What happens when a patient is injured in a clinical trial in Australia, will there be the care necessary to nurse them back to full health or at least to the best that they can be with their condition? Will that care be provided quickly, and will all needs be covered? Currently our understanding rests in a piece of paper, referred to in consent forms.

The most seminal session at the ARCS Conference 2022, which justifies a groundswell for further action, was bravely and respectfully discussed in person, by the injured clinical trial participant, their solicitor, the Icon Group Executive Manager for Research, Dr Sophie Mepham and the AccessCR Managing Director, Dr Janelle Bowden – the last two being long-term advocates for quality and consumer participation in clinical trials in Australia – and both well known to ARCS members.

Unfortunately, with even the safest medicine adverse events can happen, and in this case, it was a checkpoint (PD-1/PDL-1) inhibitor at the centre of a series of serious adverse events (SAEs) causing long-term injuries to a trial patient; a member of a relatively new drug class which has brought hope to many with advanced cancer, where conventional small molecule or antibody drugs no longer worked.

This blog is not a criticism of the protocol, the medicine, the care or the oversight leading up to the SAEs. It is to shine a light on an example of how the system was found wanting when used to respond to trial events that may and do happen, despite all precautions and care.

First some history and a disclosure, I was involved as a contributor to the Medicines Australian Indemnity and Compensation Guidelines, which I believe all commercially sponsored clinical trials are required to follow. My recollection was that it was drafted by Medicines Australia to set a common standard and expectation of support for the burgeoning clinical trial sector, including hospitals, in Australia. Prior to this common agreement, each protocol and trial insurance arrangements were sent to hospital lawyers to determine its acceptability on a case-by-case basis. This was time-consuming, significant work for lawyers, but a flawed system. I directly observed that two Victorian hospitals had simultaneous but markedly different advice on the same protocol and company’s insurance documentation from two solicitors at the same Victorian law firm!

Coming back to the recent past and this concerning and unfortunate case for a trial participant in the relatively recent past. The guideline requires, irrespective of consent and foreseeability, that claims be dealt with expeditiouslyand to deal with the most serious type of injury being disabling and enduring. In the recent case, the trial medicine caused an immunogenic-like reaction, affecting multiple organ systems throughout their body.

Also, worrying is that participation in a clinical trial means the usual health service arrangements for indemnity do not apply and the responsibility seems to be split between site, sponsor, insurer and HREC, though the delineation of their respective responsibilities and overall oversight of patient care and support is not abundantly clear.

In this case it was years of delay from lawyers and the insurance company for the local sponsor and later a second step of review by international lawyers for the Pharma company.

What does expeditious mean? Who pays for the tests, the assessment and the care as well as loss of earnings whilst it is being considered? Who is meant to have oversight?

Fortunately, Icon Group paid for all costs for their patient whilst the case was being considered, and I am pleased to say eventually, compensation was agreed by lawyers and the insurance company.

Let’s go back to the documents supporting clinical research in Australia. A second document, well known to our sector is the NHMRC National Statement on Ethical Conduct in Human Research (updated 2018; the National Statement; section 2.2.6(c)), states information on the “provision of services to participants adversely affected by the research” should be communicated as part of the consent process, but in many multiple years of reviewing consent forms there seems to be little or no documentation on this – is this communicated effectively?

A further scan of other documents and I note there is a May 2014 NHRMC report on Indemnity and Insurance Arrangements, which does not cover this issue. The National Statement goes on to state (sections 5.1.38-39) “…that sponsors of clinical trials have indemnity, insurance and compensation arrangements in accordance with applicable regulatory requirements.” and “…arrangements to compensate participants for harm resulting from negligence in research.” In short, neither details continuity of care whilst insurance issues are being considered, and the compensation section seems to deal more with negligence.

To me this is a call to identify and characterise if this is widespread and if it is, a call for action. For this a survey of the sector will help us identify the extent. A quick solution thereafter may be to have a no-fault Australia-wide indemnity fund, which will support patients who suffer a significant and likely-related trial injury without any admissions, until such time it can go through legal considerations.  Should it be found that it is likely related to participation in the study (whether negligent care or not), then the fund would be later reimbursed by the responsible party.

It also means there should be an independent medical umpire to rapidly consider injuries and initiate care, diagnosis, treatment and patient support until the lawyers/courts go through the details of the case. I would suggest that this may be part of a cross-jurisdictional Office for Clinical Trial Support, to be established as a body independent to hospitals/clinics, sponsors and HRECs to remove any perception of admission or bias, which can initiate these actions and keep continuity of care for the most vulnerable in our community, who are often the participants in clinical trials.

Clinical trials are a necessary and important factor in improving patient care, please join with us in calling for further improvements to make our clinical trial sector world-class in all respects.

A/Prof Adrian Bootes

Director of Drug Development & Regulatory Affairs

Sophie Mepham