Application for additional orders relating to a clinical trial previously approved by the Tribunal and known as the SPICE III Trial [2015] NSWCATGD 24

NSW Civil and Administrative Tribunal New South Wales Medium Neutral Citation: Application for additional orders relating to a clinical trial previously approved by the Tribunal and known as the SPICE III Trial [2015] NSWCATGD 24 Hearing dates: 27 April 201519 June 2015 Date of orders: 19 June 2015 Decision date: 19 June 2015 Jurisdiction: Guardianship Division Before: Schyvens M, Deputy President Wroth M, Senior Member (Professional) Laurence K, General Member (Community) Decision: SPICE III Trial approved at additional trial sites. Function of giving or withholding consent to be exercised by persons responsible. Catchwords: CLINICAL TRIAL – previously approved trial – request to extend approval to additional trial sites – no longer unethical or impractical to seek consent of person responsible Legislation Cited: Guardianship Act 1987 (NSW) Category: Principal judgment Parties: Dr Yahya Shehabi (Applicant) Representation: Nil File Number(s): CT 7/2015 Publication restriction: Nil

REASONS FOR DECISION 1. 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.

INTRODUCTION 1. 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. 2. 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). 3. 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. 1. 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)). 1. 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. 2. 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) . 3. 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. 4. 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.