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University of Otago Law Festschrifts |
Last Updated: 31 May 2019
“WITHOUT LEGAL COMMITMENT”: COMPENSATION FOR RESEARCH-RELATED INJURY IN COMMERCIALLY-SPONSORED CLINICAL TRIALS IN NEW ZEALAND
Joanna Manning
It is a privilege and pleasure to submit this essay to this volume, written in honour of Professor Peter Skegg, New Zealand’s founding professor of medical law. I was fortunate to be able to collaborate with Peter on two book projects he led, a highlight of my own academic legal career, and to read, enjoy and benefit from his rigorously analytical and insightful research, spanning across a host of topics in medical law. His encouragement and support to many, including myself, always generously given, was gratefully received. Due in no small part to Peter’s enormous contribution and leadership, medical law in New Zealand has gone from an arcane area of “special interest” to an important and growing field, essential for inclusion in legal curricula, meriting of serious scholarship, and recognised in its own right as a specialism in legal practice.
INTRODUCTION
In 2012 two participants in separate commercially-sponsored clinical trials suffered serious injuries in New Zealand. 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 trial had been approved by the Multi-Centre Ethics Committee in November 2011.1 The second involved a man who suffered atrial fibrillation days after taking a new gout medicine. He had agreed to participate in a Phase III, randomised, double-blind, placebo-controlled, combination study of a gout medicine, also approved by the Multi-Centre Ethics Committee in February 2012.2 The aim of the CRYSTAL study was to compare
See MEC Ref 11/1/092 “A Comparison of LY2605541 versus Insulin Glargine as Basal Insulin Treatment in Combination with Oral Anti_Hyperglycaemia Medications in Insulin-Naïve Patients with Type 2 Diabetes Mellitus: A Double-Blind, Randomized Study” Multi-region Ethics Committee Minutes (15 November 2011). Hereinafter “the Insulin Variant trial”.
See MEC Ref 12/02/013 “A Phase 3 Randomised, Double-Blind, Multicentre, Placebo-
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the effectiveness and safety of the investigational drug taken in combination with a standard gout medicine against the standard gout medicine alone in reducing the excretion of uric acid, high levels of which cause crystals to form in and around joints found in people suffering from Tophaceous gout.
The Participant Information Sheets for each study warned participants that if they suffered injury as a result of participation in the trial, they would not be eligible for cover under the Accident Compensation scheme (ACC). The reason for this is that the accident compensation legislation provides that participants injured in clinical trials which are “conducted principally for the benefit of the manufacturer or distributor of the medicine or item being trialled” are not eligible for compensation under the scheme. The Participant Information Sheet for the Insulin Variant trial stated that:3
... if you follow the directions of the doctors in charge of this study and you are physically injured due to any substance or procedure given to you in accordance with the plan for this study, [name of pharmaceutical company sponsoring the trial] will pay the medical expenses for the treatment of that injury which are not covered by your medical insurance or by any other third party in accordance with the New Zealand Researched Medicines Industry Guidelines on Clinical Trials - Compensation for Injury resulting from Participation in Industry-sponsored Clinical Trials. Those guidelines say that compensation should be no less than would be awarded under the accident compensation scheme.
The Participant Information Sheet for the CRYSTAL trial stated that: “compensation will be provided by [name of pharmaceutical company sponsoring the trial] in accordance with the New Zealand Researched Medicines Industry Guidelines on Clinical Trials - Compensation for Injury resulting from Participation in Industry-sponsored Clinical Trials.”4 Neither Participant Information Sheet stated that the sponsors’ obligation to pay compensation in the event of participant injury was without legal commitment.
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
Controlled, Combination Study to Evaluate the Efficacy and Safety of
Lesinurad and Febuxostat Compared to Febuxostat alone at Lowering
Serum Uric
Acid and Resolving Tophi in Subjects with Tophaceous Gout” Multi-region
Ethics Committee Minutes (21 February 2012).
Hereinafter “the CRYSTAL
trial”.
3 See Participant Information and Consent Form for the Insulin
Variant trial at 7.
4 Participant Information Sheet for the CRYSTAL trial at
14.
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.5 A major obstacle to achieving a settlement was that the sponsor’s insurance company took over management of the claim, and it took a strict commercial approach to the claim. Despite the Minister for ACC, Hon Nikki Kaye, writing in October 2015 to remind the sponsor in the insulin variant trial of the condition attached to ethics approval of the availability of ACC-equivalent compensation and to put pressure on it to agree a date for mediation and to reach a settlement,6 at the date of writing, despite also obtaining legal representation, the injured subject has not received any compensation from the sponsoring company.
Since 1992 participants have been excluded from ACC cover and access to compensation for injuries suffered as a result of participation in commercially sponsored clinical trials in New Zealand, while participants in what might be called investigator-driven or non-industry, publically-funded trials are covered by the scheme. In 2007 the chairs of the country’s Health and Disability Ethics Committees (HDECs) called for repeal of this statutory exclusion.7 And, in a report in 2010 to the Minister of Health advising him on the Health Select Committee’s “Inquiry into Improving New Zealand’s Environment to Support Innovation through Clinical Trials”, the National Ethics Advisory Committee (NEAC)8 added its voice to calls for its repeal or at least a review of it. Its primary concern was that the exclusion disadvantages participants in industry trials compared to all other participants in clinical research in New Zealand. It questioned whether exclusion from ACC cover and compensation could be justified “as doing the right thing” in respect of these participants. It remained difficult, it said, to meet the reasonable expectations of participants of at least ACC-equivalent compensation for injuries in industry-sponsored trials,9 even though NEAC had itself set at least this benchmark as the ethical requirement for compensation in these trials just the year before in its Ethical Guidelines for
5 NEAC Advice to Associate Minister of Health on Compensation for Treatment Injury in Clinical
Trials Report No 20141482 (21 November 2014).
7 NEAC NEAC Analysis – Clinical trials
(14 September 2010) at [54].
8 NEAC is an advisory committee established
under the New Zealand Public Health and
Disability Services Act 2000 to advise the Minister of Health on ethical
issues in health services and research and to determine national
ethical
standards for the health sector.
9 NEAC NEAC Analysis – Clinical
trials (14 September 2010) at [46]-[57].
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Intervention Studies.10 Industry had already adjusted its guidelines to reflect that ethical standard in 2008, when NEAC’s Discussion Document foreshadowing that it would require ACC-equivalent compensation, had been issued.11
After learning of the experience of the men in the two cases, NEAC again called for repeal of the exclusion in a report in 2014 to the Associate Minister of Health, Hon Peter Dunne. The cases, it said, suggested that some companies conducting clinical trials in New Zealand may be:12
... 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.
It warned of the risk that “if the public became aware of the difficulties faced by these participants, it could affect future participation in and conduct of clinical trials in New Zealand.”13 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.14 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. They considered that, while it would appear from the two cases that the regulatory framework for ethics approval was not sufficiently robust to ensure the welfare of participants in the event of injury, industry should continue to meet the costs of compensation for trials they choose to conduct in New Zealand. The relative disadvantage of these subjects was not the only relevant issue. Appropriate allocation of costs was necessary to ensure that companies were incentivised to identify and appropriately manage
10 NEAC Ethical Guidelines for Intervention Studies (Wellington: Ministry of Health, 2009) at cl 8.4.
11 See NEAC Ethics of Intervention Studies: Discussion Document and Draft Ethical Guidelines for Intervention Studies (Wellington: Ministry of Health, June 2008) at 44; Researched Medicines Industry Guidelines on Clinical Trials Compensation for Injury resulting from Participation in an Industry-sponsored Clinical Trial (2008) at cl 4.1.
12 NEAC Advice to Associate Minister of Health on Compensation for Treatment Injury in Clinical Trials Report No 20141482 (21 November 2014) at [iii] (released under OIA) <http:// neac.health.govt.nz/publications-and-resources/advice-minister-health-0/neac-advicecompensation-treatment-injury-0> .
13 NEAC Advice to Associate Minister of Health on Compensation for Treatment Injury in Clinical Trials Report No 20141482 (21 November 2014) at [16].
14 Memo, Senior Policy Advisor MBIE to Manager, Health, Safety and Compensation Systems Policy Team, Ministry of Health (9 March 2015) (released under OIA).
injury risks.15 HDECs had sufficient power to protect participants without the law change, as “ethics committees should not be approving research unless satisfied appropriate arrangements for injury have been made.”16 On 2 December 2015 Dunne wrote to NEAC advising that he and the Minister for ACC did not support a change in the legislation at that time.17
This essay addresses the unacceptable situation in which subjects injured in commercially sponsored clinical trials in New Zealand currently find themselves in, in terms of receiving appropriate compensation for their injuries. Excluded from ACC cover and statutory entitlements, they must look instead to researchers and sponsors for compensation. The key deficiency of the standard compensation arrangement put in place by sponsors is that a sponsor’s obligation to pay compensation to an injured participant is “without legal commitment” and so entirely discretionary. And yet most participants enrolling in studies will be entirely unaware of this and their resulting financial exposure unless and until they are injured, because information sheets omit this fact and mislead participants in this respect. Participants in commercially sponsored trials do not receive the necessary information to enable them to give informed consent to participation. In addition, if compensation were to be provided, the arrangement does not provide for a proper claims process or adequate levels of compensation, let alone meet NEAC’s ethical expectation of ACC-equivalent compensation. By contrast, participants in non-industry trials have the benefit of access to legally enforceable, comprehensive, no fault cover and clearly defined and reasonably comprehensive compensation entitlements under the ACC scheme. The different treatment of research participants according to the nature of the trial in which they participate and suffer injury is, it is argued, inequitable and discriminatory. What is to be done to remedy the financial vulnerability of injured participants in industry trials?
In Part 1 of this essay I describe the consensus among commentators that there is a moral obligation to compensate injured research participants. Because the well-known deficiencies of the tort action are even more serious in relation to
15 Briefing to Minister for ACC Nikki Kaye from Manager, Accident Compensation Policy (7 August 2015) (released under OIA).
16 ACC and Ministry of Business, Innovation and Employment Clinical trials and ACC cover – advice provided to Minister for ACC’s office (undated) at 3 (released under OIA).
17 Letter Hon Peter Dunne to Chair, NEAC (2 December 2015) (released under OIA) <http:// neac.health.govt.nz/publications-and-resources/advice-minister-health-0/neac-advicecompensation-treatment-injury-0> . The Minister asked NEAC to provide further advice on the issue at the time it completes its ongoing review of its ethical guidelines, Ethical Guidelines for Observational Studies and Ethical Guidelines for Intervention Studies.
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research-related injuries than in medical negligence generally, there is general agreement also that no fault is the best ethical response to such injuries. In Part 2 I outline the current law and compensation arrangements for research-related injury in New Zealand, focussing on injuries in commercially sponsored trials and the compensation arrangement under the current MNZ Guidelines.18 I trace how the New Zealand Government and HDECs adopted the practice that had developed in the UK under the equivalent British industry guidelines of providing inadequate information about this arrangement in information sheets. Although HDECs have not declined approval for these studies despite knowing that the compensation arrangement in place is not ACC-equivalent, I describe how some have attempted to put pressure on companies to live up to NEAC’s ethical expectation to pay no fault compensation to at least an ACC-equivalent standard and in a timely manner by inserting such commitments in information sheets. These are, however, of limited effectiveness, when payment of compensation is legally unenforceable in the first place.
In addition to their lack of legal force, I describe in Part 3 the other deficiencies of the MNZ Guidelines noted by earlier researchers in terms of providing satisfactory compensation. In the final part (Part 4) I outline possible responses and alternative options that participants, HDECs and the Government might adopt to address this unsatisfactory situation. I argue that the preferable course is to bring injuries suffered by participants in commercially sponsored clinical trials back within ACC cover, in order to provide equal access to legally enforceable, timely, and fair compensation, as with all other injured participants in clinical research. Concerns about companies lacking incentives to minimise the risks to participants in their trials and being motivated to use New Zealand as a laboratory in which to test risky drugs, because of their ability to externalise their costs of compensating injuries on to ACC, are an important consideration, but should be addressed by other means.
1. MORAL OBLIGATION TO COMPENSATE RESEARCH PARTICIPANTS ON A NO FAULT BASIS
In the last fifty years there has been an explosion of new and improved medicines and treatments, which have increased life expectancies, improved quality of life,
18 See Medicines New Zealand (MNZ) Guidelines on Clinical Trials Compensation for Injury resulting from Participation in an Industry-sponsored Clinical Trial (February 2015). Hereinafter “the MNZ Guidelines”. Medicines New Zealand, formerly known as the Researched Medicines Industry (RMI), is the industry association representing companies engaged in the research, development, manufacture and marketing of pharmaceutical medicines.
and reduced rates of morbidity and disability. All of these have had to be tested in clinical trials for the first time on humans not suffering from the relevant condition, followed at some point on patient-volunteers. Society’s interests are advanced by ongoing clinical research and individuals’ participation in trials. The greatest benefit is obviously to people afflicted by diseases and injury through the availability of new, (generally) safe, and effective medical therapies. But the population as a whole benefits from advancements in scientific knowledge, even if there is no immediate benefit to a specific individual.
This progress comes at a cost to a minority of participants who suffer research-related injuries. There are notorious cases of deaths and catastrophic injuries: the French drug trial disaster in 2016, which left one participant brain dead and five others critically ill after taking an experimental drug made by Portuguese drug company Bial;19 and the infamous Northwick Park study in 2006 in which eight healthy men in London participated in a first-in-human trial of a novel monoclonal antibody TGN 1412 manufactured by TeGenero. Within 12 hours the six who received the medicine being tested suffered life-threatening conditions involving multi-organ failure. Many suffered lasting injury that left them unable to work and reliant on ongoing medical care.20 Eventually the injured men received limited compensation after a legal battle because TeGenero, the drug’s German manufacturer, which went bankrupt, lacked sufficient insurance coverage.21 But, these horror stories aside, harm is also caused to a small number of participants in routine clinical research, as the two New Zealand cases indicate. Though there is little recent data on its incidence, the incidence of research-related injury is claimed to be low, especially for major and catastrophic injuries.22 It is said to be no greater than in ordinary medical treatment itself.23 Injuries can vary from trivial (for
19 Angelique Chrisafis “French drug trial leaves one brain dead and five critically ill” The Guardian (United Kingdom, 15 January 2016).
20 Susan Major “Severe adverse reactions prompt call for trial design changes” (2006) 332 BMJ 683.
21 See Renuka Munshi and Urmila Thatte “Compensation for research-related injury” (2013) 4 Perspect Clin Res 61.
22 The most widely quoted is a 1976 US survey of investigators conducting
research on nearly 133,000 participants over three years,
which showed that of
the 93,000 participants in nontherapeutic research, 0.8 % were reported injured:
no-one died, one was permanently
disabled, 37 were temporarily disabled and 673
suffered trivial injuries. Of the 39,000 therapeutic research participants,
10.8%
reported injuries: 43 deaths, 13 were permanently disabled, 937 were
temporarily disabled, and 3,253 suffered trivial injuries. See
David Resnik
“Compensation for research-related injuries: Ethical and legal
issues” (2006) 27 Journal of Legal Med 263
at 265; Noel Snell “Human
volunteer studies – Safety considerations in an era of highly
active biological agents” (2006) 20(5) Int’l J Pharm Med 293.
23
It was suggested that the risk associated with non-therapeutic research might be
no greater
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example, minor bruising, temporary nausea) to major (temporary disability, organ damage) to catastrophic, including death and serious permanent impairment. The care required afterwards ranges from acute to long-term, continuing care. Harm can be physical, psychological, social and economic.
The fundamental difference between ordinary medical care and clinical research lies in the respective goals of each. Ordinary medical treatment aims to benefit a specific patient. The doctor weighs the risks and benefits of a procedure or treatment and recommends a personalised regimen only where the potential benefits outweigh the risks for that individual. Biomedical research, by contrast, is undeniably utilitarian. The sole goal is to produce generalizable knowledge that can be used to benefit future patients. Research is specifically designed to undertake an activity to test a hypothesis, draw conclusions, and thereby develop generalizable knowledge. Benefitting individual participants is never an aim; deference to a participant’s individual needs and preferences is a limiting factor. The methodologies of research, such as randomisation, double-blinding and placebo control, must often subordinate a participant’s personal best interests to the dictates of the protocol. This is clearest in non-therapeutic research, such as a Phase I trial on healthy volunteers, which is designed to test for safety, toxicity, or dosage levels, and in which the participant is exposed to unknown hazards with no expectation or prospect of offsetting benefit. But, even in therapeutic research, where the patient-participant suffers from the condition the drug is being developed to treat, the research is not designed to benefit any particular individual. Any benefit to individual participants is fortuitous and incidental, not a goal of the research.24 Clinical research thus requires participants to assume additional risk for the benefit of society and future patients.
Since the 1960s a consensus has developed as to the existence of a moral obligation to compensate for research-related injury. High-level national commissions in the US25 and leading ethicists agree, with few dissentients.26 Childress appealed to the
than that experienced in everyday life and in therapeutic research, no greater than those of treatment in other settings, see Phillippe Cardon, William Dommel and Robert Trumble “Injuries to research subjects: A survey of investigators” (1976) 295 NEJM 650 at 653-54.
24 See Haavi Morreim “Litigation in clinical research: Malpractice doctrines versus research realities” (2004) 32 JLME 474 at 475.
25 For a description of the series of US national bioethics commissions and committees over forty years, from 1978 until 2011, all of which have concluded that compensating injured research participants is morally required, see Elizabeth Pike “Recovering from research: A no-fault proposal to compensate injured research participants” (2012) 38 Am J of Law & Med 7 at 17-23.
26 See James Childress “Compensating injured research subjects: I. The moral argument” (1976) 6 Hastings Center Rep 21; Carl Elliott “Justice for injured research subject” (2012) 367
moral principle of fairness and compensatory justice to justify a moral obligation on society to compensate injured research subjects and to acknowledge the fact that participants have exposed themselves to risk for the benefit of society through the advancement of medical knowledge. The moral obligation exists regardless of the participant’s subjective motives for participating, and despite consent to participate, which merely enables the research to proceed in the first place and does not amount to a waiver of compensation. While the paradigm case in which the societal moral obligation is owed is nontherapeutic research, he argued that the possibility of the subject benefiting in therapeutic research does not cancel the obligation, because there is uncertainty about the best treatment or procedure and the subject still accepts a position of risk for the benefit of society.27 Other moral justifications include: intuition (compensating participants for the harm suffered seems obviously the right thing to do); reparative justice (focusing on the needs of the injured participant and compensating to repair the harm); distributive justice (ensuring fairness in the distribution of the benefits and burdens of research as between investigators, sponsors, participants, and future patients by shifting some of the benefits of the research from those likely to derive benefits from it to participants who have been disproportionately and unfairly burdened by research-related injury); utilitarian justifications (to encourage participation in research); economic justifications (to incentivise investigators and sponsors to consider carefully what research to conduct and to manage and minimise its associated risks by requiring them to internalise the true costs of the injuries they cause in their risk-benefit calculus); and to avert a loss of public trust in researchers, sponsors and medical experimentation likely to result from injured participants being left to bear the medical and financial costs of their injuries.28
There is also general agreement that no-fault compensation is the best normative response to research-related injury. The poor job that tort law performs as a compensation mechanism is notorious, particularly in medical negligence cases. It is expensive, adversarial, stressful, time-consuming and antithetic to rehabilitation, involves long delays before any compensation is paid, and is a “forensic lottery” in that it tends to over-compensate a few select “winners”, while inadequately compensating many “losers” most of whom never sue or cannot prove their claim. Tort law is even worse at compensating injured research participants than
NEJM 6; Ari VanderWalde and Seth Kurzban “Paying human subjects in research: Where we are, how did we get here, and now what?” (2011) 39(3) JLME 535 at 545-8.
27 See James Childress “Compensating injured research subjects: I. The moral argument” (1976) 6 Hastings Center Rep 21.
28 See John Robertson “Compensating injured research subjects: II The Law” (1976) 6 Hastings Center Rep 29; Elizabeth Pike “Recovering from research: A no-fault proposal to compensate injured research participants” (2012) 38 Am J of Law & Med 7 at 19-20.
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injured patients. The key cause of action is negligence. Research-related injuries are an inappropriate fit with the elements of a negligence claim so the chances of succeeding against investigators and sponsors are extremely limited. The most serious obstacle lies in a participant’s difficulty proving fault on behalf of researchers and sponsors. Some risks in research are unpredictable and unforeseen, even if the research is carried out carefully. The nature of a research study is that unforeseeable events are to be expected. When injury occurs, it is often because such a risk occurred, rather than any negligence or deviation from the research protocol by researcher or sponsor. The chances of successful litigation are highest from non-compliant research, which causes a minority of research-related injuries. Thus, participants are likely to experience major difficulty proving that harm was reasonably foreseeable in the ordinary course of events, because unforeseeable events are inevitable in experimental research.29
The second key barrier is that proof of the causal link between the research procedures and interventions, and the injury is particularly difficult in clinical research and often requires expert analysis. Participants often encounter difficulty, especially in therapeutic trials where the same person is both patient and research participant, in proving that their injury was attributable to participation in the clinical trial (i.e. to the administration of the trial product or any clinical intervention or procedure provided for by the protocol, that would not have occurred but for the patient’s inclusion in the trial), as opposed to progression of their underlying condition, the inefficacy of treatment, or adverse reactions from the comparison intervention. Or it may only be possible to show that the research intervention increased the statistical chance of contracting a condition (such as cancer) in the future, rather than that it caused it to develop or materially contributed to the subject developing it. This does not satisfy proof of causation in most jurisdictions.30
Hence, as Pike says, the tort system is “uniquely difficult for injured research participants, even as compared with injured medical patients” in ways that are difficult to overcome, resulting in substantial unfairness.31 Tort law is an unjust system of compensation for such injuries, because, despite undertaking the risks of the research in the interests of future patients and society, injured participants
29 These points are made by many, see for example Elizabeth Pike “Recovering from research: A no-fault proposal to compensate injured research participants” (2012) 38 Am J of Law & Med 7 at 26-7.
30 Elizabeth Pike “Recovering from research: A no-fault proposal to compensate injured research participants” (2012) 38 Am J of Law & Med 7 at 28.
31 Elizabeth Pike “Recovering from Research: A no-fault proposal to compensate injured research participants” (2012) 38 Am J of Law & Med 7 at 26.
are almost always left to bear the full financial burden of their injuries, to which researchers and sponsors (and indeed society), all of whom benefit from research, are not required to contribute. By contrast, only no-fault compensation will adequately protect participants in clinical trials in respect of injuries for which negligence cannot be established. For ACC cover, proof of the causal connection between the injury and the investigational drug or interventions specified in the protocol that would not have been necessary but for inclusion in the trial is all that is required, although, as indicated, this is itself difficult. As Avilés says, “the no fault compensation system is the expression of the society’s ethical obligation to indemnify injured research subjects who accept the risks and suffer thereby” at society’s behest and for its benefit.32 The ethical superiority of no fault is reflected in some international ethical guidance33 and by the fact that most of the US blue-ribbon bioethics advisory committees as well as the Pearson Commission in the UK in 1978 have concluded by recommending systematic no fault compensation for injured subjects in clinical trials.34
2. COMPENSATION ARRANGEMENTS FOR RESEARCH-RELATED INJURY IN NEW ZEALAND
The Accident Compensation Act 2001 (the Act) provides that there is cover for “treatment injury” for personal injury suffered by a person as a result of treatment given as part of a clinical trial in two circumstances: first (not relevant here), where the claimant did not agree in writing to participate in the trial35 and, secondly, where:36
(a) an ethics committee—
(i) approved the trial; and
32 Miguel Avilés “Compensation for research-related injuries in the European Union” (2014) 21 Eur J Health Law 473 at 482.
33 See for example, Council for International Organisations of Medical Sciences (CIOMS) International Ethical Guidelines for Biomedical Research Involving Human Subjects (2002) Guideline 19 and Commentary. Compared to the World Medical Association’s Declaration of Helsinki which merely states that “appropriate compensation and treatment for subjects who are harmed as a result of participating in research must be ensured”. (Principle 15).
34 See Elizabeth Pike “Recovering from research: A no-fault proposal to
compensate injured research participants” (2012)
38 Am J of Law & Med
7 at 22. See also Royal Commission on Civil Liability and Compensation for
Personal Injury: Report (vol
1, Cmnd 7054-I, 1978) at [1339]-[1341].
35
Accident Compensation Act 2001, s 32(5).
36 Accident Compensation Act 2001, s
32(6).
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(ii) was satisfied that the trial was not to be conducted principally for the benefit of the manufacturer or distributor of the medicine or item being trialled.
If the ethics committee determines that the principal beneficiary of the trial is the manufacturer or distributor of the product, the Act provides that an injured participant has no ACC cover. Criteria have been developed to assist this determination, the most important, though not determinative, of which is whether the sponsoring company is providing funding or materials for the proposed research.37 Essentially, these are trials sponsored by pharmaceutical companies, where a company’s plan is to obtain market authorisation and derive profits from sale of the product. Thus, by agreeing to participate in a commercially sponsored trial, a subject surrenders cover and access to compensation that s/he would otherwise have under the ACC scheme. Instead, the pharmaceutical industry is primarily responsible to compensate injured participants in its trials and to put in place insurance cover for any such liability.
It is necessary to describe how these separate compensation arrangements, in place since 1992, came about. From its inception, research-related injuries were covered by the ACC scheme, first under the broad, undefined phrase “personal injury by accident”, and later under the similarly undefined phrase “medical misadventure”.38 But in 1992 the Government passed a new Act governing the scheme which significantly reduced the extent of ACC cover and kinds and levels of compensation entitlements enjoyed by participants. Its key motivation was to reduce what were then perceived as the burgeoning and unsustainable costs of the whole scheme.39 In respect of excluding cover for injuries in commercially sponsored trials,40 the reasoning was also that since industry would enjoy the profits from medicines trialled on New Zealanders and subsequently authorised for sale on the market, it should meet the costs of providing appropriate compensation for injuries in its trials, which should not be passed on to New Zealand levy payers. The exclusion was also motivated by a concern that New Zealand might be targeted by industry seeking to conduct questionable clinical trials, which would
37 See Standard Operating Procedures for Health and Disability Ethics Committees (version 2, 2014) at [145].
38 See Accident Compensation Act 1972 and 1982, s 2. For an example of a notorious clinical trial the Court of Appeal held to be covered by the ACC scheme viz. the unfortunate experiment at National Women’s Hospital, see Green v Matheson [1989] NZCA 195; [1989] 3 NZLR 564 (CA).
39 See generally, Bill Birch Accident Compensation: A Fairer Scheme (New Zealand Government, Wellington, 1991).
40 Participant injuries in all clinical trials were at first excluded from ACC cover in the 1992 Act when passed, but in 1993 the Act was amended with retrospective effect to exclude only those injured from participation in commercially sponsored trials, see Accident Rehabilitation and Compensation Amendment Act (No 2) 1993.
then leave New Zealanders to bear the cost.41 If required to bear the costs of indemnity or insurance as happened elsewhere, international companies would not be overly influenced to choose to conduct their trials in New Zealand and, further, they might be incentivised to increase safety in their trials.42
Because the exclusion of commercially sponsored trials from ACC cover was insufficiently foreshadowed, it caused unexpected problems for researchers, sponsors, and HDECs, as it was realised that participants in industry trials were without financial protection apart from the tort action. The Ministry of Health and ACC, with assistance from the Researched Medicines Industry (RMI), responded by adopting RMI-drafted guidelines virtually identical to the Association of the British Pharmaceutical Industry’s (ABPI) 1991 Guidelines then in use in the UK,43 whereby sponsors would agree to follow the guidelines, pursuant to which they accepted a moral obligation (only) to pay no fault compensation for injury.44 Some background about the evolution of the ABPI’s guidelines is also necessary in order to understand the current approach of HDECs in New Zealand.
41 See NEAC NEAC Analysis – Clinical trials (14 September 2010) at [47].
42 ACC and Ministry of Business, Innovation and Employment Clinical trials and ACC cover – advice provided to Minister for ACC’s office (undated) at 2 (released under OIA).
43 The ABPI is the UK organisation which represents the interests of the pharmaceutical industry. The UK’s compensation system in industry trials is based on the Guidelines on Compensation
for Trial Related Injuries (2014) issued by the ABPI. The current version is very similar to
the 1991 ones on which the interim RMI Guidelines were
based. The ABPI Guidelines have
been adopted by South Africa,
Australia and (de facto) Singapore, see Medicines Australia
Guidelines for Compensation resulting from Participation in a Company-sponsored Clinical Trial (2004); South African Department of Health Guidelines for Good Practice in the Conduct of Clinical Trials with Human Participants in South Africa (2nd ed, Pretoria, South Africa, 2006) at [4.11]. Most of the clinical trial centres in Singapore adopt the APBI Guidelines. See also Urmilla Thatte, Renuka Kulkarni and Samidha Kalekar “Review of policies for injuries to research participants in India” (2009) 35 J Med Ethics 133.
44 The first Guidelines were released in December 1993 on an interim basis, see RMI, Interim Guidelines on Clinical Trials – Compensation for Injury resulting from Participation in an
Industry-sponsored Clinical Trial. A revised, final version was released in 1997. The ACC and
the Ministry also issued guidelines outlining the role of
ethics committees to certify who is the
principal beneficiary of the trial
and the criteria for making the determination, and prescribing
the two forms for statutory declarations to be made by the investigator on the basis of which
HDECs would make that determination. Form A declared the trial
eligible for ACC coverage,
while Form B was for commercially sponsored trials
and required the investigator to declare
that participants would receive an acceptable level of compensation from the sponsoring company in the event of injury, see Ministry of Health and ACC Guidelines: Compensation for Injuries caused as a result of Participation in a Clinical Trial and the Role of Ethics Committees (1993).
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The ABPI has always taken a different approach in its guidelines for compensation of healthy volunteers than for patient-volunteers. The former recommends that sponsors put in place a legally enforceable commitment to pay no fault compensation to injured subjects, whereas any obligation to compensate the latter in Phase II and III trials has always been made “without legal commitment.” The reason given for the difference is that participants in Phase I trials are considered to be a special group for two reasons: they are more vulnerable because they expose themselves to an unknown (usually greater) risk of harm (this being the first time the medicine is tested in humans); and there is no possibility of personal benefit from participation to compensate for the risks being undertaken. Without a legally binding commitment to compensate for injury, recruitment would be very difficult. The ABPI’s first Guidelines relating to staff volunteers in 1970 recommended a separate, legally enforceable contract entered into with each volunteer to provide no fault compensation. After the death in 1985 of a medical student in a Phase I trial, followed by pressure from the BMJ and a Royal College of Physicians report, the ABPI issued Guidelines recommending the same contractual arrangement with all healthy volunteers to its members.45 The current UK Guidelines for Phase I trials “require”, rather than “recommend” as under the previous version, that member companies ensure that arrangements are put in place that create a legally binding obligation to pay no fault compensation.46 “Any significant deterioration in health or wellbeing” is compensatable,47 while under the ABPI Guidelines for Phase II and III studies, only “more serious injuries of an enduring and disabling character” are compensatable, though “without legal commitment.”48
Under pressure from ethics committees for assurances that harmed patients in Phase II and III studies would also be appropriately compensated, the ABPI issued its first guidelines for them in 1983. These recommended that member companies “favourably consider” “without legal commitment” the provision of compensation for injury, including death, suffered by patients without the requirement for
45 See “Death of a volunteer” (1985) 290 BMJ 1369; Royal College of Physicians Research on healthy volunteers (Royal College of Physicians, London, 1986); ABPI Guidelines for Medical Experiments in Non-Patient Human Volunteers (1990); JD Harry “Research on healthy volunteers – a report of the Royal College of Physicians” (1987) 23 Br J Clin Pharmac 379.
46 ABPI Clinical Trial Compensation Guidelines: Phase I Clinical Trial Compensation Guidelines (2014). They apply also to patients in Phase I trials who have no prospect of direct benefit, as well as to healthy volunteers.
47 ABPI Clinical Trial Compensation Guidelines: Phase I Clinical Trial
Compensation Guidelines (2014) at cl 4(i).
48 ABPI Clinical Trial
Compensation Guidelines: Phase II, III & IV (2014) at [1.1] and
[1.4].
negligence to be proved.49 An influential Commentary accompanying the Guidelines advised that a legally enforceable commitment to individual subjects via a contract with each patient would be “cumbersome”, “inadvisable and unworkable” and that injured patients would not ultimately benefit, while at the same time inexplicably asserting that “[f]or healthy volunteers a separate legal contract with each healthy volunteer is feasible, and the draft contract recommended in 1970 ... admirable”. They said further that, while the “favourably consider” and “without legal commitment” wording “might be thought at first sight to offer nothing”, this deliberate choice of words “clearly denote[d] an intention that compensation should be provided.” While that may have been so, implementation of any such intention could not be enforced by the participant. Even though they had no legal force, the commentators cited their experience that major companies did in reality honour the obligation to pay, and they claimed that the Guidelines reflected “acceptance of the pharmaceutical industry as a whole of this attitude”.50 They did advance some “patient-friendly” interpretations of the broad language and uncertainties in the Guidelines.
Setting a somewhat discordant note, given the profession’s preparedness to put its trust in the industry (the former would not be bearing any risk of injury) on behalf of patients (who would) that it would honour voluntary guidelines, the ABPI responded that the views were the commentators’ own, not necessarily those of the ABPI, and that, in any event, the Guidelines were “recommendations to member companies and it is they who w[ould] operate and interpret them”.51 In light of this, Garden advised that the pragmatic response adopted by her ethics committee for the time being was that patients’ interests would be adequately protected if the company “agreed in writing to follow the ABPI guidelines as regards compensation for injury”.52 While this approach may have avoided conflict with sponsors and facilitated research, it is hard to see how such a statement by the sponsor provided any reassurance to the ethics committee that patients’ rights to compensation were safeguarded, in the face of Guidelines binding on the sponsor in honour only and specifying vague obligations to compensate for research-related injury.
Some companies sought to limit even their (voluntary) obligations to injured patients during this period through various narrow interpretations of the APBI
49 See A Diamond and D Laurence “Compensation and drug trials” (1983) 287 BMJ 675 at 675.
50 A Diamond and D Laurence “Compensation and drug trials” (1983)
287 BMJ 675 at 676 677.
51 Arthur Massam [Letter] “Compensation and
Drug Trials” (1983) 287 BMJ 1066.
52 Margaret Garden [Letter]
“Compensation and Drug Trials” (1983) 287 BMJ 1381.
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Guidelines.53 In response, some UK ethics committees considered it their duty to ensure that injured patients could expect no fault compensation. In 1995 members of an ethics committee shared their experience of an “acceptable” form of wording they required in protocols, so that a more uniform response might be achieved throughout the UK. The answer was, they said, to require the pharmaceutical company to agree in writing that it would “pay compensation according to the ABPI Guidelines on a no-fault basis,” as well as to attest to the fact that a suitable certificate of insurance had been obtained or applied for (to indicate ability to fulfil the responsibility to pay). The confidence of the authors that these statements, required as a condition of ethics approval, “safeguard[ed] the patient’s right to compensation” appears misplaced under Guidelines the authors themselves acknowledged to be “merely guidance notes” and “not legally enforceable”.54 Nevertheless, it became accepted practice for ethics committees to require these statements. The UK Clinical Trials Regulations implementing the requirement of the 2001 European Directive for the provision of insurance/ indemnity to cover the liability of the sponsor and investigator to protect injured subjects added no extra teeth,55 as they left the voluntary commitment under the ABPI Guidelines untouched.
And so, returning to New Zealand, the first interim RMI Guidelines introduced in 1993 replicated the ABPI ones. The current 2015 version states that “compensation should be paid regardless of whether the patient is able to prove the company has been negligent in respect of injuries caused by the medicinal product under trial,” and subjects the sponsor to strict liability in respect of injuries caused by the product.56 The MNZ Guidelines are, however, merely a recommendation by MNZ to its member companies to pay no fault compensation. Not all sponsoring companies that agree in information sheets to adhere to the MNZ Guidelines are members of MNZ. MNZ cannot require that its members, let alone non-member companies, do so. The Preamble states:57
53 See John Barton, Maureen MacMillan and Lindsay Sawyer “The compensation of patients injured in clinical trials” (1995) 21 Journal of Med Ethics 166 at 167-8 for the ways companies sought to limit their “liability” under the APBI Guidelines.
54 See John Barton, Maureen MacMillan and Lindsay Sawyer “The compensation of patients injured in clinical trials” (1995) 21 Journal of Med Ethics 166.
55 See The Medicines for Human Use (Clinical Trials) Regulations 2004, First Schedule, Part 2, cl 16. The provision also does not state the basis of liability and so liability could be restricted to negligence. The ABPI Guidelines provide for a qualified form of no fault compensation, but they are legally unenforceable.
56 MNZ Guidelines on Clinical Trials Compensation for Injury resulting from Participation in an Industry-sponsored Clinical Trial (February 2015), cl 1.7.
57 MNZ Guidelines on Clinical Trials Compensation for Injury resulting from Participation in an Industry-sponsored Clinical Trial (February 2015), Preamble (emphasis added).
Medicines New Zealand recommends ... that a member company sponsoring a clinical trial should, without legal commitment, provide to the investigator — and through him to the relevant research ethics committee — a written assurance that the following guidelines will be adhered to in the event of injury caused to a patient that is attributable to participation in the trial in question.
Note that the sponsor’s written assurance to adhere to the compensation obligations is made, not to potential participants, but to the investigator and through him/ her to the HDEC, so as to facilitate ethical approval. A sponsor’s obligation to pay compensation is legally unenforceable by the injured participant and therefore discretionary by the sponsor. Clause 1.1 states: “Notwithstanding the absence of legal commitment, ... the sponsoring company should pay compensation to patient-volunteers suffering bodily injury (including death) in accordance with these guidelines.” Note the careful use of the expression “compensation should be paid” throughout, rather than “must” or “will pay”, emphasising moral rather than legal responsibility.
The interim 1993 RMI Guidelines did not apply to Phase I studies and healthy volunteers. But neither were there separate, legally enforceable guidelines for them, as there were in the UK. Instead the 1993 Guidelines said that “[t[he company initiating the trial should establish a contract with participants in the trial to provide the insurance cover”.58 The 2015 MNZ Guidelines, by contrast, do apply to injuries in both healthy volunteers and patient-volunteers in Phase I studies.59 Thus, a New Zealand sponsor’s obligation to pay compensation to participants injured in Phase I trials is without legal commitment, despite there being no prospect of any personal benefit as compensation for the unknown, usually greater risks of testing the drug in humans for the first time. It seems extraordinary that the recommendation to sponsors to enter a legally binding contract with participants in Phase I studies in the 1993 and 1997 RMI Guidelines has been dropped, leaving participants in a worse position now than previously. And the sponsor’s lack of legal liability is in stark contrast to the fact that the ABPI has considered it ethically appropriate for sponsors to provide legally enforceable no fault compensation to these participants since 1970.
58 See RMI Guidelines on Clinical Trials Compensation for Injury resulting from Participation in an Industry-sponsored Clinical Trial (1993), cl 2.2. Note, the obligation was to provide the participant with insurance cover, not no fault compensation, leaving the injured participant to bring his/her claim directly against the insurer. The 1997 RMI Guidelines were to the same effect.
59 MNZ Guidelines on Clinical Trials Compensation for Injury resulting from Participation in an Industry-sponsored Clinical Trial (February 2015), cl 2.2.
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When the interim RMI Guidelines were introduced in New Zealand, the Ministry of Health and ACC adopted the same practice that had evolved out of the power struggle between industry and ethics committees in the UK. The prescribed form required the investigator to declare that:60
... in the event of injury arising from their participation in the research, an appropriate level of compensation in line with ... [the 1993 Guidelines] will be provided by [name of the sponsor].
One might expect that a participant’s lack of any legal entitlement to compensation would be of such importance that this would be explicitly and unequivocally spelled out to potential subjects in the information sheet. But this has never been the case. No detail of nor even a summary of the overall effect of the MNZ Guidelines and their implications for a participant’s right to compensation is given. The following is the recommended text about compensation for commercially sponsored trials in the HDECs’ own template for a Participant Information Sheet suggested for use by researchers:61
What if something goes wrong?
If you were injured as a result of treatment given in this study, which is unlikely, you won’t be eligible for compensation from ACC. However, compensation would be available from the study’s sponsor, [name of sponsor], in line with industry guidelines. We can give you a copy of these guidelines if you wish. You would be able to take action through the courts if you disagreed with the amount of compensation provided.
This does not just omit information about the absence of any legal obligation; it is positively misleading, in that it states that compensation will be available from the sponsor if something goes wrong. The Participant Information Sheets for the Insulin Variant and CRYSTAL trials quoted above similarly state that compensation “will be” available or paid. The last sentence in the HDEC template information sheet makes matters worse. It reads as referring to a dispute as to the amount of compensation provided under the MNZ Guidelines, whereas it may have been intended to refer to separate liability in negligence. By stating that court action could be taken to determine the amount of compensation if in dispute, it implies that the injured subject has a valid cause of action and the sponsor a legally
60 Ministry of Health and ACC Guidelines: Compensation for injuries caused as a result of participation in a clinical trial and the role of ethics committees (1993), Form B.
61 See HDEC “Participant Information Sheet and Consent Form Template” (July 2015) <http:// ethics.health.govt.nz/> [bold type indicates emphasis in original; italics indicates emphasis added].
enforceable obligation to pay compensation under the MNZ Guidelines in the first place. The sentence implies further that, in the event of such a dispute, a court would have power to authoritatively determine the amount of compensation payable. This is incorrect and misleading, since no court could compel payment nor decide the amount of compensation pursuant to a non-enforceable obligation in voluntary guidelines. As to liability in negligence, there is nothing about the difficulties, expense and delay involved in litigation, including the particular difficulties of establishing negligence and causation in the research context.
The template states that participants will not be given a copy of the MNZ Guidelines unless they ask for them. Apparently few do ask for and read them;62 they presumably rely on the HDEC’s scrutiny of the documents and the fact of its ethical approval as a guarantee that an appropriate arrangement for injury has been made. There is nothing in this bland statement to alert them to the importance of the MNZ Guidelines in terms of the absence of a legal right to compensation. In the unlikely event that they did ask for a copy and read it, what would they make of the apparently conflicting statements: “without legal commitment” as against “a written assurance that the following guidelines will be adhered to in the event of injury” and “the sponsor company should pay compensation ...”? If HDECs have incorrectly concluded, as the template indicates, that the amount of compensation could be set and enforced by a court, what hope is there that a participant would understand the true legal position? The likelihood is that their financial exposure would be completely unappreciated by them, unless and until they suffered an injury and sought compensation. The information about compensation required in the HDECs template is insufficient and misleading for informed consent purposes, in breach of subjects’ legal rights.63 In contrast, the recommended wording for information sheets in the UK for commercial research has developed since 1993, such that the “without legal commitment” nature of the ABPI Guidelines is now mandated information:64
We will provide compensation for any injury caused by taking part in this study in accordance with the guidelines of the Association of the British Pharmaceutical Industry (ABPI). ...
62 Advice to author by a member of an HDEC.
63 See Health and Disability Commissioner (Code of Health and Disability Services Consumers’ Rights) Regulations 1996, Rights 6(2) and 7(1).
64 Medical Research Council & NHS Health Research Authority Consent and Participation Information Sheet Preparation Guidance <http://hra-decisiontools.org.uk/consent/contentsheet-support.html> [Emphasis added].
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Any payment would be without legal commitment. (Please ask if you wish more information on this). We would not be bound by these guidelines to pay compensation where the injury resulted from a drug or procedure outside the trial protocol or where the protocol wasn’t followed.
Despite the lack of a legal commitment, the ABPI and the MNZ have apparently assured ethics committees that its members would in reality pay out.65 Not all companies are members of MNZ, but HDECs apparently accept that they too would do so, if they had agreed in writing to provide compensation “in line with industry guidelines”. The reasoning may be that companies have other interests sufficient to incentivise them to make confidential settlements with injured participants, making legally mandated compensation non-essential. A company will no doubt be anxious to protect the commercial reputation of a product in development to protect its investment. And there is the risk of a spill over from adverse events in respect of one product, if serious enough, to impact adversely on a company’s general reputation. No company will want to risk gaining a reputation, particularly an international one, for running shoddy trials, developing unsafe drugs, or treating injured participants unfairly, attracting the risk of media interest and public scandal. But it is open to question whether these interests are sufficiently pressing to override a company’s reluctance to pay out when not obliged to, in a country where the media is relatively quiescent and which is far enough away for it to be relatively easy to contain adverse publicity about research-related injury to prevent it becoming an international scandal. On the other hand, drug injuries can be very expensive to compensate, and, as Guest observed, “it is an unsatisfactory position for the injured subject that the research sponsor be faced with balancing cost against breaching a legally non-enforceable albeit moral undertaking”.66
In any event, it is not apparent how HDECs can monitor and so rely with confidence on assurances that companies would honour their moral obligation to pay out, in the absence of transparent information from sponsors about actual participant injuries in clinical research and of compensation payments made under the MNZ Guidelines. HDECs are unlikely to hear about participants’ injuries after approval, as under current procedures they no longer receive information
65 See for example, a letter dated 15 July 1997 to the Chairperson of the Southern Regional Ethics Committee from the RMI stating that the Guidelines were “RMI policy” and that once its Board ratified the 1997 version “all member companies would be encouraged to adhere, as a minimum, to the compensation guidelines.” See also A Diamond & D Laurence “Compensation and drug trials” (1983) 287 BMJ 675.
66 Stephen Guest “Compensation for subjects of medical research: the moral rights of patients and the power of research ethics committees” (1997) 23 Journal of Med Ethics 181 at 183-4.
about serious adverse events in individual trials, on the grounds that they do not have the expertise or resources to monitor trials.67 And companies guard the fact and details of any settlements under the MNZ Guidelines as confidential and commercially sensitive.68 This makes them in effect no more than appeals to the trust of researchers, HDECs and any participants aware of them. If the industry does in fact treat the MNZ Guidelines as de facto legally binding, what would be lost by making them so? Perhaps part of the answer is that, even if companies do accept that they must make some payment in a particular case, once the injured subject discovers that any payment is ex gratia, the negotiating power shifts dramatically in favour of the company (or its insurer). As a result, it is inevitable that the subject will have to be more prepared to give way in settling other disputes with the company, such as over the amount of compensation.
As indicated, in its first 2009 edition of its Ethical Guidelines for Intervention Studies NEAC imposed responsibilities on investigators and sponsors in non-ACC covered trials “to ensure alternative compensation cover for study participants to at least ACC-equivalent standard. This may include earnings-related compensation.”69 It imposed on HDECs the responsibility of ensuring the availability of alternative compensation cover to at least ACC-equivalent standard.70 The HDECs’ standard application form submitted by investigators was also amended, asking them to confirm the potential availability of all ACC entitlements, as follows:71
Researchers and sponsors must ensure that they have arrangements in place to ensure that at least ACC-equivalent compensation would be available in case of such injury.
67 Standard Operating Procedures for Health and Disability Ethics
Committees (version 2, 2014) at [208]. Annual safety reports, no longer than
two pages in length, instead are required. These are generally too
non-specific
to alert HDECs to safety problems occurring in individual trials. The
Procedures were introduced in 2012 to streamline and expedite ethics
review processes, to assist Government to achieve its aim of encouraging
international pharmaceutical companies to see New Zealand as a good place to
carry out clinical trials, see “Government Response
to the Report of the
Health Committee on its Inquiry into improving New Zealand’s
Environment to support innovation through clinical trials”
(2011).
68 For example, the settlement with the injured patient in the
CRYSTAL trial was confidential.
69 NEAC Ethical Guidelines for Intervention Studies (Wellington: Ministry of Health, 2009), cls 8.4 and 8.5.
70 NEAC Ethical Guidelines for Intervention Studies (Wellington: Ministry of Health, 2009), cls 8.4 and 8.5. The Standard Operating Procedures reiterate HDECs’ responsibility, see Standard Operating Procedures for Health and Disability Ethics Committees (version 2, 2014) at [147].
71 See HDEC “Application form (final)” <http://ethics.health.govt.nz/applying-review/how-do i-apply> question R 1.9.
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In the event of injury to a participant in your intervention study, will compensation potentially be available for all of the following entitlements, which would be available through ACC?
Nevertheless, as NEAC reported in 2010, sponsors were proving reluctant to meet NEAC’s and subjects’ “reasonable expectation” of providing at least ACC-equivalent compensation cover for participants. Some HDECs tried to apply pressure on them to do so. From the end of 2013 one HDEC, for example, became increasingly insistent that these five categories of ACC entitlements be explicitly itemised in information sheets, so as to signal to participants their availability.72 Where sponsors tried to limit what they would pay, such as by stating that it would not pay for lost wages, HDECs sometimes required the limitation to be removed from the information sheet and “required” sponsors to fulfil their obligation to provide ACC-equivalent compensation.73 But, so long as researchers and sponsors are able to state in information sheets that the company agrees to provide compensation “in line with industry guidelines”, concessions extracted by HDECs might add to the moral pressure on sponsors to pay ACC-equivalent compensation, but they cannot make any apparent commitment legally enforceable pursuant to voluntary guidelines. Ironically, however well intentioned, such a statement may have the unintended consequence of compounding the misleading assurance in the template information sheet that “compensation would be available” with the
72 See for example Ethics Ref 13/NTA/219 “A study of how effective the experimental flu drug favipiravir is, in adults with flu” Northern A Minutes (10 December 2013) at 13; Ethics Ref: 14/NTA/207 “An investigation of Apremilast for Treatment of Subjects with Active Ulcerative Colitis” Northern A Minutes (9 December 2014) at 3.
73 See Ethics Ref 15/NTA/171 “A study of EDP-494 in healthy subjects and Hepatitis C patients” Northern A HDEC Minutes (10 November 2015) at 11; Ethics Ref 15/NTA/184 “LJPC-501 in Patients with Catecholamine-Resistant Hypotension” Northern A HDEC Minutes (10 November 2015) at 26; Ethics Ref 16/NTA/23 “ATHENA trial” Northern B HDEC Minutes (16 February 2016) at 24.
further suggestion, which is apparently not being honoured in practice, that it is of ACC-equivalent standard.
Similarly, after the difficulties faced by the injured participant in negotiating with the sponsor’s insurer in the CRYSTAL trial, the Northern A HDEC became concerned about the practice of insurance companies typically taking over the management of claims under the MNZ Guidelines on behalf of sponsors. This leaves the subject in an unequal fight with an insurer for compensation, given the power imbalance between injured subjects and insurance companies, without support from the sponsor. In December 2014 the Northern A HDEC’s Minutes record members’ agreement that a sponsor should assure the HDEC that participants would be adequately supported during any disputes with insurers in relation to a claim and that it is the sponsor’s obligation to satisfy the participant of this.74 It began to ask investigators to remind sponsors and record in its Minutes that, should there be a dispute about compensation payable, it must be resolved between the sponsor and the participant, not between the participant and the sponsor’s insurer.75 Again, HDECs can do no more than exhort sponsors to comply with this commitment; enforceability remains a problem.
3. OTHER DEFICIENCIES IN THE 2015 MNZ GUIDELINES
In addition to their legal unenforceability, there are other serious deficiencies with the MNZ Guidelines that leave participants financially exposed. In 1997 academic lawyer and HDEC chair Nicola Peart and academic philosopher and HDEC member Dr Andrew Moore provided a full description of these.76 Most persist in the current version of the MNZ Guidelines. Firstly, the “obligation” to pay compensation is not truly no fault, being limited to negligence by the company only.77 No or reduced compensation will be paid for injury resulting from: wrongdoing by third parties, such as the investigator; significant departures from the agreed protocol; or the contributory negligence of the subject.78 As they pointed out, it is particularly harsh to exclude injury arising from a significant departure from the protocol, because most subjects never see it, do not agree to
74 See Northern A HDEC Minutes (9 December 2014) “General Business” at 26.
75 See for example, Ethics Ref 15/NTA/217 “A study assessing the similarity of Avastin® and the trial drug BAT1706” Northern A HDEC Minutes (18 December 2015) at 16.
76 Nicola Peart and Andrew Moore “Compensation for injuries suffered by participants in commercially sponsored trials in New Zealand” (1997) 5 Med LR 1.
77 MNZ Guidelines on Clinical Trials Compensation for Injury resulting from Participation in an Industry-sponsored Clinical Trial (February 2015), cl 1.7.
78 MNZ Guidelines on Clinical Trials Compensation for Injury resulting from Participation in an Industry-sponsored Clinical Trial (February 2015), cl 3.4.
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it, and will not be aware of or have any control over any departures from it.79 In the event of wrongdoing, the subject is expected to turn to the third party for compensation,80 which would only be forthcoming if causative negligence by it could be established and it had funds to satisfy any award.81 A second deficiency is that the clause defining the nature of the injury required for compensation is vague (“only for more serious injury of an enduring and disabling character”) and excludes “temporary pain and discomfort or less serious or curable complaints”.82 As no ultimate decision-maker is specified in the event of dispute, presumably the company determines whether the injury is compensatable. The exclusion of curable complaints is of concern, since these can be serious and disabling so as to prevent working for a lengthy period, causing devastating financial loss in the meantime, yet ultimately prove to be curative (e.g. some cancers).
In terms of assessment of compensation, the clause in the MNZ Guidelines is extremely broadly drafted.83 No categories of financial loss, nor specific amounts of compensation are identified, unlike the heads of compensation for specific kinds of loss, to which actual amounts are assigned or the means of calculation mandated, in the Accident Compensation Act. Instead assessment is a matter for the company’s judgment, at least in the first instance. In 1997 Peart and Moore reported that “most companies will not compensate for loss of earnings or any other non-medical expenses, let alone for loss of earning capacity or for dependants. And some even limit compensation purely to medical expenses”84 and then only in relation to “physical,” and not “mental” injuries.85 The key amendment to the
79 Nicola Peart and Andrew Moore “Compensation for injuries suffered by participants in commercially sponsored trials in New Zealand” (1997) 5 Med LR 1 at 10.
80 An attempt was made by the Ministry of Health and HDEC representatives to secure RMI agreement to remove the exclusion of third party negligence (cl 3.4.2) so that participants would henceforth look to the company for compensation, rather than have to prove third party fault. The company would then decide whether to pursue the third party to recoup its loss. The RMI rejected its deletion in the 1997 version of the Guidelines, on the ground that companies could not be committed to accepting liability for events beyond their control, see letter dated 15 July 1997 RMI to Chair, Southern Regional HDEC.
81 Investigators are required to demonstrate, and HDECs to check, that the investigator has professional indemnity insurance.
82 MNZ Guidelines on Clinical Trials Compensation for Injury resulting from Participation in an Industry-sponsored Clinical Trial (February 2015), cl 1.4.
83 “The amount of compensation paid should be appropriate to the nature, severity and persistence of the injury” see MNZ Guidelines on Clinical Trials Compensation for Injury resulting from Participation in an Industry-sponsored Clinical Trial (February 2015), cl 4.1.
84 Nicola Peart and Andrew Moore “Compensation for injuries suffered by participants in commercially sponsored trials in New Zealand” (1997) 5 Med LR 1 at 12.
85 John Dawson and Nicola Peart The Law of Research: A Guide (University of Otago Press, Dunedin, 2002) at 192.
MNZ Guidelines since then, brought about by NEAC’s Ethical Guidelines for Intervention Studies in 2009, is this: “The amount of compensation ... should be no less than would be awarded for similar serious injuries by New Zealand’s accident compensation scheme.”86 Though NEAC considered this a significant victory at the time,87 little has apparently changed in response. A current example of a compensation arrangement restricted to medical expenses for physical injury only, which clearly does not satisfy the requirement of ACC-equivalence, is that in the Insulin Variant trial.88 It seems clear that the commitment to pay ACC-equivalent compensation, albeit morally binding only, is not often honoured by companies, despite some HDECs’ attempts to require that sponsors fulfil their “obligation” by itemising the heads of ACC compensation in information sheets.
There is also inconsistency in the MNZ Guidelines. On the one hand, they provide that the fact that injury was “foreseeable or predictable” or that the patient freely consented to participate should not exclude a patient from consideration for compensation. On the other hand, another clause provides that compensation can be abated or excluded in light of: the degree of probability that adverse reactions will occur, and any warnings given, as well as the seriousness of the disease being treated and the benefits and risks of established treatments relative to those of the trial medicine.89 This carves out an uncertain and potentially significant exclusion from compensation. The reasoning is that it is “reasonable that the patient accept” the risk of additional injury without compensation where, for example, they are already seriously ill, they have been told of the risk, it is likely to occur (“predictable”), or there are similar risks in established treatments. There are no equivalent exclusions to these under “treatment injury”, apart from the much narrower exclusion of personal injury that is “an ordinary consequence of treatment”, which is based on similar reasoning, discussed below.90
86 MNZ Guidelines on Clinical Trials Compensation for Injury resulting from Participation in an Industry-sponsored Clinical Trial (February 2015), cl 4.1.
87 The author was a member of NEAC in 2009 when the first edition of the Ethical Guidelines for Intervention Studies (Wellington: Ministry of Health, 2009) was issued.
88 Compensation is restricted to medical expenses for physical injury not covered by the subject’s medical insurance. Yet the Participant Information and Consent Form for the Insulin Variant trial (cited above in the text accompanying note 3) goes on to state: “Those [RMI] guidelines say that compensation should be no less than would be awarded under the accident compensation scheme.” While literally true, this statement is misleading in its suggestion that injured participants would receive ACC-equivalent compensation.
89 MNZ Guidelines on Clinical Trials Compensation for Injury resulting
from Participation in an Industry-sponsored Clinical Trial (February 2015),
cl 4.2.
90 Accident Compensation Act 2001, s 32(1)(c).
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Only injuries attributable to participation in the trial are compensatable under the MNZ Guidelines. This means those attributable to the medicine being trialled and any necessary interventions or procedures specified in the protocol.91 Proof of the causal link between injury and treatment given as part of the clinical trial is notoriously difficult, as described. The MNZ Guidelines specify a standard of the balance of probabilities, often an insurmountable barrier for patients to satisfy,92 as the injured subject’s experience in the insulin variant trial indicates. The MNZ Guidelines provide that where there is a difference of opinion as to whether the injury was attributable to inclusion of the patient in the trial, it will make available at its cost the opinion of an independent mediator, but that opinion is not, however, binding.93 This always leaves the sponsor with the option of declining the claim for want of proof of causation. No further process for resolving the dispute is indicated.
Injury caused by other licensed products given for the purpose of comparison with the trial product is excluded from compensation.94 As a result the company will not compensate for injuries to patients caused by the standard treatment being compared to the trial product. It can be hard even for an expert to be sure whether the trial product or standard treatment was the causative culprit.95 Despite earlier uncertainty as to whether injuries from the standard treatment were covered by the scheme,96 ACC has agreed that they are covered as “treatment
91 Clause 3.1 provides also that no compensation should be paid for the failure of a medicinal product to have its intended effect or to provide any other benefit to the patient, see MNZ Guidelines on Clinical Trials Compensation for Injury resulting from Participation in an Industry-sponsored Clinical Trial (February 2015).
92 Avilés, for example, argues for a presumption of causation that those injuries affecting the health of the subject during the trial and in the imminent period of time following its termination have been produced as a consequence of the trial. This presumption is required to protect the most vulnerable because proof of causation is particularly difficult in the clinical research context and requires sophisticated analysis, see Miguel Avilés “Compensation for research-related injuries in the European Union” (2014) 21 Eur J Health Law 473 at 483.
93 See MNZ Guidelines on Clinical Trials Compensation for Injury resulting from Participation in an Industry-sponsored Clinical Trial (February 2015), cl 1.2.
94 See MNZ Guidelines on Clinical Trials Compensation for Injury resulting from Participation in an Industry-sponsored Clinical Trial (February 2015), cl 3.2.
95 Especially in combination trials where standard treatment and the trial product are administered to the intervention arm. A combination trial is a trial in which at least two drugs are administered to a group of patients.
96 For a number of years after introduction of the interim RMI Guidelines in 1993 there was uncertainty as to whether ACC would cover these injuries either, leaving these patients without access to any compensation at all. ACC argued that once an HDEC had certified the trial as conducted principally for the benefit of the manufacturer or distributor of the medicine or item being trialled, the trial as a whole was so certified, so that any injuries
injury”, providing the claim meets its requirements. If the company maintains that the injury was caused by standard treatment and so not its responsibility, and the mediator’s opinion does not resolve the dispute, the onus falls on the patient to press their ACC claim.97 This situation also illustrates strikingly the arbitrariness in practice of having two separate compensation arrangements. Patients injured in the very same clinical trial randomly allocated to the standard treatment arm are comparatively much better off than those injured by the trial product, being fortunate that legally enforceable, certain, and more generous compensation under the ACC scheme is available to them. Subjects would have been unaware beforehand which treatment, standard or trial, they were receiving, and it is immaterial to them afterwards when seeking compensation for their injury whether they were injured by the standard or the trial treatment. The unequal treatment of such patients in this respect offends the principle of formal equality (“treating like cases as like”).
The MNZ Guidelines provide the bare minimum of detail about the claims process.98 No time limit within which the company’s decision must be made is prescribed. The pharmaceutical company is judge and jury in its own cause, since it, or its insurer, is the decision-maker of a claim to which it is also a party with a financial interest. If the company decides that no payment should be made, there is no appeal process to an independent decision-maker. Where the company concedes that a payment should be made but disputes the amount, the MNZ Guidelines “recommend that the company agree” to seek the opinion of an arbiter at the company’s cost, whose decision on the appropriate payment is to be binding. A binding decision of an arbiter, whom the company is not obliged to consult, in MNZ Guidelines to which the sponsor has no legal commitment seems a contradiction, unless this means binding on the claimant, but not on the company. Even so, there is no defensible reason why the process should be limited to disputes over the amount of compensation, and exclude those where the company decides that no payment at all should be made, in which the patient has the greater stake. The only other legal avenue is litigation. What would a court make of patient’s civil action for damages pursuant to non-binding MNZ
occurring in the trial were not covered by ACC. By 2003 ACC had agreed to cover injuries resulting from standard treatment, see John Dawson and Nicola Peart The Law of Research: A Guide (University of Otago Press, Dunedin, 2002) at 190.
97 See MNZ Guidelines on Clinical Trials Compensation for Injury resulting from Participation in an Industry-sponsored Clinical Trial (February 2015), cl 1.2.
98 Claims are made to the company via the investigator. The patient must authorise it to review medical records relevant to the claim. Thereafter the company shall consider the claim expeditiously, see MNZ Guidelines on Clinical Trials Compensation for Injury resulting from Participation in an Industry-sponsored Clinical Trial (February 2015), cl 5.1.
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Guidelines? Disregarding a possible estoppel claim, surely it would decline to adjudicate for want of a cause of action known to the law. An injured subject’s only remaining option at this point, which many would be reluctant to take, may be to go to the media, in the hope that damage to a company’s reputation may exert pressure on it to settle the claim. In summary, the MNZ Guidelines are heavily weighted in favour of the company at virtually every turn, perhaps unsurprisingly so, since they were developed by the pharmaceutical industry for its own use in a situation touching its financial interest.
4. WHAT ARE THE ALTERNATIVE RESPONSES AND OPTIONS TO ADDRESS THE FINANCIAL EXPOSURE OF SUBJECTS IN INDUSTRY TRIALS?
This Part examines available options for injured subjects and HDECs to respond to this unsatisfactory situation in commercially sponsored trials.
4.1 Contract and Equity.
Is there room for an injured participant to argue that the statements in the HDEC’s information sheet template (if used) create a legally enforceable obligation on a sponsor to pay no fault compensation, despite the “without legal commitment” wording of the Guidelines? It is possible to do no more here than sketch possible legal arguments available to an injured participant. In 1997 Professor Stephen Guest, a legal member of a UK ethics committee, considered the prospects of this argument succeeding to be poor:99
It would be difficult to establish a contract in the absence of an express agreement with an individual subject. Particularly it would be almost impossible to establish the necessary ‘contractual intention’ because of the ‘without legal commitment’ wording [of the ABPI Guidelines].
Certainly, courts have accepted that agreements expressly stated to be binding “in honour only” are not legally binding for lack of an intention to create legal relations.100 Nevertheless, it might be argued that a binding contract exists
99 Stephen Guest “Compensation for subjects of medical research: the moral rights of patients and the power of research ethics committees” (1997) 23 J Med Ethics 181 at 183. See also Sabina Gainotti and Carlo Petrini “Insurance policies for clinical trials in the United States and in some European Countries” (2010) 1 Journal of Clinical Research and Bioethics 101 at 105.
100 John Burrows, Jeremy Finn and Stephen Todd Law of Contract in New Zealand (5th ed, LexisNexis, Wellington, 2016) at [5.4].
between the sponsor, entered into by the researcher as its agent, and the potential participant, based on all of the terms in the information sheet and signed consent form, only one of which relates to compensation. The subject provides consideration by taking the relevant treatment(s) as instructed, submitting to the other procedures and interventions called for in the protocol, and submitting to the trial’s risks and burdens. The sponsor and research team agree (inter alia) to provide the treatment(s) and other interventions, as well as to monitor the subject and treat adverse reactions and injuries in accordance with acceptable professional standards. The sponsor would argue that the MNZ Guidelines are incorporated as a contractual document by reference to them in the information sheet, with the references in the Preamble and cl 1.1 to the “absence of legal commitment” operating as an exclusion clause. The key issue would be whether the sponsor has given the participant reasonably sufficient notice of the excluding term, given its serious adverse consequences for them.101 It is certainly arguable that, by not including notice of the MNZ Guidelines’ lack of legal force in the information sheet or providing subjects with copies of them and ensuring that subjects read and understand their effect, reasonable notice of the term has not been given, and the sponsor cannot therefore rely on the clauses in the MNZ Guidelines as excluding a legal commitment to pay compensation. These principles apply, however, only in the case of unsigned documents, and the subject has signed the Information Sheet and Consent Form. The orthodox principle then applies that people are bound by writing to that which they have put their signature, irrespective of evidence of inadequate notice of the exclusion clause.102 But this principle does not apply in cases of fraud or misrepresentation. Whether or not the document has been signed, an exclusion clause will not operate if its effect has been misrepresented.103 As argued above and next, the standard text in the information sheet template, as well as the statements in the information sheets of the two trials quoted above, misrepresents the true position by suggesting that legally enforceable compensation (and in the case of the template, explicitly stated to be enforceable by a court) would be in place to protect subjects if something was to go wrong.
101 See Nalder & Biddle (Nelson) Ltd v C & F Fishing Ltd [2007] 1 NALR 721 (CA). If an exclusion clause is unusual, unexpected, or of especially onerous effect, a higher standard of notice may be required. See generally, John Burrows, Jeremy Finn and Stephen Todd Law of Contract in New Zealand (5th ed, LexisNexis, Wellington, 2016) at [7.2.2(b)].
102 L’Estrange v Graucob [1934] 2 KB 394 at 403; Toll (FGCT) Pty Ltd v Alphapharm Pty Ltd [2004] HCA 52; (2005) 219 CLR 165 (HCA).
103 Curtis Chemical Cleaning & Dyeing Co [1951] 1 KB 805. See generally, John Burrows, Jeremy Finn and Stephen Todd Law of Contract in New Zealand (5th ed, LexisNexis, Wellington, 2016) at [7.2.3], [7.2.4].
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Alternatively, another avenue might be to plead promissory or equitable estoppel, based on representations made in the HDEC template information sheet (if used). Unconscionability is the underpinning rationale of the doctrine: “equitable estoppel is aimed at preventing unconscionable conduct and seeks to prevent detriment to the promisee.” 104 Its four elements are: (1) A belief or expectation created or encouraged by the defendant; (2) To the extent that an express representation is relied upon, it is clearly and unequivocally expressed; (3) Reasonable reliance on the representation by the plaintiff to its detriment; and (4) It would be unconscionable for the defendant to depart from the belief or expectation.105 An injured participant’s theory of liability would be broadly as follows. Statements in the information sheet (“compensation would be available from the study’s sponsor in line with industry guidelines”: “you would be able to take action through the courts if you disagreed with the amount of compensation provided”) amounted to clear representations to potential participants, which induced them to assume that they would be financially protected by the availability of compensation enforceable by a court from the sponsor pursuant to industry guidelines in the event of injury. This is not a case of mere silence as to the sponsor’s lack of legal commitment. The combination of the failure to disclose that fact, together with the actual statements that compensation will be provided in accordance with the RMI Guidelines in the information sheet, amount to a misrepresentation that injured participants would have a legally enforceable right to compensation under the MNZ Guidelines.106 Detrimental reliance is present, in that, relying on these representations, participants agreed to participate in the study, as a result of which the plaintiff suffered injury for which s/he only then learns that s/he in fact has no legal right to compensation. A reasonable participant, considering enrolment in a study and consulting their own interest, would be less inclined to participate, knowing that the compensation arrangement lacked legal force. The fact that this is not clearly stated in the information sheet suggests that sponsors are well aware of its likely detrimental effect on recruitment.
Is it reasonable for subjects to rely on representations in the information sheet that legally enforceable compensation would be available, without asking for and
104 See National Westminster Finance Ltd v National Bank of NZ [1996] 1 NZLR 548 at 549 (CA, Tipping J). See generally, Waltons Stores (Interstate) Ltd v Maher [1988] 76 ALR 513 (HCA); Commonwealth v Verwayen (1990) 64 ALJR 540 (HCA); John Burrows, Jeremy Finn and Stephen Todd Law of Contract in New Zealand (5th ed, LexisNexis, Wellington, 2016) at [4.7].
105 Krukzeimer v Hanover Finance Ltd [2010] NZAR 3017 (CA) at [38]; Wilson Parking New Zealand Ltd v Fanshawe [2014] NZCA 406 at [44]; John Burrows, Jeremy Finn and Stephen
Todd Law of Contract in New Zealand (5th ed, LexisNexis, Wellington, 2016) at [4.7.3].
106 See generally, John Burrows, Jeremy Finn and Stephen Todd Law of Contract in New Zealand (5th ed, LexisNexis, Wellington, 2016) at [11.2.1(e)].
reading the MNZ Guidelines? Most do, it seems. The lack of a sponsor’s legal commitment to pay compensation for injury is highly pertinent information that a reasonable subject would need for informed consent purposes, in terms of Right 6 of the Code.107 That being the case, they are surely entitled to rely on the information that is provided, having been vetted by the HDEC prior to approval, as being comprehensive and accurate. Why would they suspect the contrary? And, in any event, even had they read the MNZ Guidelines, would they have been any the wiser? If the template’s statement about compensation is evidence of their understanding, the Ministry of Health and HDECs have themselves misunderstood subjects’ legal position. Surely the onus is on the investigator and sponsor, who have a duty to ensure that subjects give a properly informed consent to participation, to alert potential subjects to the voluntary nature of its compensation obligations, by inserting a simple, explicit warning to this effect in the information sheet. Having chosen not to do so, the argument is that it would be unconscionable for the sponsor to be able to recant on the representation as to the availability of compensation enforceable by the courts, by relying on the “without legal commitment” statement in MNZ Guidelines. The sponsor should be estopped from doing so; equity will intervene to avoid the detriment to the injured subject, by obliging the sponsor to pay compensation in accordance with the MNZ Guidelines as if they were legally binding.
4.2 HDECs insist on Proper Information for Informed Consent.
While laudable, HDECs’ attempts to wrench commitments out of sponsors are ultimately of limited utility, since any commitments are not binding if the research is approved subject to the MNZ Guidelines. At the least, therefore, if HDECs continue to approve research on the basis of the compensation arrangements in the MNZ Guidelines, they must insist that sponsors spell out in the clearest terms, in information sheets, a subject’s lack of a legal right to no fault compensation, so that the issue becomes clearly part of the research subject’s overall consent. Nothing short of the following would seem sufficient to satisfy the requirements of participant informed consent:
If you were injured as a result of treatment given in this study, you won’t be eligible for compensation from ACC. In addition, you would have no legal entitlement to compensation from the study sponsor
107 Health and Disability Commissioner (Code of Health and Disability Services Consumers’ Rights) Regulations 1996, Right 6(2) states: “Before making a choice or giving consent, every consumer has the right to the information that a reasonable consumer, in that consumer’s circumstances, needs to make an informed choice or give informed consent.”
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[x] or investigator(s) [y]. Any compensation paid to you would be paid at the sole discretion of the sponsor [x], in an amount also at its discretion, pursuant to the [MNZ 2015 Guidelines], which are not legally binding on [x]. A copy of these Guidelines is attached to this [PIS]. You are strongly advised to read them and ask any questions you have of the investigator(s) [y] if you are unsure about what they mean for you. You are also advised strongly to seek independent advice about their consequences for you.
You would be able to take action through the courts for compensation only if you were able to prove negligence on behalf of the sponsor or investigator(s), which is unlikely, and that the study medication caused your injury. It is very difficult to prove both of these matters. A court action is expensive and the process is lengthy and stressful, and you would require legal representation.
4.3 HDECs Refuse Ethics Approval unless Compensation Arrangements are Legally Enforceable; NEAC assumes Responsibility for Developing Guidelines that Secure Legally Enforceable Contractual Rights to Adequate ACC-Equivalent Compensation.
A stronger response might be for HDECs to refuse ethics approval for clinical research in the absence of a legally enforceable, no fault compensation arrangement put in place by the sponsor. In 1997 Guest noted that, since research cannot proceed without ethics approval, it was within the power of ethics committees to make its consent to research conditional upon adequate compensation arrangements being put in place. He advocated that all ethics committees lobby the ABPI for its patient guidelines to be made identical to its healthy volunteer guidelines i.e. legally enforceable by subjects, and that “LRECs [Local Research Ethics Committees] should be fully prepared, where risks are more than negligible, to refuse consent when legally enforceable no-fault compensation is lacking.”108
This advice remains just as apposite for a New Zealand HDEC today, especially for participants in Phase I studies. HDECs’ primary duty is to protect participants in clinical research.109 NEAC has imposed a duty on them to check the availability
108 Stephen Guest “Compensation for subjects of medical research: the moral rights of patients and the power of research ethics committees” (1997) 23 Journal of Med Ethics 181 at 184.
109 Regrettably, New Zealand HDECs lack a statutory basis, but are stated to have a dual function: to protect the interests of research participants, and to allow ethically sound research that will secure benefits. Research that does not secure the availability of ACC-equivalent compensation in accordance with NEAC’s ethical requirement cannot be considered “ethically sound”.
of ACC-equivalent compensation. The Standard Operating Procedures (SOPs) for HDECs also acknowledge the role of HDECs of checking that arrangements are in place so that “compensation would be available to at least ACC-equivalent standard”.110 Arguably, compensation is only “available” if it is legally enforceable. Thus HDECs have a mandate to require companies to enter into a legally enforceable arrangement to pay ACC-equivalent compensation as a condition of ethics approval. As indicated above, this is how government officials have been expecting HDECs to act all along, as indicated by their statement that HDECs “should not be approving research unless satisfied appropriate arrangements for injury have been made.”111
HDECs are instructed by the SOPs to accept copies of evidence of appropriate professional indemnity in the case of the Chief Investigator, and evidence of the insurance in place for the study (for example, a certificate of insurance) in the case of the sponsor, as sufficient evidence of the availability of ACC-equivalent compensation.112 This is problematic, since checking companies’ ability to honour any liability to pay compensation is only part of the responsibility of ensuring the availability of ACC-equivalent compensation. Insurance merely evidences the sponsor’s ability to pay for a pre-existing liability and has no effect on the existence or otherwise of that liability. Indeed, it is hard to understand quite how any legal liability by the insurer to indemnify the sponsor under the insurance contract arises in the absence of any legal commitment on the sponsor’s behalf to compensate the subject under the MNZ Guidelines in the first place. Be that as it may, HDECs are instructed to interpret ACC-equivalence in terms of parity of entitlements available,113 and so should be checking compensation availability under the MNZ Guidelines compared to what is available under the ACC regime, in order to discharge its responsibility. An HDEC could justifiably conclude that a statement by a researcher that compensation would be available “in line with industry guidelines” does not amount to sufficient evidence of the availability of ACC-equivalent compensation, despite evidence of insurance. Unsatisfied as to its availability, an HDEC could justifiably refuse ethics approval.
110 See Standard Operating Procedures for Health and Disability Ethics Committees (version 2, 2014) at [147].
111 ACC and Ministry of Business, Innovation and Employment, Clinical trials and ACC cover — advice provided to Minister for ACC’s office at 3 (released under OIA).
112 See Standard Operating Procedures for Health and Disability Ethics Committees (version 2, 2014) at [149]-[151].
113 See Standard Operating Procedures for Health and Disability Ethics Committees (version 2, 2014) at [149].
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This approach would be most effective if the Minister of Health and the Ministry supported HDECs, by making it clear to industry that Government expects sponsors to enter into a legally binding obligation with all participants in industry trials to pay ACC-equivalent compensation. This would equate participants in Phase I trials with their UK counterparts and extend the protection to patient-volunteers in later stage trials. In view of the numerous other problems inherent in the MNZ Guidelines, Government should require the development of a new standard, legally enforceable contract between sponsors and subjects, setting out sponsors’ legal obligations to pay clear and specific ACC-equivalent compensation, and require its use instead of industry-drafted guidelines which are slanted in favour of protecting the interests of the industry. Given its expressed concerns for the plight of participants, NEAC would be ideally placed to lead development of this document after consultation with patients and patient groups, researchers, and industry. HDECs would then check the sponsor’s use of this contract as a condition of ethics approval.
4.4 Repeal of s 32(6) of the Accident Compensation Act.
A fourth response is the repeal of the exclusion in s 32(6) of the Accident Compensation Act 2001 of commercially sponsored trials from ACC cover so that all personal injury suffered by a person as a result of treatment given as part of a clinical trial is covered by the scheme. Once injured, it is immaterial to participants whether they suffered injury in a commercially sponsored or a non-industry trial. Their interest lies in an efficient and independent process to provide fair, no fault compensation. Why should people surrender ACC cover just because they agree to participate in an industry-funded, as opposed to a publicly-funded trial? From the injured participants’ perspective, access to compensation is overwhelmingly superior under the accident compensation scheme than pursuant to the MNZ Guidelines. By excluding claimants injured in industry-sponsored trials from ACC cover and access to entitlements, they are treated less favourably than participants in all other clinical research in New Zealand.
ACC cover and entitlements are determined by the provisions of the Act, which are generally clearer and more precise in comparison to the broad language of the MNZ Guidelines. The criteria for “treatment injury” are significantly more liberal than previously for “medical misadventure”. “Treatment injury” is no longer dependent on proof of the negligence of a registered health professional or organisation, as formerly with cover for “medical error”. The claimant must establish that s/he suffered personal injury caused by treatment given by or at the direction of a registered health professional, or treatment sought from (but
not given or not given in a timely manner by) a registered health professional.114 There is no exclusion for less serious injuries. Proof of the causal link between treatment and personal injury is also required for ACC cover,115 but there is judicial patient-friendly interpretation of the causation requirement under the Act in recognition of the difficulty of proof for claimants.116 And if all injuries arising from participation in clinical trials were covered by the scheme, the difficulty of participants being caught in a dispute between the company and ACC as to which medicine, standard or trial, caused the injury, would fall away. Given that patients suffering injury caused by medical treatment generally, as well as participants injured in non-industry clinical trials and those injured as a result of taking the standard medication for comparison purposes in an industry trial, all have access to ACC cover and compensation, subjects suffering injury attributable to participation in a commercially sponsored trial are looking an increasingly small, anomalous group subject to unfair and discriminatory treatment in this respect.
The main exclusion from “treatment injury” is personal injury which is “a necessary part, or ordinary consequence, of the treatment”.117 “Necessary” injuries in treatment, such as a surgical incision, are relatively unproblematic, but the exclusion of “ordinary consequences of the treatment” requiring an individualised determination for each patient and each treatment, does result in significant uncertainty.118 But a patient could reasonably expect to be informed about a risk considered “an ordinary consequence” of a trial product beforehand, and if not,
114 Accident Compensation Act 2001, s 32(1)(a) and (b). There is one kind of injury which is not covered by ACC but which may attract compensation under the Guidelines if the sponsor chose to honour them viz. psychological injury unaccompanied by any physical injury suffered by a person. The latter is not covered by the accident compensation scheme by virtue of the definition of “personal injury” in s 26(1)(c). An injured subject in a non-industry trial could sue for it if able to establish the elements of a legal claim.
115 Reinforced by the exclusion of personal injury that is wholly or substantially caused by a person’s underlying health condition, see Accident Compensation Act 2001, s 32(2)(a). This maintains the fundamental, though controversial, distinction at the basis of the scheme since its inception, namely, the distinction between accidental injury and personal injury caused by disease or infection, see s 26(2).
116 See Accident Compensation Corporation v Ambros [2007] NZCA 304; [2008] 1 NZLR 340
(CA) (courts can draw an inference of causation in the presence of some evidence
of the causal link, despite that evidence not rising
to the balance of
probabilities). It is most unlikely that a pharmaceutical company would agree to
take such an approach. Given that
causation in clinical research often requires
expert analysis, it is useful that ACC can also seek independent clinical advice
to
assist it in determining a claim, see Accident Compensation Act 2001, s
62.
117 See Accident Compensation Act 2001, s 32(1)(c).
118 Compare White v Accident Compensation Corporation [2013] NZACC 189 (DC) and Porter v Accident Compensation Corporation [2010] NZACC 104 (DC) (opposite outcomes based on virtually the same clinical evidence of incidence of the risk).
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may well be covered in any event under the alternative ground of injury caused by failure to obtain informed consent.119
If eligible, claimants are legally entitled to the compensation and rehabilitation benefits specified in the Act.120 The principal one is weekly compensation, fixed at 80 per cent of loss of earnings at the time of injury for the whole period of incapacity.121 It includes limited compensation for loss of potential earning capacity.122 ACC is liable to pay for rehabilitation costs, which comprise a contribution to treatment costs, social rehabilitation,123 and vocational rehabilitation to assist return to employment. There is a modest lump-sum entitlement for permanent physical injury,124 although, controversially, none for pain and suffering and loss of amenities since abolition in 1992. Where the injury is fatal, there are funeral and survivor’s grants, and most importantly, weekly compensation for the spouse or partner, children, and other dependents where the deceased was an earner.125
The statutory process for deciding claims and settling disputes is also vastly superior, especially in terms of fairness and independence. ACC is not commercially motivated by profit126 and has statutory duties to decide claims on reasonable grounds, in a timely manner, and in accordance with the statutory criteria.127 It must assist claimants to establish cover and access entitlements.128 Time limits within which it must decide claims are specified, of which failure to meet may result in the claimant being deemed to have cover.129 Any decision of ACC’s on
119 See Accident Compensation Act 2001, s 33(1)(e).
120 See generally
Accident Compensation Act 2001, ss 67, 68, 69, 165 and the First
Schedule.
121 The ACC scheme is particularly disadvantageous for
non-earners.
122 Accident Compensation Act 2001, First Schedule, cl 47.
123 These can be significant and include disability aids and equipment (such as wheelchairs), attendant care, home help, educational support, home modifications, and providing or contributing to the costs of transport which can include modifying or purchasing a vehicle.
124 The maximum lump sum for 100 per cent whole-person impairment was set in
regulations at NZ$100,000 but is indexed. Lesser percentages
of whole-person
impairment are equated to fixed sums on a regressive basis. See the Injury
Prevention, Rehabilitation and Compensation
(Lump Sum and Independence
Allowance) Regulations 2002 (SR 2002/22), which provide a scale of lump
sums.
125 Accident Compensation Act 2001, First Schedule, cls 66, 70, 71.
126 For the balance between its social and financial objectives, see Accident Compensation Act 2001, s 262(3): it must seek to minimise the overall incidence and costs to the community of personal injury, while ensuring fair rehabilitation and compensation in a manner that is cost-effective and promotes administrative efficiency.
127 See Accident Compensation Act 2001, s 54. See also the claims process
under the ACC Code of Claimants Rights in Part 3 of the
Act.
128 See Accident
Compensation Act 2001, s 50.
129 See Accident Compensation Act 2001, s
58.
a claim, including an “unreasonable delay” in processing a claim, is amenable to review by an independent reviewer, followed by a right of general appeal to the District Court, and two levels of appeal with leave on questions of law thereafter.
Compensation is not, of course, the only objective of an accident compensation system, whether tort law or ACC. There are also legitimate societal goals of corrective justice, including accountability130 and deterrence/accident prevention. There is a valid concern that repeal of s 32(6), with the consequential loss by participants of their civil damages action in return for ACC “treatment injury” cover,131 will blunt companies’ incentives to consider carefully what research to undertake and to manage and minimise its associated risks since they are not required to internalise the true costs of participant injuries in their risk-benefit calculus, but are instead permitted to shift the costs of injuries in their trials on to ACC. Will companies see New Zealand as an attractive place to carry out riskier research, because the costs of injuries are underwritten by ACC, as proponents of the 1992 exclusion of industry trials feared? And, if not required to contribute to the costs of funding the scheme, companies are getting a free ride at the expense of those that are. If ACC cover were extended to industry trials, the legislation could be used to ensure that companies meet the additional cost to ACC of entitlements for injury resulting from treatment given in commercially sponsored trials. The obvious means would be by charging companies levies.132 Setting levy rates to reflect the claims experience of the company (“experience-rating”) would achieve a greater degree of deterrence.133 ACC does not systematically collect information on cost-of-claims from clinical trials; this may indicate that the costs to ACC arising from clinical trials are not significant.134 NEAC suggested that, as an alternative to
130 The corrective justice and accountability function in the health sector
is served in New Zealand by the complaints regime under
the jurisdiction of the
Health and Disability Commissioner as well as by disciplinary proceedings. This
paper will not consider the
extent to which injured participants’
interests in corrective justice are met, but see generally Joanna Manning
“New
Zealand’s remedial response to adverse events in
healthcare” (2008) 16 Torts Law Journal 120.
131 Accident Compensation
Act 2001, s 317(1).
132 ACC has the ability to levy registered health professionals and organisations that provide treatment or to prescribe classes of such organisations, in order to fund the Treatment Injury Account, though for unexplained reasons it has never done so, see s 228, Accident Compensation Act 2001.
133 Experience rating and the adjustment of an individual employer’s rate on that basis (s 175) are explicitly permitted for the Work Account only at present (s 169(2)). The Act would need amendment to permit this for the Treatment Injury Account.
134 NEAC NEAC Analysis — Clinical trials (14 September 2010) at [56]. ACC has made cover decisions in less than 4 claims relating to clinical trials under s 32(4) since “treatment injury” came into force in 2005. 100% of claims were declined in 2006 and 100% were accepted in 2015, see from letter ACC Treatment Injury Centre to author, May 2015.
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repeal of s 32, industry should be required to purchase ACC cover for the clinical trials it conducts in New Zealand through payment of a levy.135 Although certain people, such as the self-employed and earners who have ceased employment, are eligible to purchase the right to receive weekly compensation, for example,136 the Act does not at present allow health professionals or organisations to purchase ACC cover for patients or trial participants in the Treatment Injury Account and would require amendment to permit this. A further possibility is that, if ACC entitlements have been paid to injured participants in a commercially sponsored trial, ACC could be given a statutory right of subrogation to pursue any claim the subject may have had in negligence against the sponsor.137 The purpose would be to promote effective deterrence so that companies would be incentivised to maximise the safety of their trials by the prospect of a civil action brought against it by ACC. ACC would have a discretion to determine which claims it chose to pursue, such as those where its costs were particularly high or where the sponsor’s conduct was grossly negligent. There seems, however, no principled reason to confine ACC’s ability to chase risk creators in this respect to the sponsors of industry clinical trials. For example, the Pike River tragedy might be an example of a case where such a potential might have provided a means to incentivise Pike River Coal Ltd’s board and management to increase the priority given to the health and safety risks to the miners over its overriding focus on meeting production targets and earning revenue.138 Variations of this suggestion were made in the early days of the ACC scheme139 and may merit revisiting.
CONCLUSION
Nearly forty years ago the Pearson Commission said of healthy and patient volunteers for medical research:140
135 NEAC Advice to Associate Minister of Health on Compensation for
Treatment Injury in Clinical Trials Report No 20141482 (21 November 2014) at
[19(b)].
136 Accident Compensation Act 2001, ss 208 and 223.
137 For subrogation, see generally, John Birds, Ben Lynch and Simon Milnes
MacGillivray on Insurance Law (12th ed, Sweet
& Maxwell, London, 2012) ch 23.
138 See Royal Commission on the Pike
River Coal Mine Tragedy (October 2012) vols 1 and 2.
139 Richard Miller “The Future of New Zealand’s Accident Compensation Scheme” (1989) 11 U Haw L Rev 1; Jeffrey O’Connell, Craig Brown and Margaret Vennell “Reforming New Zealand’s Reform: Accident Compensation Revisited” [1988] NZLJ 399.
140 Royal Commission on Civil Liability and Compensation for Personal Injury: Report (vol 1, Cmnd 7054-I, 1978) 287.
We think that it is wrong that a person who exposes himself to some medical risk in the interests of the community should have to rely on ex gratia compensation in the event of injury.
Yet that is precisely the position that New Zealand subjects in commercially sponsored trials are in today, belatedly discovered in the event that they are injured as a result of participating. As is well known, the Pearson Commission’s recommendation that they should have a cause of action based on strict liability against the authority to whom s/he consented to make themselves available, never came to pass. It took the view then, as have also many other bioethicists and national commissions before and since, that society has a moral responsibility to compensate participants in clinical research for their injuries and that no fault is the best ethical response because of the special difficulties for subjects in establishing the preconditions of negligence liability. Prior to 1992 all injured participants were covered by the no fault compensation scheme, but in 1992, Government put in place different arrangements depending on the nature of the trial in question. Participants injured in commercially sponsored trials were excluded from ACC cover and were required to turn to investigators and sponsors for compensation in the event of injury.
This has proved disastrous, the key reason being that the compensation arrangement put in place with the Government’s blessing for injuries in commercially sponsored trials, which has been the same ever since, was not legally enforceable by participants. Thus, by agreeing to participate in such a trial, a subject forfeits ACC cover and access to statutorily guaranteed compensation, leaving them financially exposed in the event of injury. Yet almost all will be entirely unaware of this unless and until they are injured and seek compensation. This is because information sheets given to participants are silent about the fact that no legally enforceable arrangement is in place; indeed information sheets misinform subjects by suggesting that participants would have a legal claim for compensation under the industry guidelines enforceable by a court. As a result, participants agree to participate in commercially sponsored trials without giving fully informed consent to do so.
Not only do sponsors have no legal commitment to pay compensation, it is not being provided in accordance with NEAC’s ethical requirement of ACC-equivalence. And, faced with a claim by a subject under the MNZ Guidelines, sponsors tend to delegate responsibility for its settlement to its insurer, leaving injured subjects to negotiate very much on the back foot with a large insurance company, since any payment is voluntary. HDECs, taking seriously their primary duty to protect patients, have attempted to extract concessions from sponsors to honour moral obligation under the MNZ Guidelines to pay ACC-
COMPENSATION FOR RESEARCH-RELATED INJURY
IN
COMMERCIALLY-SPONSORED CLINICAL TRIALS IN NEW ZEALAND
equivalent compensation in a timely manner and to support subjects against the insurer during the claims process, but these are of limited utility because they are unenforceable. In addition, the MNZ Guidelines are vaguely drafted, with far-reaching exclusions and no claims and independent appeal processes detailed. Thus, injured participants are greatly disadvantaged in terms of secure access to appropriate, legally enforceable levels of no fault compensation, compared to those in non-industry trials. This is unfair and discriminatory since, once injured, the nature of the trial in which injury occurred is entirely irrelevant to the injured subject.
As far as I am aware, no injured participant in New Zealand or the UK has challenged the lack of legal enforceability of the Guidelines, on the basis of a contract between it and the sponsor, a term of which is that the latter pay no fault compensation under the MNZ Guidelines and that the “without commitment” clause is an exclusion clause is not incorporated into the contract, either for want of adequate notice to the subject of its existence, given its disastrous effect on a subject’s legal right to compensation, or because the fact of MNZ Guidelines’ unenforceability was misrepresented. Alternatively, there is potential to argue that a court could estop a sponsor from relying on the terms stating the absence of a legal commitment to pay compensation in the MNZ Guidelines, because it would be unconscionable to permit it to do so, given its decision not to draw this key provision to the subject’s notice and in the face of misleading representations in the information sheet.
Subjects are clearly not giving an informed consent to participation, based on the information provided in the HDEC’s template information sheet. HDECs must insist on proper information for informed consent purposes. In particular, the voluntary nature of the commitment under the MNZ Guidelines is a key fact which must be spelt out in information sheets and its implications for subjects explicitly drawn to their attention. If Government does not act to repeal s 32(6), it is recommended that HDECs seriously consider exercising their power to refuse ethical approval for studies when legally enforceable no-fault compensation is lacking, particularly for Phase I trials, which are riskier and have no possibility of compensating participant benefit. It is striking that UK participants in Phase I trials have the benefit of a legally enforceable contract with sponsors for the payment of no fault compensation, whereas, for unexplained reasons, New Zealand subjects in Phase I trials are subject to the same non-enforceable arrangement as patient-volunteers in Phase II and III trials.
But the best response, it is submitted, is repeal of the exclusion in s 32(6) of commercially sponsored trials from ACC cover, so that all personal injury suffered by a person as a result of treatment given as part of a clinical trial is covered by
the ACC scheme. The exclusion in s 32(6) of this small group of injured subjects in the treatment context is looking increasingly anomalous in light of the broad nature of cover for “treatment injury”, the fact that some subjects injured by the standard treatment in the same trial may have ACC cover, and that subjects in non-industry trials are covered. Once injured, the nature of the clinical trial in which they are injured, commercially sponsored or otherwise, is immaterial to participants. Their interest lies in an efficient and independent process to provide them with access to fair, legally enforceable, no fault compensation. From the injured participants’ perspective, access to compensation is overwhelmingly superior under the accident compensation scheme than pursuant to the MNZ Guidelines. It is argued that exclusion of participants injured by treatment given in commercially sponsored trials from cover and access to accident compensation is indefensible, as being anomalous, unfair and discriminatory. The ability of pharmaceutical companies to externalise their costs of compensating injuries in their trials and shift it on to ACC is certainly a valid public policy concern relating to deterrence and fairness considerations, but there are options to address this by other means, while ensuring that injured participants have the security of legally guaranteed access to fair and appropriate no fault compensation.
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URL: http://www.nzlii.org/nz/journals/OtaLawFS/2016/29.html