As a follow-up to an earlier post on how to read health news, today we are discussing the phases of clinical trials in medical research.
In the late 1800’s, drug trials were so rudimentary that aspirin’s properties were marketed and sold alongside the health benefits of heroin and cocaine. More than a century later, aspirin, the only drug from this trio still legally available for consumption, has gone on to become one of the most studied medications in the world.
Different phases of clinical trials in medical research
Today, testing of new drugs is far more systematic and thorough, with most clinical drug trials conducted in phases. The early phases of clinical trials typically involve a small number of participants to determine product safety and effectiveness. Later phases test the product in larger number of participants to collect more information on effectiveness, safety and possible side-effects. Less than 20%* of new drugs make it past Phase III testing.
Before a new intervention (drug or medical device) is used on human beings, it undergoes extensive laboratory testing to determine how a drug works, its effect on the body and to identify a safe dose. It may be several years before an intervention is deemed safe for trialling in humans.
Phase I Clinical Trials
Phase I is a first-in-human trial to test the safety and identify potential side-effects of a new intervention (drug or device). This phase, which typically lasts several months, is undertaken in 20-100 people. Participants are often observed and monitored by trained staff between and following administration of the product. If the results are promising, the intervention continues onto Phase II testing. It has been estimated that 70%* of drugs tested in Phase I, move onto Phase II.
In some instances, real-patients who have not responded to previous treatments, e.g. cancer, may opt to be involved in this early stage.
Phase II Clinical Trials
Phase II clinical trials test the intervention in a larger group of people (often, several hundred) ” ..to determine efficacy (that is, whether it works as intended) and to further evaluate its safety.” (australianclinicaltrials.gov.au). Most phase II drug trials introduce a placebo (dummy tablet) into the trial to help compare results in those on the test drug and those not on the test drug. Phase II trials can range anywhere between several months to two years to complete. Approximately 33%* of experimental drugs studied in Phase II make it to Phase III.
Phase III Clinical Trials
The efficacy of an intervention is further tested in several hundred to several thousand participants in Phase III studies. This phase can last several years. Phase III studies are also randomised, blinded clinical trials to compare the effect of the intervention and to monitor for beneficial and adverse effects in the community. Medicines in this phase must have passed Phase I and Phase II testing.
Between 70% to 90%* of drugs that enter a Phase III study successfully complete this stage. Once complete, the company that owns the intervention is able to apply for approval by the relevant pharmaceutical regulators, e.g. the Therapeutic Goods Administration in Australia or the Federal Drug Administration in the US, for the product to become available to consumers. Generally, the company manufacturing the intervention owns the patent.
Aspirin has already been on the market for over 100 years and is no longer patented. This means, the ASPREE study is a Phase IV clinical Trial.
Phase IV Clinical Trials = ASPREE Clinical Trial
Phase IV studies are undertaken after a drug or device has been approved for use in human care. These studies collect more information about the intervention, such as: long term benefits and side effects in the wider community; human safety when the intervention is used in different conditions; and human safety when it is combined with other therapies. Not every intervention requires a Phase IV clinical trial. However, every Phase IV, like all phases, does require approval from a Human Research Ethics Committee. Results from Phase IV studies can lead to new recommendations or withdrawal of an intervention from the market.
What makes ASPREE a Phase IV clinical aspirin trial?
• Aspirin has been available for public consumption for more than 100 years
• ASPREE is testing a specific dose (100mg) of aspirin in healthy older people
• It is the first primary prevention trial of aspirin ever undertaken only in older people
• ASPREE is the first study to weigh the potential benefits versus the potential risks for primary prevention in older people (other trials have already proven that daily low-dose aspirin is overall beneficial for secondary prevention – that is, to help prevent another heart attack or stroke)
• ASPREE is determining the long-term effect of low-dose aspirin on participant’s overall health, including the prevention of cardiovascular disease, cancer, depression and dementia
References (accessed February 2016)
*according to http://www.centerwatch.com/clinical-trials/overview.aspx