Table 1 Ethical imperatives and their levels of consensus (Strong Consensus [SC] 4 or 5/5; Moderate Consensus [MC] 3/5; Weak Consensus [WC] 2/5; No Consensus [NC] 1/5; Non Guideline-based Imperative [NGI])
From: What do international ethics guidelines say in terms of the scope of medical research ethics?
I Comparison of the basic principles (preambles) |
1. The interests and welfare of the human being participating in research shall prevail over the sole interest of society or science. WC |
2. Respect for persons (autonomy of autonomous agents and protection for those who lack autonomy) WC respect for persons (autonomy for autonomous agents and protection for those who lack autonomy) |
3. Beneficence WC |
3.1. Do no harm WC |
3.2. Maximize possible benefits and minimize possible harms WC |
4. Justice as fairness in distribution or what is deserved must be upheld WC |
5. It is the duty of the physician to promote and safeguard the health, well-being and rights of patients, including those who are involved in medical research. WC |
6. Medical progress is based on research that ultimately must include studies involving human subjects. WC |
7. The primary purpose of medical research involving human subjects is to understand the causes, development and effects of diseases and improve preventive, diagnostic and therapeutic interventions WC |
8. Medical research should be conducted in a manner that minimizes possible harm to the environment. NC |
9. Distinction between therapy and research must be upheld NC |
II Research collaboration |
1. Involvement of community representatives in planning research, conducting research, disseminating results and use of results to improve health NGI |
2. The details of health care services provided to subjects/community/country during and after the trial should be agreed by the sponsor, officials of the host country, other interested parties, and when appropriate, the community from which subjects are drawn. NC |
3. Research should be respectful of community’s values, circumstances, culture, and social practices. NC |
4. Distribution of tangible benefits such as authorship and intellectual property rights must be fair NGI |
5. Discussions on responsiveness should include representatives of stakeholders in the host country NC |
6. In case of capacity building, the objectives should be determined via a dialogue between external sponsor and host-country NC |
7. For equivalency trials, approval should be dependent on the joint negotiations, planning, and justification of the sponsor and health authorities of the host country NC |
III Social value |
1. Research’s social value must be enhanced NGI |
Responsiveness |
2. Research must be responsive to health needs and priorities of host country WC |
3. For minor research studies whose outcome is scientific knowledge, there must be assurance that scientific knowledge developed will be for the benefit of the population NC |
4. Research should have a potential value for the prospective beneficiaries NC |
5. Individuals/groups should benefit from the conduct and the results of the research NGI |
Reasonable availability |
6. In some instances, drugs should be made available to subjects post-authorization NC |
7. Relevant considerations of reasonable availability include the following: |
7.1. Length of time intervention will be made available to subjects, community or population NC |
7.2. Severity of medical condition NC |
7.3. Effect of withdrawing the study drug NC |
7.4. Cost to subject or health service NC |
7.5. Question of undue inducement NC |
Social value in resource-poor settings |
8. Research in poor countries whose results are used primarily for the benefit of affluent countries may be characterized as exploitative NC |
9. Negotiations on studies in poor countries should include the following: |
9.1. Health care infrastructure required NC |
9.2. Likelihood of authorization for distribution NC |
9.3. Decisions regarding payments, royalties, subsidies, technology and intellectual property; distribution costs NC |
10. The development of health-care infrastructure to be used in research and beyond in countries with limited resources must happen at the onset NC |
11. For externally sponsored collaborative research where the host country lacks the capacity to assess and ensure scientific quality and/or ethical acceptability, sponsors/investigators must ensure that the research contributes effectively to national or local capacity to design and conduct biomedical research NC |
12. In countries with limited capacity of ethical/scientific review, capacity building expected from sponsor dependent on magnitude of research NC |
13. Capacity building includes the ff: |
13.1. Establishing and strengthening independent and competent ethics review processes and monitoring NC |
13.2. Strengthening research capacity NC |
13.3. Developing technologies appropriate to health-care and biomedical research NC |
13.4. Training of research and health-care staff NC |
13.5. Educating the community from which subjects will be drawn NC |
14. Obligations of sponsor to provide health care services vary with the circumstances of particular studies and the needs of the host country NC |
Fair benefits |
15. Distribution of fair benefits to the community NGI |
IV Scientific validity |
Scientific design |
1. Scientific design and statistical methods satisfy generally accepted standards and achieve research objectives before approval and throughout research SC |
2. Study justified by previous studies and current knowledge SC |
3. Research on humans only when there is absence of alternatives WC |
4. Research offers means for information not otherwise attainable NC |
5. Assessment of scientific quality should take account of the following: |
5.1. Research design NC |
5.2. Objectives NC |
5.3. Technical feasibility NC |
5.4. Statistical methods NC |
5.5. Potential for reaching valid conclusions with the smallest possible number of participants NC |
6. Less invasive procedures should be used once they become available NC |
7. Study results must be interpretable and useful in the context of health problem NGI |
8. Research design must be feasible given the context NGI |
Protocol |
9. Design and performance of study must be justified in the protocol WC |
10. For multi-center research, any change in the protocol should be made at every collaborating center, or there must be an explicit inter-center comparability procedure NC |
Professionalism |
11. Research conducted only by scientifically qualified persons. Highest degree of skill and care required through all stages MC |
12. Physicians who supervise patients must be competent and qualified NC |
13. The current state of the art of scientific knowledge and clinical experience determine the professional standards and skills expected of professionals in the research NC |
14. Investigators should not enter into agreements that unduly interfere with their access to data, ability to analyze data independently, to prepare manuscripts, or to publish them NC |
Use of comparator |
15. Exception to the rule that study drug must be compared with established effective intervention: when established effective intervention is not available and is not likely to be available in the country. NC |
16. It is scientifically and ethically preferable to conduct equivalency trials in countries where established effective intervention (as control) is already available. NC |
17. For equivalency trials, in the event that established effective intervention is not available and will not be available in the host country, there must be assurances that investigational intervention will be made reasonably available in host country or community NC |
18. Studies that do not compare a study drug with an established effective intervention are allowed given the following: |
18.1. Responsiveness to health needs of population NC |
18.2. When marketing authorization is secured, drug will be reasonably available to the population NC |
18.3. Scientific and ethics committees satisfied that the use of established effective intervention would not yield scientifically reliable results relevant to the study population NC |
Issues with placebo |
19. Placebo may be used given the following: |
19.1. No proven intervention exists MC |
19.2. Participants on placebo not subject to additional risks or serious or irreversible harm WC |
19.3. Participants exposed to at most temporary discomfort or delay in relief of symptoms (acceptable risk) WC |
19.4. Extreme care to avoid this option NC |
19.5. Use of comparator would not yield scientifically NC reliable results |
20. Ethical acceptability of placebo trials increases as time decreases and change to active treatment (escape treatment) possible in case of intolerable symptoms NC |
21. Trials with placebo that entail only minor risks (even if noninferiority or equivalency trials are possible) may be ethically acceptable given the following: |
21.1. REC must be satisfied that the safety and human rights of subjects are fully protected NC |
21.2. Participants are fully informed about alternative treatments NC |
Reexamination |
22. When benefit/risk balance has been disturbed, the trial’s continuation should be reconsidered WC |
23. In the event of scientific developments, research should be re-examined by a competent body, REC, or DSMB. NC |
24. The purposes of re-examination of research project are the following: |
24.1. Research needs to be discontinued or if changes are necessary NC |
24.2. Research participants or their representatives need to be informed of developments NC |
24.3. Additional consent required NC |
V Participant selection |
1. Participants are selected to maximize social value and enhance the possibility of benefits to participants NGI |
2. Research population is selected to ensure compliance with scientific norms and generate valid and reliable data MC |
2.1. Underrepresented groups are given appropriate access to participation WC |
2.2. Research should not be offered only to some favored patients (for therapeutic research) or to undesirable persons (for risky research) NC |
2.3. The exclusion of groups/communities that might benefit should be ethically justified NC |
3. Research population selected to minimize risks to participants NGI |
3.1. There should be an order of preference of participants based on ability of members of the class to bear burdens and the appropriateness of placing further burdens on already burdened persons. NC |
3.2. For nontherapeutic research with risks, less burdened classes of persons should be called upon first, unless research is directly related to the condition of the more burdened class. NC |
4. Groups/communities are selected in such a manner that burdens and benefits are equitably distributed. Deviations from this must be morally justifiable. NC |
5. Subjects should be drawn from the qualifying population without prejudice, unless there is a sound scientific reason NC |
VI Favorable benefit/risk ratio |
Risks |
1. Risks and burdens minimized SC |
2. Various risks to individual subjects and others (physical, psychological, social, legal) delineated and probability and magnitude quantified to the extent possible MC |
3. No unnecessary risks WC |
4. Risks monitored, assessed, and documented WC |
5. Risks that may affect individuals, families, or society (or a part of society) must be taken into consideration NC |
6. Method to ascertain risk explicit NC |
7. Information on risk must also cover risks related to individual characteristics of the participants such as age, presence of disorders, among others NC |
8. Harm to environment must be minimized NC |
Benefits |
9. Various possible benefits to individual subjects delineated and probability and magnitude quantified to the extent possible WC |
10. Benefits to participants maximized WC |
11. Benefits to other individuals or groups affected must be carefully assessed NC |
Assessment |
12. Risk justified: risk do not outweigh potential benefits (risk to subjects outweighed by anticipated benefit to subject + anticipated benefit to society SC |
13. Risk and benefit to subjects are usually considered as carrying special weight NC |
14. Interests other than those of the subject may at times justify risks as long as subjects’ rights are protected NC |
15. In cases of direct benefit, higher risks may be acceptable provided the risks are proportional to benefits NC |
16. When assessing direct benefits, a particular course of action must be judged in the light of the participant’s specific health problem. NC |
17. Therapeutic interventions are justified, in light of benefits and risks, that they will at least be as advantageous to subjects as any available alternative. NC |
18. Nontherapeutic interventions justified by expected benefits to society NC |
19. Risks of nontherapeutic interventions must be reasonable in relation to knowledge to be gained NC |
20. Nontherapeutic research must entail no more than acceptable risk and burden to the participant NC |
21. In nontherapeutic research, the level of risk and burden to individuals able to consent may be higher compared to those not able to consent NC |
22. For nontherapeutic research, when assessing an intervention, it must meet the criteria of relevance and proportionality between the aim pursued and means employed. NC |
23. In assessing risks and benefits of a protocol to a population, it is appropriate to consider the harm that could result by foregoing the research. NC |
24. Determine if estimates of risks and benefits are reasonable NC |
25. Net risk: knowledge to be gained justifies risk NGI |
VII Independent review |
Research Ethics Committee (REC) Composition/requirements |
1. Independent and competent MC |
2. REC provides reasons for decision WC |
3. REC members should declare possible conflict of interest WC |
4. REC member with interest on a proposal should not take part in assessment WC |
5. REC must be multidisciplinary WC |
6. Potential conflict of interest, as well as the perception of it, may be as important as actual conflicts. NC |
7. Review process transparent NC |
8. REC members who withdraw due to conflict of interest should be allowed to offer comments or respond to questions. NC |
9. REC members replaced periodically NC |
10. Financial assistance should not be provided directly to the REC to avoid conflict of interest and to safeguard the independence of their review. Instead, funds should be made available to appropriate authorities or to the host research institute. NC |
11. Participation of laypersons important; the layperson should not be a healthcare professional nor have experience in carrying out biomedical research NC |
12. Thought should also be given to gender and cultural balance in the REC composition. NC |
Rights and responsibilities of RECs |
13. An REC must examine the following: |
13.1. Scientific merit: aim study design, safety provisions MC |
13.2. risks justified and benefits maximized WC |
13.3. if monetary and in-kind recompense constitute undue inducement WC |
13.4. IC procedures satisfactory NC |
13.5. Subject selection equitable NC |
13.6. clear wording of info sheet NC |
13.7. when intimidation may be present in securing IC, REC consider whether a neutral 3rd party should seek IC NC |
13.8. ethical acceptability of placebo NC |
13.9. if procedures are sufficient to verify if subject is capable of consent NC |
13.10. In terms of compensation, REC should determine the ff in advance |
13.10.1. Injuries for which subjects will receive free treatment and in case of impairment be compensated NC |
13.10.2. Injuries for which they will not be compensated NC |
14. RECs have the right to report to institutional or governmental authorities any serious or continuing non-compliance. NC |
15. Unexpected or unforeseen adverse reactions must be presumed compensable NC |
16. When risks are significant, there should be extraordinary insistence by REC on justification NC |
For the investigator/sponsor |
17. Every interventional study should be submitted to an REC for independent examination and approval. MC |
18. At the end, final report with summary of findings and conclusions must be submitted to REC. WC |
19. Research project should be submitted to the state where research is to take place. NC |
20. All information necessary for ethical assessment shall be provided in writing to the REC. NC |
21. The following shall be provided to the REC: |
21.1. Info about principal researcher NC |
21.2. Aim and justification of research NC |
21.3. Methods and procedures including statistical and other analytical techniques NC |
21.4. Summary of the project NC |
21.5. Statement on previous and concurrent submissions of the project NC |
21.6. Justification for involving human beings NC |
21.7. Inclusion/exclusion criteria NC |
21.8. Reasons for the use or absence of control groups NC |
21.9. Nature and degree of foreseeable risks NC |
21.10. Nature, extent, and duration of interventions NC |
21.11. Arrangements to monitor, evaluate, and react to contingencies NC |
21.12. Timing and details of info and the means proposed for the provision of info NC |
21.13. Documentation for IC/authorization for participation NC |
21.14. Arrangements to ensure privacy and confidentiality NC |
21.15. Arrangements for information generated during research which may be relevant to the health of the participant NC |
21.16. Details of all payments/rewards NC |
21.17. Conflict of interest of researchers NC |
21.18. Details of potential further uses, including commercial, of results, data, or biological materials NC |
21.19. Other ethical issues perceived by researcher NC |
21.20. Insurance or indemnity to cover for damages that may arise during research NC |
22. REC may request for additional necessary information NC |
23. No protocol amendment w/o REC approval NC |
24. Unexpected or unforeseen adverse reactions must be reported to the REC for prompt review as they occur. NC |
25. REC should be informed of the reasons for premature termination of a project NC |
Externally sponsored studies |
26. Ethical standards outside the country of the sponsor should be no less stringent WC |
27. Local or national REC reviewing proposals for an external sponsor should have members who are thoroughly familiar with customs and traditions and sensitive to human rights issues. NC |
28. Local RECs are usually not authorized to change doses of drugs, inclusion criteria, or similar modifications. NC |
29. Changes recommended/demanded by local RECs should be reported to the sponsor for action to ensure protection of other subjects and validity across sites. NC |
30. The REC and the health authorities of the host country should verify if the research is responsive to the health needs and priorities of the host country. NC |
31. Ethical reviews should be done in both the country of the sponsor and of the host. NC |
32. When sponsor is an international organization, review of protocol must be in accordance with its own independent ethical review of standards and procedures. NC |
33. RECs within the sponsoring country/international org should determine the following: |
33.1. Scientific methods sound and suitable to the aims of the research NC |
33.2. Adequate standards of safety NC |
33.3. Sound justification for conducting the study in the host country NC |
33.4. Research in compliance with ethical standards of the sponsor country/international organization NC |
34. When the host country has a developed capacity for independent ethical review, review in the sponsor country may be limited to ensuring compliance with broadly stated ethical standards. NC |
35. When host country does not have a developed capacity for review, full review in the sponsoring country or international organization is necessary NC |
36. Multiple reviews should be minimized and reconciled NC |
When deception/incomplete disclosure is involved |
37. When deception is necessary in the research’s methodology, the REC should look into the following: |
37.1. Consequences for subjects being deceived NC |
37.2. Adequate plan for debriefing subjects (whether and how) results NC |
37.3. Justification of sponsor that no other research method would suffice NC |
37.4. Justification from sponsor that significant advances could result from the research NC |
37.5. That nothing has been withheld that, if divulged, would cause a reasonable person to refuse to participate NC |
38. In case of research involving incomplete disclosure, the REC should look at the following: |
38.1. Incomplete disclosure is truly necessary in the research NC |
38.2. No undisclosed risk that is more than minimal NC |
38.3. Adequate plan for debriefing subjects and disseminating results to them NC |
39. REC should review and approve all proposals to deceive persons other than the subjects NC |
40. In cases when other persons (not the subjects) are to be deceived, REC must determine whether these other persons are similarly entitled to the prompt and honest answering of questions NC |
41. When subjects cannot be told that information in the IC has been withheld, explicit REC approval necessary NC |
Studies affecting groups |
42. In studies such as epidemiology or sociology where risks to groups may exist, REC must ensure that interests of all concerned have been given due consideration. NC |
VIII Informed consent (IC) |
Culture-appropriate consent |
1. Disclosure forms and procedures are sensitive to culture, language, context SC |
2. Recruitment procedures and incentives are consistent with cultural, political, and social practices NGI |
3. Mechanisms to symbolize consent are consistent with culture and context NGI |
Securing consent |
4. Consent preferably in writing; if not, must be formally documented and witnessed MC |
5. IC a process begun with initial contact and continues throughout the course of the study NC |
6. Consent process has three elements, all of which must be given importance: information, comprehension, and voluntariness NC |
Information |
7. Potential participants must be informed of the following: |
7.1. Anticipated benefits SC |
7.2. Right to withdraw without reprisal SC |
7.3. Aims MC |
7.4. Methods/procedures MC |
7.5. Sources of funding MC |
7.6. Institutional affiliations of researchers MC |
7.7. All risks and discomforts that a reasonable person would consider material MC |
7.8. Any current alternative interventions MC |
7.9. After completion of the study, subjects will at least be given the option to be informed of the findings of the research MC |
7.10. Post-study provisions WC |
7.11. Rights to refuse to participate WC |
7.12. After completion of the study, subjects informed of findings that relate to their individual health status WC |
7.13. Subjects have rights to access their data on demand, unless otherwise approved by REC WC |
7.14. Provisions to ensure privacy and confidentiality WC |
7.15. Possible research uses of the subjects medical records and biological specimens taken in the course of clinical care WC |
7.16. Whether commercial products may be developed from biological specimens and whether the participant will receive monetary or other benefits WC |
7.17. Extent of investigator’s/sponsor’s responsibility to provide medical services to participants WC |
7.18. Explanation of how research differs from routine medical care WC |
7.19. Treatment will be provided free of charge for specified types of research-related injuries or complications, nature and duration of such care, who will provide care, and uncertainties if any WC |
7.20. Compensation, if any, in case of damage, disability or death WC |
7.21. That an REC has approved the protocol WC |
7.22. Conflict of interest NC |
7.23. Rights and safeguards prescribed by law for the subjects’ protection NC |
7.24. Rights and safeguards prescribed by law for those not able to consent to research NC |
7.25. That the individual is invited to participate NC |
7.26. Reasons for considering the individual suitable for the research NC |
7.27. Participation is voluntary NC |
7.28. For controlled trials, explanation of the features of the research design (e.g., randomization, double-blinding) NC |
7.29. Limits to confidentiality and possible consequences of breaches NC |
7.30. Policy on use of results of genetic tests and familial genetic info, and precautions to prevent disclosure of results to others without consent. NC |
7.31. Sponsors of the research NC |
7.32. Whether it is planned that biological specimens collected in the research will be destroyed at its conclusion, and if not, details about storage and possible future use NC |
7.33. Subjects have right to decide about the future use of their biological specimens collected during research, to refuse storage, and to have the material destroyed NC |
7.34. Whether investigator is only investigator or both investigator and subject’s physician NC |
7.35. Whether or not compensation is guaranteed in the country NC |
7.36. Offering the subject to ask questions NC |
7.37. Duration of participation (including number and duration of visits NC |
7.38. Possibility of early termination of trial or of participation NC |
7.39. Compensation for participation NC |
7.40. Prospective subjects need to be informed that they do not need to take legal action to secure free medical treatment or compensation for injury NC |
8. Information complete, accurate, and not overwhelming. WC |
9. Sometimes, it may be advisable to give info sheets NC |
10. IC process should not contain words that absolve the investigator from responsibility in case of accidental injury, or would imply that subjects waive their right to seek compensation for impairment, disability, or handicap NC |
11. If a person wishes to not receive detailed information on any are, this should be respected so long as he/she has received sufficient info to give IC NC |
12. The wish of a participant to not receive info should be recorded NC |
13. When incomplete disclosure/deception is involved, subjects must be asked to consent to remain uninformed of the purpose of some procedures until research is completed WC |
14. When incomplete disclosure/deception is involved, participants provided with omitted info after the study NC |
Comprehension |
15. Participants’ comprehension of information must be ensured SC |
16. Subjects should have the opportunity to ask questions and receive truthful answers before or during research MC |
17. Means must be used to ensure potential participant’s understanding of procedure WC |
18. Obligation to ascertain comprehension increases with risk NC |
Voluntariness |
19. The voluntary consent of the participants must be ensured SC |
20. IC must be voluntarily obtained for all biomedical research involving humans WC |
21. Participants must be actually free to refuse or to withdraw WC |
22. Potential participant must be given enough time to decide WC |
23. Prospective subject must not be exposed to undue influence (e.g., asking spouse or community leader to influence decision) WC |
24. Payments/services should not lead to undue inducement to participate WC |
25. Voluntariness demands that consent is free from coercion and undue influence NC |
26. In case of a dependent relationship or duress, IC must be sought by a an independent and qualified individual NC |
27. Intimidation in any form invalidates IC NC |
28. Especially in nontherapeutic research that present more than minimal risk, sponsor/investigator should avoid undue material inducement NC |
Competence |
29. When the capacity of a person to give consent is in doubt, arrangements must be in place to verify this capacity NC |
30. For studies where some subjects may be rendered incapable of IC, the initial protocol submitted for approval should anticipate that some patients may be incapable of consent and propose a form of proxy consent NC |
Renewing consent |
31. Promptly renewing of consent necessary when new information may affect the willingness of a participants, when material changes occur in the conditions or the procedures, and also periodically in long-term studies NC |
32. Any new info relevant to participation must be conveyed to research participants or their representatives, if applicable, in a timely manner NC |
Withdrawal of consent |
33. Withdrawal of a patient’s consent must be acted on immediately NC |
34. In cases when consent is withdrawn but the abrupt discontinuation of therapy could be hazardous to the patient, the healthcare professional must do the following: |
34.1. Explain the risk of discontinuing NC |
34.2. Seek consent to continue in the study/treatment NC |
Person obtaining consent |
35. Person obtaining informed consent must be knowledgeable about the research and is capable of answering questions NC |
36. The nature of research, needs of potential participant, national practice, and/or law should determine who should provide information to subjects NC |
Use of data/specimen |
37. IC necessary for research using identifiable human material or data; when consent is impossible or impracticable, permission from REC still necessary. NC |
38. Consent forms should include a separate section (or a separate consent form) for subjects who are requested for consent for the use of their biological specimens for research NC |
39. Records and specimens of individuals who previously rejected to consent may only be used in public health emergencies NC |
40. On secondary use of research records/biological specimens, secondary uses are usually constrained by the conditions specified in the original consent NC |
41. It is essential that the original consent process anticipates foreseeable plans for future use NC |
42. In terms of consent for secondary use, consent must ask for the following: |
42.1. Whether there will be secondary use and whether such use will be limited to the type of study NC |
42.2. Conditions under which investigators will be required to contact the research subjects for additional authorization NC |
42.3. Investigator’s plan, if any, to destroy or to anonymize the records or specimens NC |
42.4. The rights of subjects to request destruction or anonymization NC |
Waiver of IC |
43. Waiver of IC must be considered uncommon and exceptional and must in all cases be approved by REC NC |
44. Waiver of signed IC may be granted if: |
44.1. No more than minimal risk NC |
44.2. Procedures are those for which signed consent forms are not customarily required NC |
44.3. Also, when the existence of a signed consent form would be an unjustified threat to the subject’s confidentiality NC |
45. Waiver of IC may be granted if: |
45.1. No more than minimal risk NC |
45.2. IC would make the research impracticable NC |
46. Consent for the use of medical records/biological specimens may be waived if: |
46.1. Research poses minimal risk NC |
46.2. Rights/interests of patients not violated NC |
46.3. Privacy and confidentiality or anonymity assured NC |
46.4. IC would make the study impracticable NC |
47. Refusal or reluctance of individuals to participate is not an evidence of impracticability NC |
Supplementary consent |
48. While supplementary consents or permissions may be obtained, there must be ways to ensure that the individual can still decide independent of spouse or community leader, for example. NC |
49. In studies affecting groups (e.g., epidemiology, sociology) where risk to groups may exist, it is advisable supplement IC with community consultation NC |
IX Respect for participants |
Participant safety |
1. Health of participant monitored to minimize harms: One of the functions of the Data and Safety Monitoring Board is to protect subjects from previously unknown adverse reactions or unnecessarily prolonged exposure to inferior therapy MC |
2. Criteria for changing dose or procedures for stopping the study for the health of the participants must be adequate WC |
3. All reasonable means should be taken to ensure safety (that death or disabling injury will not occur) WC |
4. To protect participants from injury, disability or death, |
4.1. Adequate health-care facilities provided and incorporated in study for the safe conduct of research WC |
4.2. Proper preparations made NC |
5. In some research, counseling (about acquiring a disease unless they take precautions) for the participants may be necessary NC |
6. When prospective or actual subjects are found to have a disease unrelated to the research or cannot be enrolled because they do not meet health criteria, they must be referred to/be advised to obtain medical care NC |
7. Research shall not delay nor deprive participants of medically necessary preventative, diagnostic, or therapeutic procedures. Treatment of patient should not be altered in a detrimental manner to facilitate research. NC |
8. Participants assigned to control groups shall be assured of proven methods of intervention available in the country or region. NC |
9. To minimize risk, when intervention to be tested is designed to prevent or postpone a lethal or disabling outcome, therapy that is known to be superior to the intervention being tested must not be withheld (unless it can be ethically justified) NC |
10. An individual may choose to take part in research a number of times or regularly provided that it does not endanger the participant’s health NC |
11. All steps taken to assess the state of health of human beings prior to inclusion in research and to ensure that those with increased risk are excluded. NC |
12. Where research is undertaken on persons in their reproductive stage, particular consideration must be given to possible adverse impact on current or future pregnancy and the health of the embryo, fetus, or child. NC |
Dissemination of research results to participants/community |
13. Everyone is entitled to know the information collected about one’s health; however, one’s wishes to not be informed shall be respected. NC |
14. If research gives rise to information relevant to current or future health or quality of life of research participants, this information shall be offered to them within a framework of health care or counseling NC |
15. In some circumstances, the right to know or not to know may be restricted for the patient’s interest or in order to protect the rights of a third party or a specified public interest NC |
16. In the course of a study, sponsors should disclose to proper health authorities information that might be of public health concern. NC |
17. There must be sufficient care on the manner of disseminating research results to the participants and the community NC |
Privacy/confidentiality |
18. Confidentiality procedures must be effectively implemented WC |
19. The confidentiality of the subject’s research data must be protected WC |
20. Everyone has a right to respect for one’s private life in relation to information about his/her health NC |
Participant care |
21. Free and appropriate medical treatment for injuries incurred due to research participation MC |
22. There must be adequate plans for care for participants after research NC |
Compensation |
23. There must be appropriate compensation for subjects harmed due to research participation; in case of death, compensation goes to dependents MC |
24. Subjects must not be required to demonstrate the investigator’s negligence or lack of reasonable skill to claim free medical treatment or compensation. NC |
25. A subject who withdraws due to research related reasons (such as unacceptable side-effects) or due to health grounds should be paid in full. NC |
26. A subject who withdraws for any other reason other than research or health related should be paid in proportion to the amount of participation NC |
27. Subject must not be asked to waive right to compensation NC |
28. The payment to a subject who has been removed from a study due to willful noncompliance may be partly or wholly withheld. NC |
Sociological/epidemiological studies |
29. These studies may have the risk of group stigmatization or expose its members to discrimination. The following must be observed: |
29.1. Maintain confidentiality during and after the study NC |
29.2. Publish resulting data in a manner respectful to all concerned, or in some circumstances not publish at all NC |
Physicians and participants |
30. Clinical professional who supervises the research should always be accessible to the participants and ready to respond to their health concerns WC |
31. Physician involved in research must protect the life, health, dignity, integrity, right to self-determination, privacy, and confidentiality of personal info of research subject NC |
32. Physicians who combine research and medical care should involve their patients only if |
32.1. This involvement may be justified by the potential value of the research NC |
32.2. There is good reason to believe that the health of the patients will not be adversely affected NC |
X Publication and Registration |
Publication |
1. Conflict of interest, sources of funding, and institutional affiliation must be declared in publications WC |
2. Publishers should retract any article that has been subsequently found to contain falsified or fabricated data or has been based on unethical research. NC |
3. Complete and accurate research results must be publicly available NC |
Registration in a database |
4. Every research involving human subjects must be registered in a publicly-available database before recruitment NC |
XI Regulatory Sanctions |
1. Disciplinary sanctions must be used as last resort. Preferred methods include cultivation of atmosphere of mutual trust, education and support to promote the capacity for ethical conduct in research. NC |
2. Drug regulatory authorities should consider refusal to accept unethically obtained data submitted in support of a marketing authorization application. However, they should also consider the deprivation of benefit to the intended segment of society. NC |
XI Special populations |
Vulnerable population in general |
1. safeguards in place to protect the vulnerable depending on their circumstance (age, gender, economic deprivation, social marginalization, clinical status, etcetera) from being involved in research solely for admin convenience or because they are easy to manipulate. MC |
2. Research must be justified by its responsiveness to health needs/priorities of the group. Group stands to benefit from knowledge, practice, or interventions that result. WC |
3. Research on vulnerable population justified only when research of comparable effectiveness cannot be carried out on a non-vulnerable group. WC |
4. Justification required in inviting vulnerable individuals as research subjects. WC |
5. RECs reviewing proposals directed at specific diseases or impairments or involving vulnerable people should invite representatives or advocates. NC |
6. Though socioeconomically vulnerable people should not disproportionately carry the burden of research, they shouldn’t also be categorically excluded, especially when research addresses a problem prevalent in the group. NC |
7. Overuse of certain groups is unjust. NC |
8. Research subjects and other members of vulnerable class must be assured of reasonable access to diagnostic, preventive, or therapeutic products that may become available. NC |
Persons not able to consent (including minors) |
9. Research on a person without the capacity to consent may be undertaken only if all are met: |
9.1. Necessary authorization given specifically in writing by the legal representative, taking into account the individual’s previously expressed wishes and objections. SC |
9.2. Assent is secured and dissent respected SC |
9.3. Research of comparable effectiveness cannot be carried out on individuals capable of consent (i.e., condition necessary characteristic of the research group) MC |
9.4. Results of the research must have the potential to produce real and direct benefit NC |
9.5. Person undergoing research has been informed of his/her rights and safeguards prescribed by law, unless this person is not in a state to receive info. NC |
9.6. An adult not able to consent shall as far as possible take part in the authorization procedure. The opinion of a minor shall be taken into consideration as an increasingly determining factor in proportion to age and degree of maturity. NC |
10. Non-therapeutic research may be authorized subject to the following: |
10.1. Minimal (low) risk and minimal (low) burden (i.e., medical test standard); any consideration of additional potential benefits of the research shall not be used to justify an increased level of risk or burden WC |
10.2. Research aims to contribute through significant improvement in scientific understanding of the individual’s condition, disease or disorder NC |
11. When risk is above low on researches on individuals unable to consent, the following must be ensured: |
11.1. Research is designed to be responsive to disease or conditions they are particularly susceptible to NC |
11.2. Risks are only slightly greater than low-risk NC |
11.3. Objective of the research sufficiently important to justify exposure of subjects to increased risk NC |
11.4. Interventions are reasonably commensurate to the condition under investigation NC |
11.5. REC approval NC |
12. For studies with individuals unable to consent, such studies may be approved without special substantive or procedural protective measures if the study is low-risk (routine medical tests standard) NC |
13. When subjects initially unable to consent becomes capable of consenting, their consent for continued participation must be secured NC |
14. Objection to participation, refusal to give authorization or withdrawal of authorization shall not lead to any form of discrimination against the person concerned, in particular regarding the right to medical care. NC |
15. Patients with an acute condition that renders them incapable of giving consent may be eligible for inclusion in a trial in which the majority of the prospective subjects will be capable of consent. NC |
Third party authorization |
16. Third parties are those most likely to understand the incompetent subject’s situation and to act in that person’s best interest NC |
17. Person authorized to act on behalf of a subject should be given an opportunity to observe the research NC |
18. The guardian asked to give permission should be offered no recompense other than a refund of travel and related expenses NC |
19. For individuals physically or mentally unable to consent, and consent from a legal rep cannot be obtained, study may proceed provided that reasons stated in protocol and REC approved. Consent must be secured asap. NC |
Emergency research |
20. REC approval must be secured first prior to initiating such a study. WC |
21. In emergency research where prior research is not possible, participants, or their representatives if relevant, should be given all relevant information as soon as they are in the state to receive it, and their consent to continued participation should be obtained as soon as is reasonably possible WC |
22. The REC and the investigator must set a day when IC must be secured; beyond this day, participation must be discontinued. NC |
23. There must be sufficient effort to locate an individual who can give surrogate consent NC |
24. Research of comparable effectiveness cannot be carried out in persons in non-emergency situations NC |
25. As much as possible, there must be the attempt to identify a population that is likely to develop the condition to be studied for the possibility of securing the IC of these prospective subjects NC |
26. Where appropriate, plans to conduct emergency research without prior consent of subjects should be publicized within the community in which it will be carried out NC |
27. If acceptability of research is in question, there must be community consultation NC |
28. Research should have substantial community support NC |
29. Previously expressed objections shall be respected. NC |
30. Nontherapeutic emergency research may be justifiable given the following, |
30.1. it aims to contribute through significant improvement in the scientific understanding of the individual’s condition, disease, or disorder NC |
30.2. Minimal risk and minimal burden NC |
Pregnant women |
31. Pregnant women should be presumed to be eligible for participation in biomedical research. NC |
32. Investigators and ethical review committees should ensure that prospective subjects who are pregnant are adequately informed about the risks and benefits to themselves, their pregnancies, the fetus and their subsequent offspring, and to their fertility. NC |
33. Research in this population should be performed only if |
33.1. it is relevant to the particular health needs of a pregnant woman or her fetus, or to the health needs of pregnant women in general (broadly understood) NC |
33.2. Though the decision about acceptability of risk should be made by the mother as part of the informed consent process, it is desirable in research directed at the health of the fetus to obtain the father’s opinion also, when possible. NC |
33.3. Special safeguards should be established to prevent undue inducement to pregnant women to participate in research in which interventions hold out the prospect of direct benefit to the fetus NC |
33.4. Where fetal abnormality is not recognized as an indication for abortion, pregnant women should not be recruited for research in which there is a realistic basis for concern that fetal abnormality may occur as a consequence of participation as a subject in research. NC |
33.5. Investigators should include in protocols on research on pregnant women a plan for monitoring the outcome of the pregnancy with regard to both the health of the woman and the short-term and long-term health of the child. NC |
34. Research on a pregnant woman which does not have the potential to produce results of direct benefit to her health, or to that of her embryo, fetus or child after birth, may only be undertaken if the following additional conditions are met: |
34.1. the research has the aim of contributing to the ultimate attainment of results capable of conferring benefit to other women in relation to reproduction or to other embryos, fetuses or children, broadly understood NC |
34.2. research of comparable effectiveness cannot be carried out on women who are not pregnant NC |
34.3. the research entails only minimal risk and minimal burden NC |
35. Where research is undertaken on a breastfeeding woman, particular care shall be taken to avoid any adverse impact on the health of the child NC |