Application for approval for adults unable to consent to their own treatment to participate in a clinical trial (intranasal insulin for the management of delirium) [2017] NSWCATGD 39

Statutory framework

1. Part 5 of the Act governs the conduct of clinical trials involving persons with a decision-making disability. Part 5 of the Act applies to patients who are aged 16 years or over and who are incapable of giving consent to the carrying out of medical or dental treatment: s 34(1) of the Act.
2. Section 33(2) of the Act states that for the purposes of Pt 5 of the Act, a person is regarded as being incapable of giving consent to the carrying out of medical treatment if the person: 1. is incapable of understanding the general nature and effect of the proposed treatment, or 2. is incapable of indicating whether or not he or she consents or does not consent to the treatment being carried out.
3. "Medical treatment" is defined in s 33(1) of the Act to include: medical treatment (including any medical or surgical procedure, operation or examination and any prophylactic, palliative or rehabilitative care) normally carried out by or under the supervision of a medical practitioner (and, in the case of treatment in the course of a clinical trial, is taken to include the giving of placebos to some of the participants in the trial) ...[subject to a number of exceptions which are not relevant for present purposes]…
4. "Clinical trial" is defined in s 33(1) of the Act to mean "a trial of drugs or techniques that necessarily involves the carrying out of medical or dental treatment on the participants in the trial".
5. The Tribunal may approve a clinical trial as a trial in which patients who are unable to give a valid consent to their own treatment may take part: s 45AA(1) of the Act. Before doing so, the Tribunal must be satisfied as to each of the criteria set out in s 45AA(2) of the Act. Section 45AA of the Act states: 45AA Tribunal may approve clinical trials (1) The Tribunal may approve, in accordance with this section, a clinical trial as a trial in which patients to whom this Part applies may participate. (2) The Tribunal may give an approval under this section only if it is satisfied that: (a) the drugs or techniques being tested in the clinical trial are intended to cure or alleviate a particular condition from which the patients suffer, and (b) the trial will not involve any known substantial risk to the patients (or, if there are existing treatments for the condition concerned, will not involve material risks greater than the risks associated with those treatments), and (c) the development of the drugs or techniques has reached a stage at which safety and ethical considerations make it appropriate that the drugs or techniques be available to patients who suffer from that condition even if those patients are not able to consent to taking part in the trial, and (d) having regard to the potential benefits (as well as the potential risks) of participation in the trial, it is in the best interests of patients who suffer from that condition that they take part in the trial, and (e) the trial has been approved by a relevant ethics committee and complies with any relevant guidelines issued by the National Health and Medical Research Council. (3) The fact that a clinical trial will or may involve the giving of placebos to some of the participants in the trial does not prevent the Tribunal from being satisfied that it is in the best interests of patients that they take part in the trial. (4) The Tribunal's approval of a clinical trial under this section does not operate as a consent to the participation in the trial of any particular patient to whom this Part applies. The appropriate consent must be obtained under Division 3 or 4 before any medical or dental treatment in the course of the trial is carried out on the patient. (5) In this section: "ethics committee" means: (a) for so long as there is any relevant Institutional Ethics Committee registered by the Australian Health Ethics Committee established under the National Health and Medical Research Council Act 1992 of the Commonwealth--an Institutional Ethics Committee so registered, or (b) in the absence of such a committee, an ethics committee established by: (i) a local health district or a public hospital, or (ii) a university, being an ethics committee concerned, wholly or partly, with medical research, or(iii) the National Health and Medical Research Council.
6. If satisfied of the matters specified in s 45AA(2) of the Act, the Tribunal may make one of the following orders listed in s 45AB of the Act, providing it is satisfied that the proposed form for granting consent provides "sufficient information to enable the persons responsible to decide whether or not it is appropriate that the patients should take part in the trial". Section 45AB of the Act states: 45AB Consent for participation in clinical trials in individual cases (1) If the Tribunal is satisfied as to the matters specified in section 45AA(2) in relation to a clinical trial, it may, by order, determine: (a) that the function of giving or withholding consent for the carrying out of medical or dental treatment on patients in the course of the trial is to be exercised by the persons responsible for the patients (in which case Division 3 applies), or (b) that the Tribunal is to exercise that function itself (in which case Division 4 applies). (2) Before making a determination referred to in subsection (1) (a), the Tribunal must be satisfied that the form for granting consent and the information available about the trial provide sufficient information to enable the persons responsible to decide whether or not it is appropriate that the patients should take part in the trial.
7. As explained by the Appeal Panel in Shehabi v Attorney General (NSW) [2016] NSWCATAP 137 at [67], ss 45AA and 45AB of the Act establish a three-step process for obtaining consent to medical treatment as part of a clinical trial for patients to whom Pt 5 of the Act applies: 1. First, the Tribunal must determine whether to approve the trial under s 45AA of the Act but that approval does not operate, by itself, as consent to the participation in the trial by any particular patient. 2. Second, if the Tribunal is satisfied in accordance with s 45AA(2) of the Act that the clinical trial should be approved, the Tribunal then has to determine whether consent to treatment as part of that trial should be given by the 'person responsible' or by the Tribunal. 3. Third, depending on whether the consent is to be obtained from the 'person responsible' or the Tribunal, consent must then be obtained under s 40 of the Act or under ss 42 to 45 of the Act, respectively, for the medical treatment in the course of the trial to be carried out on the patient.
8. In exercising the power conferred by Pt 5 of the Act to approve a clinical trial, the Tribunal must observe the "general principles" listed in s 4 of the Act: 4 General principles It is the duty of everyone exercising functions under this Act with respect to persons who have disabilities to observe the following principles: (a) the welfare and interests of such persons should be given paramount consideration, (b) the freedom of decision and freedom of action of such persons should be restricted as little as possible, (c) such persons should be encouraged, as far as possible, to live a normal life in the community, (d) the views of such persons in relation to the exercise of those functions should be taken into consideration, (e) the importance of preserving the family relationships and the cultural and linguistic environments of such persons should be recognised, (f) such persons should be encouraged, as far as possible, to be self-reliant in matters relating to their personal, domestic and financial affairs, (g) such persons should be protected from neglect, abuse and exploitation, (h) the community should be encouraged to apply and promote these principles.

Does the trial meet the requirements of s 45AA of the Act?

Is the trial drug intended to cure or alleviate a particular condition from which the patients suffer?

1. Yes. The Trial drug is intended to cure or alleviate the symptoms of delirium.

Will the Trial involve any known substantial risk to the patients (or, if there are existing treatments for the condition concerned, will not involve material risks greater than the risks associated with those treatments)?

1. The Trial is a Phase 3 trial, that is, a clinical trial that has undergone two previous trials: a Phase 1 trial evaluates the safety of the trial drug on a small group of people (e.g. to determine a safe dosage range and identify side effects); a Phase 2 trial is used to determine efficacy (that is, whether the drug works as intended) and to further evaluate the safety of the trial drug. (National Health and Medical Research Council https://www.australianclinicaltrials.gov.au/what-clinical-trial/phases-clinical-trials.)
2. A/Prof Caplan reports that insulin has been used safely in humans for over 80 years. According to the Protocol, intranasal insulin has been used in several reported trials involving elderly and cognitively impaired patients, with no severe treatment-related adverse events. In addition, the Protocol claims that previous trials reveal that intranasal insulin are well tolerated, causing at most some mild nasal irritation.
3. We are satisfied the Trial does involve any known substantial risk to patients.

Has the development of the use of intranasal insulin reached a stage at which safety and ethical considerations make it appropriate that intranasal reached be available to patients who suffer from delirium even if those patients are not able to consent to taking part in the Trial?

1. As noted above, the Trial is in its third phase. The Protocol claims that to date, there have been no reported adverse consequences associated with the use of intranasal insulin. We are satisfied that the development of intranasal insulin has now reached a stage at which safety and ethical considerations make it appropriate that intranasal insulin be available to patients with delirium, including those who are not able to consent to taking part in the Trial.

Having regard to the potential benefits (as well as the potential risks) of participation in the Trial, it is in the best interests of patients who suffer from delirium that they take part in the Trial?

1. The available material indicates that there are no known substantial risks associated with the use of intranasal insulin in people over the age of 65 years. Nonetheless, as conceded by A/Prof Caplan the safety and efficacy profile of the use of intranasal insulin in patients with delirium has not been fully tested.
2. The risk of using intranasal insulin for patients with delirium in circumstances where it has not been fully tested, must be weighed against the potential benefits of using the drug. As stated above, the sequelae of delirium are multiple and significant and include increased mortality rates and longer hospital admissions. In addition, delirium is a risk factor for cognitive impairment and accelerating the progress of dementia.
3. According to A/Prof Caplan the standard treatments currently used for patients with delirium, treat the symptoms not the pathology of the condition. These treatments include various drugs, including antipsychotics, benzodiazepines and narcotics. The latter can only be used if the patient is on a cardiac monitor. According to A/Prof Caplan, previous studies reveal that these drugs, at best, resolve the symptoms of delirium and are not risk free. The use of narcotics and antipsychotics in many individuals can make the delirium worse.
4. The treatment currently available to persons with delirium is neither risk-free nor particularly effective. A cautious approach must always be taken before using a drug that has not yet been fully tested on patients suffering from the relevant condition. This is especially the case where the person proposed to participate in the trial lacks the capacity to evaluate the risks and benefits of the proposed trial. However, on the material available, the potential benefits of the use of insulin would appear to outweigh the likely risks. We are satisfied that it is in the best interests of persons who suffer from delirium that they have the opportunity to take part in the Trial.

Has the Trial has been approved by a relevant ethics committee and does it comply with any relevant guidelines issued by the National Health and Medical Research Council?

1. As noted above the Trial has been approved by the South Eastern Sydney Local Health District Human Research Ethics Committee. That Committee is registered with the National Health and Medical Research Council and as a consequence of its registration must comply with the National Statement on Ethical Conduct in Human Research, 2007 (updated March 2014).

Summary

1. Each of the criteria listed in s 45AA(2) of the Act is satisfied.

Should the Tribunal leave the issue of consent to 'persons responsible'?

1. Section 45AB of the Act states: 45AB Consent for participation in clinical trials in individual cases (1) If the Tribunal is satisfied as to the matters specified in section 45AA (2) in relation to a clinical trial, it may, by order, determine: (a) that the function of giving or withholding consent for the carrying out of medical or dental treatment on patients in the course of the trial is to be exercised by the persons responsible for the patients (in which case Division 3 applies), or (b) that the Tribunal is to exercise that function itself (in which case Division 4 applies). (2) Before making a determination referred to in subsection (1) (a), the Tribunal must be satisfied that the form for granting consent and the information available about the trial provide sufficient information to enable the persons responsible to decide whether or not it is appropriate that the patients should take part in the trial.
2. Section 45AB of the Act requires us to decide whether the function of giving or withholding consent for the carrying out of medical treatment on patients in the course of the Trial should be exercised by the 'persons responsible' for the relevant patients, or the Tribunal. The Act provides no express guidance on the factors to take into account in making this determination.
3. A/Prof Caplan seeks the function of giving or withholding consent to be exercised by the 'persons responsible' for the patients. (See s 33A of the Act for the definition of "person responsible".)
4. In our view, in the circumstances of this Application, where decisions will need to be made in a short timeframe and the factors to be taken into account in deciding whether to consent or not to consent on behalf of the proposed participant in the Trial are relatively simple, it is preferable that the function of giving and withholding consent is exercised by the person responsible, not the Tribunal.

Does the proposed form for granting consent and the information available about the Trial provide sufficient information to enable the 'person responsible' to decide whether or not it is appropriate that the patients should take part in the Trial?

1. Before making a final decision about whether the Tribunal or the relevant 'person responsible' should be given the function of giving or withholding consent to participating in the Trial, s 45AB(2) of the Act directs that we be satisfied that the form for granting consent, and the information available about the Trial proposed to be provided to the 'persons responsible', provide sufficient information to enable the 'persons responsible' to decide whether or not it is appropriate that the patients should take part in the Trial.

A proposed substitute consent form and information sheet was filed in support of the Application.

1. The proposed substitute consent form and information sheet were written in plain English using simple language. Together they gave a cogent explanation of the purpose of the Trial and the known side effects of insulin. While the material refers to the possible benefits of the use of intranasal insulin, it did not overstate the potential benefits. The substitute consent form and information sheet appeared to be capable of being understood by individuals with limited education and language skills.
2. We are satisfied that the proposed substitute consent form and information sheet provide sufficient information to enable 'persons responsible' to decide whether or not it is appropriate that the patients should take part in the Trial.

Summary of Conclusions

1. The preconditions to giving approval under s 45AA of the Act are satisfied. Given the potential benefits of intranasal insulin to persons with delirium, we have concluded that the power to approve the Trial should be exercised. In addition, we have decided that the function of giving or withholding consent to participate in the Trial should be exercised by the 'persons responsible', not the Tribunal. Further, we are satisfied that the proposed form for granting consent and the information sheet about the Trial will enable 'persons responsible' to make an informed decision about whether consent to participate in the Trial should be given.

I hereby certify that this is a true and accurate record of the reasons for decision of the Civil and Administrative Tribunal of New South Wales. Registrar DISCLAIMER - Every effort has been made to comply with suppression orders or statutory provisions prohibiting publication that may apply to this judgment or decision. The onus remains on any person using material in the judgment or decision to ensure that the intended use of that material does not breach any such order or provision. Further enquiries may be directed to the Registry of the Court or Tribunal in which it was generated. Decision last updated: 05 July 2018