Committee: / Northern A Health and Disability Ethics Committee
Meeting date: / 15 August 2017
Meeting venue: / Novotel Ellerslie, 72-112 Greenlane Rd East, Ellerslie, Auckland
Time / Item of business
1.00pm / Welcome
1.05pm / Confirmation of minutes of meeting of 18 July 2017
1.30pm / New applications (see over for details)
i 17/NTA/122
ii 17/NTA/151
iii 17/NTA/153
iv 17/NTA/154
v 17/NTA/156
vi 17/NTA/159
vii 17/NTA/161
viii 17/NTA/162
ix 17/NTA/163
x 17/NTA/164
Review of approved studies (see over for details)
i NTX/10/08/082
ii AKL/96/080
7.45pm / General business:
  • Noting section of agenda

8.00pm / Meeting ends
Member Name / Member Category / Appointed / Term Expires / Apologies?
Dr Brian Fergus / Lay (consumer/community perspectives) / 11/11/2015 / 11/11/2018 / Present
Dr Karen Bartholomew / Non-lay (intervention studies) / 13/05/2016 / 13/05/2019 / Present
Dr Christine Crooks / Non-lay (intervention studies) / 11/11/2015 / 11/11/2018 / Present
Mrs Kate O'Connor / Lay (ethical/moral reasoning) / NTB CO OPTÅ / NTB CO OPT / Present
Dr Kate Parker / Non-lay (observational studies) / 11/11/2015 / 11/11/2018 / Present
Dr Catherine Jackson / Non-lay (health/disability service provision) / 11/11/2016 / 11/11/2019 / Present
Ms Toni Millar / Lay (consumer/community perspectives) / 11/11/2016 / 11/11/2019 / Present
Ms Rochelle Style / Lay (ethical/moral reasoning) / 14/06/2017 / 14/06/2020 / Present

Welcome

The Chair opened the meeting at 1.10pm and welcomed Committee members.

The Chair noted that it would be necessary to co-opt members of other HDECs in accordance with the SOPs. Mrs Kate O’Connor confirmed her eligibility, and was co-opted by the Chair as members of the Committee for the duration of the meeting.

The Chair noted that the meeting was quorate.

The Committee noted and agreed the agenda for the meeting.

Confirmation of previous minutes

The minutes of the meeting of 18 July were confirmed.

New applications

1 / Ethics ref: / 17/NTA/122
Title: / The Genetics of Discoid Lupus Eythematosus in Māori and Pacific People
Principal Investigator: / Dr Paul Jarrett
Sponsor:
Clock Start Date: / 06 July 2017

Dr Paul Jarrett and Associate Professor Klaus Lehnert were present in person for discussion of this application.

Potential conflicts of interest

The Chair asked members to declare any potential conflicts of interest related to this application.

No potential conflicts of interest related to this application were declared by any member.

Summary of Study

  1. The Researcher(s) the explained that Māori and Pacific people, especially women, in South Auckland have much a higher rate of an illness called discoid lupus erythematosus compared to European New Zealanders. It causes long lasting skin scarring, sadness and a bad quality of life. This illness is very difficult to treat.
  2. The Researcher(s) want to see if a genetic cause can be found for this illness, which will lead to better treatments. This will help Māori and Pacific people in South Auckland and hopefully other sufferers all around the world.

Summary of ethical issues (outstanding)

The main ethical issues considered by the Committee and which require addressing by the Researcher are as follows.

  1. The researchers noted that the sample may be consumed in the analyses overseas, but they would like to use any leftover for study-specific future unspecified research.
  2. There are currently two PIS: one for participants aged 18 and over; and another one for the parents of some of those participants. Both PIS’ should contain very similar information as detailed below. Currently, the parental PIS contains typographical errors (for example, it refers to ‘you and your parents”). Please check this PIS carefully. There should also be a total of:
  • Two PIS’ for each group (the participants and their parents): a PIS which covers the general research and a separate PIS for Future Unspecified Research (“FUR”)
  • Two consent forms for each group (the participants and their parents): a consent form which covers the general research and a separate consent form which covers FUR
  1. The Committee noted that if samples were planned to be stored for future unspecified research the consent to seek those samples must be compliant with http://www.health.govt.nz/publication/guidelines-use-human-tissue-future-unspecified-research-purposes-0. The Committee noted that there is a checklist at https://ethics.health.govt.nz/ called Features Of Informed Consent that contains a list of requirements that must be included in the participant information sheet, as well as a template for future unspecified research Participant Information Sheets. The Committee also noted that the Auckland Regional Tissue Bank (University of Auckland) might be considered for future unspecified research, and encouraged the researchers to discuss the study with the Bank – the Bank has its own generic information sheet and consent form.
  2. The Committee noted that the Protocol is very minimal and suggested the researchers review the Protocol using a standard Protocol format (eg WHO or SPIRIT guidelines), with a particular focus on selection/recruitment, data management and management of findings and mitigation of potential harms as per below.
  3. The Committee asked how incidental findings, including genetic findings, would be managed with participants. The Researcher(s) explained that it was possible to find a genetic predisposition to breast cancer, for example. If such an event occurred they would first discuss the findings with a clinical geneticist in order to determine the clinical relevance of the finding before discussing with participants. The researcher confirmed they were aware of the range of guidelines for return of results for clinically significant incidental finding, but that they would be following the ACMG recommendations of return of results for 53 incidental conditions.
  4. The Committee queried what would occur in cases where the clinical relevance was unclear or low. The Researcher(s) stated they would take guidance from the clinical geneticists.
  5. The Committee stated that it must be very clear for participants around what incidental findings could occur by participating. Participants should have options around what information comes back to them at the time of consent. The Researcher(s) should also address how findings will impact the wider family, as findings may be genetic. Please view ACMG guidelines.
  6. Please use Statistics New Zealand's ethnicity classifications (Ethnicity Data Protocols for the Health and Disability Sector) when collecting ethnicity data to ensure the options available are suitable for New Zealand participants. These classifications are: New Zealand European, Maori, Samoan, Cook Islands Maori, Tongan, Niuean, Chinese, Indian, Other (such as Dutch, Japanese, Tokelauan).
  7. The Researcher(s) confirmed participants were 18 years old and above and the parents of those participants would be contacted to participate.
  8. The Committee asked whether paternity issues could arise from the testing. The Researcher(s) stated they would exclude that data from the study.
  9. The Committee asked for clarification about what information is being sought through the NHI. The Researcher(s) stated most information will be collected through clinics, but being able to link is useful to check data, for example parents who forgot a diagnosis. The Committee also asked for clarification about whether information in different data sets will be linked.
  10. The proposal suggests that information about siblings and DLE will also be sought. This is not mentioned elsewhere in the documentation. Please clarify for the Committee.
  11. Please confirm in writing that no identifiable records will be sent overseas, noting some co-investigators are overseas.
  12. Provide details on data security, both electronic and paper based.
  13. The Committee noted two different types of genomic analysis will be undertaken overseas. Please explain if the contractors that these organisations receive only de-identified data.

The Committee requested the following changes to the Participant Information Sheet and Consent Form:

  1. Please amend/clarify the section of the PIS’, which refer to the confidentiality of the samples. The PIS correctly states that: “If a participant withdraws before analysis, the information will be destroyed.” However, it also says if the analysis has been done, it will also be destroyed. This depends upon whether the sample, post-analysis is identifiable or re-identifiable. Unidentifiable information cannot be withdrawn or destroyed, irrespective of publication date.
  2. Please make informing the GP on the Participant Information Sheet optional.
  3. Please remove yes or no options in the consent form if the statement is not truly optional.
  4. Please make it clear that samples are sent overseas and provide details about their storage location.
  5. The Committee noted that discussing and approaching biological parents must be treated with care and sensitivity as participants may have complicated relationships with their family or may live or were raised with family that is not biologically related. Please provide an overview of how this aspect of the study will be managed to reduce risks of harm.
  6. The Participant Information Sheet should explain in greater detail the reasons for seeking parental involvement and highlighting the risks that might occur in telling the parents.
  7. Full review of the information sheets, particularly for parents clarifying the points above and clearly writing it from their point of view as a participant.
  8. Please address multiple typos, including reference to “dependents” rather than “parents” in several places.
  9. Provide a consent form for the parents who are donating genetic material
  10. The Committee queried the lack of a Māori tissue statement in the Participant Information Sheet. The committee recommended the following statement after confirmation that it is appropriate for the site: “You may hold beliefs about a sacred and shared value of all or any tissue samples removed. The cultural issues associated with sending your samples overseas and/or storing your tissue should be discussed with your family/whanau as appropriate. There are a range of views held by Māori around these issues; some iwi disagree with storage of samples citing whakapapa and advise their people to consult prior to participation in research where this occurs. However, it is acknowledged that individuals have the right to choose.”
  11. Whether future unspecified use is being included or not, the Committee noted that for the main study there must be more information on what happens to tissue – please view the checklist mentioned above to view information that must be included.
  12. Please include Māori cultural support contact details.
  13. Please update the Participant Information Sheet clause on compensation using the below wording:

If you were injured in this study, which is unlikely, you would be eligible to apply for compensation from ACC just as you would be if you were injured in an accident at work or at home. This does not mean that your claim will automatically be accepted. You will have to lodge a claim with ACC, which may take some time to assess. If your claim is accepted, you will receive funding to assist in your recovery. If you have private health or life insurance, you may wish to check with your insurer that taking part in this study won’t affect your cover.

  1. Add what information will be accessed from clinical records using NHI.
  2. Under the heading “confidentiality” - clarify what information will be destroyed if the testing has already been performed.
  3. The Committee queried if lupus always cause the symptoms outlined - if not add the word “may” before ‘causes”.

Decision

This application was declined by consensus, as the Committee did not consider that the study would meet the following ethical standards.

  • Please amend the information sheet and consent form taking into account the suggestions made by the Committee (Ethical Guidelines for Observation Studies para 6.11).
  • Please provide a separate Participant Information Sheet and Consent Form for the use of tissue for future unspecified research (Guidelines for the Use of Human Tissue for Future Unspecified Research Purposes, para 2).
  • Address outstanding ethical issues in a cover letter (Ethical Guidelines for Observation Studies para 5.5).

2 / Ethics ref: / 17/NTA/151
Title: / PL3397-A-U126
Principal Investigator: / Prof Robert Matthew Strother
Sponsor: / Daiichi Sankyo Incorporated
Clock Start Date: / 03 August 2017

Prof Robert Matthew Strother was present by teleconference for discussion of this application.

Potential conflicts of interest

The Chair asked members to declare any potential conflicts of interest related to this application.

No potential conflicts of interest related to this application were declared by any member.

Summary of Study

  1. The primary objective of the study is to evaluate the safety and effectiveness of pexidartinib on the pharmacokinetic parameters of single dose midazolam and S-Warfarin.
  2. Pexidartinib is an investigational drug and has not been approved by the United States Food and Drug Administration.
  3. This study will enrol approximately 30 patients with a diagnosis of tenosynovial giant cell tumour, kit-mutant melanoma, kit-mutant gastrointestinal stromal tumour (GIST), leukaemia or other tumours for which there is no other standard systemic therapy.
  4. Participants will be assessed for safety and efficacy. An optional tumour biopsy or archival tumour specimen will be collected at Screening and during pexidartinib treatment for exploratory analysis of tumour biomarkers. Pexidartinib will be administered twice daily. Following the efficacy and safety analysis participants remaining on pexadartinib with on going clinical benefit may continue in the study.

Summary of ethical issues (resolved)

The main ethical issues considered by the Committee and addressed by the Researcher are as follows.

  1. The Researcher(s) confirmed this is a phase I trial, clarifying that it is conducted in a target patient population.
  2. The Researcher(s) explained the scientific background relating to the potential benefit for patients receiving the study drug: Pexidartinib is a novel inhibitor that has demonstrated pharmacologic and anti-tumour activity in a variety of in vitro, tumour models and is currently being investigated in Phrase 1-3 clinical studies.
  3. The Committee asked why independent data safety monitoring was not required. The Researcher(s) stated for phase I investigators are involved in group meetings either weekly or monthly, and work very closely with the patient(s). The Researcher(s) stated this kind of monitoring is prototypical for phase I setting in oncology. The Committee accepted this response
  4. The Committee asked about interactions with warfarin. The Researcher(s) explained the procedures that mitigated risks about co-interactions.
  5. The Researcher(s) confirmed there are additional CT and MRI scans.
  6. The Researcher(s) confirmed that there are no standard of care options for participants.

Summary of ethical issues (outstanding)

The main ethical issues considered by the Committee and which require addressing by the Researcher are as follows.

  1. The Committee noted the insurance certificate has one million dollars per claim and a one million dollar aggregate. The Committee stated compensation must be ACC equivalent see chapter 8 of National Ethics Advisory Committee guidelines and provide assurance that ACC level compensation is available for participants in the study.

The Committee requested the following changes to the Participant Information Sheet and Consent Form:

  1. The Committee asked whether this was a therapeutic study. The Researcher(s) stated in oncology context these trials are called therapeutic, as there is an underlying, yet unproven, evidence base that the study drug will be beneficial. The Researcher(s) acknowledged that the purpose of the study is not to determine efficacy. The Committee requested the study is described as a phase one drug interaction study, not a therapeutic study, in the participant information as this is more accurate as a descriptionIncluding why they are studying the interaction with these two particular drugs
  2. Please ensure all statements in the PIS reflect this.
  3. The Committee noted generally there are a number of typos – please revise and correct.
  4. Page 3 – add monitoring information.
  5. The Committee asked if bloods are collected and analysed centrally. The Researcher(s) confirmed they were. Please add name of lab, address and information on how long samples are stored for.
  6. The Committee noted PGX Information Sheet has the same grammar and typing errors that must be addressed. For example: First sentence, semicolon, TGCT – please fix. And the first sentence under the heading “What are the alternatives to participation?”
  7. The Committee noted samples that were planned to be stored for future unspecified research the consent to seek those samples must be compliant with http://www.health.govt.nz/publication/guidelines-use-human-tissue-future-unspecified-research-purposes-0. The Committee noted that there is a checklist at https://ethics.health.govt.nz/ called features of informed consent that contains a list of requirements that must be included in the participant information sheet, as well as a template for future unspecified research Participant Information Sheets.
  8. Please explain whether participants are informed of results from the Future Unspecified Research.
  9. Page 5 – what if something goes wrong? Please do not reference to other documentation, make the document standalone.
  10. The Committee asked if participants would have side effects (drowsiness) after some study drugs. The Researcher(s) stated unlikely but will also monitor while any drugs are active.
  11. Regarding the compensation information, Revise to the standard text, please see the HDEC informed consent template for guidance.
  12. The Committee explained that national ethics guidelines clearly state that it is not acceptable to stop studies purely for commercial reasons. The Researcher(s) stated sometimes the companies stop manufacturing the drug, though it is rare event, stating they suspect that is why the language is in there. The Committee stated it should be clarified in Participant Information Sheet that it would not be stopped for commercial reasons.
  13. The Committee noted the statement that participants must pay for medications to alleviate side effects of the study drug. The Researcher(s) stated this will be removed and was not accurate.
  14. The Researcher(s) explained our own site does monitoring for side effects. The Committee stated the process around side effects and treatments must be clearly explained.
  15. The Committee suggested using tables in the Participant Information Sheet to enhance study visits, timelines and procedures.
  16. Use the word assessment not exam throughout (e.g., page 2 of the Participant Information Sheet under screening visit and under treatment, part 1)
  17. Include estimated length of time involved in participating in the study.
  18. The study involves more CTs than standard of care. This should be mentioned in the risk section that discusses CTs.
  19. Add risk quantification where available for risks and side-effects. Use numeric descriptors (eg: 1 in 100 people) and avoid verbal descriptors where possible.
  20. Use bullet points for risks consistently.
  21. Include statements in the PIS about tissue and data being sent overseas. Add in destruction provisions (both in NZ and overseas).
  22. Include in the consent form consent (or not) to the collection of health information from other health services for the purposes of research (and ensure this is explained in the PIS)

The Committee requested the following changes to the optional pharmacogenomics and biomarker tumour biopsy Participant Information Sheet and Consent Forms: