In the media: VAD in Victoria; the thalidomide assistance scheme; sexual misconduct reforms in health care

This post is just a brief discussion of three media contributions I have made in the last few months.

Interview on SIX News about Victorian VAD laws

I was interviewed in December last year for the Six News Australia program Between Parkes Place and Capital Hill about a judgment of November 2023, delivered by Abraham J as a single judge of the Federal Court of Australia. The judgment concerned the validity and operation of certain provisions of the Victorian euthanasia law — the Voluntary Assisted Dying Act 2017 (Vic) (VAD Act).

That decision of Abraham J, in the case of Carr v Attorney-General (Cth) [2023] FCA 1500 (30 November 2023), found that certain sections of the VAD Act (s 57(a); and ss 19(1)(d)–(e) and 28(1)(d)–(e)) were inoperative because they authorised a form of assisting suicide that was inconsistent with sections of the Commonwealth Criminal Code Act 1995 (Cth) — namely, ss 474.29A and 474.29B. Those criminal provisions, which were inserted into the Code in 2005 by the Howard government in the context of an earlier stage of the euthanasia debate, made aiding and abetting suicide by a carriage service a criminal offence. See, eg, section 474.29A(1) below (noting that the many subsections that follow sub (1) are omitted here):

It was unsurprising, I guess, in view of the legislative history of the Code provisions that, on a purposive analysis, Abraham J would find that the criminal Code was intended to criminalise the very thing authorised by the Victorian VAD Act.

The implications for the applicant doctor in this case, and for the operation of the VAD Act in Victoria, were considerable. That’s no surprise, however, as this was really a test case to determine a question of law: namely, whether a doctor discussing assisted dying with a patient over the phone would be prosecutable under the Cth criminal law. In other words, the doctor-applicant here saw his and his peers’ exposure to criminal liability as a possibility and was proved correct in going to the FCA to ensure that he would (or would not) be so exposed if he were to discuss suicide with any of his relevant patients under the Victorian law.

The interview is about 30 minutes’ long, and I thank the presenters for their detailed discussion. Oh — and one last note. I was alerted just yesterday that Kate Chaney MP has moved a Bill — which is here — that would amend the Criminal Code so as to make the Victorian law operative again.

Comments on the thalidomide inquiry and the federal government’s response

Also in December, my brief comments appeared in a short news story on thalidomide, which was published in the wake of a report published by the Senate Community Affairs References Committee about thalidomide, titled Support for Australia’s thalidomide survivors, and following the apology in Parliament by the Prime Minister to those who survived thalidomide and their families for the trauma and harms caused them in the 1960s.

There is a lot to say about the Australian thalidomide episode; however, what is unusual about the Senate Report is its discussion of and request for legal advice received by Australian MPs regarding the question of the Commonwealth’s liability or ‘obligations’ after it permitted thalidomide to be supplied in the Australian therapeutic goods market. Ultimately, the Report recommended that the legal advice be published to the public. However, that recommendation was not accepted by the government; it was merely noted, with no reasons or any response.

As the Senate report states (footnotes removed):

2.87. Early in the inquiry the committee was advised that the former Minister for Health, the Hon. Sussan Ley MP, commissioned advice from Maddocks Lawyers about Australia’s obligations to its thalidomide survivors.

2.88. On 19 June 2018, the Senate agreed that a copy of the document should be provided to the Senate by 20 June 2018. On 16 August 2018, Senator the Hon. Bridget McKenzie, representing the Minister for Health in the Senate, made a public interest immunity claim over the document. Senator McKenzie’s public interest immunity claim was based on the fact that the document was legal advice to government:

It has been the long-standing practice of successive Australian Governments to not disclose privileged legal advice, including advice that canvasses possible constitutional issues.

2.89 In the interim report the committee requested that a copy of the advice be
made available to the committee to help it to understand the options available
to the Australian Government.

2.90 The Maddocks Lawyers’ advice was not made available to the committee and
the committee was unable to verify or consider the contents of the advice. This
is important as the advice could have provided the committee with a better
understanding of the legal context in which the Australian Government is
being asked to respond to the Thalidomide Group Australia’s requests. The
advice could have also provided the committee with important information
regarding the current options available to the Australian Government for
supporting thalidomide survivors.

2.91 Instead, the only evidence the committee has about the advice comes to it
indirectly. The committee received some evidence that a ministerial adviser
revealed some of the content of that advice to the Director of the Thalidomide
Group Australia, Ms Lisa McManus. According to Ms McManus, the adviser
provided her with the following information about the advice:

– the advice is 23 pages long;
– it provided five possible options;
– one of the options was to ‘do nothing’; and
– it concluded that the Australian Government had no legal obligation, but
that the Australian Government has a ‘moral responsibility’ to assist
thalidomide survivors.

Committee view
2.92. The committee considers that Australian governments have a moral obligation
to Australia’s thalidomide survivors. The committee notes that both the
Australian Government and the state governments failed to monitor drug
safety at a time when other governments around the world did so. Documents
provided to the committee demonstrate that the Australian Government was
aware that more could be done to safeguard public health from dangerous
drugs. The committee notes that the formation of the Therapeutic Goods
Administration was a direct result of the thalidomide disaster and notes
evidence to the inquiry that suggests such a body could have been, and should
have been, established earlier.

Parl Info

Obviously, whether the Maddocks advice might have suggested or explored any cause of action against the Commonwealth for historical negligence is of immense interest to victims (and to a lesser extent legal scholars). It does seem to me that there would not be very high prospects of a case on today’s law. However, if the Maddocks advice included five possible courses of action, one of which was ‘do nothing,’ what were the others? Are any of those options not canvassed by the Senate Committee?

What really strikes me as difficult about this issue is that the Committee was not itself able to review the advice, in circumstances where one might expect that Senators, as sworn officers of the Commonwealth, might be entrusted with such documents. After all, the lawyers who wrote the advice, while also bound by legal professional privilege, are not sworn officer of the Commonwealth. But I digress. It may be left to negligence scholars such as myself to guess and theorise about what liability might, on a given historical account, be affixed to the Commonwealth — if any.

Sexual misconduct reforms to health practitioner law

Proposed reforms to the Health Practitioner Regulation National Law, or National Law, have been circulated for consultation recently. The National Law is an Act separately enacted in most of the different states as part of a national scheme for regulating health practitioners called the National Registration and Accreditation Scheme, or NRAS. Technically, the NRAS is designed as an applied laws scheme, because the template is a Queensland law that then gets ‘applied’ in other jurisdictions. But because not every state applies the Queensland law (NSW enacts the law itself), it’s actually probably best described as a ‘combination scheme.’ In any event, it’s a co-operative scheme between the states and Commonwealth; however, there is no Commonwealth-level legislation.

I wrote about these promising reforms for The Conversation here. In essence, the reforms aim to put a stop to the rising rates of notified sexual misconduct and boundary violations that are emanating from the clinical practices of health practitioners nationwide. However, a few notes I might now add include the following.

First, much credit for the shape and substance of the reforms should be duly extended to Prof Jenni Millbank of UTS, whose several detailed publications on the National Law have really unearthed the difficulties that these reforms attempt to address. For instance, the second proposal, which is about bringing other states’ reinstatement processes up to the same level of strictness as the process in NSW, would probably not have been possible to float unless Millbank had identified and argued about this problem in one of her excellent refereed articles.

Second, the NSW version of the National Law has been stricter from the very beginning (2009), and the reform processes hence have — in my view inevitably — been a slow and somewhat agonising process of watching all the other states catch up to where NSW began.

In my view, this has also really been the consequence of the National Registration and Accreditation Implementation Project (NRAIP) team not really clicking with the NSW participants in its original discussion in 2008. While the NSW advocates were clear and compelling in arguing for the preferability of the existing NSW practitioner law (and on that basis ‘carved out’ parts of the NRAS to retain those preferable laws), the NRAIP team seemed wedded to the template, and may have failed to identify all the real virtues of the stricter NSW system. That was the NSW system which had developed, in short, in response to several scandals — principally, Chelmsford, “Butcher of Bega,” and Dr Sood, and which, in 1983, created the first ‘HCE’ (health complaints entity) — namely, the HCCC — in the world.

Alright — thanks for reading.

November–December 2023 updates: AABHL presentation; thalidomide apology; unlawful welfare convictions

Just a quick blog post to note a few news items

  • In late November, I presented the following presentation remotely at the Australasian Association of Bioethics and Heath Law (AABHL) on ‘risk-based regulation.’ My abstract was as follows:

What risk? A critical analysis of risk-based regulation of therapeutic goods, from stem cell medicine to osseointegration devices

Therapeutic goods (medicines, biologicals and devices) are regulated both in Australia and globally via ‘risk-based regulation’ (RBR). Recently, the OECD has described RBR as rules that are ‘science-based, targeted, effective and efficient,’ invoking the paradigmatic ‘risk-benefit analysis.’ But, as this paper contends, this description is misleading. In essence, RBR is neither health-focused nor harm-minimising but about ‘less-is-more’ governance. As with other neoliberal creations, RBR’s aim has been to prioritise private sector remediation (eg, civil litigation) and self-regulation over centralised governmental control. While the impact of RBR in the financial sector has been studied in detail, scarce legal scholarship has examined the state’s devolution of responsibility and control over therapeutic goods law to private individuals and organisations, such as hospitals or private practitioners.

As this paper will illustrate, while therapeutic goods legislation does control risk and experimentation (‘innovation’), it does so only for high-risk therapies: ie, those ‘worth’ regulating. Two examples are on point: the practice of stem-cell medicine and the use of osseointegration devices. In pursuit of efficiency, RBR eschews ‘overregulation’ and avoids duplication of oversight and enforcement. In concert with the Australian Civil Liability Acts, RBR has arguably achieved its implicit goal of ‘deresponsibilisation.’ However, a regulatory vacuum for unregulated or unapproved experimentation, creating confusion among practitioners and leaving regulators open to accusations of arbitrary decision-making. While better ‘upfront’ guidance for practitioners may assist, I contend that better-publicised reasons by regulators will enhance standard-setting.

A video recording of the presentation is below:

  • On 7 December, I was quoted in the Guardian in a story written by Paul Karp about two people remain in jail for welfare fraud offences based on defective and unlawful evidence. That defectiveness and unlawfulness has been recognised by the Ombudsman and the welfare agencies, and even, seemingly, the Cth Director of Public Prosecutions. I make the point that more should be done to facilitate the review of these cases. The CDPP have disclosure obligations, but it appears to me that the nature of the disclosures may be narrow (notifying of a potential problem) or broad (giving detail as to the nature of the evidentiary issues). The story is here.

Exa-cel on review at the FDA

Just last week, on 31 October, the FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee met to discuss Vertex Pharma’s Biologics License Application for Exagamglogene autotemcel (or exa-cel, and formerly known as CTX-001) — a cell-based gene therapy designed to treat sickle-cell diseases.

I have written about exa-cel many times before, both on this blog (here) and in published academic writing too. I have also spoken about it in this podcast. Exa-cel is a therapeutic product that is composed of the patient’s own (autologous) hematopoietic stem cells; however, those cells — specifically differentiation 34+ (CD34+) cells, have been edited using CRISPR/Cas 9 editing machinery (CRISPR).

In short, a CRISPR-Cas endonuclease system (CRISPRs) is a naturally occurring adaptive immune system that exists in most bacteria. These systems prevent bacteria from being infected by foreign genetic elements, such as viruses and phages. Where an infection exists, the Cas9 protein in the CRISPR will cleave or cut one strand each of double-stranded DNA to cause a double-strand break and thus decrease production of progeny viruses. Following that DSB, the genome will be repaired naturally, usually through a naturally occurring process called non-homologous end joining or NHEJ.

But this CRISPR/Cas 9 system can be ‘hijacked’ by science for therapeutic purposes. Using a guided template, the DSBs made by the Cas9 protein can be repaired in a precise and controllable manner, allowing the editing machinery of cell repair to be redirected toward doing repairs or edits that it would otherwise not do unguided.

This is how exa-cel works (in a nutshell). After the patient’s cells have been extracted, they are subject to guided disruption and repair by CRISPR. The CRISPR system make precise DSBs at the erythroid lineage specific enhancer region of B-cell lymphoma/leukemia 11A (BCL11A) gene on chromosome 2. In turn, this process disrupts GATA1 binding and abrogates BCL11A expression. Having turned off the expression of BCL11A, another gene, γ-globin (HBG1/HGB2) is expressed, creating fetal hemoglobin (HbF) production. It is quite complicated; but, in essence, the production of fetal hemoglobin allows people with sickle-cell diseases (red blood cells shaped like sickles because the cells are starved of oxygen) to be restored to health.

There are many issues and risks with this therapy, including the fact that sickle-cell disorder could be a protective disorder against malaria. But one especially concerning prospect, which is really at the core of the BLA on review currently, is the chance that the CRISPR may create cuts or DSBs at a site on the genome locus that is not in the right place. These misplaced or unforeseen cuts are known as ‘off-target effects’ or, alternatively, as indels — which means (usually unintended) insertions or deletions. The BLA puts the risks well:

One of the main concerns related to genome editing technology is risk of cleavage of genomic DNA at unintended sites due to imperfect pairing between the gRNA and the target DNA sequence. A subset of these imperfectly paired sites can be cleaved by the Cas9 endonuclease resulting in unintended edits across the genome. These sites can tolerate up to 6-mismatches between the gRNA and the genomic DNA. Since unintended edits can disrupt gene expression if present in the coding or regulatory DNA sequences, it is critical that the specificity of the gRNA be thoroughly screened to ensure off-target genome editing is minimized.

https://www.fda.gov/media/173414/download

I am still trying to get my head around the recent report of the results of the off-target analysis present in the BLA. The FDA’s BLA report states as follows:

For the cellular off-target analysis, the Applicant used three samples from healthy donors and three samples from subjects with SCD of African American ethnicity. Given the impact of the SCD on [hematopoietic stem cell] function, which can potentially change the chromatin landscape and can impact off-target editing, the merits of using healthy donor samples for such analysis is not clear.

Additionally, it is not clear if the small number of samples used in the cellular GUIDE-seq offtarget analysis is sufficient to adequately assess off-target editing in exa-cel.

https://www.fda.gov/media/173414/download

The report then continues:

4.1.1.1 In Silico Analysis Off-Target Analysis Data for Exa-cel

The Applicant used three publicly available in silico algorithms to nominate potential off-target sites for the sgRNA SPY101 (Figure 6) based on its homology to the reference sequence.

https://www.fda.gov/media/173414/download

Notably, however, when you get to the next page on the analysis of these risks, there are a number of redactions, no doubt because these are commercially protected contents that the regulator must not disclose. On first view, it appears that these ‘in silico algorithms’ to nominate potential off-target sites is, as is said below, a ‘part of the tool.’ I am not quite sure whether that means that the tool — the CRISPR system used be Vertex — is also the same system that conducts the off-target search, or something else. Have a read:

In any case, it looks like the so-called ‘indel frequency’ is very low. As the report noted later, “In this analysis, there were no statistically significant off-target editing events observed at any of the off-targets nominated using in silico analysis.” Although it remains unclear to me precisely how the indel assessment takes place, it is worth noting that the report’s view of the findings of the sponsor are very ambiguous, and tend towards a finding that the results of the study are inadequate. As the report notes in its conclusion of the safety summary section (4.1.2):

These changes have the potential to impact the chromatin landscape of SCD donor derived CD34+ HSPCs. Since chromatin accessibility can influence off-target activity, it is not clear if GUIDE-seq analysis of healthy donor derived CD34+ HSPCs can adequately capture potential off-target editing occurring in patient cells. However, availability of SCD donor cells can be limited and should also be considered. The Applicant used a total of four samples that were from donors of African American ethnicity. Three of these samples were from SCD donors that were used in the GUIDE-seq experiment and hybrid capture sequencing experiment, and one sample was from healthy donor that was used in the hybrid capture sequencing experiment. Given the limited number of SCD samples that were used in the cellular off-target analysis, it is not clear if the GUIDE-seq analysis adequately assessed the potential off-target editing by exa-cel.

Given the ambiguity of the FDA’s assessment, which states that Vertex’s pharmacovigilance plan is still under review, it remains to be seen whether more studies will need to be provided before the FDA consider exa-cel ready for the clinic.