Should we be Phased about the Phasing out of the Phased trial Paradigm?
19 July 2019
It was an enlightening 3 days in a sunny Manchester at the ‘Phase I – where science becomes medicine’ conference as we ask and endeavoured to answer 2 key questions:
- Why are Phase I trials changing?
- Should every cancer patient have comprehensive genomic profiling prior to each experimental therapy?
In the opening session Keynote speaker Professor Lillian Siu, explained how Phase I trials need to be more efficient and how results in Phase I could be used to lead accelerated approval applications. Challenging the traditional drug development paradigm she showed how past and present Phase I trials are changing with much larger patient numbers, many more sites located globally rather than just Europe and North America leading to more data collected and an increase in overall complexity of the early phase trials. Making early phase trials act more like those traditionally in the later phases. She even suggested that in the future the use of ‘Phase’ could be ‘phased’ out!
With cost, efficiency and speed to market complicated by the critical safety piece the cons of skipping steps are becoming clearer. Exposure of more patients to potentially toxic doses, complex protocols with often many amendments, sharing of safety information in a timely manner, lack of identified endpoints and statistical goals, to name but a few. The dilution of the clinical and administrational skills and resource available in such a large number of sites is also a major problem here. As with all challenges, they need to be faced up to and methods of working need to be reviewed and brought up to date to match the changing face of the clinical trial environment. In fact, there are some real improvements being seen with respect to adoption of more modern, technology focussed methods of communication and file sharing and organisation. Generally, technology brings more control and standardisation of processes and of course the all-important accessibility of data and documents to not only key study personnel but also back-up personnel. All of the above proving to save time and increase efficiency.
In summary – Phase I trials are playing an increasingly critical role for go-no-go in drug development. Finding the right patient match for the trial – making the trials happen quicker – preserving safety – and keeping all key stakeholders informed and engaged as Phase I trials evolve in the drug development paradigm will be critical.
I mentioned finding the right patient match for the trial above and this was covered in a debate session asking the question:
Should every cancer patient have comprehensive genomic profiling prior to each experimental therapy?
In an initial vote in the room, there was a clear 74% vs 26% majority in favour at the onset. However following two presentations in the ‘for’ camp and two in the ‘against’ how would a more informed audience feel?
Professor Jeff Evans had chosen the ‘against’ straw (much to his displeasure) however, he did make a compelling argument showing positive evidence of progression-free survival where no profiling had taken place and accompanying this with the potential cost of profiling such large numbers of patients. Current figures indicate that 2% of the UK population (66.7m) are living with cancer multiply this number by the average commercial cost for each test and you find yourself with a bill in excess of £7bn. That is 96% of the current overall cancer spend for the NHS. Surely unattainable?
Fighting for the ‘fors’ Dr Tim Yap clearly stated that cancer evolution is real and needs addressing head on in order to optimise patient benefit. There are validated and more affordable technologies and assays out there and we must change it up and begin to use them. All experimental therapies carry risks and toxicities. Putting patients on trials blindly is bad for patients, drug development and ultimately cost. Whereas profiling each individual to find the best treatment available to them will increase the odds of success and this has to surely take the casting vote!
The final vote was taken and whilst there was a slight shift in thinking the overall majority were still definitely for more profiling to take place. It will be interesting to see how this continues to unfold.
Professor Lillian Siu
Professor Jeff Evans
Professor Jeff Evans is a Professor of Translational Cancer Research and Clinical Lead/Deputy Director of the Institute of Cancer Sciences, University of Glasgow, Honorary Consultant in Medical Oncology at the Beatson West of Scotland Cancer Centre , Glasgow, and Lead of the Glasgow Experimental Cancer Medicine Centre (ECMC).
Dr Tim Yap
Dr. Tim Yap is a Medical Oncologist and Physician-Scientist based at the University of Texas MD Anderson Cancer Centre.