Securing the benefits of research for people who lack capacity

  1. There are three categories of adults who may lack capacity to consent to their participation in research: firstly, individuals whose diminished capacity is enduring due to a mental or physical impairment; secondly, individuals who temporarily lack capacity, but whose capacity will return; and, thirdly, those with progressively deteriorating capacity.

  2. Historically, people with intellectual disabilities have experienced disadvantage, over- protection and abuse where their right to give informed consent has been ignored.733 Additionally, research involving temporarily unconscious patients may involve the use of an innovative practice or the evaluation of an established therapeutic treatment in emergency situations where it is not possible to obtain informed consent from the individual concerned.

  3. As the New Zealand population ages, research on the aging process, and conditions and diseases that disproportionately affect older persons has become increasingly important. Social science research is essential for understanding the social phenomena of aging, such as the increase in residential care for older adults,734 and through observation and understanding the experiences of adults who lack capacity and those who support them.735

  4. Research participation can be direct, where the person is actively involved in a study and may receive a new treatment, or indirect, where the person’s information or DNA samples are collected and analysed to better understand underlying causes of a particular disorder. This is especially true in biobanks where genetic research is focused on complex impairments such as psychiatric disorders or dementia.736

  5. Research involving adults who lack capacity to consent can lead to innovations in healthcare that can substantially improve their health and quality of life and that of others with similar conditions. It is therefore important that these adults are given the opportunity to participate in such research.737 To exclude them from any research would be discriminatory and would diminish their ability to participate as fully as possible in society.738

733 A Bray Research Involving People with Intellectual Disabilities: Issues of Informed Consent and Participation (Donald Beasley Institute, Dunedin, 1998).

734 There is growing literature internationally about ageing, death and dying. For example, Atul Gwande in his book, Being Mortal: Medicine and What Matters in the End (Henry Holt/Profile Books, New York and London, 2014) calls for a change in the philosophy of healthcare, explores the different models of social housing and care for older adults, recognising the process of older people losing their independence and ways to improve their well-being.

735 In a qualitative assessment of how support workers caring for adults with intellectual disability perceived substitute decision-making under the MCA, Dunn and others found that the MCA extended this to all areas of personal care, not just to invasive and controversial medical treatment decisions. M Dunn, I Clare and A Holland “‘Living a Life Like Ours’: Support Workers’ Accounts of Substitute Decision Making in Residential Care Homes for Adults with Intellectual Disabilities” (2010) 54 JIDR 144.

736 E Togni, K Dierickx, C Porteri “Participation in biobanks for research by incapacitated adults: review and discussion of current guidelines” (2014) 29 Int J Geriatr Psychiatry 670.

737 See for example, A Murray “The Mental Capacity Act Dementia Research” (2013) 25(3) Nurs Older People 14.

738 Human Rights Act 1993, s 21(1)(h); United Nations Convention on the Rights of Persons with Disabilities, (CRPD) art 5.

Right 7(4) and legal justification for research without consent
  1. Research involving unconscious patients or those with diminished capacity to consent or refuse participation in the research differs from standard research because participants are unable to give informed consent.

  2. In general terms, an individual’s ability to give valid consent or to refuse to participate in research will depend on the person’s ability to understand what the research entails, provided they have been given sufficient information to make an informed decision. The degree of detail required will vary according to the needs of the individual patient and the complexity of the procedures involved. In particular, assessment of risk (an important part of decision- making in all forms of healthcare) takes on greater significance in this sphere, since research can involve a degree of uncertainty of the risk involved.739

  3. In New Zealand, the requirement of informed consent to any health research is codified in the HDC Code, and is affirmed in human rights instruments.740 The Cartwright Report also intended that research participants should have access to the Health and Disability Commissioner process, to protect their rights.741

  4. The rights in the HDC Code extend to health and disability research, although the extent to which the HDC Code protects the interests of research participants is unclear because “health research” or “disability research” are not defined in the HDC Code or Act. 742 Research in which participants are unable to consent is not expressly contemplated under Right 7(4). Right 9 states: The rights in this Code extend to those occasions when a consumer is participating in, or it is proposed that a consumer participate in, teaching or research.

  5. In addition, the HDC Code applies only to research involving provision of healthcare, so it does not apply to all relevant research, for example observational research, or non- therapeutic health and disability research carried out by people other than healthcare practitioners.743

  6. Right 7(4) sets out the legal position concerning research involving the treatment of patients who do not have capacity to consent, where there is no legally authorised person available to give consent: it provides an exception to the usual requirement for informed consent and gives decision-making powers to the clinician-investigator so long as they have taken the steps set out in Right 7(4), to reach the conclusion that participation in the research will be in the patient’s “best interests”.744 Right 7(4) can therefore be interpreted as authorising a decision to enrol a patient in research involving treatment, even though the consent of the patient or a substitute decision-maker has not been obtained. It provides a legal justification for research without consent, but only in some limited situations.

739 Letts, above n 282 at 142.

740 HDC Code, Right 5 (right to effective communication), Right 6 (right to be fully informed) and Right 7 (right to make an informed choice and give informed consent). Section 10 of the New Zealand Bill of Rights Act 1990 also provides for the right not to be subject to medical or scientific experimentation without consent. Article 15 of the CRPD requires State Parties to have effective measures to prevent persons with disabilities, on an equal basis as others, from being subjected to torture or cruel or inhuman or degrading treatment or punishment and, in particular,” no one should be subjected without his or her free consent to medical or scientific experimentation.”

741 S Cartwright The Report of the Committee of Inquiry into allegations concerning the treatment of Cervical Cancer at National Women's Hospital and into other related matters (Government Printing Office, Auckland, 1988).

742 Health research “administered to or carried out in respect of any person” by a “healthcare provider” comes within the applicable definition of “healthcare procedure” and within the Code’s definition of “services”. Right 7(6) of the HDC Code, and the requirement that informed consent to a healthcare procedure (including participation in any research) must be in writing, contains important qualifications which reduce its impact in this context. Right 7(6) only applies to situations where consent “is required”. Therefore, written consent from those patients who are unable to consent (sometimes referred to as unconsentable) will not be required so long as the ethics committee is satisfied that the criteria in Right 7(4) are met.

743 L Wadsworth “Rights and Research: An Examination of Research under New Zealand’s Code of Health and Disability Services Consumers’ Rights” (2013) 21 JLM 187.

744 Right 7(4) requires either, reasonable steps have been taken to ascertain the views of the consumer, and if those views have been ascertained, the provider believes, on reasonable grounds, that the provision of services is consistent with the informed choice the consumer would make if he or she were competent: Right 7(4) (b) and (c)(i); or, if the consumer’s views have not been ascertained, the provider takes into account the views of other suitable persons who are interested in the welfare of the consumer and available to advise the provider: Right 7(4)(c)(ii).

The problems with Right 7(4) of the HDC Code
  1. Right 7(4) sits within a list of protections for patients in Right 7, but it largely provides a defence to Code liability for researchers, rather than a safeguard for participants based on the common law doctrine of necessity.745 There will be situations where it cannot be said that the research is in the individual’s best interests, as often the point of research is not to benefit them but to benefit others in future who may be suffering from a similar condition.746

  2. The National Ethics Advisory Committee Guidelines for Intervention Studies (NEAC Guidelines) place legal responsibility for non-consensual studies under Right 7(4) with the investigator, not the ethics committee, reflecting the position that ethics committees have no power to rule on the law.747 The NEAC Guidelines stop short of stating that the law prohibits non-consensual studies.748 Moreover, the status of the NEAC Guidelines and their interface with the Standard Operating Procedures (referred to as procedural, not ethical guidance), to which ethics committees are to adhere, is unclear, as is how they assist ethics committees when considering research that might be justified under Right 7(4).749

  3. The problems with relying on Right 7(4) in the context of non-consensual health research came to a head in 2014. In a letter to ethics committees, the Chief Legal Advisor to the Ministry of Health advised that the NEAC Guidelines for non-consensual studies “are intended for application only to studies that are ‘lawful’”.750 The effect of this directive has been to halt the process of ethics committees reviewing the ethics of a study, including risks and benefits, if participants are not able to give informed consent. Researchers are left in the invidious position of having to confirm the legality of the research based on their own assessment of what is in a person’s individual best interests (and implicitly of the risks) under Right 7(4). As Manning says, “researchers are being forced to run the gauntlet of the law.”751

745 Re F, above n 124. Clause 3 of the HDC Code states that a provider is not in breach of the Code if the provider “has taken reasonable actions in the circumstances” to give effect to the rights, and comply with the duties, in the Code. Clause 3 specifically provides that in this context “the circumstances” means all the relevant circumstances, “including the consumer’s clinical circumstances”.

746 Ashton, above n 25 at 272.

747 NEAC Guidelines, above n 726 at 24 [6.27]. The NEAC Guidelines do not presume that participation in health research is limited to individuals who can give informed consent. They suggest that if there is a question as to the competence of a participant, the investigator should consider obtaining dual consent, from the participant and “the informed agreement of another person who is interested in, or has responsibilities for, that person’s welfare”.

748 NEAC Guidelines, above n 726 at 24 [6.24] – [6.29].

749 NEAC Guidelines are created under delegated legislation by the New Zealand Public Health and Disability Act 2000, ss 16(1) and (2). NEAC is charged with determining nationally consistent ethical standards and scrutinising health research and standards, for both interventional and observational health research studies. New Zealand Law Society submission to the National Ethics Advisory Committee (12 June 2012). http://www.lawsociety.org.nz/__data/assets/pdf_file/0020/53183/l-NEAC-ethical_guidelines_review-120612.pdf.

750 Letter from P Knipe, Chief Legal Advisor, Ministry of Health to Health and Disability Ethics Committees regarding informed consent for ethics approval for trials (7 April 2014). The committees were reminded that they do not have authority to consent on behalf of participants who do not have capacity to consent (implying that this was in fact happening), and that in terms of Right 7(4), investigators must satisfy the committee that the proposed research is “lawful”.

751 J Manning, above n 722 at 517.

The PPPR Act – limitation on powers of substitute decision-makers to consent
  1. Where the person concerned is incapable of giving consent to healthcare, in the context of research, the first requirement of Right 7(4) is that a clinician-investigator attempt to obtain informed consent from someone entitled to give consent on the person’s behalf, such as a welfare guardian appointed by the court or an attorney appointed under an EPOA, who has the authority to make health decisions on the person’s behalf (a substitute decision-maker). The problem, however, is that section 18(1)(f) of the PPPR Act prevents such a substitute decision-maker from giving a legally effective consent to: 752
    any medical experiment other than one to be conducted for the purpose of saving that person’s life or preventing serious damage to that person’s health.
  2. This rule prevents the substitute decision-maker consenting to research participation on behalf of the person for whom they act, except in very limited situations. The paramount consideration of a welfare guardian is the promotion and protection of the welfare and best interests of the person for whom they are acting.753 It is not to authorise enrolment of the person in research for the purpose of benefiting other people in future. But Right 7(4) may permit them to give substitute consent to research on a person that is carried out in an emergency department or ICU within a hospital where the treatment or new drug being studied is considered the best treatment or option available.754 This is because the treatment being trialled might save that person’s life or prevent serious damage to their health, so providing substitute consent would not be prevented by section 18(1)(f).

  3. These provisions on substitute consent to research under the PPPR Act are outdated. They do not take into account the broad range of health and disability research conducted beyond the clinical environment of emergency treatment, and they substantially limit the powers of others to consent to the inclusion in research of a person who lacks capacity to consent, in situations where their participation would be ethically justified. In the emergency setting, where the patient may be unconscious, there may also be difficulty in identifying whether the person has an appointed substitute decision-maker or not.755

752 The same limitation of powers that apply to welfare guardians under s 18(1)(f) applies to attorneys appointed in relation to personal care and welfare (EPOAs) under s 98(4).

753 Protection of Personal and Property Rights Act 1988, ss 18(3) and 98A(2).

754 For a fuller discussion see Skegg, above n 580 at 227. Skegg states that if s 18(1)(f) precludes a welfare guardian from giving legally effective consent in such circumstances, the common law justification or “additionally or alternatively, for the purpose of Code liability under Right 7(4) of the Code of Rights”, would suffice.

755 An electronic register of EPOAs and court orders would potentially solve this particular problem. There are similar problems with identifying whether a person has a legally valid advance directive under Right 7(5) of the HDC Code.

Individual best interests and societal benefit
  1. If no substitute decision-maker is available, Right 7(4)(a) requires the clinician-investigator, having taken the steps to ascertain the views of the person or others required by Right 7(4), to reach the conclusion that participation in the research will be in the person’s “best interests”. This includes a clinical assessment by the clinician-investigator that there is a need for treatment to proceed, and, in the case of research, confirmation that the research is in the best interests of the individual concerned.

  2. The dual roles of the clinician-investigator can divert attention from the ethical conflict involved in both caring for the patient and potentially enrolling them in a study that may expose them to unacceptable risks.756 Other than applying the “best interests” test to the proposed treatment, Right 7(4) does not give the investigator any guidance on how to address this conflict of roles and requires the investigator to make the decision whether or not to enrol the patient in the research in the absence of independent advice or oversight.

  3. More often than not, it is not known in advance whether research will be in the best interests of the person, even though the research may subsequently prove to be beneficial and is not known to be harmful. In some research, there may be “clinical equipoise”, where there is genuine uncertainty in the expert medical community over whether a treatment will be beneficial.757 An argument can also be made that there is an “inclusion benefit” in clinical trials: by simply participating in a trial, the participants get more attention and monitoring than similar patients being treated in the same institution who are not involved in research.758

  4. There is an important distinction between research that is undertaken in a situation where a therapeutic intervention is needed (and the most promising treatment available is provided),759 compared to research where the alternative treatment is less likely to benefit the patient (for example, receiving a placebo in a randomised clinical trial),760 or where the new treatment being trialled is no more than equivalent to the standard treatment (“non-inferiority clinical trials”).761 In the former situation, there is likelihood of direct benefit to the individual, whereas in the latter situations there may only be societal benefits resulting from the research. Such research may still be ethically justified, but it may not be in the best interests of the individual participating in the research, as required under Right 7(4).

756 TL Beauchamp and JF Childress Principles of Biomedical Ethics (5th ed, Oxford University Press, New York, 2001) at 319; A Jonsen, M Siegler and M Winslade Clinical Ethics: A Practical Approach to Ethical Decisions in Clinical Medicine (3rd ed, McGraw Hill, New York, 1992) at 147; F G Miller and D L Rosenstein, “The Therapeutic Orientation of Clinical Trials” (2003) 348 NEJM 1383 at 1384.

757 B Freedman “Equipoise and the Ethics of Clinical Research” (1987) 317 NEJM 141. The “equipoise standard” is referred to in the NEAC Guidelines as the balancing of risks and benefits where there is a comparison of two or more interventions designed to meet the equipoise standard and there is usually use of a placebo or no intervention as a control.

758 J Lantos “The Inclusion Benefit in Clinical Trials” (1999) 134 J Paeds 30 at 31; Miller and Rosenstein, above n 756 at 1383.

759 For an example of a Phase 3 single arm study where the treatment was the best available see the RE-VERSE-AD study discussed below.

760 For an example of a Phase 2 randomised controlled trial, see the CLEMATIS study discussed below.

761 A non-inferiority clinical trial is one where the treatment or drug is said to be “as good as” or “not inferior to” standard treatment. For example, ASPECT: A double-blind study to assess the safety and efficacy of intravenous Ceftolozane/Tazobactam with that of Meropenem in ventilated nosocomial pneumonia. This was a Phase 3 trial to see whether a new antibiotic was as effective as an existing antibiotic, rather than superior. Conditional approval was granted on the basis that the researcher provide information that participation in the research would be in the patients’ best interests. (Northern A Health and Disability Ethics Committee Minutes, 11 March 2014, www.ethics.health.govt.nz). For a fuller discussion of this study, considered at the same time as the CLEMATIS study, see Manning, above n 722 at 518.

Some examples
RE-VERSE-AD: Right 7(4) applied where the treatment being researched was in the individual’s best interests, even though the investigator had both clinical and research roles
  1. This multi-centre clinical study was testing the efficacy and safety of a drug designed to reverse the blood-thinning effects of an anticoagulant drug to reduce the risk of bleeding. It received ethical approval on the basis that the research could be lawfully justified under Right 7(4).762 Prior to the study, patients on the anticoagulant had limited options available to control bleeding. Some of these patients were in a life-threatening emergency situation and required immediate surgical or medical intervention to manage their bleeding.763 In the large majority of cases in this study, no substitute decision-maker was available for the investigator to consult under Right 7(4).764 As there was potential to reverse a serious, life-threatening condition with the best treatment available, the principal investigator was able to confirm to the ethics committee that the research was in the best interests of individual participants, and so to proceed would meet the criteria under Right 7(4).

  2. The study has been successful, with a significant number of “unconsentable” patients enrolled who had positive medical outcomes. In this way, New Zealand researchers have played a major role in globally demonstrating that the study drug is effective and safe.765

  3. At the outset of this study, the principal investigator initiated the practice of seeking a second opinion from another doctor not directly involved in the study (a “disinterested colleague”) on the enrolment of a patient, when this would be justified under Right 7(4). The investigator explains the ethical conflict as follows:766 In cases where the decision as to whether treatment is in the patient’s interests rests predominantly on the clinician, the clinician’s judgment can be coloured by the wish to recruit patients to the trial. Even in cases where no bias is present, the possibility of perception of bias leading to an error of medical judgment cannot be excluded.

762 Central Health and Disability Ethics Committee Minutes “Reversal of the Anticoagulant Effect of Dabigatran Using Idarucizumab” ethics ref. 14/CEN/58/AM03 (22 April 2014) www.ethics.health.govt.nz at 8. The writer subsequently provided one of two legal opinions submitted to the ethics committee when amendments were made to the consent forms: (Central HDEC approval letter dated 1 May 2015).

763 This is a Phase 3 single arm study and all patients enrolled in the study receive the study drug.

764 Email communication from Dr Gordon Royle, Haematologist, Middlemore Hospital, New Zealand principal investigator for the RE-VERSE-AD study to Alison Douglass (29 February 2016).

765 Email communication from Dr Gordon Royle, Haematologist, Middlemore Hospital, New Zealand principal investigator for the RE-VERSE-AD study to Alison Douglass (2 March 2016).

766 Royle, above n 764. The ethics committee did not initially require a second opinion but subsequently approved the process for unconsentable participants as set out in the “Form for participants who are not able to give written informed consent”. The form also has a procedure should the patient subsequently regain capacity post-treatment.

CLEMATIS study: Randomised control trial, justified ethically by the societal benefit; exclusion of adults as research not in their best interests, but not children with parental consent
  1. When the benefits to an individual are less clear, or there is no imminent risk to health or safety that can be mitigated by the intervention, research participation is unlikely to be justified in terms of Right 7(4). The CLEMATIS study was a multi-centred clinical trial investigating a drug intended to enhance cognition and learning in people with Down syndrome. Approval for the study was initially declined, based on legal advice that it was not clear that the proposed research would be in the best interests of the participants.767

  2. The application was resubmitted in July 2014 and was given approval for children whose parents could give consent for participation and for adults who had the capacity to give informed consent.768 Ethical approval was declined for adults with Down syndrome who lacked capacity to consent, even though the drug could not effectively be tested in persons without Down syndrome.

  3. The ‘necessity’ principle in research, as it applies to children, is that research should only be carried out on children if comparable research with adults could not answer the same question.769 The decision to allow for substituted consent in one vulnerable population (children), but not to extend it to adults who lack capacity undermines this ethical principle and discriminates between two vulnerable groups.770 Under Right 7(4) no account can be taken of wider societal benefits of the research, or of the fact that this particular study drug was aimed at providing treatment for people affected by Down syndrome, even though the study had been approved for adults in eight countries,771 including meeting the standards of the Clinical Trial Regulations in the United Kingdom.772
Proposal to amend Right 7(4) of the HDC Code
  1. In the absence of clear legislative direction, these examples highlight the problematic terms of Right 7(4) when applied to research with participants unable to consent. Accordingly, in 2009, Commissioner Paterson recommended a change to Right 7(4) that might permit more research on unconscious or incompetent patients, provided the research was approved by an ethics committee.773 The recommendation was that Right 7(4)(a) should be amended so as to justify healthcare proceeding where: It is in the best interests of the consumer, or in the case of research, is not known to be contrary to the best interests of the consumer and has received the approval of an ethics committee.

767 Northern A Health and Disability Ethics Committee “A Study of RG1662 in Adults and Adolescents with Down syndrome (CLEMATIS)” (8 April 2014) www.ethics.health.govt.nz at 3. The study was a Phase 2 randomised clinical trial of the safety, efficacy and tolerability of a cognitive enhancing drug in people with Down Syndrome between the ages of 12 and 30.

768 The Care of Children Act 2004 allows parents of children under 16 to give proxy consent for medical treatment. Guidelines have extended this to include participation in research, N Peart and D Holdaway “Legal and Ethical Issues of Health Research with Children” (1998) 2 Children’s Issues Centre 42 (www.hrc.govt.nz). The recently released report by the Nuffield Council on Bioethics Children and Clinical Research: Ethical Issues (2015) states that an understanding of a child’s longer-term welfare can include contributing to wider social goods, and parental consent to research should consider whether participation in the proposed research is compatible with their child’s immediate and longer-term interests (Chapter 4).

769 See, for example the HRC’s Guidelines for Health Research with Children www.hrc.govt.nz/sites/default/files/HRC%20Guidelines%20for%20Health%20Research%20with%20Children.pdf. The Guidelines are derived from the Guidelines of the Royal College of Paediatrics and Child Health 1999 and the European Convention for the Protection of Human Rights and Dignity of the Human Being with Regard to the Application of Biology and Medicine 1996. The ‘necessity principle’ is discussed below under the MCA.

770 J Lenagh-Glue “Resolving the Irreconcilable: Informed Consent and Participation in Medical Research for Adults with Intellectual Disability” (LLB (Hons) Dissertation, University of Otago, 2014).

771 LuMind “Clinical Trials UPDATE: Roche Initiates RG1662 Phase II Clinical Trials for Individuals with Down syndrome” (19 May 2014) www.plus15campaign.wordpress.com.

772 Clinical Trials Regulation (UK) http://www.ukctg.nihr.ac.uk/trials/trial-details/trial-details?trialNumber=NCT02024789.

773 In an earlier review of the HDC Code in 2004, Commissioner Paterson recommended the specific provision relating to research on unconscious or incompetent patients with appropriate safeguards rather than wholesale change to Right 7(4) to cover treatment of incompetent patients generally (not just research). See Health and Disability Commissioner Report to the Minister of Health (June 2009) at 14. http://www.hdc.org.nz/media/21835/theact-review2004.pdf.

  1. This proposed amendment (introducing the “not known to be contrary to” formula) in effect sets a lower threshold for establishing what is in a patient’s best interests. The double negative formulation used does not guide ethics committees as to what factors they should take into account, however, in deciding what is not harmful (and not contrary) to the interests of research participants, or whether the assessment of best interests can consider benefits over and above direct benefits to an individual. It also continues to confuse the role of Right 7(4), a justification for proceeding with treatment in limited circumstances, with the need to have adequate safeguards in place for research participants.

  2. In the 2014 review of the HDC Code, Commissioner Hill did not revisit the 2009 recommendation for changes to Right 7(4).774 What is required is separate legislation that would provide similar protections for research participants who lack capacity as are found in the MCA, and in the Adults with Incapacity (Scotland) Act 2000.

774 New Zealand Law Society submission on the Review of the Health and Disability Commissioner Act 1994 and the Code of Health and Disability Consumers’ Rights (17 February 2014) www.lawsociety.org.nz/__data/assets/pdf_file/0012/75999/l-HDC-Act-and-Code-Review-17-02-14.pdf

  © 2020 Alison Douglass