These Reasons for Decision relate to the orders made by the Tribunal on 19 June 2015 concerning a prospective multicentre randomised controlled trial of early goal directed sedation compared with standard care in mechanically ventilated patients in intensive care (SPICE III) as described in protocol version 3.10 dated 8 June 2015 ("the Trial"). The orders are replicated in Appendix A to these Reasons for Decision.
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INTRODUCTION
The Applicant in these proceedings is Dr Yahya Shehabi, Senior Intensivist at the Prince of Wales Hospital, Randwick, NSW, Associate Professor at the Clinical School of Medicine, University of New South Wales and Medical Director of Acute Care and Director of Intensive Care Research at the Prince of Wales Hospital, Randwick.
The Trial has previously been considered by the Tribunal, and the predecessor to the Tribunal, the Guardianship Tribunal of NSW. The Applicant first lodged his application seeking approval for an earlier iteration of the Trial (version 2 dated 24 January 2013) on 1 August 2013. The Tribunal registry recorded those proceedings as CT 10/2013. By the time the Tribunal made orders on 23 December 2014, a further amended version of the protocol was before the Tribunal for approval (version 3 dated 24 June 2013).
The hypotheses to be tested, and the methodology of the Trial were succinctly described by the Tribunal in the Reasons for Decision relating to the orders issued by the Tribunal on 23 December 2014 approving CT 10/2013 [paragraphs 3 to 6]:
3 The hypothesis sought to be tested in the current study (as set out in the Study Protocol, page 9) is that Early Goal Directed Sedation, compared to standard care sedation, reduces 90-day all-cause mortality in critically ill patients who require mechanical ventilation. The primary aim is therefore to determine whether Early Goal-Directed Sedation, compared to standard care sedation, reduces 90 day mortality in critically ill patients who are expected to require mechanical ventilation for longer than 24 hours.
4 The Study Protocol (page 19) describes the study as a process of care sedation trial whereby the sedative agents used in both arms, individually or in combination, are accepted sedatives currently used for mechanically ventilated ICU patients. The Study Protocol notes that many randomised control trials have documented the efficiency and safety in isolation of the three agents (propofol, midazolam and dexmedetomidine) used in the trial and these agents have also been recommended by the most recent International Sedation Guidelines and have been deemed not different in providing sedation to ventilated ICU patients.
5 Dexmedetomidine (also known as Precedex) has been used as a sedative agent in ICUs for a number of years. It is licensed by the Therapeutic Goods Administration ('TGA') for sedation of initially intubated patients during treatment in an intensive care setting for up to 24 hours. It is also licensed for sedation of non-intubated patients prior to and/or during surgical or other procedures.
6 The study proposes the use of dexmedetomidine for a period longer than 24 hours and is thereby proposed for use outside of its licensed parameters.
Upon completion of hearings conducted on 17 December 2013, 8 May 2014, and 15 October 2014 the Tribunal issued the following orders on 23 December 2014:
1. The Tribunal has considered the clinical trial known as SPICE III: A Prospective Multicentre Randomised Controlled Trial of Early Goal Directed Sedation Compared with Standard Care in Mechanically Ventilated Patients in Intensive Care.
2. The Tribunal is satisfied that in relation to the above-named clinical trial, all the requirements of section 45AA(2) of the Guardianship Act have been met.
3. The Tribunal approves the clinical trial as one in which adults unable to consent to their own treatment may participate. Unless the Tribunal subsequently orders otherwise, this approval remains current until that trial has been concluded in New South Wales.
4. The Tribunal approves the clinical trial at the following sites:
Prince of Wales Hospital, Nepean Hospital, Hornsby Ku-ring-gai Hospital, St Vincent's Hospital, Westmead Hospital and Lismore Hospital.
This approval is subject to the following condition(s):
5. The Tribunal orders that 'persons responsible' for those unable to consent to their own medical treatment may not exercise the function of giving or withholding consent to the carrying out of medical treatment on the person they are 'person responsible' for in the course of the clinical trial.
6. The Tribunal is not satisfied that the forms for granting consent and the information sheet provided to the Tribunal by:
Prince of Wales Hospital, Nepean Hospital, Hornsby Ku-ring-gai Hospital, St Vincent's Hospital, Westmead Hospital and Lismore Hospital.
are sufficient to enable 'persons responsible' to decide whether or not it is appropriate that those persons they are 'person responsible' for should take part in the clinical trial.
7. The Tribunal orders that the Tribunal is required to exercise the function of giving or withholding consent for the carrying out of medical treatment on patients in the course of the clinical trial (s 45AB(1)(b)).
On 24 April 2015 the Applicant lodged a further application with the Tribunal in relation to the previously approved trial. In his application Dr Shehabi requested: (a) approval from the Tribunal to extend the previously approved trial to additional sites to those approved by the Tribunals orders of 23 December 2014; and (b) that persons responsible be authorised to give or withhold consent for the treatment contemplated by the trial. At the time the application was lodged Dr Shehabi submitted for approval a further amended protocol in relation to the clinical trial (version 3.6 dated 26 April 2015) together with the proposed forms intended to provide information and seek substitute consent from persons responsible for persons sought to be recruited into the trial.
As the Applicant requested that his application be dealt with urgently, the Tribunal convened a directions hearing by telephone on 27 April 2015. During the course of this directions hearing the Tribunal made a number of suggestions to the Applicant as to how the proposed person responsible information and consent form could be improved upon so that it might satisfy s 45AB (2) of the Guardianship Act 1987 (NSW) .
On 16 June 2015 the Applicant lodged a further amended protocol relating to the trial (version 3.10 dated 8 June 2015) and amended proposed information and consent form for persons responsible and again reiterated his request that the matter be dealt with expeditiously.
In recognition of the Applicant's request for expedition, the Tribunal listed the matter on 19 June 2015 by means of a telephone hearing. The Applicant was the only participant to the hearing, advising that representatives from the Human Research Ethics Committee for the Prince of Wales Hospital ("the Ethics Committee"), who had participated in previous hearings, had indicated they would not be participating in this matter. The Tribunal proceeded to hear the matter on 19 June 2015 and issued its orders granting the Applicant's requests at the conclusion of the hearing.
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Guardianship Act 1987 (NSW)
The provisions relating to clinical trials are contained within Part 5 of the Guardianship Act 1987 (NSW) ("the Act"). Part 5 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)).
For the purposes of Part 5, a person is regarded as being incapable of giving consent to the carrying out of medical or dental 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 (s 33(2)).
Under s 45AA(1) of the Act, 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. Before doing so, the Tribunal must be satisfied as to all of the criteria set out in s 45AA(2) of the Act.
Section 45AA provides as follows:
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.
As is clear from s 45AA(4), if the Tribunal approves a trial as one in which patients who are unable to give a valid consent to their own treatment may take part, consent for the participation of particular patients in the trial must be obtained under Division 3 or 4 before any medical or dental treatment in the course of the trial may carried out in relation to the patient.
The Tribunal may determine, pursuant to s 45AB(1), 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
the Tribunal is to exercise that function itself (in which case Division 4 applies).
Before making a determination that the function of giving or withholding consent for the carrying out of medical or dental treatment on patients in the course of a trial is to be exercised by the persons responsible for the patients, 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 (s 45AB(2)).
In determining whether the forms proposed are sufficient to permit a person responsible to fulfil the role contemplated by Part 5 the Tribunal must have regard to the statutory requirements of decision making imposed upon persons responsible as outlined in Division 3 of Part 5 of the Act. Section 40 , which constitutes the entirety of Division 3, provides:
40 Consents given by persons responsible for patients
(1) Any person may request a person responsible for a patient to whom this Part applies for that person's consent to the carrying out of medical or dental treatment on the patient.
(2) Such a request shall specify:
(a) the grounds on which it is alleged that the patient is a patient to whom this Part applies,
(b) the particular condition of the patient that requires treatment,
(c) the alternative courses of treatment that are available in relation to that condition,
(d) the general nature and effect of each of those courses of treatment,
(e) the nature and degree of the significant risks (if any) associated with each of those courses of treatment, and
(f) the reasons for which it is proposed that any particular course of treatment should be carried out.
(3) In considering such an application, the person responsible for the patient shall have regard to:
(a) the views (if any) of the patient,
(b) the matters referred to in subsection (2), and
(c) the objects of this Part.
(4) The regulations may make provision for the manner and form in which:
(a) requests under this section shall be made, and
(b) consents under this section shall be given.
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MATTERS FOR DETERMINATION
The Applicant advised the Tribunal, in both his written application and at the hearing of 19 June 2015, that in practical terms he was seeking additional orders to those issued by the Tribunal on 23 December 2014 approving the Trial. Dr Shehabi requested that the Tribunal provide additional orders so that consent for inclusion in the trial, for persons who could not provide their own consent, could be given (or withheld) by a person responsible. The orders issued by the Tribunal on 23 December 2014 only permitted consent in such circumstances to be given by the Tribunal. Further, Dr Shehabi sought approval for the Trial to be conducted at more sites than those approved in the Tribunal's previous order.
In requesting such orders from the Tribunal Dr Shehabi submitted an amended protocol compared to the protocol that was before the Tribunal in relation to the orders of 23 December 2014. The protocol that was before the Tribunal at that time was recorded as version 3 dated 24 June 2013. The protocol before the Tribunal as at the hearing on 19 June 2015 was recorded as version 3.10 dated 8 June 2015. The Applicant also submitted to the Tribunal a letter from the Ethics Committee dated 12 June 2015 and authored by Mr Andrew Bohlken, Acting Executive Officer of that Committee ("the Ethics Committee letter of 12 June 2015"). That letter confirmed, amongst other things, that the latest protocol of the Trial (version 3.10 dated 8 June 2015) had been approved by the Ethics Committee.
The Applicant advised the Tribunal that the clinical trial described in the latest protocol was "one in the same trial" as the protocol that was before the Tribunal and approved by the Tribunal orders of 23 December 2014. The only variation in the protocols related to the consent regime permitted for those patients who could not provide their own consent. The Applicant made it clear to the Tribunal that he was not requesting the Tribunal on this occasion to re-evaluate the clinical trial in terms of the criteria provided in s 45AA(2) of the Act (if such revaluation was jurisdictionally possible). Rather, he was requesting orders which extended upon the Tribunal's previous orders, allowing substitute consent for treatment pursuant to the Trial to be sought from persons responsible, and for the Trial to be conducting at more sites than originally approved.
To support his submission that the underlying clinical trial, that was described in the version of the protocol previously approved, had not changed other than to allow for amendment of the consent regime, Dr Shehabi provided the Tribunal with a comparative version of the protocol "marked up" illustrating those changes to the protocol compared to that previously approved by the Tribunal.
The Tribunal concluded that a review of the "marked up" amended protocol supported the Applicant's position. The amendments all dealt with changes to the protocol for consent for participation in the trial rather than any changes to the hypotheses or methodology of the trial itself.
In these circumstances, the Tribunal agreed with the position put by the Applicant, that is, that it was not required to conduct an analysis of the Trial to determine whether it satisfied the criteria provided in s 45AA(2). That task had been undertaken by the Tribunal which issued orders on 23 December 2014 and those orders remained in place as the substance of the Trial had not changed. What had changed was the consent regime and that was the matter for determination before the Tribunal on this occasion, together with the issue of whether to approve of the Trial being conducted at additional sites.
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REQUEST FOR PERSONS RESPONSIBLE TO BE AUTHORISED TO GIVE AND WITHOLD CONSENT
The orders made by the Tribunal in relation to the trial on 23 December 2014 made it clear that persons responsible were not authorised to exercise the function of giving or withholding consent to the carrying out of medical treatment on the person they are person responsible for in the course of the trial. The Tribunal provided the following explanation for such order in its Reasons for Decision [paragraphs 116 to 119]:
116 At the conclusion of the hearing on 8 May 2014, the Tribunal adjourned the hearing. The Tribunal did so after indicating to the applicant that, whilst it had not arrived at final determination, it was minded to approve the study as a clinical trial and, as a result, noted that the draft 'person responsible' forms submitted along with the original application would need to be amended and resubmitted to the Tribunal in order to remove all references to 'delayed consent' if the applicant wished to have the Tribunal authorise persons responsible to provide consent for individuals to enter into the trial.
117 The Tribunal subsequently received an email from Dr Shehabi dated 12 August 2014 that attached a letter dated 14 July 2014 from Ms Deborah Adrian, Executive Officer of the SESLHD Human Research Ethics Committee, that advised that the Committee had considered the proposed amendment to the draft 'person responsible' forms and rejected the amendments for the following reasons:
The amendment compromises the scientific validity of the study
The amendment would introduce an insurmountable logistical obstacle in that obtaining consent (either from the patient or person responsible) would necessitate a delay in treatment which would be highly unethical
For the above reasons the proposed amendment would prevent the success of this important study. The Committee has therefore determined that obtaining consent from a person responsible prior to participant enrolment in this study is in itself unethical.
118 The person responsible forms submitted to the Tribunal do not, in the Tribunal's view, meet the requirements of section 45AB(2) as they are drafted on the basis of 'delayed consent'. They do not provide sufficient information to enable a person responsible for a patient to decide whether or not the patient should enter into the trial. Rather, the focus of the forms as drafted is whether or not the patient should remain enrolled in the trial.
119 Given this finding, the Tribunal was left with no alternative but to determine, pursuant to section 45AB(1)(b), that the Tribunal is to exercise the function of giving or withholding consent to an individual patient's participation in the trial.
In making his further application to the Tribunal, Dr Shehabi, and subsequently the Ethics Committee, had altered their view to that previously expressed to the Tribunal. As a result of the position previously taken by the Applicant, supported by the Ethics Committee, the Tribunal had no alternative but to limit the function of providing (or withholding) substitute consent to participate in the Trial to the Tribunal. This meant that if a person was unable to provide their own consent, an application was required to be made to the Tribunal and a hearing conducted to determine whether consent should be provided by the Tribunal for that individual to participate in the Trial. From the application made and the supporting evidence, both Dr Shehabi and the Ethics Committee were now of the view that it was not unethical, or impractical, to seek the consent of a person responsible. Dr Shehabi was now of the view that it was possible to obtain substitute consent from a person responsible in many circumstances, and where possible, this was preferable to seeking consent from the Tribunal given the narrow time window for treatment to be engaged upon in relation to the Trial.
To determine whether to grant the order sought by the Applicant pursuant to s 45AB(1)(a) the Tribunal must review the information intended to be provided to a person responsible prior to obtaining substitute consent and determine whether it provides sufficient information to enable a person responsible to decide whether or not they should provide the consent sought (s 45 AB(2)).
As previously noted, the Tribunal, at a directions hearing conducted on 27 April 2015, made suggestions as to how the person responsible information and consent form lodged with the application could be improved upon. These suggestions were adopted by the Applicant and subsequently approved by Ethics Committee which resulted in the Tribunal having before it at the hearing on 19 June 2015 a revised person responsible information and consent form identified as "NSW Master PIS & CF (person responsible) version 3 dated 27 April 2015" ("the information and consent form"). The Ethics Committee letter of 12 June 2015 confirmed that the information and consent form had the approval of the Ethics Committee.
The Tribunal reviewed the information and consent form and compared it to the information available in the latest version of the Trial protocol. The Tribunal concluded that the information was an accurate summary of the protocol, and provided sufficient information that would permit a person responsible to make a substitute decision as to whether to give or withhold consent to treatment as part of the Trial in accordance with Division 3 of Part 5 of the Act, and otherwise in accordance with the objects of Part 5 of the Act. The information provided outlined: (a) the circumstances by which the patient, for whom a person has been identified as their person responsible, required the treatment regimes contemplated by the Trial and how such treatment is intended to assist with their medical condition(s); (b) the nature and degree of known risks or side effects of the possible treatments; and (c) warned of the possibility of unknown or unforeseeable risks associated with the possible treatments.
In circumstances where the Trial in question has previously been approved by the Tribunal pursuant to s 45AA(1), where the Tribunal was satisfied that the information and consent form satisfied the requirements of s 45AB(2), and where the Ethics Committee had now approved an amended version of the Trial protocol which permitted consent to be obtained from a person responsible and also approved the information and consent form intended for this purpose, the Tribunal determined that it was satisfied that it should grant the order requested by the applicant. As permitted by s 45AB(1)(a), the Tribunal ordered that the function of giving or withholding consent for the carrying out of medical treatment on patients in the course of the Trial is to be exercised by the persons responsible for such patients.
APPROVAL OF ADDITIONAL TRIAL SITES
Before the Tribunal may approve a clinical trial it must be satisfied that the trial has been approved by a "relevant ethics committee" (s 45AA(2)). As such committees provide approval for clinical trials at specific sites, usually hospitals, the Tribunal limits the orders it makes approving clinical trials to those sites in NSW which have been approved by a relevant ethics committee to ensure compliance with s 45AA(2).
The Tribunal's orders of 23 December 2014 gave approval for the Trial to be conducted at the following sites in NSW:
Prince of Wales Hospital, Nepean Hospital, Hornsby Ku-ring-gai Hospital, St Vincent's Hospital, Westmead Hospital and Lismore Hospital
In his application lodged with the Tribunal on 24 April 2015 Dr Shehabi identified the sites that the Trial was to be conducted at as Prince of Wales Hospital, Nepean Hospital, Westmead Hospital, St Vincent's Hospital, Royal North Shore Hospital, Lismore Hospital and Blacktown Hospital. As such, the Tribunal understood at that time that the applicant was seeking approval for the Trial to be conducted at two sites not previously approved by the Tribunal, namely Royal North Shore Hospital and Blacktown Hospital.
At the hearing conducted on 19 June 2015 Dr Shehabi advised the Tribunal that he was in fact seeking approval for 3 sites in addition to those named in the Tribunal's order of 23 December 2014: Prince of Wales Private Hospital; Royal North Shore Hospital; and Gosford Hospital. Approval for Blacktown Hospital was no longer sought by the Applicant.
The Ethics Committee letter of 12 June 2015 confirmed that the Trial had been approved by the Ethics Committee to be conducted at the following sites:
Prince of Wales Hospital, Nepean Hospital, Hornsby Ku Ring Gai Hospital, St Vincent's Hospital (Sydney), Lismore Base Hospital, Westmead Hospital, Royal North Shore Hospital, Prince of Wales Private Hospital, and Gosford Hospital.
The Tribunal was satisfied that a "relevant ethics committee" had given approval for the Trial to be conducted at three sites in NSW which were in addition to those sites previously approved by the Tribunal and accordingly granted the Applicant's request for approval for the Trial to take place at those three additional sites, namely:
Prince of Wales Private Hospital, Royal North Shore Hospital, and Gosford Hospital.
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APPENDIX A
1. The Tribunal has considered the clinical trial known as SPICE III: A Prospective Multicentre Randomised Controlled Trial of Early Goal Directed Sedation Compared with Standard Care in Mechanically Ventilated Patients in Intensive Care as described in Protocol v3.10 dated 8 June 2015.
2. The Tribunal is satisfied that in relation to the above-named clinical trial, all the requirements of section 45AA(2) of the Guardianship Act 1987 (NSW) have been met.
3. The Tribunal approves the clinical trial as one in which adults unable to consent to their own treatment may participate. Unless the Tribunal subsequently orders otherwise, this approval remains current until that trial has been concluded in New South Wales.
4. The Tribunal approves the clinical trial at the following sites:
Prince of Wales Hospital, Prince of Wales Private Hospital, Nepean Hospital, Hornsby Ku-Ring-Gai Hospital, St Vincent's Hospital, Lismore Base Hospital, Westmead Hospital, Royal North Shore Hospital, Gosford Hospital
5. The Tribunal orders that 'persons responsible' for those unable to consent to their own medical treatment may exercise the function of giving or withholding consent to the carrying out of medical treatment on the person they are 'person responsible' for in the course of the above-named clinical trial.
6. The Tribunal is satisfied that the form for granting consent and the information sheet provided to the Tribunal by the applicant described as NSW Master PIS&CF (person responsible) version 3 dated 27 April 2015 is sufficient to enable 'persons responsible' to decide whether or not it is appropriate that those persons they are 'person responsible' for should take part in the above-named clinical trial.
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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
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Amendments
05 November 2015 - Catchwords field in Cover sheet - the word 'ethical' is amended to 'unethical'
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 November 2015