National Ethics Advisory Committee
Kāhui Matatika o te Motu
Responsible research conduct involves an enduring commitment to carrying out investigations with integrity. Researchers must be aware of established professional standards and ethical principles, and apply them in performing all their study activities. Conducting research responsibly is critical to achieving research excellence, and to maintaining public trust in health care. This chapter focuses on the essential aspects of responsible research conduct in relation to participants.
11.1 The principal researcher or sponsor of a study has primary responsibility for the conduct of the study (including compliance with relevant law, regulations and guidelines) in New Zealand.
11.1.a In this context, the essential duty of a research institution extends only to educating researchers on how to conduct research responsibly and ethically.
11.2 In the case of clinical trials, researchers must register their study in a WHO-approved clinical trial registry before commencing the study. They should also provide results of the study to the public database of the registry.
11.2.a Registering research promotes transparency, reduces publication bias, avoids unnecessary duplication, reduces the burden on participants and prevents the suppression of data in research (Canadian Institute of Health Research et al. 2014).
11.2.b While this Standard focuses on clinical trials, transparency and reduction of unnecessary duplication and reporting bias are important for other types of research including public health intervention studies, observational studies, implementation research and pre-clinical studies of experimental therapeutics and preventives.
Researchers have a primary duty of care to participants throughout the life cycle of a study, under the Te Ara Tika principle of whakapapa.
11.3 Researchers must safeguard the health and welfare of participants during their study.
11.3.a Whakapapa is an analytical tool for understanding why relationships have been formed and for monitoring how those relationships progress and develop over time. A common saying amongst Māori is “mai i te whai ao ki te ao Mārama” (“from the dawn light to the bright light of day”) which is a metaphor for understanding or enlightenment. In the context of decision-making, whakapapa refers to the quality of relationships and the structures or processes that have been established to support them. The development and maintenance of meaningful relationships between researcher and research participant is an indicator of ethical researcher conduct.
11.4 Researchers must also ensure that participants experience no gaps in care when their study participation concludes.
Effective recruitment is critical; researchers must enrol a sufficient number of participants to reliably answer their study questions.
11.5 To select study participants, researchers must use a fair, equitable process, and include ethnic, educational, socioeconomic and gender diversity appropriate to the health or disability condition under study.
11.5.a It may be ethically justifiable for clinicians and other health care providers involved in a patient’s care to use their records to identify or pre-screen potential research participants. This method entails certain benefits: researchers can be sure that those they approach are potentially eligible, that research options are available to potentially eligible people so they may consider participation, and individuals are not exposed to risks unnecessarily. Researchers may use this method provided that:
11.6 In some cases, an outside researcher may wish to review records or obtain lists of patients, medical records, test results or other clinical information, so that they can approach potential participants. Such a researcher must be able to justify how this review is ethical without gaining prior consent from the individuals linked to the health records concerned.
Many methods of recruiting participants are available to researchers. A chosen method must be appropriate for the potential participants and the study. In determining appropriate recruitment methods, researchers should consider:
The same standards apply if a patient (or their family or friends) approaches their health practitioner or a researcher about participating in a study.
11.7 Researchers must choose a method of selecting and approaching participants that avoids unduly influencing potential participants.
11.7.a Depending on the study question and design, researchers may approach a potential participant directly (e.g. by advertisement, telephone or letter) or indirectly (e.g. through the participant’s own doctor or relevant health professional).
11.7.b The person who contacts potential research participants should be knowledgeable about the study, and able to discuss study details and answer questions in plain language. In some cases, the first contact may be a referral to someone who is knowledgeable.
11.7.c When patients are recruited as prospective participants, the people directly involved in their care should make the first approach, rather than researchers the patients do not know. In limited circumstances, it may be justifiable for both the researcher and the health care provider to make the first approach (e.g. in a joint letter), or for the researcher to do so with reference to the health care provider.
11.7.d In terms of different approaches to recruitment, relevant considerations include whether the method used would put undue pressure on people to participate (or not participate) due to the power imbalance between clinician and participant; confidentiality (the clinician will know who the potential participants are already); and potential bias when the clinician makes decisions about who is a suitable candidate for the research (e.g. they may exclude participants because they think they are too difficult to involve, they disagree with their viewpoint or they assume the person may not be interested).
11.8 Incentives offered for participation in research should not unduly influence an individual’s decision to participate. Researchers should determine the value of incentives in a transparent way. Similarly, researchers should ethically justify costs to participants to an ethics committee, ensuring that they avoid discrimination and that recruitment is fair.
11.9 All recruitment efforts must respect personal rights to privacy and confidentiality, comply with health information privacy regulations and avoid unduly influencing participants.
11.10 Advertisements seeking participants for a study should not inflate the potential benefit of participation or imply that a health outcome is certain.
11.11 The design of recruitment advertisements must avoid deceiving or unduly influencing potential research participants.
11.12 The information provided in advertisements should be limited to basic study information written in plain language. It may include:
11.13 Advertisements may include study remuneration but this must not be emphasised, especially when potential participants are vulnerable to financial incentives.
Recruitment through social media has novel aspects compared with other recruitment methods, in that it involves:
11.14 When recruiting through social media, researchers should examine the terms and conditions of the websites they use, considering:
11.15 Researchers should not disclose a participant’s sensitive information to others without that participant’s explicit permission, nor engage in online interactions that would allow others to infer sensitive information about participants or potential participants. They should avoid such disclosure even if that information has already been made public in a different context.
11.16 Researchers should be mindful of the values and potential vulnerabilities of people they approach on social media.
11.17 Researchers must be transparent in their use of social media for active recruitment. They must avoid deception, and should not fabricate online identities to gain access to online communities. They should seek access through alternative means, such as asking for explicit permission from a moderator or site administrator.
11.17.a Where a researcher has gained permission from a moderator or site administrator to recruit participants, this permission should be advertised on the site.
11.18 Researchers must avoid covert surveillance for the purposes of identifying potential participants on a site where users reasonably expect that recruitment activity will not occur and could justifiably object to such activity.
11.19 Researchers should obtain authorisation from current or potential research participants before using their online network for recruitment purposes, or to enlist current or potential participants to approach members of their network directly on the research team’s behalf. Exceptions to this requirement may be justified in situations where the researcher independently identifies the relevant individuals for study recruitment without using the online network of the current or potential participant.
11.20 In considering the possibility of undue influence in research involving financial or other incentives, researchers should be sensitive to issues such as participants’ economic circumstances, age and capacity; the customs and practices of the community involved; and the magnitude and probability of harms.
11.20.a Researchers may seek to create legitimate motivation for people to participate in studies, but must not exert undue influence by offering inappropriate incentives. Conversely, they should take care to avoid causing undue financial disadvantage to participants; for example, through travel costs and parking charges.
11.21 Researchers should avoid exploitation by not paying participants enough for their time.
11.22 Researchers should state at the outset of the study in what circumstances participant withdrawal will affect payments or koha, and what that effect will be.
11.23 Researchers must identify and minimise any conflict of interest or commitment (or perception of such conflict).
11.23.a In the research context, a conflict of interest is any situation in which the possibility of financial, professional or other personal gain has the potential to compromise a researcher’s professional judgement and objectivity. This may occur during study design, conduct or reporting. Unmanaged conflict of interest may harm study participants, particularly in clinical research, and damage the research enterprise by reducing the trust and confidence that people generally have in research.
11.23.b Researchers must identify real, potential and perceived conflicts of interest, and then manage, reduce or eliminate them. They must assess conflicts of interest in terms of both their likelihood and their consequences. Proper management of a conflict entails full and prompt disclosure (to an ethics committee, participant or other researchers) and implementation of appropriate safeguards, such as modifying the research plan or arranging for independent monitoring.
11.23.c Financial conflicts of interest are the most visible and measurable type of conflict, but other types can have a powerful influence. Conflicts of commitment involve two sets of professional obligations competing for focus and effort when an individual has multiple roles; for example, as both a health care provider and a researcher.
Conducting research on one’s own patients can be a legitimate way of creating knowledge for researchers and participants. However, dual-role researchers can face significant ethical challenges, involving issues such as undue influence, compromising the voluntary nature of participation, informed consent and privacy.
11.24 Researchers should consider options for managing these issues, including:
Most studies involving human participants require a safety monitoring plan. The degree of monitoring and oversight required depends on the study’s particular features. This section outlines different types of monitoring arrangements: trial oversight committees, coordinating centres or database monitoring, and on-site monitoring.
11.25 Researchers must have a plan for monitoring and reporting the safety of participants. The level of safety oversight must be appropriate to the study phase, design and cultural context.
11.25.a Any safety monitoring plan should include a mechanism by which researchers may remove participants for safety reasons. It should also provide a way of pausing or stopping clinical trials if they are found to be unsafe, futile or ineffective. Mechanisms for safety monitoring include trial oversight committees, a trial coordinating centre and on-site monitors.
11.26 Informal data safety monitoring is more likely to be appropriate in a single centre setting, either in minimal/low-risk observational studies or clinical trials with no dose escalation planned and using previously assessed dose regimen(s).
A DSMC is generally an independent body, although in some circumstances it may be internal to the study and include representation from the trial steering committee and/or the study sponsor.[1]
11.27 Table 11.1 indicates the most appropriate form of DSMC monitoring for different types of intervention studies.
11.27.a Members of the DSMC, especially the chair and the biostatistician,[2] should have prior DSMC experience.
| Type of setting1 | Imperatives | Need for DMC | ||
|---|---|---|---|---|
| Ethical integrity | Credibility | Independent DMC | Internal DMC | |
| Setting 1 | ||||
| Randomised trials (phases IIb, III, IV) | Yes | Yes | Yes | Likely2 |
| Randomised trials (phases I, IIa) | Yes | Likely | Maybe | Likely2 |
| Non-randomised trials | Yes | Maybe | Unlikely | |
| Setting 2 | ||||
| Randomised trials (any phase) | Unlikely | Likely | Unlikely3 | Maybe2 |
| Non-randomised trials | Unlikely | Unlikely | No | Unlikely |
A trial coordinating centre monitors data as it enters the database during the trial. Such monitoring includes: checking the data against the protocol and for internal logic; and checking eligibility, recruitment rates, withdrawals, missing data and loss to follow-up.
11.28 The coordinating centre should monitor all trials to ensure integrity of study data.
11.29 An on-site monitoring process involves monitors visiting study sites to check adherence to study protocol and good clinical practice guidelines. This monitoring normally includes checking informed consent and eligibility, checking data on study case report forms against source data, and checking adverse event reporting.
11.29.a The appropriate extent of on-site monitoring depends on factors such as degree of risk, complexity of the study, study blinding and the experience of sites.
Every study must have a mechanism in place for responding to potential safety concerns.
11.30 In general, reliable interpretation of safety signals requires an interim report on safety and efficacy, in a form unblinded by intervention arm.
11.30.a Any study with potential for serious treatment-related adverse events must have a mechanism in place for promptly reporting, recognising and responding to serious adverse events and suspected unexpected serious adverse reactions and unexpected serious adverse reactions (SUSARS).
11.31 The protocol and/or monitoring plan of any study should state the study’s processes and responsibilities for identifying, coding, analysing and reporting adverse events.
11.31.a The degree of monitoring should be proportionate to the risk and complexity of the study.
11.32 To reliably interpret adverse events, it is necessary to code them according to body system and severity using established systems, and compare grouped data across intervention arms (considering the benefit and risk profile).
See Table 11. for definitions of key terms in relation to adverse event monitoring.
11.33 Researchers should prioritise prompt reporting of SUSARs.
| Term | Definition |
|---|---|
| Adverse event | An event with negative or unfavourable reactions or results that are unintended, unexpected or unplanned. In practice this is most often understood as an event which results in harm or has the potential to result in harm to the participant. |
| Adverse drug reaction[3] | Any untoward and unintended response in a subject to an intervention that is related to any dose administered to that participant. |
| Unexpected adverse reaction | Any adverse reaction the nature and severity of which are not consistent with information about the intervention in the investigator’s brochure (or, for a product with marketing authorisation, in the summary of product characteristics for that product). |
| Serious adverse event, serious adverse drug reaction or unexpected serious adverse reaction | Any adverse event, adverse drug reaction, or unexpected adverse reaction, that:
|
| Suspected unexpected serious adverse reaction (SUSAR) | Any unexpected serious adverse reaction that is suspected to be related to the intervention under study. |
Source: MHRA 2009
11.34 In some circumstances, it may be appropriate to end a study early.
11.35 For any study that has a data safety monitoring committee (DSMC), the monitoring plan should contain criteria and processes for early termination of the study. If the study is ended early, the process for termination should follow the study’s monitoring plan and the advice of the DSMC.
11.36 For any study that does not have a DSMC, the study’s monitoring plan should comment on the conditions under which early termination of the study would be considered.
11.37 Therapeutic studies where participants are potentially receiving therapeutic benefit must not be terminated simply for reasons of commercial interest.
Researchers must promptly report new information that may affect the safety or ongoing consent of participants to appropriate regulatory bodies and to participants.
11.38 When a researcher identifies new information that may impact on participants, they must review affected aspects of the research to ascertain whether participants are adversely impacted. If they are, researchers must make changes to the study to remedy this.
11.39 New information includes:
11.40 In cases where the new information contains acute safety information, informing participants of the new information should not be delayed by the development and approval of updated informed consent documents.
Researchers’ responsibilities to inform other health professionals of a participant’s research involvement depend on the nature of the research. Certain areas of research (eg, research involving children at risk of abuse or studies of criminal behaviour) are more likely to put researchers in positions of tension between the ethical duty of confidentiality and a duty to disclose particular information to third parties.
11.41 Researchers must protect individuals’ privacy and confidentiality.
11.41.a The only exception to this is where they have an overriding ethical concern (for example, the health or safety of participants or others) justifying the release of participants’ information, or where such release is required by law. If researchers must breach privacy or confidentiality, they should first make a reasonable attempt to inform participants of the breach.
11.42 Researchers should be aware of ethical codes or laws that may require them to disclose certain information they may gain as researchers (e.g. suspected abuse), and of where to report such information.
11.43 In such situations, researchers should decide on appropriate conduct on a case-by-case basis, in consultation with colleagues, relevant professional bodies and legal advisors, as relevant, taking into account the requirements of the Health Information Privacy Code 1994(external link).
11.44 In certain situations, in the interests of the safety and wellbeing of a particular participant, researchers should, with the participant’s consent, inform the health professional responsible for that person’s health care about the person’s participation (usually at the time of enrolment in the research), and any possible health implications of this involvement.
11.44.a If a participant withholds their consent to contact the health professional, the researcher should consider whether it is ethical to enrol the participant in the study.
11.44.b In other situations, informing relevant health professionals is desirable if the participant consents, but is not mandatory for safety.
Incidental findings are observations of potential clinical significance that are unexpectedly discovered in research. There is an ethical difference between findings participants may expect from analysis they consented to as part of their care or research participation, and findings that are unexpected or incidental. Researchers have a duty or responsibility to inform participants of such findings, arrange counselling (e.g. genetic counselling or mental health counselling) for them if necessary and ensure adequate follow-up. In some cases, researchers themselves may not know if incidental findings are clinically relevant, particularly in the case of genetic findings. Follow-up may involve referring participants to a suitable health professional or specialist.
11.45 Researchers should inform participants of any expected or possible implications of the study analysis.
11.45.a For example, individual study results may impact on a participant’s ability to obtain insurance, employment or loans, and may also have social implications (e.g. by revealing previously unknown paternity information).
11.46 Researchers should also consider whether any study results have direct implications for the health of a participant’s friends or family.
11.47 The protocol must set out what will happen should such information be available, and this information should be included in the information provided to participants prior to obtaining their informed consent.
11.48 Before conducting research, researchers must develop and record a plan for how they will handle incidental findings.
11.48.a In developing such a plan, researchers should consider whether to communicate to participants findings that are not clinically actionable, noting that participants have the right to information that a reasonable participant in that participant’s circumstance would expect to receive, including being informed of the results of tests (Code of Health and Disability Services Consumers’ Rights 1996(external link)).
11.49 Researchers should give participants the choice of opting out of receiving individual results of analyses that are not clinically significant, or for which treatment is not available.
11.49.a It may be appropriate to offer this choice to participants at two points of the research: when they initially enrol in the research study and at their final study visit.
11.49.b In this case, researchers should signal to participants when they enrol that they will be routinely asked to reaffirm their informed consent at the second point, and that this request will not be due to the nature of their results.
Communicating study results is essential, to realise the merit of the research.
11.50 Researchers must report their research results accurately, with integrity and in a timely manner, whether the results are positive or negative.
11.51 Researchers must release their results in a way that recognises cultural sensitivities, avoids stigmatising individuals or groups and does not identify individual participants without their consent.
11.52 Researchers must offer participants a summary of research results that is written for non-specialists in plain language.
11.52.a Researchers should avoid sending participants a link to study results that are behind a pay-wall.
11.53 Researchers should communicate their study results in a time-sensitive and appropriate way, so that benefits to the community are maximised and fairly distributed.
11.54 Researchers should not enter into contracts that limit, or apply unreasonable time restrictions to, the release of research results.
11.54.a Any proposed restrictions on publications must include an ethically acceptable justification; for example, in limited circumstances, where a study intervention is in the product development cycle. The onus to justify restrictions on disseminating or accessing data lies with the party seeking to make the restriction.
11.54.b Researchers have an ethical obligation to advocate for the release of information that is in the public interest, even when governmental or commercial sponsors retain the data.
11.55 Researchers must strive to report study results accurately. They should anticipate and avoid misinterpretation of those results.
11.56 Conflict may arise for researchers between doing no harm and openly disclosing research results. In this case, researchers must attempt to present data in a way that protects the interests of those at risk while it maintains research integrity.
11.56.a In framing their analyses, researchers must avoid deficit thinking (a catch-all term for theories conjecturing that poor health outcomes are the fault of people’s ethnicity, sexuality, gender, culture and/or socioeconomic status). For example, researchers must not look on the health disadvantages Māori experience as inherent to Māori ethnicity.
11.56.b Similarly, analysis of the causes of disparities experienced by disabled people should include a focus on their broad causes or drivers (including determinants of health and health system issues), and the consequences of systemic disadvantage. Ethical research should aim to provide analysis that brings advantages and opportunities to the groups under study, and therefore help to counteract negative stereotypes.
11.57 Researchers must avoid deficit thinking.
11.57.a Deficit thinking is an important component of research that focuses on improving outcomes for Māori. Including Māori researchers in decision-making roles within the research team can help to address this risk.
11.57.b It the responsibility of the research team as a whole to ensure that the study is ethical. In this context, effective localised relationships are a very important part of ensuring results are interpreted correctly. See ‘Research and Māori’ for more information.
If research results are not communicated within a reasonable time, their value may be diminished or lost, and the value of participants’ contributions reduced. It can be difficult to determine the optimal time for releasing research results. Both premature release and unnecessary delay in release can be harmful to individuals and communities.
11.58 Where making results available would immediately benefit participants, researchers are responsible for making results available to those affected as soon as practicable.
11.59 Releasing all research results helps to prevent reporting bias. It is normally not appropriate to release incomplete research results (e.g. release of early results, secondary end-point results or results from only some research sites), because such results may be misleading.
11.60 Researchers must also effectively communicate negative results, because these too add to collective knowledge, and may allow other researchers studying the same intervention to avoid wasting resources.
People who are already burdened by poor health or disability are in general a potentially vulnerable group. Asking them to contribute money in exchange for being involved in research raises serious concerns about justice, autonomy and the potential for exploitation.
11.61 Researchers may be able to justify charging participants to receive trial products or procedures in a very limited set of circumstances, including where:
11.62 Researchers may sometimes be required to undertake activities in situations that put themselves at risk. For example, they may need to interview participants in their own homes or undertake research in an unfamiliar cultural or social context. In these cases, researchers must make suitable arrangements for their own safety, and document these in a safety protocol.
11.63 Given the variety of situations and activities that may be involved, no standard format exists for such a protocol. Usually, it includes arranging for colleagues or someone else to be aware of the researcher’s travel plans or interviewing schedules, having suitable contact networks in the field and establishing a clear confirmation communication process before and after an appointment. In some cases, it may be appropriate for a colleague to accompany a researcher to a meeting with a participant.
11.64 It is not usually acceptable for researchers to use their own homes to conduct research with participants.
11.65 Researchers travelling overseas need to be familiar with how best to conduct research within the culture and jurisdiction to which they are travelling.
[1] For further guidance about operating plans for DSMCs, see information on the HRC’s website(external link).
[2] The biostatistician has a multi-faceted role in clinical trials and is responsible for such as things as defining the sample size of research and, in relation to participant safety, planning and undertaking interim analysis.
[3] For guidance on reporting adverse events in New Zealand see Severity Assessment Code (SAC) rating and triage tool for adverse event reporting(external link) on the Health Quality & Safety Commission website.
