Nine Keys To Running Successful Decentralized Clinical Trials

In today’s pharmaceutical development process, decentralized clinical trials (DCTs)  have helped researchers overcome a number of hurdles that have been associated with  the traditional trial model, including:

  • Lack of adequate participant population
  • High participant attrition rates
  • Inconsistent and low-quality data

However, despite successfully addressing these issues, the use of decentralized clinical trial methodologies has still not become an industry standard. According to a June 2020 Society for Clinical Research Sites (SCRS) survey, only 40% of clinicians have participated in a hybrid DCT or a virtual clinical trial. 

This reluctance in adoption may be due to the perceived complexities of setting up and running decentralized trials. 

Fortunately, DCTs don’t have to be complicated. Below are some of the best practices and key questions that need to be answered to run a successful decentralized clinical trial.

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1. Determine if the study can rely on a decentralized model

While decentralized trials have many benefits for s, sponsors, and CROs, not all clinical studies can be conducted utilizing a decentralized approach.

Some studies, for example, may require specialized procedures such as MRIs or surgery that can only be done at the sites where the specialized equipment resides. Additionally, some procedures may require face-to-face visits at the site. For example, specialized laboratory draws.  

It is therefore essential to weigh the requirements of each study and the risks associated with the study before deciding whether a fully decentralized approach,  a hybrid model, or a traditional model is the best.

2. Determine if there are country or state-specific regulations that need consideration

Due to the challenges with technological infrastructure and regulation barriers, decentralized clinical trials have had a slow adoption. 

Every regulatory agency may have specific regulations on what is acceptable in terms of utilizing a decentralized model. Those regulations can include specifics on safety reporting, data collection, use of technology, etc. Some regulatory agencies also offer guidance documents on utilizing this type of model especially now during the pandemic. For example, the FDA has a guidance document for sponsors and investigators on conducting clinical trials during the COVID-19 health emergency [see https://www.fda.gov/media/136238/download].

Before deciding on whether a decentralized trial model fits the study, ensure that all regulations, guidance documents and guidelines are reviewed for all countries that the study will be conducted in.

3. Determine the equipment and personnel training needed

The primary aim of DCTs is to bring clinical trials closer to the participant. The success of remote monitoring of decentralized clinical trials largely depends on the technology and equipment used plus the expertise of the personnel[1].

Decentralized trials rely on digital technologies, therefore, part of the study start-up has to include creating an online ecosystem that is comfortable for all users (e.g. investigators, site staff and participants). This has to include what types of technologies will be used (e.g. wearable detectors to measure vital signs, electronic diaries for participant self-reporting of adverse events, virtual reminders for adhering to the study requirements, etc.); training materials and how training will be conducted for both site staff and the participant; and validation and maintenance of the technology being used to ensure that it will perform as needed during the duration of the study.

Additionally, operational considerations must be taken into account.

For example, in a non-interventional study conducted in Switzerland studying low back pain, one operational difference seen between the decentralized arm and traditional arm was the average duration between the final signed ICF until the last contact was longer in the decentralized arm [1]. This was primarily due to the shipment of the devices being utilized for the study. It took some participants several days to pick their devices up from the postal service [1].

Having plans in place for dealing with both technological and operational issues and all of the logistics associated with the trial is crucial in the success of decentralized trials. 

4. Determine how safety data will be captured

It is extremely important that a plan is put into place to manage participant safety remotely. This necessitates that all parties (e.g. site staff, vendors, CRO, etc.) involved in the decentralized trial are trained on remote safety monitoring.  Procedures should be put into place on the collection of safety data, monitoring of that data, communication and escalation of any issues regarding the safety of the participant.

Additionally, like traditional clinical trials, the participant needs to be informed on what type of adverse events can be reasonably anticipated during the study and what to do if something does happen. The participant must also know what to do if an event of a serious nature occurs.

Utilizing digital technologies creates a unique situation for safety reporting. In most cases, the devices report data in real-time presenting the participant with information that they may not know how to interpret[2].

This can result in under-reporting or over-reporting of safety events, therefore, it is important that all participants are carefully trained on the device and, where appropriate, the safety signals that do and do not need to be reported[2]

5. Understand what data points the study wants to capture

Some clinical studies are complex, and they require close monitoring to ensure data accuracy. This means understanding how the data needed for the study will be captured.

During a decentralized trial, data is collected from several different sources, therefore it is important that there is a clear understanding on what measured outcomes can be reliably reported by the participant, by the mobile healthcare provider (if appropriate) or when collection is required by a visit to the clinical site or physician’s office[2]

Understanding this upfront can help to avoid collection of redundant data, ensure safety data is reported appropriately and can protect data integrity. 

As a study progresses, the data should be centrally monitored to ensure all endpoints for the study have been collected and there are no issues with data integrity. Audits of the study can also add assurance that the data is being collected per the protocol and has not been compromised.

6. Consider ethical recruitment of patients

The success of any clinical trial depends on participant recruitment and retention. Decentralized trials seek to bring trials closer to the participant to ensure better retention and to allow for recruiting participants that are not centrally located to a trial site.

Most traditional trials fail because the majority of participants live more than 20 miles away from the trial sites[3]. 

Therefore, before the trial begins, it is important to determine what the target population for the study is, the locations of the potential participants (e.g. urban or rural), and how participating in the trial may affect their day-to-day work and family lives. This information can help determine what type of digital technologies are to be used to be able to recruit and retain participants that would not necessarily decide to participate in a study because the clinical site is too far away.

7. Privacy concerns with the use of technology/remote tools

Protecting a participant’s privacy and confidentiality is of utmost importance no matter which type of clinical trial method is utilized.. Undeniably, the success of any DCT depends on the use of technology and other remote tools, however, these tools can collect a large amount of data that could potentially compromise a participant’s privacy. Ethical considerations and regulatory requirements when dealing with participant data online should be reviewed prior to study start and the risks should be considered.

Risks can range from the mobile health application requesting permission to access unrelated apps or information on a participant’s device to the technology manufacturer retaining all data collected by their apps which could be used for reasons that are not determined[4].

Participants need protection from their personal data getting into the hands of unwanted people. Additionally, utilizing mobile healthcare providers in a participant’s home can pose a concern regarding privacy affecting both the participant or someone else living in their home[4].  

Mitigation strategies for handling the risks associated with participants’ privacy and confidentiality should be put into place prior to the start of the study.

Strategies should include a thorough informed consent which explains to the participant who will have access to their data and how it is being used; limiting data collection to only what is necessary to meet the objective of the trial; privacy and confidentiality training for all mobile healthcare providers; and ensuring data agreements are in place with all software vendors as to the collection and retention of all data for the study.

Sponsors and investigators should ensure that all software vendors have methods in place to protect all data being collected throughout the trial.

.Finally, the participant has the right to know  if the trial requirements change which would impact their participation, changes in who has access to their data, or when their data has been compromised. A plan should be created on how to communicate this information prior to the start of the trial and reviewed periodically as the trial is conducted.

8. Determine whether a hybrid approach might be necessary

A hybrid approach to a decentralized trial might be necessary for studies with complex procedures. This approach combines both the utilization of digital technology with some visits being conducted at the clinical site.

This may be utilized when procedures such as surgery, radiological procedures or complicated blood draws are necessary for the trial. The determination of utilizing a hybrid approach should be determined prior to study start.

What procedures are to be conducted virtually and which ones will require an onsite visit be outlined in the protocol and should be clearly explained to the participant during the informed consent process so that they can make an informed decision about participating in the study.

9. Risk mitigation

Finally, for a successful DCT, an analysis of the risk associated with utilizing this method should be conducted. All risks should be considered from those seen in traditional clinical trials (i.e. data collection, recruitment and retention) to those that may be unique to decentralized trials (e.g. technology failures, logistic and operational issues, etc.).

Mitigation strategies should be put into place and reviewed periodically throughout the lifecycle of the study.

In conclusion, all types of studies depend on determining feasibility measures. Both traditional and decentralized trial methods have pros and cons. Taking the key concerns presented here can help aid in the determination of the best approach for the participants, investigators, and sponsors to lead to a successful clinical trial.


References
  1. Sommer, C., Zuccolin, D., Arnera, V., Schmitz, N., Adolfsson, P., Colombo, N., Gilg, R., & McDowell, B. (2018). Building clinical trials around patients: Evaluation and comparison of decentralized and conventional site models in patients with low back pain. Contemporary clinical trials communications, 11, 120–126.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6072894/
  2. Advarra, Inc. (2021, Aug 20). Ethical Issues in the Design and Review of Decentralized Research (white paper), 5. https://info.advarra.com/ethical-issues-in-design-of-decentralized-clinical-trials.html
  3. Leira E, C, Viscoli C, M, Polgreen L, A, Gorman M, Kernan W, N: Distance from Home to Research Center: A Barrier to In-Person Visits but Not Treatment Adherence in a Stroke Trial. Neuroepidemiology 2018;50:137-143. https://www.karger.com/Article/Fulltext/486315 
  4. Advarra, Inc. (2021, Aug 20). Ethical Issues in the Design and Review of Decentralized Research (white paper), 6. https://info.advarra.com/ethical-issues-in-design-of-decentralized-clinical-trials.html