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

On miners and bots – the future of the Medical Affairs Department
It’s 2025 and I would like you to join me in welcoming the new colleagues to the Medical Affairs Department:
A data scientist, an AI bot and a digital capabilities specialist. Who are they and how could they enhance the work a Medical Affairs team does? Let’s take a look back where things started, where we are now and where we are headed.

From the initial compound screen through to regulatory approval, reimbursement and commercial supply, drug development involves scientists in operational and medical functions to run the studies and operations. The Medical Affairs team uses the data generated by Research and Development to communicate and get insights from HCPs, payors and often, although indirectly, patients. The insights they are receiving contributes to the mission to bring a new drug to patients, improve an existing therapy or expand an indication. Along this long journey, the Medical Affairs team often provides education internally and externally, ensures scientific accuracy of promotional activities and facilitates opportunities to collaborate with academic centres and key HCPs to identify further data gaps or get insights on the therapeutic landscape.

Nowadays the Medical Affairs function has evolved from the “MSL trademark” established in 1980 that was described as an educational service to initiate studies and develop workshops around drug related medical topics to now being a strategic partner connecting internal and external stakeholders.

Over 40 years have gone by from the first trademark to today and the Medical Affairs role has changed and expanded into a multi-facetted role. At the same time, the speed of data generation and the way of communication has also changed. The digital revolution has led to digital record keeping and digital communication. The first mobile phone came out as a brick in the 70s, computers/laptops with internet have become an everyday item, social networking which started in the early 2000s is now part of everyday communication and smart phone are now part of everyday life. At the same time data generation by scientific research was accelerated at speed. The PCR (polymerase chain reaction) for example was invented in 1985 and formed the basis for assays like deep sequencing, generating huge amounts of big data that can no longer be analysed by one person. In the wake of this are in-coming: your new colleagues the digital capabilities specialist, the AI bot and the data scientist.

We all experienced how the global pandemic fast forwarded digital engagement initiatives and might forever change the way Medical Affairs communicates. Digital capability experts quickly became a new set of stakeholders that needed to be engaged to organise webinars, virtual advisory boards or work on an application that helps to ensure the Quality Use of Medicines (QUM).

Artificial intelligence (AI) is the science of machine learning algorithms, artificial neural networks that have the capability to learn to abstract outputs based on their inputs. An example is IBM Watson, a cloud-based machine learning service that can be trained to deploy AI powered applications. Another impressive example is the use of AI to analyse biopsy images and it has already been shown to outperform the specialists in recognising abnormal cell growth.

The data scientist role has developed due to the large amounts of data generated by scientific research or by companies collecting insights from their respective fields. These specialised scientists mine, collect and analyse large amounts of data from databases, RWD (Real-World Data) evidence or disease registries.

These new Medical Affairs functions will work in close collaboration with the traditional Medical Affairs colleagues. Companies who start engaging data scientists and AI to obtain and analyse data will be able to move faster by gaining insights from large amounts of medical and scientific data sources to drive research and development and increase commercial value. An experienced Medical Affairs team who employs a data scientist could add value to medical innovation and research by linking this information to clinical outcomes. They could work in close collaboration with medical specialists to identify needs for digital capabilities such as remote patient monitoring for drug adherence and to detect potential side effects much earlier. Insights could be gained from internal databases or Real-World data sources to identify open questions, to feed into medical strategy, identify educational needs or open research questions to further drug development. Real- World data mining, performed by data scientists can support discussions around health technology assessments (HTA) with payors, to the extent that AI could identify complex biological patterns in large datasets from clinical trials to identify responders and non-responders to a therapy.

While some of this might sound very abstract and far away, if I had a data scientist at hand, I would have asked them to research and analyse the history of the Medical Affairs function and then used an AI bot to come up with an algorithm to determine future solutions. It would provide all the relevant info within minutes and helped write this blog. In all seriousness it’s probably time to start familiarising ourselves with these new functions and embracing their capabilities and the opportunities they provide to a Medical Affairs function.

Clinical Development Team

Radiopharmaceuticals are radioisotopes that have been bound to biological molecules to target specific cells, organs or tissues. These relatively new drugs are being increasingly used for both the diagnosis and treatment of a number of diseases including: prostate cancer, renal cancer and glioblastoma. These medicines may allow for better diagnosis and more effective therapies.
At the virtual 2020 AusBiotech + Invest conference, a panel of leading industry experts discussed the current and future trends in the drug development of radiopharmaceuticals and how these may improve the quality of life of cancer patients.

These products are typically made up of three key parts including the ‘delivery vehicle’ (a targeting moiety – a small molecule or macromolecule such as an antibody), a proprietary linker and the ‘payload’ (a radioactive isotope). The delivery vehicle can bind to specific cancer cell transmembrane proteins (e.g PMSA in prostate cancer) where the radioactive isotope can be delivered and achieve the desired imaging or therapeutic effect. These novel agents are administered systemically and unlike older, conventional therapies (e.g radiation therapy, chemotherapy, surgery) can deliver precise, targeted radiation treatment to the cancer, (including small, distant metastases) which may not have been possible with other therapies.

Radiopharmaceuticals are referred to as Molecularly Targeted Radiation (MTR) products. The development of MTR products typically occurs in ‘theranostic’ pairs where generally the development of an imaging asset leads to the development of the paired therapeutic asset for a disease. Clinicians can utilize this mode of treatment to ‘’See it, Treat it’’, meaning that diagnostic isotopes (e.g 68Ga, 89ZR) enable accurate PET imaging of the cancer while therapeutic isotopes (e.g 177Lu, 131I) enable precise radiation therapy to be delivered directly to the cancer cells. An advantage of this approach is that radiopharmaceutical dosing can be tailored to the individual patient and clinicians are able to readily evaluate patient response to treatment.

Interestingly, the design of radiopharmaceuticals is somewhat like a ‘meccano’ set. That is, the three key elements can be disassembled and reconfigured to make a different style of related drug which can be used for a multitude of different applications. For example, the radioactive isotope of a traditional product may be substituted for an alpha emitter which is able to deliver a different type of high energy radiation with less penetration therefore making it effective for more disseminated hematological cancers (e.g Multiple Myeloma).

These products are not hoping to replace the current standard of care for cancer treatments. Instead, MTR products should be used as a synergistic, additive to current treatments. In prostate cancer, radiopharmaceuticals are being used in combination with androgen deprivation therapies and chemotherapy while in renal cell carcinoma they are being combined with immuno-oncology products such as checkpoint inhibitors to improve response rate, survival rates and most importantly patient quality of life.

Clinical Development Team 

A  revealing final session of the “AusBiotech and Invest 2020” conference addressed the opportunities and risks for the Australian Biotechnology sector. A discussion between diverse industry experts painted an optimistic future for the industry as recent government policy movements have provided a golden opportunity for Australian Biotech to showcase its value. It was unanimously agreed that a key barrier for the success of the industry centred on the collective agreement on how to measure industry value.

Most recently, it was anticipated that a $1.8 billion reduction in investment was upon the industry, instead there was a $2 billion investment handed out through tax incentives; a backflip that surprised many industry leaders. The continued support reaffirms the government’s goals to be a global leader in medical research and has thus abolished investor uncertainty in the future of the industry. It now falls to industry to seize the opportunity and demonstrate the output of this government investment.

One of the initial challenges outlined by the panel was the need for the industry to have a universal agreement on shared goals. Currently, individual biotech companies’ goals vary greatly from one another, this was established to be a disadvantage. From an agreement on common goals, mechanisms of quantification could be developed which will display the achievement in these shared outcomes. Metrics could then be adopted in the industry’s narrative to convey causality between investment and output to substantiate to policymakers the value in developing Australia’s Biotechnology sector.

Quantifying value is dependant on a robust definition of commercial success, a standard that Australia’s industry is yet to decide upon. Should this definition be developed on the grounds of the amount of capital raised by a venture? One of the panel members argued that capital only enables a company to be successful but is not useful as a metric for success. Does academic output demonstrate the potential for commercial translation and success? Or potentially the political environment for a company to flourish perhaps even comparison of company performance in a global context should be the primary mechanism for defining success?

Following the discussion on the industry needing to agree on definitions and goals, Australian biotech’s access to the market was discussed. It was established that Australia is disadvantaged due to its geographical isolation and time zone from value chains. “In Boston, you’ve got your academic researcher, your laboratory, your investor and your pharmaceutical company all in one location” it was explained by one of the panel members, thus Australia could to better in ensuring the proximity to key development infrastructure. The isolation could be a hindrance in establishing new relationships and completing the commercialisation chain – this will be particularly present in the current environment when international travel is not possible. It was speculated it may be necessary to have permanent staff in other countries to develop these cross-national relationships with a personal element.

There are many barriers to Australian companies accessing global markets and this story has not been successfully conveyed to the government to ease this pressure. Although, it was also argued that it was a shame that the Australian industry was encouraged to concentrate commercial efforts overseas when it would be beneficial to Australia to keep it within national borders. It was suggested to overcome this – preferential regulatory pathways could be established with the Therapeutic Goods Administration (TGA) to incentivise Australian companies to begin on local soil before extending out globally. The Medical Research Future Fund is a mechanism in which the government aims to provide long term funding for Australian health and medical research and there was a discussion on the potential for politicisation of this program. It was countered that more effort in establishing value and metrics would facilitate the public’s trust in this program.

The overall message that was conveyed from this discussion is that a narrative needs to be constructed by Australian Biotech; one that incorporates metrics universally decided to measure the success of the industry. This narrative then needs to be conveyed to policymakers with emphasis on how barriers can be removed to further enable Australian Biotech to flourish. If this can be achieved, the future of Australian Biotech is all but secured.

The role of digital health in clinical trials

Rose-Marie Pennisi – Pharmaceutical Manager

Digital tools and technologies are transforming the way clinical trials are being conducted and creating better engagement with more empowered trial participants and better collaboration between trial sites, clinicians, vendors and sponsors. Not only can these new innovative electronic tools and platforms improve site selection, patient recruitment, retention, monitoring and collection of trial data they can also reduce costs. 

At this year’s virtual AusBiotech + Invest 2020 conference, a panel of leading industry experts discussed how the adoption of digital health technologies introduces a range of significant benefits and advances to clinical trial programs for the life science industry.

Fundamental changes are happening and with virtual trials now possible, making them much more patient-centric. Technology can now keep patients from dropping out of trials since they no longer need to keep going to the trial site.

COVID-19 has accelerated adoption of digital platforms and technologies and the use of simple technology such as Zoom, has enabled clinical trials to continue during the COVID-19 pandemic when in the past without this technology these trials would have been put on hold and patients would have to wait. Zoom has allowed sites to get support digitally, supporting both the clinical team and patients. Simple technology such as this opens up new opportunities.

Digital platforms are enabling online meetings for ethics committees, electronic submissions, electronic signatures and are having quite a profound impact on how trials are designed and the type of data that can be generated. Use of digital technologies enables KOLs and investigators opportunities to provide input into meetings they might otherwise not be able to attend and engage with all stakeholders. Better tools are available for trial planning, design and forecasting phases using activity-based costing for more accurate and efficient costing and digital whiteboards to facilitate brainstorming across geographic areas.

With greater technology comes a greater level of patient engagement and age should be no barrier with participation. For the technology to be effective patients need to be able to readily interact with their devices and engagement should be made easier and more fun. Patient-centric platforms including e-consent platforms can now include animations and videos and user manuals available in multiple languages having the potential for better patient engagement, troubleshooting and reduction in trial costs.

Innovative technologies are empowering patients to look for information, be engaged in their condition and be more proactive. They are also able to gather more accurate real-time data using digital biomarkers, novel digital endpoints and telehealth. We’ve come a long way since handwritten diaries.

Automatic data logging provides a better understanding of how a patient interacts with and uses their device and can collect many more data points. This has the potential to generate real-world evidence in a post-market situation.

Simply pushing technology won’t work and there are many considerations when adopting it. It needs to be seamless, embraced by and enjoyed by a range of users and suit the workflow. Other factors to consider are compliance and regulatory considerations around data security, cybersecurity, data privacy, sharing of data and audit trails. Also critical is compatibility and integration with other systems e.g. hospitals, medical records.

These innovative digital platforms and technologies have revolutionised the way we conduct clinical trials and opportunities and possibilities that a few years ago we couldn’t even imagine.

If you’re interested in incorporating digital tools and technologies into your clinical trials, contact My Medical Department to find out how we can help.

Rose-Marie Pennisi – Pharmaceutical Manager

With the costs of new product development now estimated to be around $1.4 billion USD, Real World Evidence (RWE) is more important than ever with companies looking for ways to do more with less. RWE) is emerging as invaluable in the clinical evidence landscape and transforming the way we collect clinical data. The evolution of the healthcare landscape is driving the need for change and we need to think differently about evidence approaches.

At the recent ARCS Virtual Summit 2020, a daily feature of the program was exploring different perspectives on RWE. The presentations focused on why RWE is now more important than ever, the Australian landscape and various stakeholder perspectives, the long-lasting impact that COVID-19 has had on RWE and its impact on clinical care, registration and market access applications.

Some of the major trends that are impacting this landscape are today’s significant costs of development, the growth in rare and orphan drugs coming to market (in 2018, these were 58% of FDA approved medicines), advances in personalised and precision medicine where target populations are very small numbers (in 2018, these were 46% of FDA approved medicines) and accelerated approval pathways for innovative medicines.

These trends are resulting in fewer products coming to market with traditional data packages, fewer blockbusters coming to market with common approaches and huge target populations, smaller and more dispersed patient numbers for rare diseases and precision medicines and products coming to market with lighter clinical evidence. These present great clinical challenges and RWE is part of the solution in developing these innovative and smaller population medicines and evolving healthcare.

While randomised controlled trials (RCTs) remain the gold standard, real world evidence (RWE) comes in many forms and has the flexibility to address a broad range of research questions across the life cycle. It’s not about lowering the bar with RWE. It is about having an ethically and practically driven approach that is scientifically robust. By combining RWE and RCTs, we can get the best of both worlds and create higher standards using both. Collection of RWE creates a holistic evidence package that can address limitations and uncertainties and overcome challenges of RCTs by filling data gaps and unmet needs.

With all it offers, RWE does present some challenges which can limit its utility to varying degrees. Key barriers can include the quality of the data collected, lack of standardised processes and methodologies, access to data being challenging due to separate and fragmented sources, governance, privacy issues and lack of experience.

Relative to major developed markets, Australia is earlier in the RWE journey. While the Australian ecosystem contains a breadth and depth of high-quality data, it is somewhat fragmented due to being available in separate sources. These sources include MBS and PBS data in federal systems, hospital data in state systems, claims databases, registries, mobile and digital devices, and commercially owned data sets (e.g., retail pharmacy data), private providers with electronic medical records (EMR) registry-based datasets, academic and research sectors.

So what is Real World Data?

RWD can be generated in early development, pre-launch and in-market phases, and can come from cost-effective sources such as survey questionnaires for healthcare professionals and patients, chart reviews, database studies using retrospective analysis and EMR, prospective, eCRFs and PROs from non-interventional study (NIS) and pragmatic RCTs and use of single arm trial designs as pivotal evidence.

RWE has an immense potential to transform the healthcare landscape and engaging stakeholders in government, regulators, payers, HCPs, policy makers, HTA, patients, patient organisations, industry, academics, researchers, data custodians and HRECs will be key to this integration into regulatory and market access applications to support regulatory decision making, accelerate innovation and enable access to innovative medicines and ultimately drive improvements in clinical care.

There is a realisation that these opportunities will require significant work and collaboration across the healthcare sector, between industry, government and other stakeholders.

One of the speakers used the analogy of Netflix. Netflix is not a one size fits all approach and has revolutionised and personalised TV entertainment. So too will innovative, specialised and personalised medicines require customised, cost-effective, out of the box approaches to development.

Innovative Medicines require Innovative Approaches

As Australia’s premier life science conference, AusBiotech brings together all levels of industry to establish and develop client relationships, network with like-minded service providers and build awareness of their unique customer value proposition within the international life sciences community.

At this year’s event, My Medical Department had the privilege to connect with many remarkable Australian and international biotech leaders. Panel discussions and key themes covered such topics as: regulation, clinical trials, new markets, business development, emerging technologies and research translational strategies.

We found our interactions to be extremely gratifying and we would like to thank all exhibitors and delegates that we encountered for taking the time to stop by and discuss possible collaborations, introduce their services or even just have a chat.

We look forward to connecting and working with you in the future!

Contact My Medical Department, your independent medical consultancy, for Pharmaceutical and Medical expertise, anytime, anywhere.

Many products make claims about their health effects. This does not necessarily mean that they are therapeutic goods. However, the desire to extract more health benefits from our cosmetics and foods has made it hard to tell and raises the question: what is my product?

Depending on its use, it’s important to decide the intended purpose early. If you are not building the correct supporting evidence during development, you might find you need to modify your claims or re-do work to meet regulatory requirements. Here’s some general guidance on navigating through the regulations.

A therapeutic good is broadly defined as a product for use in humans in connection with;
• preventing, diagnosing, curing or alleviating a disease or injury
• influencing, inhibiting or modifying a physiological process
• testing a person for a disease
• preventing conception or testing for pregnancy
If your product has one or more of these intentions it is likely a medicine or device and will be regulated as a therapeutic good.

Sometimes it can be unclear as to whether a product is a complementary medicine or a food. To start, product presentation may help determine whether it is a food. For example, orange juice is a food. However, if vitamin C is extracted, concentrated and marketed in a tablet with claims that it may ‘relieve cold and flu symptoms’ it’s considered a therapeutic good. 

Foods may not make claims that are therapeutic in nature. They may not refer to the prevention, diagnosis, cure or alleviation of a condition. However, they can make nutrition content claims (e.g. good source of dietary fibre or source of vitamin C) and some health claims (e.g. enhances bone mineral density, reduces blood cholesterol, necessary for normal bone structure, contributes to regular laxation, contributes to heart health) if they meet specific conditions. 

In addition to foods, cosmetics may not make claims that are therapeutic in nature. They also are not to refer to the prevention, diagnosis, cure or alleviation of a condition. Even if a product is intended to be a cosmetic, it may be classified as a medicine depending on its ingredients, the route of administration and if therapeutic claims are made on its label, or in advertising.

At the end of the day it can be hard to make the call as to which regulations apply to your product. Regulations also vary from country to country if you intend launching your product globally. It’s wise to consult a regulatory expert for advice to ensure you’re aware of the requirements. 

Contact My Medical Department, your independent medical consultancy, for Pharmaceutical and Medical expertise, anytime, anywhere.