The food, beverage and supplement companies racing to generate clinical trial data face challenges. Companies want to test their products in diverse populations that reflect their markets, leading them to work with contract research organizations (CRO) that enroll subjects at multiple third-party sites. Yet, while this boosts diversity, it forces the sponsor to cede control, threatening data quality.
Interest in testing food, infant formula, probiotics and many other products in humans has soared in recent years as companies have sought to convince consumers and regulators of the effectiveness of their products using data to justify marketing and health claims. The trend is exemplified by the 37% increase in clinical trial filings featuring the word “probiotic” from 2016 to 2018.1
If the US Food and Drug Administration (FDA) and the European Food Safety Authority (EFSA) are to accept clinical data, the study must comply with good clinical practices set by the International Conference on Harmonisation Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH-GCPs). These standards place burdens, such as double data entry, on CROs and sponsors but companies must follow them if the results are to be reproducible and widely accepted by regulators.
CROs and sponsors can ensure ICH-GCP compliance by keeping tight control of the protocol but this approach affects other aspects of their studies. Notably, the vast majority of CROs outsource the task of enrolling and assessing subjects to multiple third-party sites to ensure the study quickly recruits a diverse pool of participants. In doing so, these CROs cede control of the protocol.
This creates a dilemma. While single-center studies maximize control, multi-center trials offer access to more diverse populations that better reflect the countries in which they are used. Such diversity is scientifically desirable as genotypes affect outcomes. The performance of one-fifth of drugs approved over a six-year was affected by race and ethnicity.2 Race and ethnicity influence folate status and the effect of potassium on blood pressure, too.3,4
Despite this, clinical trial populations have historically been unrepresentative of society. In 1997, 92% of clinical trial participants were white.5 By 2014, the figure had only fallen to 86%. In recent years, FDA has stepped up its efforts to make clinical trial populations more representative of the U.S. by creating resources such as Spanish-language fact sheets about participating in studies.6
There are signs these efforts are having the desired effect. When FDA analyzed the study populations of all the drugs it approved in 2015, it found 79% of the participants were white.7 By 2018, the figure had dropped to 69%.8 Over the same period, the proportion of women and black or African American people in clinical trials increased by 40% and 120%, respectively.
Conducting multi-center studies to ICH-GCPs
If the food industry is to conduct ICH-GCP clinical trials and contribute to the FDA’s efforts to make studies more representative, it will need to find a model that balances control and diversity. This cannot be achieved by cherry picking subjects to artificially create study populations that are representative of the wider society as regulators require trials to accept participants as they present. This prohibits the selection of subjects to create diverse study populations.
One way to resolve the problem is to use multiple study sites that are all owned and operated by a single CRO or a group of CROs, rather than activate third-party hospitals and medical centers. This approach to multi-center randomized clinical trials provides enough sites to capture a diverse subject population without ceding control to centers that may compromise ICH-GCP compliance.
In the past, this multi-center model has required multiple CROs to work together. One CRO serves as the master site and runs the trial protocol across its own operation and those of other secondary site CROs that follow ICH-GCPs. These secondary sites provide recruitment services and run the subjects through their own facilities to enable the master site to access a larger, more diverse population,
Now, Atlantia Food Clinical Trials, a CRO, is expanding its operation so it can single handedly conduct multi-center, multinational trials and thereby create a new model that tackles the tension between diversity and control. Atlantia has built its business up to this point upon a site in Cork, Ireland that it owns and operates. The Cork facility employs statisticians, dieticians, nutritionists, project managers, nurses, doctors and regulatory affairs specialists who perform every step in the clinical trial process at the site.
Atlantia’s model gives it far greater control over its studies than is typical in the CRO sector, enabling it to consistently comply with ICH-GCPs, but it limits the pool of participants it can recruit to the area around its facility. By building a diverse database of 14,000 people, Atlantia has mitigated this issue but ultimately the population around Cork will always be an imperfect facsimile of society in the U.S.
Recognizing that, Atlantia is bringing its owned-and-operated model to Chicago. The Illinois facility will follow the same operational blueprint as the Cork site, meaning it will only conduct ICH-GCP studies and will perform all clinical trial tasks on site. Atlantia will enroll subjects from a database of volunteers based around Chicago and bring them to the facility. The wealth of specialists employed at the Chicago site will then take samples and administer the intervention as per the protocol.
Sponsors have already recognized the benefits of bringing Atlantia’s tightly-controlled clinical trial model to a new geography. One sponsor that worked with Atlantia on a study in Cork has signed up to replicate the trial in Chicago. The new trial will use a near-identical protocol to the earlier study but, as Cork and Chicago are demographically very different, it will nonetheless fulfill the sponsor’s desire to test its product in a different population.
Building a unique service offering
The Atlantia facility in Chicago will also meet the needs of companies that want to enter the US with the support of a CRO based in the country. While the FDA’s acceptance of ICH-GCPs means sponsors can use data generated in Cork to support claims about the effect of products on the structure or function of the human body in the US, some companies prefer to work with service providers that are on the ground in the country. Atlantia is now such a service provider.
Owning and operating facilities in Cork and Chicago makes Atlantia a unique CRO. There are very few, perhaps no, other food CROs that have the sort of multinational, multi-center capabilities Atlantia established with the opening of its Chicago facility.
Atlantia is now working to improve its service and further differentiate its offering from other CROs. Over the next five years, Atlantia plans to open several more sites in the midwest and one on each US coast. In doing so, Atlantia will significantly increase its access to large, diverse subject populations without relinquishing the high level of control that defines its Cork facility.
The US expansion strategy thereby stands to permanently resolve the tension between diversity and control. Sponsors that partner with Atlantia will gain access to tens of thousands people who reflect their communities in Europe and the US, while realizing the benefits of working with one CRO that performs each step in the clinical trial process itself to ICH-GCP standards.
References
1. Search of: probiotic - List Results - ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/results?cond=&term=probiotic&cntry=&state=&city=&dist=. (Accessed: 18th February 2019)
2. Ramamoorthy, A., Pacanowski, M. A., Bull, J. & Zhang, L. Racial/ethnic differences in drug disposition and response: review of recently approved drugs. Clin. Pharmacol. Ther. 97, 263–273 (2015).
3. Perry, C. A. et al. Ethnicity and race influence the folate status response to controlled folate intakes in young women. J. Nutr. 134, 1786–1792 (2004).
4. Houston, M. C. The importance of potassium in managing hypertension. Curr. Hypertens. Rep. 13, 309–317 (2011).
5. Knepper, T. C. & McLeod, H. L. When will clinical trials finally reflect diversity? Nature 557, 157–159 (2018).
6. FDA Unveils Clinical Trial Diversity Tools - ACRP. ACRP (2017). Available at: https://www.acrpnet.org/2017/01/23/fda-unveils-clinical-trial-diversity-tools/. (Accessed: 18th February 2019)
7. 2015-2016 DRUG TRIALS SNAPSHOTS SUMMARY REPORT. Available at: https://www.fda.gov/downloads/Drugs/InformationOnDrugs/UCM541327.pdf. (Accessed: 18th February 2019)
8. 2018 DRUG TRIALS SNAPSHOTS SUMMARY REPORT. Available at: https://www.fda.gov/downloads/Drugs/InformationOnDrugs/UCM630226.pdf. (Accessed: 18th February 2019)
