DCT + Traditional Tech for Clinical Trials?
Doug Bain, Chief Technology Officer at KCR
Running clinical trials with different stakeholders in different countries, including the most critical contributor — the participant — is not easy. Technologies have emerged over the last 30 years to make this possible, and ideally easier.
The eClinical technology puzzle can be quite complex with functions like Drug safety, trial management, supplies and data management all operating within their own ‘silo’ of systems with associated data and metadata. The following simplified diagram defines a typical technology map that applies to mid sized commercial studies from 2015. [I will not expand on the various acronyms for brevity here.]
A typical clinical trial involves the setup, testing/validation, execution and archiving of the associated systems that are necessary to support the clinical trial activities. Many companies use technologies from different vendors. CRO’s often use different technologies from a variety of vendors across their portfolio of individual clinical trials.
The Impact of DCT
Decentralized Clinical Trials attempt to re-define how clinical trials are typically run by bringing some (or all) of the activities that might otherwise be carried out at the site, directly to the participants. The activities are carried out either solely by the patient, or by the patient with the assistance of a Videolink or an HCP (e.g. a Home Health Nurse).
With the decentralization of the activities away from the site to the patient, we see an increasing demand for technologies to support the patient, and their associated support network. This expands the technology footprint with the following component technologies;
- Recruitment and pre-screening tools assist in the onboarding of a patient to a study.
- Electronic consent provides remote or site-based consent and re-consent.
- Electronic Clinical Outcome Assessment (eCOA) gets carried forward from our V1 model.
- Patient Supplies Management is necessary to support all trial patients by providing supplies directly to them.
- Concierge services ensure that a patient receives appropriate, script-approved support throughout the study.
- Patient engagement and Video conferencing provides the tools to provide virtual support and encouragement during the life of the trial.
DCT + / — Legacy ?
The vast majority of decentralized clinical trials will be hybrid. This means sites will continue to perform some activities on a traditional — patient at site — basis, and the technology that supports these sites will persist as is. In other words, DCTs will require continued functionality of existing EDC, CTMS, RTSM, Safety and eTMF technologies as shown in Figure 3.
As you can see, that takes what was already complicated, to very complicated mix, and this is without adding the points of integration that make each of these systems function. The additional annotations show some of the common points of integration between components.
The resulting technology map demonstrates what we see in a typical hybrid Decentralized Clinical Trial today. There is often a misunderstanding that DCT and Traditional systems do not need to work together. As a result we see manual integrations where a person re-enters key information between 2 or more systems. This re-entry results in extensive reconciliation, management, and data cleaning at best, and the late delivery of status and data at the worst.
The question this raises is whether this combined model remains viable and sustainable in the future? Sites are already overloaded with technologies used in a clinical trial. Is this one step too far for most investigator sites?
So, what are the options to address these complexity challenges? We have 3 options in achieving a combined Hybrid DCT technology environment
Option 1 — Building up from traditional Clinical Platforms
Companies like Veeva have already seen success in applying a single platform to Sponsor and Site activities. Medidata has also shown success in providing their EDC to COVID trials with the DCT functions built on top.
Logically, it’s clear that traditional trial vendors are looking towards DCT as their next step. So what are the barriers to success here?
- Patient Privacy — traditional trial platforms are not designed to fully separate sponsor/site data from site/patient only data. Sponsors cannot continue to have access to, or control access to the private site / patient data. Adding this security model retrospectively is harder that it might seem.
- User experience, dynamic workflow, and multi-lingual communications — Any successful solution considering these functions must adequately support the preparation of complex, multi-stakeholder workflow while upholding a simple experience for patients and inexperienced users. Users are not stopped to undertake eLearning, so the system must allow for built in self-educating & support.
Some vendors will rely on heavy sales and marketing, especially in the DCT space where detailed satisfaction feedback from patients is virtually impossible to uncover. In the end, case studies and peer reviewed articles will reveal the best implementations.
Option 2 — Building down from DCT Systems
Decentralized Clinical Trial system vendors are starting to add non DCT features in order to provide a complete clinical trial solution. EDC is the most obvious choice with most companies likely starting with the provision of an EDC ‘Lite’ solution. EDC Lite is very difficult to be successful with. When running complex DCT trials, the bar for adequate EDC is high. If data is not recorded, cleaned and delivered for timely analysis, benefits of using part decentralised methods may be lost.
Option 3 — Developing a dedicated end-to-end DCT Platform
The development of an end-to-end solution as opposed to the extension of a bottom-up or top-down DCT system provides central and de-centralized security and metadata that are purpose-built to support both models. Interfaces within the components are largely removed as they share a common database and security model. On the cloud, they should be single instance & multi-tenanted and scalable horizontally and vertically.
This model is further supported by recent FDA and EMA regulatory guidance clarifying the investigators continued responsibility for the integrity (review) of both efficacy and safety data from patients, including DCTs as described
The difficulty is that the ‘size’ of the solution demands a commitment from a sponsor willing to buy into the end-to-end platform together with a long-term commitment from the vendor to achieve and maintain financial and operational success. This is a ‘long game’ solution.
The 38Million EUR funded IMI Trials@Home initiative demonstrates an example of the application of a single end-to-end DCT platform where all of the primary clinical trial lifecycle components exist and are applied. This project is the first example I am aware of where we can compare traditional, hybrid and DCT to measure value and benefits for all stakeheolers. This is likely to offer present a model that will be replicated with new DCT vendors in this space in the future.
Will separate DCT + Traditional technologies persist into the future?
Of course, we have an Option 4 that persists Figure 4 above, in combining the two worlds of traditional technology at the bottom, on the sponsor side, and DCT technologies at the top, on the participant side.
Clinical Research has been incredibly inefficient in the past with favor given to the creation of new silos as opposed to busting down traditional silos and methods. This has led to a proliferation of technologies that have practically overwhelmed investigator sites.
Adding dedicated, disconnected DCT technologies on top of this already crowded tech space will result in extra costs, slower study implementation and discontent from the sites. One of the most critical challenges though lies at the end of the study. With multiple disconnected systems, it is difficult to achieve a full archive?
In many ways, archiving of clinical trials is like the global warming of clinical research. Few people really understand it. Those that do prefer not to talk about it, but it is a potential looming disaster.
Will studies run according to the Figure 4 model meet regulatory requirements with regards archive accessibility within their retention period? — probably not.
Given the example in Figure 4, we have 11 instances of systems, metadata and data that all need to be managed from an archive perspective at the end of the study. If these systems are multi-tenant, then they must manifest a studies worth of data in a form that is accessible for the term of the retention period. Today, vendors are either poorly supporting this requirement or worse, not supporting this at all. Look out for an extended article on this topic in the future.
Let’s hope that the solutions that evolve from today simplify and improve the complexity we see today, ensuring clinical trials become faster, cheaper and ultimately better for all stakeholders, most especially our trial participants.
This article was originally published on LinkedIn by Doug Bain, Chief Technology Officer at KCR