Category Archives: News

Cannabidiol: Reaching a New High


The curling wheeze and tight-lipped breathing of inflammatory lung conditions (1), the severe abdominal pain and gastrointestinal disruption of inflammatory bowel disease (IBD) (2), and the arduous stiffness associated with rheumatoid arthritis (RA) (3) are common inflammatory ailments that globally prevail. Though the aetiology of each disease is not well understood, each share a similar pathophysiology of unaccounted immune cell recruitment and inflammation (1, 2, 3). With this gap in knowledge, current therapies aim at managing symptoms and preventing further damage by targeting inflammatory pathways (1,2,3). However, the toxicity associated with immune modulators has created an urgency into finding alternative therapies.

Recently, Incannex Healthcare received approval for a phase I study investigating the safety profile of IHL-675A, a novel anti-inflammatory that is indicated for the treatment of inflammatory diseases including inflammatory lung conditions, IBD, and RA (4). IHL-675A is comprised of cannabidiol (CBD) and hydroxychloroquine (HCQ) (4). Currently, CBD has only been approved for the treatment of seizure disorders (Lennox-Gastaut syndrome and Dravet syndrome) (5).

Over the years, the importance of the endocannabinoid system in controlling homeostasis and mediating metabolic and inflammatory pathways has become a popular target for pharmacotherapy (6). CBD is one of the main active cannabinoids found in Cannabis sativa (5). Cannabinoids are an exogenous molecule that share structural and chemical similarities to cannabinoids (6). Though the mechanism of action remains elusive, pre-clinical studies have shown that CBD indirectly improves anti-inflammatory pathways by inhibiting T cell proliferation, inducing T cell apoptosis, and reducing the migration and adhesion of immune cells (6).

Conversely, HCQ is a well-tolerated anti-malarial and anti-inflammatory compound that has been traditionally indicated for the treatment of RA and malaria (7). Despite the anti-inflammatory mechanism remaining unclear, studies have shown that HCQ disrupts antigen-presentation and processing, preventing activation and differential of CD4+ T cells (7). Furthermore, studies have shown that HCQ induces apoptosis of autoreactive T cells, and interferes with the activation of the humoral immune response, thus reducing the presence and production of inflammatory cytokines (7).

Despite both compounds have individually shown anti-inflammatory properties, preclinical studies conducted by Incannex into IHL-675A has demonstrated that CBD and HCQ act synergistically to inhibit the production of inflammatory cytokines (IL-1, Il-6, TNFα, IL-12, and IFN-γ) in mouse models (7). Furthermore, IHL-675A demonstrated greater anti-inflammatory properties compared to CBD by 109% to 767% from 24 hours post-drug administration (7). These preclinical studies, though minimal, show promising results for the treatment of inflammatory conditions in humans.

Though the hurdle of a phase I trial is hard to surpass, the idea of a safe and effective treatment provides silver-lining to the treacherous battle of chronic inflammatory conditions. The competitiveness of the pharmaceutical industry is the foundation of innovative drug developments.  IHL-675A has shown to be a strong competitor within this battle, and hopefully within a few years, a solution to inflammatory conditions is approved.


  1. Agarwal A., et al., Chronic Obstructive Pulmonary Disease, 2022. StatPearls Publishing, Available at
  2. McDowell C., et al., Inflammatory Bowel Disease, 2022. StatPearls Publishing, Available at
  3. Chauhan K., et al,m Rheumatoid Arthritis, 2022. StatPearls Publishing, Available at
  4. SmallCaps, Incannex Healthcare to begin phase 1 clinical trial for IHL-675A following ethics approval, Nicholaos L., 2022, Available at [Accessed 11AUG2022]
  5. Meissner H., et al., Cannabidiol (CBD), 2022. StatPearls Publishing, Available at
  6. Atalay S., et al., Antioxidative and Anti-Inflammatory Properties of Cannabidiol. Antioxidants, 2020; 9(1) 20
  7. Bansal P., et al., Hydroxychloroquine: a comprehensive review and its controversial role in coronavirus disease 2019. Annals of Medicine, 2021; 53(1): p. 117-134
  8. Incannex, Positive In vivo results confirm strong synergistic activity of IHL-675A to inhibit inflammation, Incannex, 2020, Available at [Accessed 11AUG2022]

Ecopharmacovigilance: A greener look at PV through an environmental perspective



The rate at which modern medicine is progressing is astonishing. Production and usage of medicines across the globe continue to grow substantially. The global pharmaceutical market is estimated to exceed USD 1.5 Trillion in the coming years. No doubt these new medicines have improved quality of life and saved lives for some of the most terrible diseases and conditions, however their unwanted presence in the environment is raising alarm bells. As a result, a concept combining pharmacovigilance and environmental pharmacology, was first introduced as Pharmaco Environmentology in 2006 by Syed Ziaur Rahman. 

This concept has slowly evolved into Ecopharmacovigilance which is defined as “the science and activities concerning detection, assessment, understanding and prevention of adverse effects or other problems related to the presence of pharmaceuticals in the environment, which affect both human and the other animal species”.

Ecopharmacovigilance aims to ensure that significant environmental issues associated with pharmaceuticals in the environment are identified in a timely way and addressed appropriately. Ecopharmacovigilance is of significant concern these days since the unwanted presence of even trace amounts of active pharmacological ingredients in the environment may pose a risk.

There are various ways by which pharmacological pollutants may end up in the environment, such as in the patients’ excreta in the sewerage system and via release into the waste waters by manufacturers or hospitals and the terrestrial depositions. The largest release of medicines into the environment comes from the humans or animals taking them. Medicines are excreted from the body either in their unchanged form or as metabolites in faeces and urine and find their way into sewers or sewage treatment plants.

Several studies have documented the effects of pharmaceutical pollution on various animal species, such as vultures and fish. Ecopharmacovigilance is emerging as a promising approach to prevent the environmental risks posed by unwanted pharmaceutical agents ending up in the environment. However, it is impractical to implement rigorous EPV processes for all the pharmaceutical substances with complex and diversified chemical, biological or toxicological properties. Consequently, the concept of “targeted EPV” has evolved and is aimed at targeted detection, evaluation, understanding, and prevention of adverse effects of high-priority hazardous pharmaceuticals in the environment.

“Targeted EPV” implementation focusses on targeted monitoring of the presence of high-risk agents in the environment, targeted reporting of over-standard discharge, targeted management of main emission sources, targeted legislation and conduct of research on high-priority pharmaceutical pollutants, as well as targeted educational strategies for specific areas and key populations.

Although the detected concentrations of pharmaceuticals in the environment are generally low, (ng/L to μg/L) potential direct and indirect risks for human and animal populations do exist and hence should be carefully monitored. This is of further importance in the case of special populations including pregnant women, children and older patients, who may be vulnerable to even very low concentrations of medicines.

Addressing issues related to pharmaceutical pollution is one of the key current aims of Ecopharmacovigilance in managing the environmental safety of medicines. Environmental safety of medicines will be another challenge that regulators and researchers will need to face and work on collaboratively to address this vital issue and develop new strategies to minimise environmental risks.

The US, EU and Canada is already regulating in this area and undertaking Environmental Risk Assessment (ERA) in pharmaceuticals. At present there are no specific guidelines for ERA of pharmaceuticals in Japan, Australia and many other countries.

It will be important to watch this space and stay abreast of developments in this area and see what challenges and opportunities present themselves.


1. Silva LJG, Lino CM, Meisel L, Barceló D, Pena A. Ecopharmacovigilance. In: Barcelo D, editor.

The Handbook of Environmental Chemistry. Germany: Springer-Verlag Berlin and Heidelberg

GmbH & Co. KG; 2012. pp. 213–42.

2. Holm, G., Snape, J. R., Murray-Smith, R., Talbot, J., Taylor, D., and Sörme, P. (2013). Implementing Ecopharmacovigilance in Practice: Challenges and Potential Opportunities. Drug Saf. 36 (7), 533–546. doi:10.1007/s40264-013-0049-3

3. Wang, J., He, B., Yan, D., and Hu, X. (2017). Implementing Ecopharmacovigilance (EPV) from a Pharmacy Perspective: A Focus on Non-steroidal Anti-inflammatory Drugs. Sci. Total Environ. 603-604, 772–784. doi:10.1016/j.scitotenv.2017.02.209

Beyond the “Gift” that COVID Brought


Amongst many things, the COVID-19 pandemic questioned our traditional, separated work-home lifestyle divide ingrained over generations. The paradigm shift, to working from home (WFH) promised individuals the return of and flexibility with time – no more commutes, distractions, nor concrete set hours. Initially, this “gift” from COVID provided nuclear families and co-habitants with more time together, gave flexibility and some freedoms back to the individual, and overall was beneficial to many. However, underneath the rose petals of WFH, the thorns of raised risks of cardiovascular diseases (CVDs) present a menacing and longer-term health threat.

CVDs are characterised as a group of diseases (not exhaustive) including myocardial infarction, congestive heart failure, and myocardial ischemia, which affect the heart and blood vessels1. Currently, CVDs are the leading cause of death globally2. Though pharmaceutical intervention has helped reduce CVD prevalence and mitigate the risk of mortality over the years, its pathogenesis from multifactorial causes emphasises the importance of managing behavioural risk factors2. More specifically, tabacco use, alcohol, physical inactivity, hypertension, obesity, and inadequate dietary intakes are proportional to CVD risk2.

The impact of predisposing CVDs on COVID infection risks and outcomes has been extensively researched. However, the relationship of COVID infection and changed behaviours on the emergence of CVDs remains a novel topic. When SARS-Cov-2 spread and lockdowns commenced, communities and people were forced to stay in their homes, the subsequent lifestyle changes posed a physiological threat. As established, physical activity has a prophylactic effect on CVD2. The decrease in activity to just basal metabolic rate from removing daily activities such as commuting to work, and the consequence of increased sedentary time due to longer work hours, increases the risk of cardiovascular disease by promoting weight gain3.

Weight gain leads to increased obesity rates. Studies have suggested that 1/3 Australians gained weight during the pandemic, as well as 42% of Americans stating weight gain, with more than 16 United States of America states now having obesity rates of 35% or higher7. The accepted hypothesis linking obesity to CVD is centred on the ability of adipose tissue to produce pro-inflammatory cytokines, which directly impair myocardial function and contribute to the formation of atherosclerotic plaques8. This weight gain and consequential increased CVD risk is compounded further by irregular eating behaviours such as snacking and increased consumption of highly processed foods, which also promote atherosclerosis of blood vessels and hypertensive characteristics1.

The complex impacts of WFH also exacerbate other pre-disposing CVD risk factors through behavioural changes1. During lockdown, alcohol sales increased by 29% with tobacco expenditure increasing by 13%4,5, being used by some to mitigate the psychosocial pressure of lockdown. Increased tobacco and alcohol intakes indirectly increase CVD risk through blood pressure elevation, increases in cholesterol, and increases in triglyceride levels6.

COVID-19 presented WFH as a lifestyle delicacy on a silver platter. However, masked by the initial charade of increased work flexibility and freedom, the menacing wave of CVD health risks threatens the community in the longer term. CVD risks are multifactorial, whereby control of the modifiable risk factors can help mitigate the risk and severity. With WFH becoming the normalised practice, community programs should be initiated to emphasise the importance of staying active, eating healthy, and reducing alcohol and tobacco intake. As a community, we were able to slow but not stop COVID-19 from taking our breath away, but individually we can stop behavioural and lifestyle changes from contributing to our community’s longer-term CVD and mortality. 


  1. Ruan Y., et al., Cardiovascular disease (CVD) and associated risk factors among older adults in six low-and middle-income countries: results from SAGE Wave 1. Biomed Central, 2018, 18(1): p. 778
  2. Muhammad D.G. et al, COVID-19 lockdown may increase cardiovascular disease risk factors. The Egyptian Heart Journal, 2021, 73(1): p. 2
  3. Powell-Wiley T.M., et al, Obesity and Cardiovascular Disease: A Scientific Statement From the American Heart Association. Circulation, 2021, 143(21): e984–e1010
  4. Huge increase in Australian alcohol sales during the COVID-19 pandemic, Meacham S., 9NEWS, 2022, Accessed 14JUL2022, Available at
  5. Lee B.P., et al., Retail Alcohol and Tobacco Sales During COVID-19. Annals of Internal Medicine, 2021
  6. Larsson S.C., et al., Alcohol Consumption and Cardiovascular Disease. Circulation, 2020, 13(3): e002814
  7. Has the Pandemic Affected Obesity Rates?, Beaumont, [Unknown Author], 2022, Accessed 14JUL2022, Available at
  8. Carbone S., et al., Obesity paradox in cardiovascular disease: where do we stand?. Vascular Health and Management Risk, 2019, 15(1): p. 89-100

The practice of medicine, from a distance

Blog Post

In a rapidly changing world where technological developments happen on a daily basis, it is only logical that advanced telecommunications and computer technologies are used to improve health care and expand access to health services. The necessity to provide high quality and accessible medical attention was highlighted with the COVID-19 pandemic where interpersonal interactions were minimised to reduce contagion. Governments needed to provide a quick response to the high-volume demand and rapidly expanded telemedicine services4,5. Telecommunications posed a solution to harness the power of technology and connectivity to transmit knowledge from the healthcare worker right to the patient’s home6.

Telemedicine can be defined as “the use of electronic information and communication technologies to provide and support health care when distance separates the participants”2. It consists of the virtual interaction, synchronous or asynchronous, between the physician and the patient; whereas telehealth (a term commonly used interchangeably with telemedicine) is the flow of information6,7. One of the first telemedicine experiences can be traced all the way back to the 1860s, where the telegraph and morse code were used during war to transmit messages from wounded soldiers to the medical teams3. Major inventions followed including the radio, telephone, and television, but it wasn’t until the 20th century that they were repurposed to provide medical care (e.g., to assist sailors when at sea or to provide training to healthcare students). With the age of connectivity starting during the 2000s, telemedicine rapidly expanded with the creation of telephone networks, use of satellites and space technology, and the development of the internet. This rapid evolution allowed telemedicine companies to grow exponentially and evolve into more efficient services3.

With the dependency of telecommunication during the COVID-19 pandemic, an unparalleled opportunity has been presented to consider not only the ethical and legal issues, but also the social concerns that these services bring foward4,6,7.

Firstly, is an informed consent needed before each telemedicine consult? Will the patient-physician relationship be altered? What are the privacy and confidentiality concerns? How do we identify patients? Do we trust that the patients are who they say they are? Is the patient’s autonomy being respected? How do healthcare providers document each consultation and where will that data be stored? What is the risk of misdiagnosing during a virtual visit? These represent some of the many ethical and legal questions posed that were overshadowed by the urgency of the pandemic.

Secondly, in terms of the main social issues that need to be address, international organisations and governments need to argue and decide whether a low socioeconomic country should spend part of their money on improving telemedicine services rather than on, for example, agricultural insecurity, water safety or education. Health equity and access is a major topic to address, especially for the elderly, disadvantaged and minorities with no access to technology or to an effective connectivity network4. How do we reduce these disparities, whilst agreeing on local guidelines to protect the patient’s health and information?

Several guidelines and codes of ethics have been drafted to address these concerns1,8. However, these guidelines cannot be unanimously adopted by every country due to cultural and socioeconomic differences as well as local stakeholder’s viewpoints7. Not all of these questions have answers, and telemedicine services appear to be so vulnerable in every aspect. But is clear that in those countries in which telemedicine is a step forward, efforts need to be put into establishing guidelines that address quality and relationships, access, consent, and privacy; regulatory policies and regulations need to include issues of cybersecurity, licensure, liability, and malpractice7.

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  1. American Medical Association (2021). AMA Telehealth quick guide. Accessed 10 July 2020 from
  2. Institute of Medicine (US) Committee on Evaluating Clinical Applications of Telemedicine; Field MJ, editor. Telemedicine: A Guide to Assessing Telecommunications in Health Care. Washington (DC): National Academies Press (US); 1996. 1, Introduction and Background. Available from:
  3. Jagarapu J, Savani RC. A brief history of telemedicine and the evolution of teleneonatology. Seminars in perinatology. 2021;45(5). doi:10.1016/j.semperi.2021.151416
  4. Kaplan B. Ethics, guidelines, standards, and policy: telemedicine, covid-19, and broadening the ethical scope. Cambridge quarterly of healthcare ethics: cq : the international journal of healthcare ethics committees. 2022;31(1):105-118. doi:10.1017/S0963180121000852
  5. Kaplan B. Revisiting health information technology ethical, legal, and social issues and evaluation: telehealth/telemedicine and covid-19. International journal of medical informatics. 2020;143:104239-104239. doi:10.1016/j.ijmedinf.2020.104239
  6. Nittari G, Khuman R, Baldoni S, et al. Telemedicine practice: review of the current ethical and legal challenges. Telemedicine and e-health. 2020;26(12):1427-1437. doi:10.1089/tmj.2019.0158.
  7. Shafizadeh H, Larijani B, Mojtahedzadeh R, Shamsi Gooshki E, Nedjat S. Initial drafting of telemedicine’s code of ethics through a stakeholders’ participatory process. Journal of medical ethics and history of medicine. 2021;14:24-24. doi:10.18502/jmehm.v14i24.8184

World Medical Association (2020). Statement on the Ethics of Telemedicine. Accessed 10 July 2022 from

Exercise is medicine

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Physical activity presents as a prevention strategy for numerous chronic health conditions, including coronary heart disease, insulin resistance, hypertension and breast, colon, and endometrial cancer.1 However, for individuals with existing chronic health conditions, evidence is growing to support the integration of regular exercise into their treatment plans.

Multiple sclerosis

Multiple sclerosis (MS) is a chronic disease that affects the central nervous system, typically resulting in progressive and gradual disability. Approximately 25,600 Australians live with MS.2 Diagnosis of MS typically occurs between the ages of 20 and 40 years, and 75% of people with MS are women.2 There is currently no cure for MS and current therapies are aimed at easing symptoms and modifying the progression of the disease.

A systematic review published in 2013 examined 54 studies and found strong evidence that moderate intensity exercise performed two times per week increases aerobic capacity and muscular strength in MS patients with mild to moderate disability.3 The authors concluded that exercise training is effective for improving aerobic capacity and muscular strength and may improve mobility, fatigue, and health-related quality of life for people living with MS.3

It appears that the benefits of exercise for people living with MS is not limited to functional capacity and health-related quality of life. Several studies have demonstrated a positive impact of exercise on cognitive status of people living with MS4, as well as a lower annual relapse rate in people living with MS.5   

Type 2 Diabetes

Type 2 diabetes, a condition in which the body becomes resistant to the normal effects of insulin and gradually loses the capacity to produce enough insulin in the pancreas, has strong genetic risk factors and is often associated with modifiable lifestyle risk factors. In 2017-8 it was estimated that 4.9% of Australia’s total population had diabetes and approximately 1.2 million hospitalisations were associated with diabetes.6 Complications associated with type 2 diabetes include stroke, lower limb ischemia, nephropathy, retinopathy, and diabetic maculopathy.7 There is a high incidence of other risk factors for these complications among patients with type 2 diabetes e.g., hypertension, hyperlipidaemia, and cardiac and endothelial dysfunction.7  

The idea of exercise as treatment for type 2 diabetes is not new, and there is an international consensus that physical activity, along with diet and pharmaceuticals, are the foundations in the treatment of type 2 diabetes.8 There is extensive literature demonstrating the positive effects of exercise on metabolic control, fitness, muscle strength and motivation in patients with type 2 diabetes.9 Furthermore, regular exercise has several documented effects that are important for patients with type 2 diabetes such as reduction in systolic blood pressure and improvements in cardiac and endothelial vasodilatory function.9


Dementia describes a collection of symptoms that are caused by disorders affecting the brain. Dementia affects thinking, behaviour, and the ability to perform everyday tasks and due to the aging population, the number of people with dementia is constantly increasing.10 Estimations from Dementia Australia suggest that 487,500 Australians are currently living with dementia, and that the age of onset of dementia is gradually declining.11 A major challenge concerning dementia treatment is the management of neuropsychiatric symptoms such as agitation, anxiety, and depression, all of which are associated with low quality of life and increased caregiver burden.10

A recent systematic review including 13 studies and 1925 dementia patients demonstrated that regular aerobic exercise performed three to five times per week has a positive effect on neuropsychiatric symptoms.11 Interestingly the review demonstrated that combined exercise programs (aerobic and resistance exercise) did not appear to be as effective as aerobic exercise alone. Nevertheless, the study determined that resistance training programs are beneficial for dementia patients with mobility problems, with demonstrated reductions in symptoms of depression and behavioural problems.

The evidence pertaining to the benefits exercise as a treatment for chronic health conditions is growing rapidly and is not limited to the conditions discussed in this article. There is existing and emerging evidence relating to a wide range on chronic diseases including chronic obstructive pulmonary disease, asthma, osteoporosis, polycystic ovarian syndrome, obesity, Parkinson’s disease, depression, and anxiety.9 Indeed, further work is required to determine the efficacy and safety of exercise prescription for specific chronic health conditions. Nevertheless, perhaps a scenario where we see exercise prescription integrated into the treatment guidelines for most chronic health conditions is not too far away.

Sarah Joyce, PhD (Senior Consultant at My Medical Department)   


  1. Booth FW, Roberts CK, Laye MJ. Lack of exercise is a major cause of chronic diseases. Compr Physiol. 2012;2(2):1143-211.
  2. What is Multiple Sclerosis (MS)? MS Australia. Accessed July 8, 2022.
  3. Latimer-Cheung AE, Pilutti LA, Hicks LA, Martin Gini KA. Effects of Exercise Training on Fitness, Mobility, Fatigue, and Health-Related Quality of Life Among Adults with Multiple Sclerosis: A Systematic Review to Inform Guideline Development. Arch. Phys. 2013; 94(9): 1800-1823.
  4. Kalron A, Zeilig G. Efficacy of exercise intervention programs on cognition in people suffering from multiple sclerosis, stroke and Parkinson’s disease: A systematic review and meta-analysis of current evidence. NeuroRehabilitation. 2015;37(2):273–89.
  5. Pilutti LA, Platta ME, Motl RW, Latimer-Cheung AE. The safety of exercise training in multiple sclerosis: a systematic review. J Neurol Sci. 2014; 343(1–2):3–7.
  6. Diabetes. Australian Institute of Health and Welfare. Accessed July 8, 2022.
  7. Goyal R, Jialal I. Diabetes Mellitus Type 2. Treasure Island (FL): StatPearls Publishing; 2022. Accessed July 8, 2022.
  8. American Diabetes Association. Clinical practice recommendations. Diabetes Care. 2002:S1-s147.
  9. Pedersen BK, Saltin B. Exercise as medicine – evidence for prescribing exercise as therapy in 26 different chronic diseases. Scand J Med Sci Sports. 2015; 25(S3):1-72.
  10. Kouloutbani K, Venetsanou F, Markati A, Karteroliotis K, Politis A. The effectiveness of physical exercise interventions in the management of neuropsychiatric symptoms in dementia patients: A systematic review. International Psychogeriatrics. 2022;34(2)177-190.
  11. Dementia Statistics. Dementia Australia. Accessed July 8, 2022.

Getting the Clinical Trial Compensation Process Right


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.

Blog Arcs 2022

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

Adrian Bootes

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Sophie Mepham

An overview of depression and potential biomarkers for monitoring treatment response

Depression is a complex multifactorial neuropsychiatric condition which is associated with a high burden of disease [1-3]. Depression disturbs mood and cognition resulting in poor functioning and a significant detriment to the quality of life [1, 3-5]. It is one of the most prevalent disorders affecting more than 300 million individuals globally [6]. Five per cent of the Australian population suffer from depression each year [7]. Depression is characterised by a high recurrence rate; 40% of the treated patients relapse within 12 months [1]. Moreover, 20% to 30% of patients receiving a treatment for depression, achieve partial remission [1]. These patients continue to experience partial negative symptoms and suffer from daily life limitations. Depressive disorders are heterogenous and include a wide variety of biological and psychopathological endophenotypes [8]. Psychopathological endophenotypes include depressed mood, anhedonia, impaired learning and memory, appetite change, diurnal variation and stress [9]. Biological endophenotypes include REM sleep abnormalities, catecholamine depletion, downregulation of serotonin (5-HT) receptors, tryptophan (L-Trp) depletion and high cortisol levels [9]. The current diagnosis of depressive disorders and monitoring treatment success involve the use of depression assessment scales [9]. These scales are based on subjective markers; patients’ symptoms. Hence, the current diagnosis and treatment of depression can be affected by clinicians’ bias to a higher extent in the absence of accurate biomarkers guiding the diagnosis and treatment of depression.

To date, there are no acknowledged objective markers employed to monitor treatment response of antidepressants in practice. The delayed response of antidepressants and the lack of accurate markers guiding the treatment therapy hinders physicians’ clinical decisions during the initial weeks of treatment. Having objective biological markers to study depressive symptoms can improve the initial treatment of depression by modelling patients’ disease state and their responses to antidepressant interventions.

Initially, depression was linked to a relative deficiency of monoamine neurotransmitters in the synaptic cleft such as 5-HT and noradrenaline (NA) [3, 5]. This is known as the monoamine theory of depression [3, 14]. 5-HT levels were used as a marker to guide the efficacy of treatment for depression. Soon after, researchers discovered the limitations of the monoamine hypothesis. Although, antidepressants medications correct the levels of neurotransmitters at the synapse within a few hours after the first dose, a period of four to six weeks is needed to achieve the full antidepressant effects in improving patients’ mood as outlined in Figure 1 [15]. Additionally, the current antidepressants medications have a success rate of approximately 60% [15]. This highlights a limitation in this theory and suggests the involvement of alternative mechanisms to ameliorate mood other than the direct effect of antidepressants on the level of neurotransmitters at the synapse.

Mina Blog
Adapted from Steiner et al 2011 – List of abbreviations: selective serotonin reuptake inhibitors (SSRIs), serotonin and noradrenaline reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), serotonin (5-HT) , cyclic adenosine monophosphate (cAMP), cAMP response element binding (CREB) , brain derived neurotrophic factor (BDNF), N-methyl-D-aspartate receptor (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), Ca2+-calmodulin-dependent protein kinase (CAMK) and protein kinase A (PKA).

Figure 1 – Overview of mechanisms involved in depression and antidepressants mechanism of actions

Many studies identified relevant biological markers that are associated with depression. Recent evidence suggests a correlation between depression and neuroinflammation causing a disruption to L-tryptophan (Trp) and kynurenine pathway (KP) along with the neopterin to biopterin (N/B) ratio [10-12]. Several studies focused on the Trp depletion and upregulation of the KP in certain endophenotypes of depression whereas limited studies have investigated the potential of using neopterin to biopterin (N/B) ratio as a marker to monitor antidepressants’ treatment response. Evidence suggests that a rise in N/B ratio in depressed patients correlates with the severity depressive symptoms [12].

 Overall, depression remains on of the most prevalent conditions with a high disease burden. Current depression treatments have a 60% success rate require four to six weeks to show their full effect. Understanding the different mechanisms that may be involved in the pathophysiology of depression, will assist identifying novel, more effective treatments and relevant biomarkers that can monitor treatment response.

Mina Malek, BBiomedSc, MPharm (Senior Scientific Advisor at My Medical Department)   


1.            Peter M. Ellis IH, Smith. aDAR. Australian and New Zealand clinical practice guidelines for the treatment of depression Royal Australian and New Zealand College of Psychiatrists Clinical Practice Guidelines Team for Depression. Australian and New Zealand Journal of Psychiatry. 2004;38:389-407.

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What is Patient Centricity – and do we have the consumers/patients at all of our decision-making tables and at the right time?

Pleasingly, the world is moving on from solely considering the Drs, Scientists, Regulators and Drug Developers’ opinions in considering what a future patient really needs.  The recent ARCS Conference had an outstanding presentation from Ms Gillian Mason, which helped me think more about the needs of the consumer/patient.

Extrapolating from what I heard, we need to carefully consider the prioritisation of undertaking and completing important studies and build the endpoints within them (the researched outcomes) with input from patients.  By this, I mean thinking about what study endpoints reflect patients living improved lives, in particular those with long-term debilitating conditions?  To me this may influence what primary endpoint is chosen vs what a secondary endpoint may be, or what additional secondary endpoints should be there to provide meaningful data and clearly reflect the patient needs and the effect of the therapy to the regulators and payers. I think the desired future of studies for chronic illnesses will be studies including more endpoints that demonstrate patients/consumers continuing and improving their everyday lives, and we as scientists don’t always know what the relative impacts are and what is most important to them. Patient centricity should also mean considering clinical studies being patient friendly and accessible, which minimise patient dropouts from unnecessary and onerous procedures and also have the best chance of being approved by proving the benefit of the therapy beyond doubt to regulators and payers.

With these thoughts in mind, we the scientists need to sit back and see how can we bring the patients/consumers in for their advice in a safe, inclusive and accessible way that minimises the power imbalance and scientific-speak that big corporate and big government engages in and which may by its nature, excludes an individual consumer/patient. We need to hear and incorporate their views as much as possible.

After personally spending 30 years in drug development and sitting on all sides of the fence, I think I speak for everyone in desiring a real patient or consumer advocate as a peer and partner in decision making, for all steps of drug development, including clinical research, regulation, pharmacovigilance and reimbursement. I suggest taking a helicopter view of your job and thinking does it tick all the boxes for a current or future patient, those being boxes which make what you are developing most meaningful for patients?  If not let’s think of a way to get this advice in future, let’s make more linkages with patient groups from an early stage. Their input will only help us do a better job!

Adj. A/Prof Adrian Bootes on behalf of My Medical Department.

On miners and bots – the future of the Medical Affairs Department

On Miners And Bots 1170x613

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.