHO PRACTICE MEDICINE ARE PROFESSIONAL CHARACTERISTICS OF PROFESSIONAL ARE : SUFFICIENT COMPETENCE IN SCIENSE AND TECHNOLOGY ACCEPTABLE CLINICAL SKILL ETHICALLY ACCOUNTABLE CONDUCT

16. Medicine as a life science develops progressively, especially after the second part of 18 th century. All these developments could not have taken place without research, especially biomedical research. After insecticides, Researches that started in the laboratory (in vitro), moved quickly into area of real life (in vivo), using animal as well as human being, Tissues, organs or total human body were used as subjects. It seems that in their copious enthusiasm to defeat the disease and prolonging life, the researchers suffered of a loss of one important human character, namely, sense of respect to human being.

17. An unequivocal and famous examples to this phenomenon were various studies conducted by Doctors in Germany, during the 2 nd World War, using prisoners as subjects. Advances in biomedical sciences and technology, and their application in the practice of medicine, raise some anxiety among the public, and confronting society with new ethical problems. Society devises measure to protect against possible abuses. The first international code of ethics for research involving human subjects ---- Nuremberg Code--- was a response to the atrocities committed by the Nazy research physician, revealed at the Nuremberg War Crimes Trials. The Nuremberg Code, issued in 1947, laid down the standard for carrying out human experimentation, emphasizing the subject’s voluntary consent.

18. The next important step was taken by the World Medical Assembly, in 1964, which adopted the Declaration of Helsinki, recently revised in Rep. of South Africa, 1996, which lays down ethical guidelines for research involving human subjects In 1982, in view of special circumstances of developing countries in regard to the applicability of the Nuremberg Code and the Declaration of Helsinki, the Council of International Organization of Medical Sciences (CIOMS) and WHO, issued Proposed International Guidelines for Biomedical Research Involving Human Subjects.

19. In accordance to these guidelines, similar committees were established in many countries. In USA, in 1974 they have National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Medical Research Council of Canada, formed in 1976, a Committee, which is called Working Group on Human Experimentation. In England, it is the Royal College of Medicine who is in charge. In Indonesia, the first initiative was taken by the School of Medicine, University of Indonesia. An agreement was made during a workshop in 1986 that every medical institute should have a Committee who will be responsible in reviewing all biomedical research proposal involving human subjects. In Bandung Ethical Committee for Biomedical Research was established in 1993.

20. GUIDELINES FOR MEDICAL RESEARCH World Medical Association Declaration Helsinki. Basic Principles • 1. Biomedical research involving human subjects must conform to generally accepted scientific principles and should be based on adequately performed laboratory and animal experimentation and on a thorough knowledge of the scientific literature • 2. The design and performance of each experimental procedure involving human subjects should be clearly formulated in an experimental protocol which should be transmitted for consideration, comment and guidance to a specially appointed committee independent of the investigator and the sponsor provided that this independent committee is in conformity with the laws and regulations of the country in which the research experiments is performed. • 3. Biomedical research involving human subjects should be conducted only by scientifically qualified persons and under the supervision of a clinically competent medical persons. The responsibility for the human subjects must always rest with a medically qualified person and never rest on the subject of the research, even though the subject has given his or her consent. • 4. Biomedical research involving human subjects cannot legitimately be carried out unless the important of the objective is in proportion to the inherent risk to the subject.

21. 5. Every biomedical research project involving human subjects should be preceded by careful assessment of predictable risks in comparison with foreseeable benefits to the subjects or to others. Concern for interest of the subject must always prevail over the interests of science and society. • 6. The right of the research subject to safeguard his or her integrity must always be respected. Every precaution should be taken to respect the privacy of the subject and to minimize the impact of the study on the subject’s physical and mental integrity and on the personality of the subject. • 7. Physicians should abstain from engaging in research project involving human subjects unless they are satisfied that the hazards involved are believed to be predictable. Physicians should cease any investigation if the hazards are found to outweigh the potential benefits. • 8. In publication of his or her research, the physician is obliged to preserve the accuracy of the results. Reports on experimentation not in accordance with the principles laid down in this Declaration should not be accepted for publication.

22. 9. In any research on human beings, each potential subject must be adequately informed of the aims, methods, anticipated benefits and potential hazards of the study and the discomfort it may entail. He or her should be informed that he or she is at liberty to abstain from participation at any time. The physician should then obtain the subject’s freely given informed consent, preferably in writing. • 10. When obtaining informed consent for the research project the physician should particularly cautious if the subject is in a dependent relationship to him or her or may consent under duress. In that case the informed consent should be obtained by a physician who is not engage in the investigation and who is completely independent of this official relationship • 11. In case of legal incompetence, informed consent should be obtained from the legal guardian in accordance with national legislation. Where physical or metal incapacity makes it impossible to obtain informed consent, or when the subject is minor, permission from the responsible relative replace that of the subject in accordance with national legislation. Whenever the minor child is in fact able to give a consent, the minor’s consent must be obtained in addition to the consent of the minor’s legal guardian. • 12. The research protocol should always contain a statement of the ethical considerations involved and should indicate that the principles enunciated in the present Declaration are complied with.

23. MEDICAL RESEARCH COMBINED WITH PROFESSIONAL CARE (CLINICAL RESEARCH) • In the treatment of the sick person, the physician must be free to use a new diagnostic and therapeutic measure, if in his or her judgment it offers hope of saving life, reestablishing health or alleviating suffering. • The potential benefits, hazards and discomfort of a new method should be weighed against the advantages of the best current diagnostic and therapeutic methods. • In any medical study, every patient – including those of a control group, if any – should be assured of the best proven diagnostic and therapeutic method. This does not exclude the use of inert placebo in studies where no proven diagnostic and therapeutic method exists.

24. The refusal of the patient to participate in the study must never interfere with the physician-patient relationship. • If the physician considers it essential not to obtain informed consent, the specific reasons for this proposal should be stated in the experimental protocol for transmission to the independent committee • The physician can combined medical research with professional care, the objectives being the acquisition of new medical knowledge, only to the extent that medical research is justified by its potential diagnostic and therapeutic value for the patient

25. NON-THERAPEUTIC BIOMEDICAL RESEARCH INVOLVING HUMAN SUBJECTS (NON-CLINICAL BIOMEDICAL RESEARCH) • In the purely scientific application of medical research carried out on human being, it is the duty of the physician to remain the protector of the life and health of that person on whom biomedical research is being carried out. • The subjects should be volunteers – either healthy persons or patients for whom the experimental design is not related to patient’s illness • The investigator or the investigating team should discontinue the research if in his / her or their judgment it may, if continued, be harmful to the individual. • In research on man, the interest of science and society should never take precedence over considerations related to the well being of the subject.

26. INTERNATIONAL ETHICAL GUIDELINES FOR BIOMEDICAL RESEARCH INVOLVING HUMAN SUBJECTS This guidelines was adopted in 1982, as a result of collaboration between WHO and CIOMS. The AIDS epidemic, particularly the need to carry out vaccine and drugs trial, has raised ethical questions that were not foreseen when the Declaration of Helsinki was formulated. Two points which merit special attention. • All research involving human subjects should be conducted in accordance with three basic ethical principles, namely respect for persons, beneficence and justice • Scientific review and ethical review can not be clearly separated: scientifically unsound research on human subjects is ipso facto unethical in that it may expose subjects to risk and inconvenience to no purpose

27. GUIDELINES FOR GOOD CLINICAL PRACTICE IN INDONESIA CLINICAL TRIAL = IS A COMMON TECHNICAL TERM FOR EVERY STUDIES ON DRUGS OR MEDICAL DEVICES USING HUMAN SUBJECTS It can only be used on human subjects after a complete satisfactory animal experiment Clinical Trial consist of 4 phases. Phase 1. The study is conducted in hospital or health institution under strict professional supervision. Subjects consist of a small number of healthy volunteers. The objective is to study the kinetic and dynamic of the drug on healthy person. Ethically speaking. Phase 1 belongs to non therapeutic research. Phase II In this phase, a small number patients is used, with the objective to study the therapeutic effect of the drug. Selection of subjects and implementation of study must be carried out under a very strict supervision of competent clinicians. Data as obtained in Phase I are also recorded Phase III The drug is given to a bigger number patients, which is to be a representative of population. It means that selection of patients is not too strict and the distribution of drug can be supervised by General Physician. Rare side effect may be encountered during this phase. If the effectiveness and safety of the drug is confirmed, then it is ready for marketing Phase IV (Post Marketing Study)

28. The study design for Phase IV • Should be meticulously prepared • The team must consist of clinician, epidemiologist and statistician. • Separated Ethical Clearance must be obtained. As most the subjects are common people, special precaution should be exercised to protect them, such as providing facilities to overcome side effects. • Evaluation should be done periodically. INFORMED CONSENT. Is consent given by a competent individual who has received the necessary information; who has adequately understood the information; and who after considering the information, has arrived at the decision without having been subjected to coercion, undue influence or inducement, or intimidation.

29. ESSENTIAL INFORMATION FOR PROSPECTIVE RESEARCH SUBJECTS • The expected duration of subject’s participation • The aims and methods of research • The benefits that might be expected to the subject or to the others • Any foreseeable risks and discomfort associated with participation in the research • Any alternative procedures or courses of treatment that might be advantageous to the subject as the procedures or treatment being tested. • The extent of confidentiality • The extent of investigator’s responsibility, if any, to provide free of charge medical services, for specified types of research – related injury • Whether the subject or subject’s family or dependants will be compensated for disability or death resulting from such injury • The individual is free to refuse to participate and will be free to withdraw from the research at any time without penalty or loss of benefits to which he or she would otherwise be entitled

30. RESEARCHES INVOLVING SPECIAL SUBJECTS • Research Involving Children. • The participation of children is indispensable for research into diseases of childhood or conditions to which children are particularly susceptible. • Children will not be involved in research that might equally well be carried out with adults. • The purpose of the research is to obtain knowledge relevant to the health needs of children. • The parent or legal guardian of each child has given proxy consent • The consent of each child has been obtained to the extent the child’s capability

31. Research Involving Pregnant or Nursing (breastfeeding) women. Pregnant or nursing women should in no circumstances be the subjects of non – clinical research unless the research carries no more then minimal risks to the fetus or nursing infant and the object of the research is to obtain new knowledge about pregnancy and lactation ( e.g. Trial designed to test the safety and efficacy of a drug for reducing perinatal transmission of HIV infection from mother to child).

32. Research Involving Persons with Mental or Behavioral Disorders. Such persons will not be subjects of research that might equally be carried out on persons in full possession of their mental faculties. The purpose of the research is to obtain knowledge relevant to particular health needs of persons with mental or behavioral disorders. The consent of each subject has been obtained to the extent that subject’s capabilities. In the case of incompetent subject, informed consent is obtained from the legal guardian or duly authorized person.

33. Research Involving Persons with Vulnerable Social Status. The quality of consent given by this group should be carefully scrutinized because their participation might be influenced by the benefits they are supposed to get from this research. They are medical or nursing students, persons working in hospitals, laboratory and pharmaceutical industry, prisoners and member of military unit.

34. Research in the Developing Communities. Most of the people involved are layman who have no idee about the importance of the research. In this case the consent should be obtained from the local leaders, who will be responsible for conveying the necessary information

35. ETHICAL ASPECTS IN SCIENTIFIC MEDICAL WRITING If a study has been completed, the investigator has to make a final scientific report, which should be widely published, if possible in the international journal. Without publication he might be considered as being ignorant to the true meaning of research and science. In fact from the ethical point of view, one may found him as more or less guilty, because the principle objective of research is to discover the relative truth of the law of nature and all the things related to it. His discovery is expected to be beneficial to the community. Without publication, nothing can be expected. In the early stage of study, it is common for every investigators to make literature study or ask for consultation to other people to complete his research protocol. Afterward he will need more information to analyze and compare his result. Therefore it is only reasonable for them to publish their results as a compensation for what they get before. In Medical research the need for new information based on proper biomedical research is imperative, because any new discovery may have a colossal impact to the well fare or mankind.

36. Every scientist preparing for his scientific article, should start with only one intention, namely, to write the truth, nothing but the truth. Using imaginary or fictitious data can only means self deceiving and his name will be tainted. His false information might also be detrimental to other people. In the sense of the law of nature as a whole, he is also guilty of being dishonest to the Creator of the universe. Consequently, a scientific writer must have a clean soul, honest with noble intention. One big problem in research and scientific writing is that there is no law against this kind of violation. Only ethical sanction could be applied. As scientists, we are responsible to uphold this ethic conduct, so that the integrity of Indonesian scientists could be accounted to internationally.

37. The Standard Structure of Scientific Writing. • Title • Name of author (s) • Address of institution • Summery • Introduction • Materials and Methods • Results • Discussion and Conclusion • Acknowledgement • References

38. There are two ethical issues in scientific writing, namely General and Specific issues

39. General Ethical Issues. • An article can only be published, once. • It is not permissible to publish an article in two different journal. • If a writer wants to publish an article which has been published elsewhere, he must ask for permission from the related journal. • For articles which have been presented in the congress or symposium, permission must be asked from the committee. When the article is published, a footnote must be added to state that the article has presented in the congress. • It is unethical, if one whole article be published as a series of small articles with the intention of procuring extra profit • It is unethical to make several articles based on the same data, by putting some variation • It is unethical if part of the data belongs to other investigator, yet the related person is not included in preparation of the paper. • To use data belonging to other persons, such as table, graph, photo etc., permission must be asked first from the writer, or at least the source must be stated.

40. Specific Ethical Issues. These issues are related to each element of standard structure of article as mentioned above, for the sake of simplicity, not all elements will elaborated

41. Title. • Must be precise, correct, logic and accurate. • A bombastic title should avoided • It must not be a part of propaganda or promotion • It is unethical to show off personal interest • The title must has some bearing to the issues being studied. Name of Author (s). • Only persons who are actively involved from the beginning to the end can be considered as author (s) • Persons not directly involved may not be included, whatever the reason might be • It is unethical include someone’s name, just because he or she is well known person, the head of the institution or his or her superior. • Everyone whose name is printed in a publication must be aware of it, and has a full responsibility to the content and form of the article. • Sequence of the author’s name must have some bearing to their role in the research • The name of a candidate researcher, performing his study under supervision of his senior, should not be neglected. In fact, he could become the main author, and his senior as co author

42. The Influence of Chloramphenicol and Ampicillin on the Population and Toxin of Clostridium difficille in the Stool of Patients with Typhoid Fever and Pneumonia (In Relation to the Incidence of Colitis due to the Use of Antibiotics) The Effect of Citric Acid and Ferrosulfate as Suplement on Oxbile Media to Culture of Salmonella typhi

43. References. • World Medical Association Declaration of Helsinki, 48 th General Assembly, Rep. of South Africa. • International Ethical Guidelines for Biomedical Research Involving Human Subjects, CIOMS / WHO Geneva, 1993. • Guidelines for Good Clinical Practice in Indonesia. Badan Pengawas Obat dan Makanan. Dep. Kes / Kes. Sos.

44. Dank U well Syukron & Thank you