By Jess Fowler, Todd Johnson, and John Ferraro
Decentralized trials, hybrid trials, and agile trials — these are all a few broad modifications to the standard brick-and-mortar clinical trials we’ve been accustomed to since COVID-19 changed the standard of clinical operations. Now that our industry has become familiar with flexible design, we’ve noticed the discussion points on these designs continue to stay high-level, relegated to more broad-spectrum adjustments. But at what cost?
We’ve noticed the downside of keeping the conversation broad is a disconnect on the applicability of decentralized and hybrid trials across therapeutic areas. It’s critical to understand that each clinical trial is truly unique — just like each patient — and not all decentralized or hybrid design elements will be applicable across trials. Understanding the bigger picture requires slowing down to take more time to gather the necessary patient feedback that’s essential in the planning process.
This is why we want to home in on a few therapeutic areas and share our observations and recommendations to highlight examples that may bring decentralized and hybrid trials to a more tangible and realistic view and, in essence, make them more executable.
Understanding Opportunities And Limitations Of Implementing Decentralized & Hybrid Trials For Specific Therapeutic Areas
Decentralized trials (DCTs) are often discussed and detailed in general terms regarding the elements, technologies, and tactics employed and instituted. This accomplishes the goal of introducing DCTs to the industry and creating a familiarization; however, it does a disservice to the clinical trial team’s design and implementation plan.
We’d like to debunk a common belief that DCTs are universally applicable to all phases of a trial and therapeutic areas. This can be misleading and untrue. Sponsors have more than just hammers in their toolkit, so every problem does not need to look like a nail. A sponsor will need to take a deeper look at the therapeutic area of their product as well as the patients that will be enrolled into the protocol to understand the types of DCT elements, technologies, and tactics that can be used.
Let’s take a look at a few therapeutic area examples to compare and contrast opportunities and challenges:
- CNS (central nervous system) trials tend to have many types of scales (verbal and visual) and interview types of assessments that appear amenable to DCT tactics; however, depending on the type of assessment and whether the assessment could be standardized with differing methods and locations is a challenge that cannot be overlooked in the design process.
- Many sponsors believe it would be a challenge to employ DCT tactics in oncology trials, but the COVID-19 pandemic didn’t stop many oncology trials from morphing into successful DCT trials with at-home infusions and local radiographic testing (CTs and MRIs).
- Cardiovascular clinical trials usually include some version of an intervention and, depending on the type of intervention, this could dictate the DCT elements used. It could even be a full DCT, as opposed to an ophthalmologic trial that requires a specific piece of complicated equipment that is only in use at three or four academic centers in the U.S.
Why Patient Insight Should Drive Clinical Trial Design
When implementing a DCT, sponsors should first consider their therapeutic area, their product, and the feasibility of implementing a fully virtual trial versus implementing a hybrid trial with DCT elements.
Here are a few questions to consider in the planning phase:
- Do you want to utilize real-world evidence in which most, if not all, data can be captured remotely?
- Or is your study more complex and requires frequent in-person monitoring, such as a Phase 1 oncology trial, coupled with the need for pharmacokinetic and biomarker samples to be collected on-site?
It is also important to evaluate the degree to which DCT elements can realistically be implemented. Some examples of DCT elements include: eConsent, electronic patient reported outcomes (ePROs), investigational product and clinical delivery to patients, sample collection from a patient’s home or local site, telehealth, and home health visits. Once you identify those elements, you’ll need to consider if your trial is conducive to introducing some of these elements or if your trial and the patient population are able to utilize all of these elements.
We often observe sponsors jumping into the traditional protocol development process and remaining hyper-focused only on the engagement of stakeholders and key opinion leaders (KOLs) later in the process to gather feedback. But this approach is a missed opportunity to engage patients, patient advocates, caregivers, and sites on a study design that will lead to the development of a DCT that is right for those patients.
Prior to engaging patients, patient advocates, caregivers, and sites, you should strategize on the DCT elements that may be newly introduced. For example, for previous trials that were conducted in oncology, were patients required to come to the study site to have the assessment conducted as part of their study visit? Think through the following questions:
- Is that assessment necessary? If not, remove the assessment to further streamline the protocol and minimize patient burden.
- If the assessment is necessary, can it be conducted remotely, and can the data be collected by utilizing a digital device or can the assessment be conducted at a local site or close to the patient’s home, rather than having the patient travel to the clinical site?
Share Endpoints And Schedule Of Assessments Early On For Feedback
The next step as a sponsor would be to create a list of endpoints of interest and incorporate the appropriate assessments into your schedule of assessments, which is a clearly defined list of activities that are to be performed for the research of the study in the clinical trial protocol. Once this is created, consider hosting a roundtable discussion or interviews with patients, caregivers, patient advocates, and sites. It is during these sessions and interviews that you will have the opportunity to analyze the experience of the patients and assess feasibility. This feedback provides further insight on how the protocol can be designed in a way that is focused on the patient and appropriate for a particular therapeutic area. Until you hear first-hand from the patients, caregivers, and patient advocates, you should not assume you are aware of the patients’ needs.
In parallel to engaging patients for their feedback on the protocol design, sponsors should reach out to service providers that specialize in the integration of DCT elements to discuss the DCT options and technologies that are available and could potentially be suitable for your trial.
Lastly, once the protocol has been developed and the schedule of assessments has been fine-tuned, consider pressure testing the protocol by conducting a protocol simulation with patient and site participants to determine if the study design and the DCT elements are appropriate. While this approach will require an initial investment of time and financial resources, it will avoid amendments in the future, which could have more significant impacts on timelines and budgets.
To achieve success in developing a DCT, it is important to engage the patients early in the protocol development process to ensure the protocol reflects the patients’ needs. It is apparent to all stakeholders, but most importantly to the patients, when a protocol was developed without the engagement of patients, patient advocates, caregivers, and study sites.
About The Lead Author:
Jessica Fowler is a senior consultant at Halloran Consulting Group. She has 15 years of experience in research and development in roles that span cross-functional project management, clinical development, and clinical operations. Jessica focuses on facilitating continuous improvement through the mapping of processes, authoring and reviewing SOPs, and developing quality systems. Jessica also provides strategic and operational guidance in the development and execution of clinical programs.