Decentralized Clinical Trials— The Tomorrow of Clinical Research

The Coronavirus disease 2019 (COVID-19) pandemic has led to many changes in the way different processes are handled. In particular, it is profoundly disrupting clinical research. Many start-up activities for new clinical trials may be deferred and recruitment suspended. However, the COVID-19 pandemic also creates opportunities for innovative trial designs. There have been new proposals and options for performing clinical trials, which  take advantage of modern technologies. 

One such technology was called a Decentralized Clinical Trial (DCT).(1) Some different phrases are used when discussing DCTs, for instance, “remote,” “virtual,” “direct-to-patient,” “site-less,” and “hub-and-spoke” clinical trials. For the purposes of common terminology, the term ‘decentralized clinical trials (DCTs)’ are accepted in general.

DCTs allow the development  of tasks that traditionally could only be done face-fo-face to be done remotely and involve new technologies through telemedicine, mobile, or local providers,(1) that are more efficient and cost-effective.(2) Furthermore, These technologies offer an opportunity to collect novel forms of data in real-world environments, offering the potential to improve the reliability, generalizability, and applicability of research findings.(3)

Decentralized clinical trial models can have a variety of advantages for patients.  The key benefits of DCTs include, but not limited to easy and faster trial participant recruitment, improved trial participant retention, increased participant diversity, reduction on patient burden, better control and comfort for participants, improve data quality, patient experience and improved clinical trial continuity. Additional benefits may be to improve the generalizability or external validity of the evidence obtained from clinical trials, without significant sacrifices in internal validity.   

DCTs have been gaining impetus for several years, supported by mobile technologies and novel innovations. The US Food and Drug Administration (FDA) has  promoted the DCT as an alternative to traditional trials, which did not appear with the pandemic, but rather have been gaining traction for the lasts few years, as more and more technologies have made them more approachable and realistic.  Many proponents also have been in favor, because it would allow more people to take part in the trials, improving the results.(4)

However, DCTs have not been adopted very quickly. Some biological pharma companies have done pilot studies, but have not decided to take them on as an equivalent to traditional trials. There is limited knowledge about best practices, awareness, and general willingness to work on DCTs, which have been the key obstacles, as per the  organizations working to increase their adoption.(4)

Why are DCTs needed? Studies indicated that  with the traditional clinical trial model, 85% of trials do not recruit enough participants and 80% do not finish on time. 70% of potential participants live more than 2 hours away from their nearest study center which limits recruitment and retention. 20% are canceled due to enrollment problems.  DCTs could help reduce this set of problems.  The benefits they offer could make the trials less difficult for patients. (5)

Furthermore, DCT improves the patient´s experience, by demanding less time and allowing them to focus on their responsibilities and relationships, so they can be at home. This can also allow patients who mobility issues or those with significant issues, such as fatigue. It significantly reduces the traveling burden, which is suggested to be a significant barrier for up to 60% of trial participants. People would be able to access treatment from rural areas, other cities, and even other countries without significant financial costs. By reducing these barriers, retention and recruitment rates are also likely to improve. (5)

Regarding this point, FDA also recommended virtual assessment when possible in its guidance for conducting clinical trials during the pandemic (6) and started to work on supporting and promoting virtual trials. The COVID-19 pandemic has highlighted  the need for more remote access  and greater technology use. There have been studying results during the COVID-19 pandemic supporting the effectiveness of DCTs. For example, clinical trials for cancer have required new remote models for delivering  care and monitoring the results. This has presented challenges but also suggests that future trials can benefit from it by becoming more cost-effective and easier to implement.(7) This also shows that under the extreme circumstances of a  pandemic, change is faster to implement and that despite challenges, DCTs can work for serious conditions and are a better alternative than simply suspending the trials indefinitely, one that is  more considerate of patients’ needs and is quite possible with the existing technologies.

There are some challenges that DCTs are facing now and will likely face in the future. The selection of the bests technologies will probably not happen right away, as concerns like patient data protection and monitoring. Regulations are also something that needs to be considered, as the development of new approaches to clinical trials will require regulatory action to protect patients and develop bests practices.(5) However, the key challenges  to DCTs at  the moment are increasing adoption, establishing best practices in regards to technology choice, and  maintaining the quality and integrity of data. Additional training, insurance, and management of adverse events (AE) as well as serious adverse events (SAE) must be considered.

What is the future of DCTs? It seems that they will be more popular and more widely used, but it does not seem likely that they will fully replace in-person trials. It appears likely that more organizations will implement hybrid trials that require the  patient to spend less time in the hospital and make more use of the available technologies to improve data collection. Improving this by making trials more convenient and easy to access will not only benefit the patients but the science as a whole, because the trials can be bigger, less expensive, and allow the researchers to gain more accurate data.  Future trials will likely be better organized and more effective, as a knowledge base and evidence for best practices is gathered. Regulatory bodies should support the inclusion of evidence-based remote assessments as clinical trial endpoints.

The benefits DCTs offer are many and can potentially make a big change in the approach to clinical trials and their effectiveness, allow more people access to treatment and the researchers access to better data. DCTs have benefits that by far outweigh the challenges, and it seems likely that the adoption of this modality is going to continue in the near future. 

References

1 Biorasi.  (2020). https://www.biorasi.com/what-are-decentralized-clinical-trials/

2 Contemp. Clin. Trials Commun.  (2018) 11, 20–26.

3 Clin. Pharm. Ther.  (2019) 106, 25–27,

4 Pharmavoice (2021) https://www.pharmavoice.com/article/2021-02-decentralized-clinical-trials/

5 FDA  (2020) Guidance on Conduct of Clinical Trials of Medical Products during the COVID-19 Public Health Emergency. Guidance for Industry, Investigators, and Institutional Review Boards. 1–35

6 Shikova, D.(2020). https://trialhub.findmecure.com/blog/articles/the-benefits-and-barriers-of-decentralized-clinical-trials/

7  The Lancet Oncology. (2021) Mar;22(3):298-301.   

About the Author

Lin Zhang, M.D., senior director of a health care industry company in the United States. With the experience in clinical medicine, biotechnology, health industry and other fields, he is responsible for the research and development of plant medicine, functional food and health products. He was a clinician and worked for the National Cancer Institute, FDA and the National Cancer Center of Japan for many years.