Introduction
Research can generate benefits for individuals now and in the future. However, all research carries some risks of harm (‘harms’ are defined in these Standards as events or experiences that set back the interests of one or more individuals).
Different studies carry different levels of risk of harm. Risks of harm to research participants are ethically acceptable only if they are outweighed by potential benefits. Framing and conceptualising research therefore involves not only identifying a gap in knowledge, but also thinking about who will benefit from the research, what risks of harm the research may create and who will be exposed to the risks. Including participants in the design of research is an important part of recognising the benefits. Striking the right balance between potential benefits and risks of harm requires paying attention to the context of the particular study. Some studies are exploratory, in which case the benefits and harms can be more difficult to anticipate.
Benefits are events or experiences that advance the interests of one or more individuals. Categories of prospective benefits include:
- direct benefit for the individual, such as improvement in health condition
- indirect benefit for the individual, such as feeling helpful, gaining access to medical care that may not be available outside of the study
- benefits to others, through generating knowledge that may improve the lives of people in the future rather than the lives of the individuals in the study.
To justify any risks of harm to study participants, research must have social and scientific value: that is, the potential to generate knowledge and methods that can protect and promote the health, wellbeing and independence of individuals, the population and groups within that population. Researchers must minimise risks and ensure that any that remain are outweighed by the potential benefits. The level of risk that is acceptable is up to the potential participants to determine.
In the New Zealand context, researchers should especially consider risks and benefits for Māori: see ‘Research and Māori’.
Identifying and assessing potential benefits and risks of harm
8.1 Researchers must identify and assess potential risks of harm. They must ensure that those risks are either outweighed by the prospect of potential benefit to the individual or appropriate in relation to the social and scientific value of the knowledge gained.
8.2 In assessing potential benefits and risks of harm, researchers must:
- identify the potential benefits and risks of harm
- assess the likelihood of potential benefits and harms occurring and their magnitude or severity
- identify who may receive the potential benefits and who may bear the risks.
8.3 Researchers must minimise risks of harm.
Managing and minimising risks of harm
In designing a study, researchers have an obligation to minimise risks of harm to participants, and manage any residual risks. Minimising risk involves assessing research aims and their importance and identifying the safest methods of achieving them.
8.4 To manage risks, researchers must ensure that:
- participants clearly understand the risks of harm associated with the research, and
- mechanisms are in place to adequately identify and manage harms that may occur at any time during the research, and the research protocol specifies these measures.
8.5 Researchers must continue to manage the risks of harm throughout the study. Where available data demonstrates that the risks of harm outweigh the potential benefits or establishes clear evidence for or against the research interventions and procedures in the study, researchers must assess whether to continue, modify or immediately stop the study.
8.6 The research protocol should document the processes for minimising and managing risks of harm. See ‘Monitoring studies’.
Benefits of research
8.7 Researchers must consider potential benefits as part of their consideration of the value of the research. Table 8.1 presents a non-exhaustive list of potential research benefits.
| Recipients of benefits |
Potential benefits |
Table 8.1 – Potential benefits for different parties involved in research
| Participants |
- Access to information
- Knowledge about diagnosis, interventions or procedures
- Opportunities to share experience and greater solidarity with others (Rennie et al. 2019)
- Koha
- Acknowledgement in publications
- Feelings of doing good and making a contribution
- Copies of reports
|
| Communities |
- Research capacity – research skills, understanding research processes
- Access to interventions
- Collection and protection of existing intellectual property
- Gaining knowledge
- Copies of reports
- Sharing in new intellectual property
- Increased knowledge about their disease or condition (Rennie et al. 2019)
- Acquisition of life skills
- Positive behavioural change
- Enhanced sense of purpose
- Bolstered self-esteem
|
| Māori |
- Community development (e.g. health-promoting events)
- Researcher development (e.g. qualifications and research experience)
- Knowledge advancement (e.g. through research outputs, hui
(meetings and seminars) and wānanga (workshops and teaching sessions))
- Development of mātauranga Māori (the knowledge, comprehension, or understanding of everything visible and invisible existing in the universe)
|
| Society |
- Knowledge advancement (e.g. through research outputs, hui and wānanga)
- Inclusiveness and diversity within the research system
|
| Researchers |
- Status and reputation, mana
- Qualifications (e.g. through research conducted for Masters and
PhD theses)
- Personal advancement, particularly enhanced publication records
- Increasing networks
- Broadened life experiences and skills
|
8.8 Researchers must also consider the risks of harm to others, such as potential stigma and whakamā to communities or groups. In addition, they must be aware of and plan to minimise potential harms for research personnel, such as the distress research assistants working with very sensitive data may experience.
8.9 Table 8.2 presents a non-exhaustive list of harms research participants may suffer.
Table 8.2 – Potential harms for research participants
| Category |
Potential harms |
| Physical harm |
- Injury, illness, pain, permanent disability, death
|
| Psychological harm |
- Feelings of worthlessness, distress, guilt, anger or fear (e.g. through disclosing sensitive or embarrassing information or learning about a genetic possibility of developing a disease)
|
| Disrespect or harm to dignity |
- Devaluation of personal worth, including being humiliated, manipulated or in other ways treated disrespectfully or unjustly
|
| Social or cultural harm |
- Damage to social networks or relationships with others; discrimination in access to benefits, services, employment or insurance; social stigmatisation; findings of a previously unknown paternity status; loss of trust; harm to wairua or mana
|
| Privacy harm |
- Identification or disclosure of private information
|
| Economic harm |
- Direct or indirect cost, I.e. cost for treatment for physical or mental harm caused by participation in the trial, particularly where the trial is not covered by ACC, and loss of earning potential from physical or mental harm caused by participation in the trial.
|
| Legal harm |
- Discovery of criminal conduct or prosecution for it
|
| Data harms |
- Surveillance, inferential harm or social harm such as stigmatisation
|
| Autonomy harm |
- Coercion, inducement, undue influence, loss of agency
|
Categories of risk
Levels of risk are used to determine ethical oversight in health research, including whether ethical review is required, and, if so, at what level. Risk levels are also relevant when considering the complexity of study documents, or whether modifications to consent procedures are ethical. In assessing risk, it is crucial to distinguish between harms that may be caused by the research participation itself and harms that are not, but rather may be caused by the life situation or characteristics of research participants.[1] Risks can also be generated for populations after the research has been completed, see Interpretation of Study Results.
8.10 Ethical oversight should be commensurate to risk. Table 8.3 describes risk categories.
| Category |
Details |
Table 8.3 – Risk categories[2]
| Negligible risk |
- Negligible-risk research is research in which the only foreseeable risk is one of inconvenience and/or discomfort. For example, participants being asked for their views about a topic rather than personal information about them is generally considered low-risk research. Research in which the risk for participants is more serious than discomfort is not low risk (NHMRC 2018).
- Discomfort includes such things as minor side-effects of medication, the discomforts related to measuring blood pressure, and anxiety induced by an interview. Discomfort however should be distinguished from distress. For example, a participant may experience whakamā (embarrassment) or stigmatisation and become distressed, at which point the risk is no longer negligible.
|
| Minimal-risk |
- Minimal-risk research is research in which the probability and magnitude of harms in research are not greater than the probability and magnitude of harms ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.
- Different populations can experience dramatic differences in levels of risks posed by daily life or routine clinical examinations and testing. These differences stem from inequalities in health, wealth, social status or social determinants of health.
- Researchers must be careful not to conduct research in ways that permit participants or groups of participants from being exposed to greater risks in research merely because they have low socio-economic status, because they are members of disadvantaged groups or because their environment exposes them to greater risks in their daily lives (e.g. poor road safety).
- Researchers must be similarly vigilant about not permitting greater research risks in populations of patients who routinely undergo risky treatments or diagnostic procedures (e.g. cancer patients).
- Researchers must compare risks in research to risks that an average, normal, healthy individual experiences in daily life or during routine examination: when the risks of an activity are considered acceptable for the population in question, and the activity is relatively similar to participating in research, then researchers can consider the same level of risk acceptable in the research context.
- These comparisons typically imply that research risks are minimal when the risk of serious harm is very unlikely and the potential harms associated with more common adverse events are small (NHMRC 2018).
|
| More than minimal risk |
- Greater-than-minimal research is research in which the probability and magnitude of harm anticipated in the research is of more than minimal risk, but not significantly greater.
- Studies that fall under this category will vary in terms of the probability of harm occurring as a result of study participation. Researchers should undertake safety monitoring depending on their assessment of that probability, ensuring adequate surveillance and protections to identify adverse events promptly and to minimise harm.
|
Examples of more than minimal risk research
| Departure from normal care |
- Something withheld from or done to a patient that deviates from normal health care constitutes more than minimal risk (for example, when extra blood samples or biopsies are taken).
|
| Use of stored samples |
- Use, collection or storage of human tissue without informed consent and use of stored samples for study purposes other than those for which they were originally collected constitutes a more than minimal risk activity.
Exceptions to this rule include
- Where participants have given informed consent to future unspecified use of human tissue.
- Where a statutory exception to the need to gain informed consent (as set out in the human tissue act 2008, section 20(f) or the code of rights, right 7(10)(c)) applies.
- Where stored samples are used by health professionals undertaking one or more of the following activities to assure or improve the quality of services:
- a professionally recognised quality assurance programme (for example, pathologists re-reading specimens to check the accuracy of their own or a peer’s work)
- an external audit of services
- an external evaluation of services.
- The justification for this is that the use is related to the primary purpose of the sample collection. See the Code of Rights, Right 7(10).
|
| Secondary use of identifiable health information without consent |
- Investigator use of identifiable health information that was primarily collected for clinical care for a secondary purpose without consent constitutes a more than minimal risk activity.
Exceptions to this rule include:
- where the individual, or the individual’s representative where the person is unable to give consent, has consented to this use or disclosure
- where the purpose for which the information is used is directly related to the purpose in connection with which the information was obtained
- where the source of the information is a publicly available publication and that, in the circumstances of the case, it would not be unfair or unreasonable to use the information
- where the information is used for statistical purposes and will not be published in a form that could reasonably be expected to identify the individual concerned
- where the use of the information for that other purpose is necessary to prevent or lessen a serious threat to:
- public health or public safety; or
- the life or health of the individual concerned or another individual;
- where it is either not desirable or not practicable to obtain authorisation from the individual concerned and the information:
- is required for the purpose of a professionally recognised accreditation of a health or disability service;
- is required for a professionally recognised external quality assurance programme; or
- is required for risk management assessment and the disclosure is solely to a person engaged by the agency for the purpose of assessing the agency’s risk; and the information will not be published in a form which could reasonably be expected to identify any individual nor disclosed by the accreditation quality assurance or risk management organisation to third parties except as required by law
The justification for this is that the use is related to the primary purpose of the data collection, and in such settings only individuals bound by a professional or an employment obligation to preserve confidentiality should have access to identified or potentially identifiable information.
|
| Significantly-greater-than-minimal-risk |
Significantly-greater-than-minimal-risk research is research in which there is a probability of an event that is serious, prolonged and/or permanent occurring as a result of study participation, or there is significant uncertainty about the nature or likelihood of adverse events.
- In undertaking research involving significantly greater than minimal risk, researchers must ensure adequate protections for foreseeable adverse events.
- In this case, researchers must also ensure additional safeguards, where feasible and appropriate. These might include:
- additional scientific, medical, cultural or ethics committee consultation
- special monitoring procedures to be followed by data safety and monitoring boards (Canadian Institutes of Health Research et al. 2014).
|
The distribution of potential benefits and risks of harm
8.11 Having identified potential benefits and risks of harm, researchers must carefully assess the likelihood and potential severity of the risks of harm to individual participants and groups, in comparison with the potential benefits.
8.11.a When doing so, researchers should consider whether to seek advice from others who have experience with the same methodology, population and research domain.
8.11.b They should also consider participants’ own perceptions of risks and benefits.
8.11.c No mathematical formula or algorithm can precisely calculate an appropriate ratio of benefit to risk of harm (Rid, 2010). Therefore, the comparison process may involve making intuitive judgements, which can be inconsistent and cause disagreement. The process must be transparent and defensible, and the results of the consideration clearly understandable.
8.12 Researchers must demonstrate a good understanding of the context in which a study is to be conducted.
8.12.a The context is especially important when the research offers direct benefits to the participants, their families and whānau, or to particular communities with whom the participants identify. In such cases, participants may be ready to take on a higher risk of harm than they would otherwise. For example, people with cancer with limited treatment options may be willing to accept research risks (such as treatment side effects) that would be unacceptable to well people.
8.13 When research interventions or procedures offer no potential individual benefits to participants, researchers must minimise the risks and ensure they are appropriate in relation to the social and scientific value of the knowledge.
8.14 In assessing potential risks and benefits, researchers must consider the relevant choices, experience, perceptions, values and vulnerabilities of different populations of participants.
8.15 Researchers should consult communities when determining whether the potential benefits of a study are outweighed by the risks of harm, or whether the balance is appropriate.
8.15.a The best approach is to follow a two-step process, looking first at potential harms and benefits to individuals, and then at potential harms and benefits to relevant groups.
8.16 In assessing potential risks and benefits, researchers should ensure that:
- the benefits of research are distributed fairly, and no group or class of people bears more than its fair share of the risks of harm
- the research does not disproportionately focus on the health needs of a limited class of people, but instead aims to address diverse health needs across different classes or groups (e.g. where the under-representation of particular groups results in or perpetuates health disparities, equity may require special efforts to include members of that group in research)
- groups that are unlikely to benefit from any knowledge gained from the research do not bear a disproportionate share of the risks of harm
- individuals, communities or populations that are socially or economically disadvantaged or marginalised are not over-represented in or unfairly exposed to risks of harm, or denied access to benefits.
8.16.a In some cases, overrepresentation may be statistically justified. Similarly, sometimes a study within a narrow group is justified, and can serve equity goals (e.g. research into subgroups of populations, where risks and benefits would not extend to whole populations).
8.17 When potential benefits or risks of harm are to be distributed unequally among individuals or groups, researchers must scientifically and ethically justify the criteria for the unequal distribution, rather than choosing them arbitrarily or conveniently.
8.18 When the potential benefits do not justify the risks of harm in a research proposal, the researchers must reconsider their research aims, the methods proposed to achieve those aims or both.
[2] These risk categories can be used by QI activities.
