HDC CONSULTATION ON NON-CONSENSUAL RESEARCH
The AWHC has finally received a response from Health & Disability Commissioner Anthony Hill to the Official Information Act request we lodged seeking information about the consultation process on patients who are enrolled in clinical trials without their consent.
The brief letter makes for very disheartening reading and reveals that very little progress has been made. The HDC is obviously in no hurry to tackle this difficult and contentious issue.
The AWHC wanted to know the date on which the consultation document will be released. The letter advised that “the date for release of the consultation document has not yet been determined.” The excuse given for the ongoing delay is that “the proposed consultation raises several complex and sensitive issues of great public importance” and the HDC is working with the Expert Advisory Group to ensure that the issues are clearly and fairly represented.
The letter goes to explain that “the details of the consultation process continue to be refined and the expected timeframe for the consultation has not yet been finalised.”
This raises serious questions about the apparent reluctance of the HDC to act with the required urgency to protect the rights of a wide range of very vulnerable patients/research participants. The topic has already received extensive media coverage and been the subject of a paper published in a reputable journal. (1) (2) Meanwhile the research continues, thus normalising the practice of enrolling an increasing range of research participants who for various reasons are unable to give consent.
The HDC goes on to state the obvious – the public will be invited to provide comments on the questions posed in the consultation document, and the consultation process will begin once the document is published.
The Commissioner is also planning to organise focus groups and/or public meetings to facilitate discussion of the issues.
The review of the literature is an ongoing process. The Commissioner says that his office and the Expert Advisory Group “have reviewed numerous publications from New Zealand and overseas during their work on the consultation document” and that “further literature may be consulted if and when new issues arise in the preparation of that document.”
The Expert Advisory Group
The AWHC also wanted to know who the members of the Expert Advisory Group are. The six members were appointed on 11 July 2016. They are:
• Ms Jane Bawden (Chair)
• Dr Colin McArthur
• Professor Alan Merry
• Dr Brigit Mirfin-Veitch
• Dr Jeanne Snelling
• Ms Teresa Wall
Ms Jane Bawden is a lawyer with a background in human rights, medical and health issues. Dr McArthur is an intensive care specialist. Professor Alan Merry practices in anaesthesia and chronic pain management, Dr Brigit Mirfin-Veitch is a sociologist, Director of the Donald Beasley Institute and has been a member of the Institute’s research team since 1994. Dr Jeanne Snelling is an academic lawyer and a Research Fellow at the Bioethics Centre in Dunedin. Ms Teresa Wall, formerly deputy director-general of Maori health in the Ministry of Health, is currently responsible for cross-government relationships and the Trans Pacific Partnership.
“The role of the Expert Advisory Group is to advise and assist me in relation to the consultation,” the HDC explains in his letter, and they “were selected primarily to provide expert advice relevant to their particular areas of knowledge and experience, rather than to represent the views of their organisation.”
Notably absent from this select group of health professionals and academics is the voice of the consumer. This is an unfortunate although not entirely unexpected omission and casts doubt on the genuineness of the consultation process before it has even begun.
Given that two and a half years after the issue hit the headlines the HDC is still not willing to even commit to a date for the publication of the consultation document, it is difficult to have much faith in what is or is not happening in the office of the HDC.
2. Professor Joanna Manning. “Non-consensual clinical research in New Zealand: Law reform urgently needed.” Journal of Law and Medicine.2016 23 JLM 516.
RESEARCH PARTICIPANTS IN NZ NOT COVERED BY ACC
The unresolved issue of NZ research participants taking part in clinical trials sponsored by international drug companies but not being entitled to ACC coverage should they be harmed as a result of being in a clinical trial, is described in an essay in a recently published book ”Law, Ethics, and Medicine.” (1) The book was written in honour of Professor Peter Skegg, New Zealand’s founding professor of medical law.
Associate Professor Jo Manning’s essay begins by describing how two people involved in two different commercially-sponsored clinical trials suffered serious harm in 2012. They then spent years fighting for compensation from the drug companies involved. While one finally achieved a financial settlement with the drug company’s insurers the other is still fighting for his compensation.
“The first trial involved a man who suffered injury in a large, Phase III, multi-country, double-blind randomised controlled trial of patients with type-2 diabetes who had never before taken insulin, comparing a new insulin variant medicine with an existing insulin treatment. The aim of the trial was not to treat participants for their condition but to demonstrate that the investigational medicine was not inferior to an existing insulin treatment, and to compare the efficacy and safety of the new drug.”
The second trial involved a man who suffered atrial fibrillation (an irregular and often rapid heart rate) days after taking a new drug for gout. The aim of the study, known as the CRYSTAL study, was to compare the effectiveness and safety of the investigational drug taken in combination with a standard gout medicine alone.
While the Participation Information Sheet (PIS) for those agreeing to take part in commercially-sponsored clinical trials is required to state that if a person suffers harm or an injury as a result of participating in the trial they will not be eligible for cover under the Accident Compensation scheme, few if any participants understand what this really means. This is partly because the PIS usually includes a reference to the sponsor’s obligation to pay compensation, in accordance with the NZ Researched Medicines Industry “Guidelines on Clinical Trials – Compensation for Injury resulting from Participation in Industry-sponsored Clinical Trials.” It is not made clear that this is not a legal obligation and they will find themselves having to take on the might of an international drug company and its insurance company’s lawyers.
As Jo Manning’s essay revealed:
“Both companies, at least initially, disputed that the men’s injuries were caused by the investigational drug. It was not until approximately three years later in 2015 that the participant in the CRYSTAL trial finally reached a confidential settlement with the sponsor of his claim for compensation, having suffered significant loss of income in the meantime and after having engaged a high profile lawyer to act for him. A major obstacle to achieving a settlement was that the sponsor’s insurance company took over management to the claim, and it took a strict commercial approach to the claim.” At the date of writing, the second man, despite also getting legal help has still not received any compensation from the sponsoring company.
As a result of drastic cuts made to ACC’s budget research participants have been excluded from being able to apply for ACC compensation for injuries suffered as a result of participation in commercially-sponsored clinical trials in New Zealand since 1992. In contrast, participants in non-industry trials are covered by ACC.
The Ministry of Health and the Health and Disability Ethics Committees have been aware of the problem for more than a decade. In 2007 the Chairs of the ethics committees called for the repeal of this statutory exclusion. In 2010 the National Ethics Advisory Committee (NEAC) added its voice to the need to review and change this unfair and unethical situation. NEAC repeated its call to repeal the exclusion again in 2014. After learning about the experience of the two men mentioned above, the committee wrote to Peter Dunne, the Associate Minister of Health in November 2014. (2)
In December 2015, NEAC received a response to the advice they had given to Peter Dunne. Both their report to the Minister and his belated response were placed on the NEAC website in April 2016. (2) It is difficult not to see this as a demonstration of their disappointment in his response.
Jo Manning reports that NEAC’s suggestion “that some companies conducting clinical trials in New Zealand may be ‘failing to comply with NEAC’s and Medicines New Zealand’s (MNZ) guidance to provide compensation cover for study participants to at least ACC-equivalent standard, and to do so in an expeditious manner.’
Its efforts did not meet with success. Some analysts within the Ministry of Health were concerned about the significant impact on injured individuals from inability to or delay in accessing compensation and agreed that the problem was best addressed by extension of ACC cover to include commercial trials. But officials from ACC and the Ministry of Business, Innovation and Employment briefing Dunne and the Minister for ACC, Hon Nikki Kaye, did not support a law change, and their view prevailed.” (1)
This is a very disturbing example of how ensuring that research participants are protected, once the core function of ethics committees, is no longer their main purpose.
Jo Manning requested that the following comment be added to this article which appeared in the November 2016 issue of the AWHC newsletter:
“It was Lynda Williams who picked up intelligence about this issue and alerted others, including myself, to it. Without NGOs monitoring the activities HDECs and researchers, (Lynda has attended HDEC monthly meeting for over a decade), worrying matters such as this will be swept under the carpet, as government and drug companies certainly have no incentive at all to bring them to light."
Jo Manning's excellent expose of the issues is divided into four parts. Part 1 describes the consensus among commentators that there is a moral obligation to compensate injured research participants. Part 2 outlines the current law and compensation arrangements. Part 3 describes the deficiencies of the MNZ Guidelines, and Part 4 outlines possible responses and alternative options that participants, ethics committees and the Government might adopt to address this most unsatisfactory situation. This essay is a must read.
1. “Law, Ethics, and Medicine: Essays in Honour of Peter Skegg.” Edited by Mark Henaghan and Jesse Wall. Published by Thomson Reuters NZ Ltd. 2016.
THE RIGHT TO SAY NO TO RESEARCH TRIALS - WHEN DID WE LOSE IT?
It has become clear over the past few months that patients cannot rely on the Code of Consumers’ Rights to protect them from being enrolled in clinical trials or other research studies without their consent having been obtained first. It is proving difficult to find out exactly when patients lost that right, and even more problematic to know how to rectify the current unsatisfactory situation.
What hasn’t changed is the fact that many patients/consumers are willing to consider the offer of becoming a research participant – provided they are first given the opportunity to read the patient information sheet about the research trial and to have their questions answered.
The AWHC was established in 1988 and held its first meeting in July that year, a month before the release of the Cartwright report of the Inquiry into the treatment of cervical cancer at National Women’s Hospital. In the wake of the report’s publication ethics committees were completely trans-formed into committees with both lay people and health professionals whose primary role was to protect the rights of patients and ensure that no-one was enrolled in any kind of research without giving their informed consent to be involved.
The office of the Health & Disability Commissioner was set up in late 1994 and consultation on a proposed Code of Consumers’ Rights began the following year. On 1 July 1996 a legislated Code of Consumers’ Rights came into effect.
Right 6, the right to be fully informed, states that every consumer has the right to the information that a reasonable consumer, in that consumer’s circumstances, would expect to receive, including -
1(d) Notification of any proposed participation in teaching or research, including whether the research requires and has received ethical approval; and
1(e) Any other information required by legal, professional, ethical, and other relevant standards.
Right 7, the right to make an informed choice and the right to give informed consent, states that:
4(c) Where a consumer is not competent to make an informed choice and give informed consent, and no person entitled to consent on behalf of the consumer is available, the provider may provide services where –
(a) It is in the best interests of the consumer.
For some unknown reason the debate about ethics committees approving research involving participants who lack the capacity to consent to participate has focused almost solely on Right 7(4) of the Code, not Right 6(1) d and e. Even the Health & Disability Commissioner’s response to the letter the AWHC wrote about the practice of enrolling people in research trials without their informed consent, focused on Right 7(4). Anthony Hill stated in his letter “as you know there are two passionately held and opposing schools of thought on Right 7(4).”
Actually, the AWHC did not know that. Having been involved in the two consultation processes during the development of the Code of Consumers’ Rights, the Council believed that the mere thought of enrolling people in research trials without their consent was illegal, utterly abhorrent and against the Declaration of Helsinki, and the NZ Code of Rights, being enshrined in legislation, protected patients from such practices. After all, this issue was at the very heart of the Cartwright Inquiry. Once the recommendations in the Cartwright Report were implemented patients would never have to worry about being enrolled in research trials without their consent ever again. Right? Apparently not.
Anthony Hill stated in his letter that “this is not a matter about which HDC has received complaints, nor is it one that prompted many submissions in the recent Act and Code review, soon to be completed.”
The AWHC did not include the issue in our submission because we did not know that in New Zealand thousands of unconscious patients in intensive care units around the country are being enrolled in clinical trials without their consent. The Council was also blissfully unaware that there was any debate going on about whether this practice was legal or not.
The Ministry of Health’s chief legal advisor, in a letter to the Ministry’s ethics committee chairs and members, dated 7 April 2014 but not posted on the ethics committee website until months later stated:
“Research involving participants who do not have the capacity to consent (and where no-one legally authorised to give consent on behalf of the participant does so) is not lawful unless it satisfies Right 7(4) of the Code of Health and Disability Services Consumers’ Rights (the Code). Committees do not have the authority to give consent on behalf of participants.” (1)
It also says: “Investigators must satisfy the committee that proposed research is lawful before the committee approves an application. Committees are not required or able to give legal advice to investigators; it is the responsibility of the investigator to ensure that the research is lawful.”
This is not at all reassuring. There is big money involved in clinical trials and both the investigators and the DHBs have a huge conflict of interest in deciding what research is lawful and what is not.
The letter from the MOH’s chief legal advisor has not been enough to stop ethics committees’ approving research involving participants who lack the capacity to consent.
The HDC, the consumer watchdog, is sitting on his hands, has refused to undertake an investigation, and is waiting to receive a complaint from someone other than the AWHC, although the Council hasn’t given up and has written to him again.
The AWHC has also written to Minister of Health Tony Ryall. As he was the Minister who pushed through the changes that ensured the focus of ethics committees would now be on approving research proposals – not protecting the rights of research participants – it is extremely unlikely that Mr Ryall is going to come to the rescue of the unconscious patients in the country’s ICUs any time soon.
LETTER TO HEALTH & DISABILITY COMMISSIONER
15 May 2014
Health & Disability Commissioner
PO Box 11934
RE: ENROLLING UNCONSCIOUS PATIENTS IN CLINICAL TRIALS
Dear Anthony Hill,
The Auckland Women’s Health Council (AWHC) is writing to you about the issue of enrolling unconscious patients in clinical trials. We first learned about this practice during the March meeting of the Northern A ethics committee.
The issue hit the headlines yesterday when the Herald made it front-page news after a reporter received a copy of the May issue of the AWHC’s newsletter (copy included). Since then some researchers, doctors, ethics committee chairpersons, DHB senior managers, and others have leapt to defend the practice.
Two members of the AWHC have been regularly attending meetings of the Ministry of Health ethics committees for the past six or seven years. We have become increasingly alarmed and are now extremely concerned at what has happened to patient rights in the current clinical trials environment. There are many clinical trials being undertaken which involve vulnerable patients, including infants, children, young adults with Down syndrome as well as unconscious patients.
Last night during an item on TV3’s 6 o’clock News on this issue it was stated “that only 5% of unconscious patients complain” when they regain consciousness and are told they have been enrolled in a clinical trial. This is a significant number as there will also be those who are not happy but feel too vulnerable to complain or even admit to wanting to withdraw from the trial. There are also those patients who are never told and never find out that they have been enrolled in a clinical trial. Under the media spotlight people’s memories of what was said during an ethics committee meeting tend to be quite different to what was actually said. I take accurate notes and find there are considerable discrepancies and omissions in the minutes that eventually find their way on to the MOH ethics committees website.
While consumers’ rights to make informed choices regarding their health care and inclusion in research trials are enshrined in legislation and listed in the Code of Consumers’ Rights, the current clinical trials environment means that New Zealand consumers are not always able to make informed decisions. There are now big loopholes which enable research studies to go ahead that previously may not have got ethics committee approval. For example, I have seen research studies that have been given ethics committee approval despite the fact that the clinical trial offers no benefit to the research participant, and no benefit to the general public – it is being carried out so that the drug company sponsoring the study can get their “me-to” drug onto the market. This is openly acknowledged during the meeting. It is our contention that unconscious patients should not be enrolled in clinical trials that are non-inferiority studies, or offer no benefits to either the patient or the general public, or do not meet the threshold of being in the best interests of the patient.
The DHBs and those involved in the clinical trials industry are now firmly focused on the thousands of dollars to be made from conducting clinical trials. Even the ethics committees are not focused on protecting research participants the way they were in the years following the Cartwright Inquiry.
The AWHC is therefore requesting that the Office of the Health and Disability Commissioner to investigate the issue of enrolling people in nonconsensual trials. We are also requesting you to take action to strengthen Right 7 (4) and Right 9 in order to prevent people from being enrolled in clinical trials without their knowledge or consent.
ENROLLING UNCONSCIOUS PATIENTS IN CLINICAL TRIALS
If there was any remaining doubt about how NZ Ministry of Health’s ethics committees are now firmly focused on paving the way for clinical trials to go ahead rather than focusing on protecting the rights of patients it was firmly dispelled at the March and April meetings of the Northern A ethics committee.
In March one of the research proposals discussed during the Northern A ethics committee meeting involved a study of a new antibiotic which would be tested on unconscious, critically ill patients unable to give prior informed consent before being enrolled in the study. It subsequently emerged that the practice of enrolling unconscious patients in these sorts of trials has been going on in New Zealand for a decade or so. In fact, in 2004 during a review of the HDC Act and Code of Consumers’ Rights there was an attempt by Ron Paterson who was the Health & Disability Commissioner at the time to get something added to the Code of Rights about the practice but his recommendation was not actioned by the government.
The current ethical dilemmas facing Ministry of Health’s ethics committees are the result of a number of events and changes both here in New Zealand and in the USA.
FDA changes the rules
Behind the latest research proposals for studies on the use of new antibiotics lies another fascinating tale about an antibiotic approved by the FDA in 2004 which was later linked to liver failure, the ensuing scandal that exposed the FDA’s failure to listen to its own advisors, the subsequent development of strict clinical guidelines for antibiotic development and the exodus of the pharmaceutical industry from the development of new antibiotics. (1) (2)
In May 2012 the FDA acknowledged the looming public health crisis of antibiotic resistance and the need for the agency to “reboot antibiotic development” by changing the rules again around clinical trial designs in order to entice the drug companies back into developing urgently needed new antibiotics. (2)
NZ changes its ethics committees
Over the past five years the current government has driven major changes to the structure and operating procedures for the Ministry of Health’s ethics committees. Alarm bells were sounded by women’s health groups, the Otago Bioethics Centre, academics and researchers and reported in the February and July 2012 issues of the AWHC newsletter. (3)
The changes effectively spelt the end of the purpose, role and function of ethics committees that were set up in the wake of the Cartwright Inquiry. The ethics committees that were established in the early 1990s were designed to provide extensive safeguards for patients. The changes that were introduced in 2012 have totally undermined these safeguards, and have resulted in a significant and worrying departure from international standards.
The motives driving the changes were financial and economic ones as the Minister of Health had been led to believe that New Zealand was missing out on millions of dollars to be had by getting more involved in the clinical trials industry. The focus needed to shift from protecting patients or “research participants” as they are now referred to – it was interfering with speedy access to the clinical trial industry – to smoothing the pathway for fast-tracked approval of research by the ethics committees.
Ethics committees can no longer be counted on to put patients first as they are now operating under new rules that do not permit them to insist on the various safeguards that were once part of their brief, or question the design and power or scientific merit of the studies that are submitted for their approval. Prior to the changes introduced in 2012 ethics committee chairpersons wanted greater protections for those enrolled in trials sponsored by international pharmaceutical companies; now they have deadlines that must be met, and enabling researchers to get those patients enrolled one way or another is the priority.
New Zealand has become known internationally for being one of the best countries to go to for getting fast-tracked and speedy approval for research studies – New Zealand is now “the first cab off the rank,” even for Phase I first-in-humans research proposals.
Testing new antibiotics
The research proposal that came before the Northern A ethics committee in March was for a study that compared treatment with a new antibiotic with an existing antibiotic. It is part of a non-inferiority trial, so there is no power in the study to prove the new antibiotic is better than the antibiotic it is being compared with.
The acceptability of non-inferiority trials is one of the changes made by the FDA who are now working to fast track approval of the introduction of new antibiotics. The study is a phase III trial. Phase II testing had shown that the new antibiotic is safe.
However, the major stumbling block to the trial obtaining ethics committee approval was the fact that nearly all of the patients being used to test the “non-inferiority” of the new antibiotic would be unable to consent to being involved in the trial until they had regained consciousness and were well enough to absorb and under-stand the information they were given about the study and give retrospective consent to being enrolled in the trial.
The current problem was that Crown Law had now become involved, and it was their opinion that patients who are unable to give consent cannot be enrolled in studies unless the study involves a life-saving treatment, and a Court order has been obtained which authorised the participation of the unconscious patient in the clinical trial.
As the testing of the antibiotic is part of a trial that is not designed to show if the new antibiotic is better than the current antibiotic, let alone a life-saving treatment, there was no prospect of getting permission through the court system. Besides, no researcher wants to have to get a court order to enrol each patient in a clinical trial.
Following a lengthy discussion with the researcher the Northern A ethics committee decided by consensus to
defer a decision, “while it seeks further information.” It was painfully clear during the discussion that the committee was focused on the need to find a way round the obstacles being put in place to prevent the enrolment of unconscious patients in clinical trials.
Ignoring the lessons of history
There was little evidence that anyone in the room was focused on the rights of patients being enrolled in non-therapeutic clinical research. The legacy of the Cartwright Inquiry with its emphasis on ethics and patient rights, informed consent and clinical research was forgotten. Judge Silvia Cartwright’s recommendations that non-therapeutic clinical research should not be undertaken on patients without their “free consent,” and then only after they have been fully informed about the study and given written consent, were consigned to the dustbin of history. (4) Nor was there any mention of Right 7 of the Code of Consumers’ Rights – the right to make an informed choice and give informed consent.
It didn’t get any better when the Northern A ethics committee reconvened in April and began the meeting with another discussion on the vexed issue of enrolling unconscious patients and getting their consent later. Following the March meeting the Ministry of Health’s Health Legal team had written to the ethics committees advising them that ethics committees cannot give consent for individuals to be involved in clinical trials, and informing them the test that must be met is that it must be in the best interests of the patient. There must be a restoration of Right 7(4) of the Code of Rights – which begs the question as to exactly when was it dismissed?
But dismissed it certainly had been – thousands of patients in ICUs (Intensive Care Units) have been enrolled in both drug company-sponsored studies as well as non-commercial studies.
What followed next was further discussion on how best to comply with Health Legal’s letter but make it possible for the clinical trials on patients unable to give informed consent that are currently underway to continue, and for the proposed trial to go ahead. Various arguments were suggested by the ethics committee members as to why unconscious patients should continue to be enrolled in clinical trials. While some were rejected it didn’t take them very long to come up with quite a list:
• The researchers believe it is in the patients’ best interests to be included in these sorts of studies
• Patients get better care when they are involved in clinical trials
• Patients enrolled in clinical trials get more tests and are more likely to get an accurate diagnosis
• Patients are all happy to be included in clinical trials; they say they want to be included, (once they have regained consciousness, that is)
All that needed to be done now was to change the Patient Information Sheet (PIS) by removing the sentence saying the study did not offer any direct benefit to the patient, and pitch it to the patient’s relative, rather the patient. The ethics committee then gave it provisional approval without a thought for where this might lead.
This saga around what happened with this research proposal is just one example of what has happened to NZ’s former watchdog ethics committees. Drug companies now see New Zealand as a soft touch for getting fast-tracked ethics committee approval for their studies. The sponsor’s demands are outrageous and are definitely not in keeping with the hard-won rights of patients or “research participants.”
Biobanking is now part of nearly all research trials with tissue samples usually being sent overseas.
The Patient Information Sheets are incompatible with patient rights in New Zealand and the sponsors won’t agree to the researchers changing them unless the ethics committees demand changes as a condition of obtaining ethics committee approval.
The drug companies also attempt to restrict patient access to their own health information, and to insist on research participants filling in a form or writing to the study’s chief investigator should they decide to withdraw from the research trial. The Northern A ethics committee has, so far, refused to comply with either of these conditions.
It’s definitely time for an inquiry!
4. Judge Silvia Cartwright. The Report of the Cervical Cancer Inquiry. 1988. Chapter 7 “Ethics and Patient Rights.” Page 133.
NEW ETHICS COMMITTEES SYSTEM START WORK
On 13 June 2012 the Ministry of Health’s seven ethics committees were formally disestablished and the new stream-lined, clinical trials-focused, pharmaceutical industry-friendly system with its four new ethics committees was established. It even came with a brand new website: http://www.ethics.health.govt.nz/
The four new ethics committees have only eight members instead of 12, resulting in a loss of expertise and a significant reduction in lay representation. Like their predecessors, the four committees are “ministerial committees” whose members are appointed by the Minister of Health. The new committees are called Northern A (Ryall’s Folly), Northern B (Ryall’s Foolery), Central (Ryall’s Flunky) and Southern (Ryall’s Fault).
At the same time the new “Standard Operating Procedures” for the new ethics committees took effect, thus completing the gradual dismantling of the world-class ethics committee system established in the wake of the Cartwright Inquiry to protect the interests of the patients, now known as research participants.
There was opposition to the proposed changes. Women’s health groups protested, wrote letters, submissions and articles in an effort to draw attention to what was happening. We weren’t the only ones. As described in an article in the February 2012 issue of the AWHC newsletter, five professors published an open letter to Minister of Health Tony Ryall regarding the proposed changes. They were the head of Otago University’s bioethics centre, Professor Gareth Jones, Professors Donald Evans, Charlotte Paul, John McCall and Auckland University’s Professor Tim Dare.
Their letter stated there were major concerns about the processes around the creation and implementation of the new policy and referred to major flaws in the quality of information received by the Select Committee that led to these changes.
It all fell on deaf ears as those in charge of the final unravelling of the ethics committee system of patient protection had dollars in their sights.
Northern A has its first meeting at 1pm Wednesday 25 July 2012 at Novotel at 72-112 Greenlane Road East, Auckland.
Northern B will meet at 12 noon on Wednesday 1 August at Novotel, 7 Alma Street, Hamilton.
Central is due to meet at 12 noon on Tuesday 24 July at the Terrace Conference Centre, 114 The Terrace, Wellington.
Southern is scheduled to meet at 12 noon on Tuesday 7 August at Copthorne Hotel at 449 Memorial Drive, Christchurch.
These meetings are open to the public so do go along and check out how the new committees are coping with their new stream-lined work loads.
MAJOR FLAWS IN SOPs for ETHICS COMMITTEES
At the end of December 2011 the AWHC received a copy of the draft Standard Operating Procedures (SOPs) for ethics committees. The changes set out in the document are the latest step in the government’s response to the Health Committee’s clinical trials inquiry.
The NZ House of Representatives report was released in June 2011 and was entitled “Inquiry into improving New Zealand’s environment to support innovation through clinical trials.” The government responded with a document containing recommendations for change, followed by the “Draft standard operating procedures (SOPs) for health and disability ethics committees (HDECs).” The changes which are due to be implemented by the middle of the year will effectively spell the end of the purpose, role and function of ethics committees that were set up in the wake of the Cartwright Inquiry.
The New Zealand ethics committees established in the early 1990s were designed to provide extensive safeguards for research participants. The changes about to be introduced will seriously undermine these safeguards, and are “a departure from international standards.” (1)
Women’s health groups are not the only ones alarmed by this major erosion of protection for research participants. At the beginning of February 2012, following the New Zealand Bioethics conference held at the end of January five professors published an open letter to Minister of Health Tony Ryall regarding the proposed changes. They were the head of Otago University’s bioethics centre, Professor Gareth Jones, Professors Donald Evans, John McCall and Charlotte Paul, and Auckland University’s Professor Tim Dare. (1)
The letter stated there were major concerns about the processes around the creation and implementation of the new policy and referred to major flaws in the quality of information received by the Select Committee that led to these changes. Even more worrying was the fact that important steps were omitted, including analysis by and consultation with the government’s own ethics advisory committee, the National Ethics Advisory Committee.
Other issues raised in their letter to Tony Ryall “are as follows:
• The reduction in number of ethics committees from seven to four, will significantly increase the workload of each committee. To meet that workload, the committees are expected to reduce the level of scrutiny of clinical trials, provide expedited review by the chair, and not review some research. The outcome is that many studies will not receive full ethical review, and some will not be reviewed at all.
• As a result of the above change, research protocols for clinical trials that will be categorised as low risk, will receive only expedited review by a committee chair. While on the surface this sounds an appropriate way of making ethical review more efficient the draft SOP shows that it is likely on occasion to prove hazardous. For example trials of probiotic use in serious illness would be categorised as not requiring full review. Yet one such trial conducted in the Netherlands and published in the Lancet 2008, reported a major excess of deaths in the probiotic group and subsequent investigation showed that the monitoring arrangements for adverse events were insufficient; hence some deaths may have been avoidable.
Student research will also not receive review by HDECs (unless it is an intervention study conducted at PhD level). Hence the research carried out by a doctor into a clinical matter for the purpose of achieving a Masters degree, would not be reviewed by the HDEC (the appropriate committee for research with public hospital patients)
• The reduction in the numbers of members of ethics committees from 12 to 8 will result in both a loss of expertise, and a reduction in lay participation.
• Ethics committees will not assess scientific validity, even though scientific validity is one of the standards required for research to be ethical.
• A central clearing house for allocating protocols will impersonalise the review process and undermine co-operation between researchers and HDECs and the communities they work in.”
The letter also echoes the issue raised by the AWHC in previous submissions and newsletter articles in stating that these concerns “raise issues about the independence of ethics committees housed within the Ministry of Health.”
Open letter to Tony Ryall
CLINICAL TRIALS UNLEASHED
In September 2011 the government issued its response to the Report of the Health Committee on its Inquiry into improving New Zealand’s environment to support innovation through clinical trials.
The government’s response makes for grim reading as it outlines how they plan to reduce the number of ethics committees from seven to four and streamline the process to make the main objective of ethics committees that of supporting clinical trials rather than protecting patients.
The Health Committee’s clinical trials report was also focused on the need to take advantage of the dollars attached to “supporting innovation through clinical trials.” The Health Committee came up with a total of 54 recommendations, comprising eight key recommendations and 46 more detailed ones.
The 8 key recommendations were:
• Simplify and streamline ethical review processes
• Collaboration between the Ministry of Health, the Ministry of Science and Innovation, the Ministry of Economic Development, and New Zealand Trade and Enterprise
• A national health research action plan that fosters innovation and commercialisation
• A national framework for clinical trial research through DHBs
• Build constructive and transparent relationships with the international biotechnology and pharmaceutical industries
• Ensure excellent scientific infrastructure to run clinical trials
• Establish a long-term objective in research and development investment
• New Zealand to urgently assess Australian and UK clinical trial reports.
Growing the clinical trial industry
The Health Committee was clearly alarmed that New Zealand was missing out on the lucrative market for clinical trials. Chapter 3 of their report described the steps that need to be taken for New Zealand to create an effective clinical trials environment. The report stated “New Zealand needs to be attractive to overseas sponsors of multinational research projects. An environment conducive to pharmaceutical companies funding these trials in New Zealand is required if the clinical trial industry is to grow.”
The Committee was told that one of the important factors for a productive clinical trial environment for pharmaceuticals was “the efficiency with which the New Zealand health system can interface with the pharmaceutical companies to deliver an efficient clinical trial outcome.” (1)
One of the things obviously standing in the way is New Zealand’s ethics committees. Hence the need for the changes which “will result in a more efficient, consistent and transparent Health & Disability ethics committee review process.” (2)
While there is a token reference to “significant ethical issues” and “the protection that committees offer to participants in such research,” the government intends to alter the structure of ethics committees to ensure that they do not obstruct the pharmaceutical industry or stand in the way of delivering “efficient clinical trial outcomes.” This is how they plan to do it.
Ethics committees prostituted
The number of ethics committees will be reduced from seven to four as of 1 July 2012 and will continue to meet monthly.
The numbers on each committee will be reduced from twelve to eight. With another token gesture, this time to the Cartwright Inquiry, the government says it is important that lay people continue to have a strong voice and that they continue to make up approximately one half of the ethics committee membership as the Cartwright Inquiry report recommended, so “at least three members” of each committee will be lay. Since when did half of eight equal three?
The number of applications that require a full review by an ethics committee will be reduced, and the number of expedited reviews for applications for some low-risk clinical trials will be increased. Who gets to decide what is “low-risk” is not stated.
The intention seems to be that all observation studies proposals will be exempted from ethical review, so issues about privacy and protection of patient data in such studies will be exempt.
It will be the responsibility of the investigator and sponsor to obtain the peer review report on the scientific merit of the proposal – how’s that for a conflict of interest? The ethics committee won't even see a copy, its role being confined to checking that this has been done. It seems that scientific aspects of a proposal are no longer the business of ethics committees, though without that information, it is impossible for them to evaluate matters such as risks/safety for participants and scientific worth (a recognised ethical issue).
New timelines for review are to be introduced and monitored. Under the updated operating procedures for ethics committees a timeline of 35 days will be imposed for a full review and 15 days for an expedited review. Ethics committees “will be required to report regularly against these time-lines, and are expected to exceed them in most cases.”
The government is also supportive of the development of electronic (online) applications and a centrally managed system for ethics committee review – meaning centrally managed by the Ministry of Health.
The ability for researchers to make minor changes to their research after it has received ethics committee approval will also be introduced. No prizes for guessing who will decide what are “minor changes.”
Fortunately the government rejected the Health Committee’s recommendation to make research a core activity undertaken by district health boards, and fund DHBs to undertake clinical research as a front-line activity. The objectives of DHBs must remain centred on “the improvement, promotion and protection of the health of people and communities, and the reduction of health disparities,” the report states.
Importance of independence
The report of the government’s response is another nail in the coffin for the concept of independent ethics committees whose primary objective is protecting patients. Those currently in charge in government and in the Ministry of Health have forgotten the lessons learned from both the Cartwright and Gisborne inquiries.
Ethics committees were never going to be appropriately managed and safe from being amended to suit professional and commercial interests by being placed within the Ministry of Health. Consumer groups have argued for more than a decade that responsibility for ethics committees should be placed within the office of the Health & Disability Commissioner.
The November 2008 issue of the AWHC’s newsletter featured an article detailing concerns being voiced by the chairperson of the Health Research Council’s Ethics Committee (HRCEC) following the slashing of ethics committees in 2004. The article raised issues about the focus of ethics committees shifting away from the protection of patients. The article is featured below.
Women’s health groups attending the Gisborne Inquiry into Cervical Screening were also strongly opposed to the National Screening Unit being placed within the Ministry of Health and warned of the risks involved if the National Cervical Screening Programme was left at the mercy of the MOH. In June 2011 the “Report of the Parliamentary Review Committee regarding the NZ Cervical Screening Programme” was released. This report also makes for grim reading. Sandra Coney’s outline of the risks involved for the NCSP if it was placed within the Ministry has been proved to be dismayingly accurate. The same has proved true for New Zealand’s ethics committees.
Right 7 (10)
One of the reassurances given to women’s health groups when Right 7 (10) of the Code was amended to permit research to proceed without patient consent when tissue removed was sought to be used for research purposes was that the ethical review process would provide a strong and effective safeguard. How hollow that reassurance now sounds!
The government’s report reveals the result of the battle between the need for independent ethics committees focused on protecting patients vs the interests of the pharmaceutical/ research industries.
The score: Drug Companies 1
1. Health Committee. “Inquiry into improving New Zealand’s environment to support innovation through clinical trials.” June 2011.
2. “Government Response to the Report of the Health Committee on its Inquiry into improving New Zealand’s environment to support innovation through clinical trials.”
Researchers also opposed to the decimation of New Zealand ethics committees -
CONCERNS OVER NZ’s ETHICS COMMITTEES
The October 2008 issue of the Health Research Council’s newsletter Ethics Notes featured a timely article that provided a critical look at some of the problems with the current system of ethical review of research in New Zealand. The article was written by Dr Tim Dare, a lawyer who is the chair of the Health Research Council’s Ethics Committee (HRCEC) and a member of the clinical ethics committees of the Auckland and Waitemata District Health boards. It confirms some of the concerns that women’s groups have had over the past decade.
Today’s structure and function of ethical review committees was established in the wake of the report of the Cartwright Inquiry that found that “the lack of the systematic seeking of consent to inclusion in research or treatment (except for operative procedures) and the inadequate procedures for approval and surveillance of research and treatment, pose a serious risk to patients’ rights.” One of Judge Silvia Cartwright’s recommendations was that all health research should be reviewed by an independent ethics committee. She also recommended that the ethics committee at National Women’s Hospital should be disbanded because it had “failed in significant areas.”
As part of a raft of measures introduced nationwide following the Cartwright Inquiry, hospital ethics committees were disbanded and independent ethics committees were established by the Area Health Boards with the expectation that they would abide by the national standard that had just been developed by the then Department of Health. The new ethics committees were comprised of 50% lay members and 50% health professionals/ scientific members with the chairperson having to be a lay member. Fifteen regional ethics committees were set up throughout the country but within a few years it was reported there were significant differences in their membership, scope and in how they operated.
In April 1993 the Department of Health announced that ethics commit-tees would be moved out of the Area Health Boards. An Interim Ethics Taskgroup was established to review both the existing ethics committees and the 1991 standard for ethics committees. This and further changes to the health system eventually resulted in the establishment of the Health and Disability Ethics Committees.
Following the passage of the New Zealand Public Health and Disability Act in 2000, the National Ethics Advisory Committee (NEAC) was established and its members were finally appointed in December 2001.
NEAC’s statutory functions are to provide advice to the Minister of Health on ethical issues of national significance regarding health and disability research and services, to determine nationally consistent ethical standards and to provide scrutiny for such research and services.
The cervical screening scandal in Gisborne resulted in a second major Inquiry in 2000 and the release of another report in 2001 that among other things recommended changes to the system of ethical review. NEAC undertook a review of the ethics committees system and a report with the committee’s recommendations went to the Minister of Health in December 2003.
Ethics committees slashed
This resulted in the number of ethics committees being reduced to six and the addition of new national multi-centre ethics committee responsible for the review of all multi-centre and national research. Whereas under the previous system each of the 13 ethics committees had its own exclusive geographical jurisdiction, the six new ethics committees had their jurisdiction widened to four regions, with the two busiest regions having two committees each. These changes were implemented in 2004.
Multi-region ethics committee
However, Dr Tim Dare’s article reveals that the new system has not worked entirely as planned. He reports that:
“The multi-region practice was creaky and time consuming, though it had some serendipitous advantages. One committee acted as the ‘lead committee,’ co-ordinating responses from the remaining committees. Though it was almost certainly not its goal, the system provided uniformity: no answer went back to researchers until the co-ordinating lead committee had seen the input from the contributing committee.”
Furthermore, the expectation that the new multi-region committee would drastically reduce the work of the six regional ethics committees was soon revealed to be totally unfounded. Dr Dare who was chair of the busiest regional ethics committee at the time of the restructuring, says it quickly became clear that there had been a miscalculation. Both the multi-region committee and some of the regional committees were swamped. Since then Dr Dare says that chairs have being raising concerns about the capacity of their committees to manage their workload ethically.
“There have been attempts to address these problems. In 2007 a system of expedited review of observational research was introduc-ed. The aim was both to assist researchers and reduce committee workloads. While the system may have reduced committee workload, it seems to have increased the work-load on chairs and deputy chairs who bear most of the burden of providing expedited reviews. More recently changes have been introduced to allow research to be sent ‘out of region’ to less busy committees.”
Lack of consultation
As Tim Dare points out, not only are these latter changes to the terms of reference inconsistent with the assumption of regional review for local research which has underpinned the system of ethical review, they were made without consulting with the Health Research Council Ethics Committee (HRCEC).
Given that one of the HRCEC’s responsibilities is “to give in relation to ethics committees established by other bodies, advice on membership, procedures, and standards to be observed by those committees,” as well as to provide second opinions for the ethics committees, such a lack of consultation is of considerable concern.
Tim Dare concludes his article with the warning:
“Not only do excessive workloads threaten ethical review directly, they also endanger the goodwill of committee members (who, given current meeting fees, may fairly be regarded as volunteers). The HRCEC remains concerned that no long-term solution to the workload pressures on ethics committees has been found.”
The above changes have all been documented in the AWHC’s newsletters over the past decade. They were always accompanied by the call for ethics committees to be made completely independent of the Ministry of Health and to be located within the Office of the Health and Disability Commissioner. We made this recommendation again when preparing our submission on the review of the H&DC Act and the Code of Consumers’ Rights in 2009.
In 2008 there were a number of events commemorating the 20th anniversary of the release of the Cartwright Report on 5 August 1988. None of them addressed the issue of what happened to the Cartwright Report’s recommendations regarding ethics committees. The report stated: “New treatment procedures are not systematically reviewed by the Ethical Committee but will be considered if put to it.” When the Area Health Board ethics committees were first established it was expected that they would review new treatment procedures, but the workload of reviewing research proposals quickly put an end to any serious attempt to fulfil that task.
As stated above the Cartwright Inquiry revealed that rights of patients at National Women’s Hospital had been seriously neglected. The Cartwright Report called for a system of ethical review to be put in place that “focused on the protection of patients.” The changes that were made in the first few years after the release of the Cartwright Report went a considerable way towards addressing the issue. However, as with some of the other areas to do with the issues that were bought to light during the Cartwright Inquiry, two decades have seen a loss of ground and a resulting tendency to focus on the needs and desires of researchers, the medical profession and the health system.
The AWHC has major concerns around what has happened to our system of ethical review after the Ministry of Health took control of the ethics committees. It is time to put the spotlight on whether they are really focused on the protection of patients, and to consider placing them under the umbrella of the Office of the Health and Disability Commissioner.
• “The Report of the Cervical Cancer Inquiry 1988”
• “Ethical review of research in New Zealand” Ethics Notes October 2008