Digital Health Technologies

by Riya Mankad, P2

Another company, Infinant Health, Inc., was also sent an FDA warning letter about their probiotic product Evivo with MCT Oil. It was also being sold in hospitals for use in preterm infants to treat or prevent disease. The product is supposed to be added to food for preterm infants. Since this product was also not being used as intended, it is considered an adulterated dietary supplement, making it the second probiotic that violated the FD&C Act and Public Health Service Act.1 Additionally, in the FDA’s letter to healthcare providers, they reference the death of a preterm infant who developed sepsis after being administered Evivo with MCT Oil as part of a preventative treatment regimen for high risk necrotizing enterocolitis.5,6 The bacterium that caused the adverse event, Bifidobacterium longum, was genetically confirmed with genomic sequencing data to come from the probiotic.3 In response, Infinant Health voluntarily recalled their product from the market.

Although there is demonstrated data about the links between the gut microbiome and various health conditons,5 careful considerations must be made before deciding to use probiotics as

What could the companies have done differently? Because they were marketing the product for health claims outside of the scope of a supplement, which is only allowed to make general claims about its effects on the structure or function of the body on the label,5 the product now needs to undergo more rigorous safety, efficacy, and manufacturing testing under FDA jurisdiction to support that claim. Companies with probiotic products wanting to make health claims, must apply for an Investigational New Drug (IND) application before trying to market their product as a treatment, mitigation, cure, or preventative therapy.6 Healthcare providers and the general public need to be cautious about the limited role that products with structure-function claims provide, and understand that these are not FDA-approved for any specific indications.

References

1. FDA Raises Concerns About Probiotic Products Sold for Use in Hospitalized Preterm Infants. U.S Food and Drug Administration. October 26, 2023. Accessed November 5, 2023. https://www.fda.gov/news-events/ press-announcements/fda-raises-concerns-about-probiotic-products-sold-use-hospitalized-preterm-infants

2. About Necrotizing Enterocolitis (NEC). Eunice Kennedy Shriver National Institute of Child Health and Human Development. Accessed. November 5, 2023. https:// www.nichd.nih.gov/health/topics/nec/conditioninfo

3. Neu J, Walker W. Necrotizing Enterocolitis. The New England Journal of Medicine. January 20, 2011. Accessed November 5, 2023. https://www.nejm.org/doi/ full/10.1056/NEJMra1005408

4. Thomas P, Raine T, Reddy S, et al. Probiotics for the prevention of necrotising enterocolitis in very low-birthweight infants: a meta-analysis and systematic review. National Library of Medicine. June 6, 2017. Accessed November 5, 2023. https://pubmed.ncbi.nlm.nih.gov/ 28471478/

5. Probiotics: What You Need To Know. National Center for Complementary and Integrative Health. Accessed November 5, 2023 https://www.nccih.nih.gov/health/ probiotics-what-you-need-to-know

6. WARNING REGARDING USE OF PROBIOTICS IN PRETERM INFANTS. U.S. Food and Drug Administration. September 29, 2023. Accessed November 5, 2023. https://www.fda.gov/media/172606/download? attachment

Digital health technologies (DHTs) are the newest addition to clinical trials to revolutionize data collection. DHTs integrate technology into clinical trials such that investigators/sponsors can collect participant data remotely, enabling real-world data collection away from a traditional clinical trial setting.1 Essentially, participants are given a remote data collection device in the form of wearable, implantable, ingestible, or external sensors that collects information and relays it to study investigators/ sponsors for review.2 The entire process of data collection and processing is highlighted in the figure above.

DHTs improve upon several of the limitations of traditional clinical trials, providing expanded data collection time-frames, easier participant recruitment/retention, and more diverse data.3 Seeing the significant improvements DHTs bring to the drug development process, FDA has expressed positive and supportive interest in the use of DHTs in clinical trials. In December 2021, the FDA published a draft guidance on Digital Health Technologies for Remote Data Acquisition in Clinical Investigations outlining the appropriate use of DHTs in clinical trials, addressing several important points including, DHT selection, verification, and use.4 For example, one of the simplest uses of DHTs can be in a trial that measures blood pressure. Participants of that trial can be given at-home blood pressure monitoring machines that directly report data to investigators, negating the need for participants to physically go to the clinical trial site for monitoring and/or keeping a log of their blood pressure at home.

While there are several benefits of integrating DHTs into clinical trials, there are some limitations as well. Specifically, there are some concerns surrounding user-friendliness, device maintenance/storage, and data confidentiality.5 However, both study sponsors and the FDA are committed to minimizing these concerns as much as possible. Several study sponsors have adopted training sessions for study investigators and par- ticipants education before the use of DHTs and also implemented appropriate DHT support infrastructure for DHT use during the trial.2 From the FDA’s side, in addition to the draft guidance, they have formed a DHT Steering Committee to appropriately evaluate DHT-based measurements and conducted DHT training workshops to educate study sponsors. Overall, the future of integrating DHT in the drug development process seems promising, especially as technology advances and people become more comfortable with digital medicine.5

References

1. Mittermaier, M., Venkatesh, K. P., & Kvedar, J. C. (2023, May 18). Digital Health Technology in clinical trials. Nature News. https://www.nature.com/articles/ s41746-023-00841-8

2. Mitsi, G., Grinnell, T., Giordano, S., Goodin, T., Sanjar, S., Marble, E., & Pikalov, A. (2022). Implementing Digital Technologies in clinical trials: Lessons learned. Innovations in clinical neuroscience. https://www.ncbi. nlm.nih.gov/pmc/articles/PMC9341314/

3. Managing data. CTTI. (2021, August 4). https://ctti-clinicaltrials.org/our-work/digital-health-trials/managingdata/

4. Center for Drug Evaluation and Research. (n.d.). Digital Health Technologies. U.S. Food and Drug Administration. https://www.fda.gov/science-research/scienceand-research-special-topics/digital-health-technolo gies-dhts-drug-development

5. Center for Drug Evaluation and Research. (n.d.-a). CDER conversation with Leonard Sacks. U.S. Food and Drug Administration.