Decentralized Clinical Trials: How about your data

One of the recent hot topics in clinical research is Decentralized Clinical Trials (DCTs), obviously driven by the COVID-19 pandemic to save disrupted clinical trials.

When DCT’s first came to my attention, it brought back memories of a phase-I trial I was involved in about a decade ago. Let’s reminisce... It concerned a trial to investigate if a certain drug could be detected in breast milk. For the trial we needed to recruit young mothers that were thinking of stopping breastfeeding. In general, study participants would be required to come to the clinic for the assessments, either for an internal stay or on regular visits. Being a recently new mom myself at the time, I knew this was going to be extremely difficult - if not impossible - to accomplish for young moms. This requirement threatened to significantly affect recruitment rates. As a team we soon realized that we would have to look ‘outside the box’ to make the trial as comfortable as possible for the breastfeeding moms. We decided to use a small bus with clinical staff and all necessary paperwork, laptops and clinical tools, and visit the mothers at their homes for our data collection. The trial was extremely successful, and the flexible approach was applauded by the client, the participants and others involved. Little did we know that this would nowadays be seen as a first step towards DCT!

Decentralization essentially means that trial participants will have some (hybrid) or all (completely decentralized) of the study assessments done outside of the involved clinical site(s): remote participation. This of course has huge benefits for the participants, especially if there are reasons that make traveling to a clinic a burden, as they are no longer bound to a geographic location. For example in the case of the young mothers as mentioned before, but also the case of pediatric patients or patients with (rare) diseases that need to travel a long time to reach a (specialized) clinic. Other benefits besides the convenience for the participants include a faster recruitement rate, a more diverse population for the trial (and thus a better representation leading to more trustworthy results) and lower drop-out rates.

Notwithstanding the advantages for participants and sites, there are some considerations to take into account. One of the main focal points in any clinical trial is data integrity, and this may warrant more attention in DCTs. It should be realized that decentralization will impact data collection, and therefore might impact the (statistical) results of the clinical trial if data collection is not handled properly. It is not uncommon that data in DCTs are collected via several methods instead of via one central EDC system. It is therefore imperative to proactively think about data quality and data security. The data flows in the DCT, including safe transfers, storage and security issues, should be clearly assessed, and any impact of the specific data collection on the endpoints of the study should be considered. Furthermore, standard monitoring/source data verification may not be possible or even considered unnecessary in DCTs, and it may therefore be essential to include statistical monitoring of the data to identify data inconsistencies/anomalies early on in the clinical trial.

New ideas always add some form of complexity in another part of the streamline and (innovative) solutions are needed to set proper controls for ensuring data integrity of the clinical trial. FDA and EMA encourage the use of DCTs, but also understand the complexity that comes with it. Both are already hinting towards (draft) guidances being prepared on the operation of DCTs, tackling endpoint analysis and data integrity. Also the CTTI is currently updating their recommendations on DCTs.

It shall come as no surprise that my advice is to always involve a knowledgable statistician into the designing stages of a DCT, to guard against unwanted data integrity issues. This will result in trustworthy data supporting the endpoint(s) of your clinical trial.

  1. Food and Drug Administration, Center for Drug Evaluation and Research. CDER 2021 Guidance Agenda: New & Revised Draft Guidance Documents Planned for Publication in Calendar Year 2021. https://www.fda.gov/media/134778/download
  2. European Medicines Agency. EMA Regulatory Science to 2025: Strategic reflection. Published 2020. https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/ema-regulatory-science-2025-strategic-reflection_en.pdf
  3. Clinical Trials Transformation Initiative (CTTI) Recommendations : Decentralized Clinical Trials. https://ctti-clinicaltrials.org/topics/mobile/supporting-a-decentralized-trial/ctti-holds-meeting-to-refresh-and-enhance-decentralized-clinical-trials-recommendations/

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