Team:NRP-UEA-Norwich/Practices/ClinicalTrial
INTEGRATED HUMAN PRACTICES
"How could we test the efficacy of our products?"
Integrated Policy and Practices
In looking forward to the possible products that our project is aiming to provide, we realised that we would need to understand how it could be brought to market in a way that would have an impact.
In our conversations with the Big C cancer charity, we learned that it might be difficult to have an impact without a government-backed scheme, or a large charitable component, and that such a wide-reaching scheme may only be supported if there was a cost-benefit to preventing cancer.
To gain such approval we need to be able to provide data that our product prevents colonic cancer in humans. Assuming, of course, that we could conduct successful animal feeding trials and get our products de-regulated and approved safe for human consumption, both of which would need to be done before they could be consumed by humans.
To work out how we would progress towards this we consulted with Dr. Peter Curtis and Dr. Vera van der Velpen, both of whom are based at the Department of Nutrition, at the Norwich Medical School at the University of East Anglia, who are currently conducting nutritional studies to determine how specific foods affect the progression of certain diseases. We learned how feeding trials are conducted and went away to consider our products and read the literature to determine what biomarkers we might be able to test for in human trials.
We therefore identified key biomarkers that measure increased apoptotic markers in the colon1 2 3 that can be tested to indicate if our products are effective. The trial population would be made up of people whose lifestyle and dietary habits (which we could confirm by further biomarkers for alcohol and fat consumption) make them predisposed to colon cancer.
Dr. Curtis gave us feedback on this initial plan and, discussing our aims in further depth, we realised that we needed to plan a series of trials:
- An initial study to prove our supplement (live culture) introduced significant amounts of butyrate in the human colon. For the probiotic we would also need to show for how long the bacteria persisted and if it was non-detrimental to the microbiome as a whole.
- A second study to quantify the rate of cell death (apoptosis) and whether this cell death was targeted appropriately to dangerously mutated cells.
- A further trial to determine if increased levels of butyrate had any detrimental effects.
- The final trial would need to be a large scale longitudinal study to prove colon cancer was prevented by our products. This could be achieved through close monitoring of a set population over many years or decades, in which we would aim to show that our experimental group had a lower incidence of colon cancer compared to control groups. Such a trial would be extremely hard to finance and conduct.
As well as our duty to the science, we also have a duty to the mental and physical well-being of all trial participants, a fact that could easily be lost in the complexities of the trials. Therefore, not only would we need to perfect the logistics of conducting the scientific aspect of the project, but also put in place a support infrastructure for those individuals taking part in the trial, without whom we could not bring our research to fruition.
With the correct test population, a trial could provide meaningful results, both physically but also mentally. We pursued the possibility of conducting a trial involving individuals who had previously been treated for colon cancer. With these participants, even if our product only prolonged further intervention and treatment, we were more likely to bring an immediate benefit that would include significant emotional benefits. This would allow us to have impact sooner as well as accruing valuable scientific data.
Clinical trials of this nature are far from clear cut - many years of planning and funding would be required to prove the beneficial effects of our products, however we might be able to realise the impact sooner by planning an appropriate trial process.
References
1. Holubec et al. 2005. Assessment of apoptosis by immunohistochemical markers compared to cellular morphology in ex vivo-stressed colonic mucosa. J Histochem Cytochem 53(2):229-35
2. West et al (2009) Apoptosis in the Colonic Crypt, Colorectal Adenomata, and Manipulation by Chemoprevention. Cancer Epidemiol Biomarkers Prev. 18(6):1680-7
3. Silva et al (2013) DNA methylation as an epigenetic biomarker in colorectal cancer. Oncol Lett. 2013 Dec; 6(6): 1687–1692.
