Clinical trialsresearch studies performed to test new treatments, tests or procedures and evaluate their effectiveness on various diseases are studies to trial new medications, devices and other treatments, and important in developing new treatments for serious diseases like cancer.
These trials are devised to explore and assess new potential ways of preventing, detecting, diagnosing or measuring disease spread, and are the best way to learn what works in treating diseases like cancer. All new treatments must go through clinical trials before being approved by the regulation body – in Australia’s case, the Therapeutic Goods Administration (TGA).
The questions these trials answer are:
- Does the new treatment / device work in people? How well does it work? Is it better than current treatment being used? If it’s not better, does it have fewer side effects? Does it work for those who aren’t being helped by current treatments?
- Is the new treatment safe? No treatment or procedure, even those currently being used, is without risk. But do the benefits of the new treatment outweigh the risks?
- Is this treatment better than the standard treatment given for this disease? Clinical trials help show if a new drug, treatment or treatment combination, works better than what is currently being used.
Each phase of the trial is designed to answer certain of these questions, whilst also keeping volunteer human participants as safe as possible.
To be approved for widespread use, these technologies have to go through ‘phases’ of development (or ‘stages’ for medical devices) to ensure these drugs or treatments work and are safe for people to use. And these processes, particularly for cancer, can take years to complete.
Phases are conducted in order so that the previous results of prior phases should influence the plan of later phases. And even before phases begin, pre-clinical studies are done by testing the new treatments on cancer cells in a test tube and on cancers in live animals. Now let’s break down the following process by looking at each phase.
Sometimes, trials start with a phase 0 or ‘pilot study’, but this type of study isn’t like the other phases of clinical trials. This phase speeds up and streamlines the treatment approval process by eliminating ineffective products early in their development, before proper trials. This is to essentially explore if and how a new drug may work.
Phase I is usually the first stage that involves people with different types of cancer, after being tested in lab and animal studies. This stage is looking at what the treatment does to the body and what the body does to the treatment to essentially to find the highest dose of new treatment that is safe without severe side effects. Placebos are not used here. The first few people involved are observed closely while they are administered a low dose of treatment; the next cohort are given a slightly higher dose, and until they’ve reached a dose level that is most effective while side effects are at an acceptable level. Safety is the main concern during this phase, not disease response. Whilst trials in this phase carry the most potential risk, sometimes they benefit those with life-threatening illnesses who have joined after all other treatment options have been exhausted.
Phase II is what Phase I trial treatments progress to if they’re found to be safe. This is where the studies are broadened to test the treatment on larger groups of people with the same type of cancer, using the dose and method found to be the safest and most effective. The benefit is determined by the treatment goal – cure, stability, or improved quality of life, and bigger groups of patients allow possible less common side effects to be observed. Placebos are still not used.
Phase III trials are to test whether the new treatment, that has passed Phase II, is better than what’s already available. So these new treatments are compared against current standard treatments in terms of safety and effectiveness. This is where placebos come in – participants are randomised to either the placebo / standard treatment, or the new treatment. These can be double-blind studies, where neither the trial staff nor the patient knows which treatment the patient is being given. Trials in these phases use much larger numbers of patients and are often carried out in many places across the country concurrently, and they take longer than Phase I and II trials. Patients are still assessed closely for any adverse effects, and if any problems occur, treatment is halted.
After Phase III has been passed, treatments are then submitted to the Therapeutic Goods Administration (TGA) for approval, after they’ve reviewed the trial’s results and other relevant information. Occasionally, after approval, treatments will go through Phase IV trials to observe the treatment’s effects on the wider population over a long period of time and answer more detailed questions concerning other aspects, such as quality of life or cost effectiveness. These Phase IV trials do not need people to “sign up”, and care is no different to standard care. They’re simply to better inform clinicians and researchers about how to continue best treating future patients.
So, as you can see, most modern medical interventions leading to improved health outcomes, reduced pain and better quality of life for patients, are a direct result of research using clinical trials. And by the stage of reaching the Australian public, they have been through rigorous safety assessments and TGA approval.
By taking part in a clinical trial, you can contribute to the advancement of scientific understanding, improved available healthcare services, and, in some cases, to improved health for yourself and others with the same illness because this is the way emerging therapies and technologies become accessible to Australians.
Authored by Dr Emily Isham