Clinical trials - the four phase process

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Much of the focus on managing and ultimately containing COVID-19 has naturally centred on the successful development of vaccines to protect people from the onset of infection. 2020 has seen an extraordinary race in the biomedical and pharmaceutical industries to find suitable candidates which can be deployed for public health programmes. Central to this process is the time taken to test drug for efficacy and safety - for the COVID vaccines, a process which normally proceeds over  years has taken only months.

Prior to proceeding to a clinical trial, compounds which constitute the drug are screened at a laboratory setting using computer modelling, tissue samples and pathology to assess which are likely to function with humans. The compounds are tested in at least two species of animals to establish performance, how they are metabolised and any side effects. After this preliminary stage, a candidate drug typically proceeds through a four stage process -

Phase 1: After approval from a human clinical trial ethics committee, and the appropriate health authority (Food and Drug Administration or FDA in the US, and the Therapeutic Goods Administration or TGA in Australia), the drug candidates which are the most promising are tested in small groups of healthy volunteers, usually young to lower middle age, non-smoking and normal body weight. For Phase 1 trials targetting life threatening diseases such as cancer, terminally ill patients as test drug recipients are included. Only one in five Phase-1 tested drugs are successful and proceed to being available for use.

Phase 2: The candidate drug is tested on a larger group of people with an illness to evaluate whether it works and to confirm safety, tolerance for patients and dosage requirements.

Phase 3: The trial is expanded for testing with hundreds or thousands of patients often in multi-institutions in various countries in what is termed a 'randomised controlled trial'. Some patients receive placebos (such as harmless sugar pill) while others receive the test drug itself. Neither doctors nor patients know whether they are using the placebo or the drug which enables an unbiased analysis of the response to the treatment and any side effects. This stage also enables measurement of how effectively the drug works in comparison to existing therapies, the economics of treatment and in quality-of-life terms.

Phase 4: Drug receives regulatory approval and is included in routine clinical practice. Ongoing surveillance studies may reveal any rare side effects or extra benefits.

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New Year 2021

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As 2020 draws to an end, people around the world could be forgiven for hoping that 2021 will prove to be an easier year and that vaccines for COVID-19 are ultimately successful in blunting the effect of the pandemic. As at December 29, 2020 there are 81.2 million cases world-wide (and this is an under estimate) and 1.8 million deaths. Staggering numbers for the 21st Century with its health systems and biomedical expertise. 

2020 has been a year of disruption, dislocation and hardship across communities in every continent. This has not meant that other critical issues have receded including regional conflicts and the many impacts of climate change which remain as constants and unrelenting. 

Wherever you may reside, may 2021 be a year of rewarded hope, good health and resilience.

Christmas 2020 in the age of COVID-19

Christmas in 2020 under the presence of COVID-19 will be memorable for the manner in which the virus creates an environment that is diametrically opposite of the meaning and purpose of this time in the calendar. 100 years ago during the Spanish Influenza pandemic (designated H1N1 influenza A) a similar impact would have been felt however there are few, if any, people alive who would be able to recall this public health catastrophe.  

Coming together at the end of the year is the traditional custom however the most effective means to prevent the transmission of COVID 19 is to do the opposite and stay apart. At this time, compassion and kindness remain key to managing the pandemic as much as control measures and vaccines.

Christmas has different meanings for different people. The word itself is derived from 'Çhrist's Mass' during the 11th Century it evolved to 'Cristenmasse' (Middle English) and the 12th Century it became Cristes-messe. It has also been translated as Christian mass.

Wherever you are, may peace and tranquility bless you during this difficult time.

COVID-19 World-wide as at the end of October 2020 - 45.5 Million

As the world continues to grapple with COVID-19, Australia now ranks 89th for the virus transmission. The staggering figure of 45.5M infected people almost certainly under-estimates the true figure due to various factors such under-reporting, different measurement of data and low testing rates in some countries. Vaccines, even with considerable advances in virology, still take time to develop and coronaviruses in general are difficult to treat.

75 Years on - Victory over Japan remembered

Australian Womens Army Service, New Guinea, 15 August 1945 (c) AWM

For Australia the 15th of August 2020 marks 75 years since the Victory over Japan (referred to as VJ Day) or Victory in the Pacific (or VP Day) and the end of World War II. Japan accepted the Allies demand for unconditional surrender and with the war with Germany already concluded, Word War II was at an end.

The war in the Pacific had been particularly cruel for Australia with over 22,000 Australian sbecoming prisoners of the Japanese. These comprised 21,000 from the Australian Army, 354 from the Royal Australian Navy and 373 from the Royal Australian Air Force. 40 nurses were also captured and hundreds of civilians placed into internment camps. Prisoners of War were formed into work partes to provide forced labour for the Imperial Japanese Army including the notorious Burma Railroad.

8,031 of the 22,376 Australian prisoners of war captured by the Japanese died in captivity leading to War Crimes Tribunals at the conclusion of the war that investigated the many reports of massacres and atrocities committed by the Japanese forces.

Australian fallen being exhumed for reinterment in the Wewak Military Cemetery 1945 (c) AWM

COVID-19 incidence and mortality as at 2 May 2020

As the novel coronavirus COVID-19 continues its movement across the world, the overall mortality rate is around 7 % of total infections based on 3.4M persons infected. This however does not accurately represent the number of deaths nor the actual burden of disease due to under-reporting in several jurisdictions, factors of co-morbidity from other conditions and poorer outcomes in several countries compared to others. The timing differential between earlier outbreaks in Europe and South East Asia and later outbreaks in Africa, the Middle East and Africa means the impact of this disease still has some way to progress.

At this point higher mortality rates are shown in the UK (15%), Italy (13%) and Spain (11%) whereas Germany has a low level of death (4%). The United States is currently tracking at 5.8%. These figures sadly can be expected to alter in varying measures with slow or fast upward swings depending on the success of control measures being adopted.

Back in March 2020, Australia was ranked around 19th in the top twenty countries with confirmed numbers of people infected with COVID-19. Using a suite of methods to reduce transmission including closure of borders, social distancing, banning of mass gatherings, shutting down non-essential services, rigorous testing and contact tracing, Australia is now ranked 47th in the world. This is a significant achievement but one which is bittersweet. It comes with significant costs for the country whether  psychological, social welfare and economic - impacts that are being reflected world-wide.

Johns Hopkins University and Medicine remains the main global surveillance site:
Coronavirus Johns Hopkins Map

Lest we forget - ANZAC Day 2020

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As ANZAC Day dawns with a change in custom due to COVID-19, nonetheless the opportunity to reflect on the sacrifices made by those who have served in the Armed Forces particularly during wartime remains as valid as ever. While much of the ritual elements of ANZAC Day find their origins on the battlefields of the First World War, particularly Gallipoli and the Western Front, the contribution of the Second World War is just as poignant.

Australia's casualties in WWII were 39,655 killed or died as a result of their injuries during the period from 3 September 1939 until 30 June 1947. World War II ended in Europe on 7 May 1945 with Germany's surrender and in the Pacific on 14 August 1945 with Japan's surrender. Over 30,000 Australian service personnel were taken prisoner by the Axis Forces of which two-thirds of these were captives taken by the Japanese during the first weeks of their advance through south-east Asia in 1942. 36 per cent of all Australian prisoners died in the captivity of the Japanese.

It was during the American Civil War, that Union General, William Tecumseh Sherman made the oft used quote that has been repeated many times in various forms:  "War is hell... war is cruelty and you cannot refine it".

Lest we forget.