Sarah McDonald
Director of Research, Myeloma UK
As our knowledge of cancer and how to treat it has grown and evolved, there has been a clear need to innovate the way we do clinical trials.
We now know every cancer is different and that a single treatment or drug won’t work for everyone. Cancer cell biology is diverse and varies between both different types of cancer but also between patients with the same cancer. This is particularly true for a relapsing-remitting cancer like myeloma, where a patient’s cell biology can vary over the course of the disease.
To successfully deliver kinder, more effective treatments for all cancer patients we need more personalised treatments tailored to a patient’s individual characteristics.
Adaptive trials are designed for flexibility
Traditional randomised, controlled clinical trials are linear and designed to answer one specific question. These fixed trial designs work well for treatments like chemotherapy drugs which were developed for a large, generalised group of cancer patients. However, they don’t work as well for more targeted, personalised treatments.
To deliver truly personalised treatments we need innovative trials that provide flexibility and the ability to answer multiple questions simultaneously. This is where adaptive trial designs come in.
Adaptive trials have several predefined review and adaptation points throughout the trial. At the adaptation points, researchers review the data collected from the trial and make changes where required; a trial arm may close, increase in recruitment for a patient cohort or a change in dose or combinations.
This innovation means that several questions can be answered at the same time without impacting the scientific integrity of the study.
Being able to learn about a new drug throughout the trial means researchers don’t need to wait until the end of the trial to find out if the drug works.
Learning earlier and faster
Adaptive designs are particularly useful in the earlier stages of drug discovery where there is more uncertainty and a lot of unanswered questions.
Researchers can merge several traditional trials into one large trial with multiple arms and review stages. This increases flexibility, helps optimise resources, and may require fewer participants.
Being able to learn about a new drug throughout the trial means researchers don’t need to wait until the end of the trial to find out if the drug works. Results are available more quickly helping make drug discovery faster and more efficient.
Adaptive trials are better for patients
The real strength of adaptive trial designs is their ability to make trials more patient-focused rather than drug focused.
Researchers can look across multiple patient groups to find the people for whom the treatment works for and why.
The on-going adaptations help maintain the balance between effectiveness and toxicity so the optimal dose is taken forward. This reduces the number of patients treated with ineffective or harmful drugs at inaccurate doses and maximises the numbers treated on more efficacious arms.
The multi-arm, multi-stage design in adaptive trials means patients can stay in the trial for longer and give clinicians flexibility to consider what the patient needs, letting them adapt treatments and make dosing changes during the trial. This is particularly beneficial for patients who did not respond to treatment, experience severe toxicities, or have relapsed early.
Innovative trials need investment
Despite the many advantages of adaptive clinical trials, adoption has been slower than expected. They need complex statistical work to maintain scientific validity so can take longer to design and be harder to pitch to funders.
To help increase the use of these innovate, patient-centred trials Myeloma UK funds the UK Myeloma Research Alliance- Myeloma UK- Concept And Access Research Programme (CARP) which aims to develop, secure funding and open early phase trials.
The first adaptive trial has secured funding and is waiting to open with several more in the development pipeline. CARP is the only UK initiative focused on the development of innovative early phase trials to meet the needs of myeloma patients so they can access novel treatments up to ten years before they are available through the NHS.
