OPINION

Rethinking Global Clinical Research In The Era of Digital Health

FIGURE 1  |  As the use, reliability, and confidence in digital tools and electronic data management systems increase, such systems will be further introduced into clinical trials.

As use of electronic data management systems continue to increase, those systems will be further introduced into clinical trials.

Taken a bit further, digital technology permits continuous real-time monitoring of participants’ well-being during and after clinical trials. This will boost the process of collecting data and will drastically increase insights into patient health and compliance, as well as safety and ectiveness of the therapy in question. Digital mHealth tools enable the swift, secure collection of large volumes of accurate and consistent data on which further analysis can then be performed on the spot, such as comparing therapies and assessing efficacy.7,8,9

These days, many clinicians are dispirited by the numerous repetitive practices required in conducting clinical trials. If digital data sources were to be fully used, many of those repetitive practices would be unnecessary. It is important to note that all stakeholders, including health authorities, have a great interest in clinical trial optimization. As an example, consider the US Food and Drug Administration’s (FDA) “Voice of the Patient” program, which aims to “systematically gather patients’ perspectives on their condition and available therapies to treat their condition.”10

While the adoption of mHealth will require transforming study teams to a new and different way of working, the digital technologies will improve trial efficiency by enhancing and supporting the role of investigators and study staff . Fresenius Medical Care will be moving toward a participant-centered clinical trial experience by minimizing geographic obstacles for participation and establishing a high level of connectivity with participants and investigators. This allows for the possibility of individual findings and overall results to be returned repeatedly to participating investigators throughout the duration of the study, thus fostering a true partnership in clinical research. mHealth will help shape a more personalized, more precise, and more supportive clinical research environment.

GLOBAL CLINICAL TRIALS: OPTIMIZING METHODS, DESIGN, AND THE REGULATORY ENVIRONMENT

Traditionally, Fresenius Medical Care’s clinical trials have been largely limited to North America and certain countries in Western Europe. The introduction of global digital clinical trials represents enormous potential in various areas, including streamlining operational costs, increasing speed and agility, and enhancing the diversity of clinical participants. Today, there is an enormous opportunity to harness digital technology to expand research activities geographically and concurrently to accelerate the pace at which evidence through clinical trials can be generated.11,12,13,14

However, this cannot be accomplished by replicating the current research processes and simply transforming them from paper to digital form. Rather, a complete rethinking and reengineering of the clinical trial concept around the participant and the clinical site is needed. While some trials could be conducted digitally in a virtual environment, many will require a hybrid of virtual and clinical site-based activities. Future digital clinical trial concepts will use micro-randomization to build and optimize individual intervention components within just-in-time adaptive interventions. These mHealth technologies aim at delivering the right intervention components at the right time and location to optimally support individuals’ health behaviors.15,16,17,18,19,20,21

Finally, the harmonization of pharmaceutical regulations is essential to transform the traditional concept of clinical trials. Significant progress on regulatory convergence has been achieved to date by agreements and close collaboration between regulators like the FDA and the European Medicines Agency. Much eff ort is still needed before a fully global harmonization can be realized.22,23,24

UTILIZING EMERGING TECHNOLOGIES FOR THE FUTURE

Medicine today primarily focuses on treating disease; in the future, it will increasingly be used to prevent disease. A dramatic transformation of the global clinical trial operational delivery model is under way, driven by ever improving digital clinical technology in a more harmonized regulatory environment. Fresenius Medical Care’s global clinical research team is prepared to responsibly and creatively adopt digital technologies to create efficiencies in a way that preserves the strength of classical clinical trials. There is ample evidence of the benefits of mHealth. 

Correspondingly, digital tools will improve clinical trial designs, yield data of higher quality at lower cost, and accelerate Fresenius Medical Care’s product development cycle times. This will ultimately permit an accelerated release of new products and therapies that improve the health of individuals living with kidney disease and provide more advanced treatment options for healthcare professionals.

Meet The Experts

 

Manuela Stauss-Grabo, PhD
Vice President, Head Clinical Research, Europe/Middle East/Africa, Asia Pacific, and Latin America, FME Global Medical Office 

References

  1. Steinhubl SR, Wolff-Hughes DL, Nilsen W, et al. Digital clinical trials: creating a vision for the future. npj Digit Med 2019;2:126. https://doi.org/10.1038/s41746-019-0203-0.
  2. Inan OT, Tenaerts P, Prindiville SA, et al. Digitizing clinical trials. npj Digit Med 2020;3:101. https://doi.org/10.1038/s41746-020-0302-y.
  3. US Department of Health & Human Services. Health information privacy: Health Insurance Portability and Accountability Act (HIPAA). https://www.hhs.gov/hipaa/index.html. Accessed May 3, 2021.
  4. European Commission. Data protection in the EU. https://ec.europa.eu/info/law/law-topic/data-protection/data-protection-eu_en. Accessed May 3, 2021.
  5. mHealth: New Horizons for Health through Mobile Technologies: Second Global Survey on eHealth. World Health Organization Global Observatory for eHealth series, vol. 3 (Geneva: WHO, 2011). https://apps.who.int/iris/handle/10665/44607.
  6. Malikova MA. Optimization of protocol design: a path to efficient, lower cost clinical trial execution. Future Science OA 2016;2(1). https://doi.org/10.4155/fso.15.89.
  7. Torgan CE. The mHealth Summit: local & global converge. Kinetics: From Lab Bench to Park Bench blog, Nov. 6, 2009. https://caroltorgan.com/mhealth-summit/.
  8. Case MA, Burwick HA, Volpp KG, et al. Accuracy of smartphone applications and wearable devices for tracking physical activity data. JAMA 2015;313(6):625-6. doi:10.1001/jama.2014.17841.
  9. Rabbi M, Klasnja P, Choudhury T, et al. “Optimizing mHealth interventions with a bandit,” in Digital Phenotyping and Mobile Sensing, eds. H. Baumeister and C. Montag (Springer, 2019), https://ambujtewari.github.io/research/rabbi19optimizing.pdf.
  10. US Food and Drug Administration. Project Patient Voice. Last updated June 23, 2020. https://www.fda.gov/about-fda/oncology-center-excellence/project-patient-voice. 
  11. Thiers F, Sinskey A, Berndt E. Trends in the globalization of clinical trials. Nat Rev Drug Discov 2008 Jan;7:13-14. doi.org/10.1038/nrd2441.
  12. Ayalew K. FDA perspective on international clinical trials. US Food and Drug Administration, Dec. 12, 2013. https://www.fda.gov/media/87406/download.
  13. Shenoy P. Multi-regional clinical trials and global drug development. Perspect Clin Res 2016 Apr-Jun;7(2):62-67. doi: 10.4103/2229-3485.179430.
  14. Lang T, Siribaddana S. Clinical trials have gone global: is this a good thing? PloS Med 2012;9(6):e1001228. doi: 10.1371/journal.pmed.1001228.
  15. Hekler EB, Michie S, Pavel M, et al. Advancing models and theories for digital behavior change interventions. Am J Prev Med 2016 Nov;51(5):825-32. doi: 10.1016/j. amepre.2016.06.013.
  16. Aung MH, Matthews M, Choudhury T. Sensing behavioral symptoms of mental health and delivering personalized interventions using mobile technologies. Depress Anxiety 2017 Jul;34(7):603-9. doi: 10.1002/da.22646.
  17. Klasnja P, Hekler EB, Shiffman S, et al. Microrandomized trials: an experimental design for developing just-in-time adaptive interventions. Health Psychol 2015 Dec;34S(0):1220-8. doi: 10.1037/hea0000305.
  18. Liao P, Klasnja P, Tewari A, Murphy SA. Sample size calculations for micro-randomized trials in mHealth. Stat Med 2016 May;35(12):1944-71. doi: 10.1002/sim.6847.
  19. Liao P, Greenewald K, Klasnja P, Murphy S. Personalized HeartSteps: a reinforcement learning algorithm for optimizing physical activity. arXiv:1909.03539, Sept. 8, 2019. https://arxiv.org/pdf/1909.03539.pdf. 
  20. NeCamp T, Sen S, Frank E, et al. Assessing real-time moderation for developing adaptive mobile health interventions for medical interns: micro-randomized trial. J Med Internet Res 2020 March;22(3):e15033. jmir.org/2020/3/e15033/.
  21.  Zerhouni E, Hamburg M. The need for global regulatory harmonization: a public health imperative. Science Translational Medicine 2016 May;8(338):338. doi: 10.1126/scitranslmed.aaf1396.
  22. Weisfeld V, Lustig TA, eds. International Regulatory Harmonization Amid Globalization of Drug Development: Workshop Summary. Forum on Drug Discovery, Development, and Translation (Washington DC: National Academies Press [US], Oct. 24, 2013).
  23. US Food and Drug Administration. Mutual Recognition Agreement (MRA). Last updated Apr. 8, 2021. https://www.fda.gov/international-programs/international-arrangements/mutual-recognition-agreement-mra.
  24. Government of Canada. Canada-United States Regulatory Cooperation Council (RCC). Last updated Nov. 19, 2020. https://www.canada.ca/en/health-canada/corporate/about-health-canada/legislation-guidelines/acts-regulations/canada-united-states-regulatory-cooperation-council.html.