Each year, new terms are bandied about as being the pharma industry’s “focus” for that year. Past examples include patient-centricity and digital therapeutics. Some of these are mirrored in the real world while others seem as if they were created in a market research group’s brainstorming session.
In 2020, however, it was the COVID pandemic that drove sweeping changes in clinical research, especially in the U.S. Because in-person contact was out, sponsor companies, institutions, and clinical sites were forced to adopt technologies that supported remote work and collaboration. Some did this more gracefully than others. In any case, this adoption happened quicker because these approaches became “must-haves” instead of “nice-to-haves”.
Let’s explore some of these remote approaches to clinical research. Let’s also parse the differences between them, as their names sound similar!
Decentralized Trials
CTTI defines decentralized trials as “those executed through telemedicine and mobile/local healthcare providers (HCPs), using procedures that vary from the traditional clinical trial model (e.g., the investigational medical product [IMP] is shipped directly to the trial participant).”
- So, this isn’t just about adopting technologies to support remote work, although that plays a role, i.e. the telemedicine piece.
- It’s also about keeping clinical trial activities local (as opposed to “central”). This means:
- Allowing local healthcare providers to participate in clinical trials (as opposed to just KOLs at big institutions or MDs who specialize in running clinical trials)
- Allowing home administration of IP
- Allowing a mix of in-home subject visits (when required) with video conferencing
- Allowing data collection via wearables or ePRO
The advantages of all this?
- Using MDs who wouldn’t normally participate in clinical trials, i.e. bringing normally “unused” parts of the healthcare system into clinical research.
- Meeting patients where they are (literally) to facilitate recruitment, comfort, diversity, and retention in the trial.
When you hear the term “decentralized trial”, most often this refers to the experience of the patient participating in the trial, rather than how the oversight or trial site monitoring is conducted.
Examples of service providers:
Centralized Site Monitoring
This type of site monitoring arose from the 2012 release of the FDA’s Guidance for Industry: Oversight of Clinical Investigations – A Risk-based Approach to Monitoring.
Before this guidance debuted, most sponsors took this conservative approach.
- 100% source document verification (SDV), which asked sponsor or CRO monitors to check every single field in the clinical database (EDC) against the subjects’ source documents (medical records).
- This 100% SDV took place at on-site monitoring visits, which also allowed sponsors to provide assurance that study documentation exists; assess the familiarity of the site’s study staff with the protocol and required procedures; and assess compliance with the protocol and investigational product accountability.
This guidance introduced and in fact, encouraged, a new approach called centralized monitoring as a complement to traditional onsite monitoring:
- FDA defines “centralized monitoring” as a remote evaluation carried out by sponsor personnel or representatives (e.g. sponsor monitors, data management personnel, or statisticians) at a location other than the sites at which the clinical investigation is being conducted.
- The extent to which centralized monitoring practices can be employed depend on various factors, including: the sponsor’s use of electronic systems, sponsor’s remote access to subjects’ electronic records, and communication tools available to the sponsor and study site.
- These may vary by study and site.
- Sponsors using centralized monitoring processes need to ensure that all these extra logistical details are captured in their monitoring plan, including supplementation of on-site monitoring for sites considered high-risk based on statistical analysis (including its trigger), if needed.
- Centralized monitoring, if done right, can allow for reduced or targeted SDV and fewer on-site visits.
- Risk-based monitoring has evolved into Risk-Based Quality Management that incorporates Risk Management Principals (e.g. Risk Assessment Categorization Tool [RACT], Key Risk Indicators [KRIs], Quality Tolerance Limits [QTLs]) that enhance the centralized monitoring toolset.
The advantages of all this?
- More efficient use of company and planetary resources by reducing monitor travel and focusing on the highest risk sites, subjects, or data points
- Potentially huge cost savigs
- Higher quality trial data
Examples of service providers:
- Any large CRO and some mid-sized CROs
- Large pharmas typically have an in-house centralized monitoring group
- Vendors offering RBQM software such as CluePoints, TriTrials, and Cyntegrity
Remote/Virtual Site Monitoring
Even though the FDA defines “centralized monitoring” as any type monitoring activity done remotely, our industry in practice has focused on solely the statistical trend/risk analysis activity. It was rare to find companies that actually moved a significant portion of their on-site monitoring activities to being remote. Remote or virtual monitoring focuses on this piece (remote SIVs, SDV, reg doc review, site engagement, drug accountability, etc.).
However, the advent of the pandemic forced sites to close or reduce their clinic hours. This in turn forced Sponsors to either halt their trials or dip their toes into remote/virtual monitoring. Whether the innovative sponsors that forged ahead with remote/virtual monitoring will revert to previous on-site visit schedules remains to be seen.
As most sites and Sponsors are still used to dealing with paper and face-to-face interactions, without technology to bridge the gap, remote/virtual monitoring is not easy. Some Sponsors resorted to quick fixes like FaceTime site tours and scanning source documents into a secure portal, and others have implemented technologies like electronic regulatory binders, electronic source documents, electronic informed consent, and 21 CFR Part 11 compliant video recording technology to allow for more seamless remote/virtual monitoring to occur.
The advantages of all this?
- More efficient use of company and planetary resources by reducing monitor travel
- Potentially huge cost savings
- Higher quality monitoring if done correctly, as site access and oversight can be more real-time
Examples of service providers:
It goes without saying that all of these approaches are needed innovations in our industry. They all have the potential to boost efficiency and save resources. However, they also have the potential to add complexity and need to be supported by great technology. That’s where Seascape Clinical comes in – our ClinOps Pro solution supports various clinical trial approaches while saving teams time and effort.
Sources
- https://www.ctti-clinicaltrials.org/sites/www.ctti-clinicaltrials.org/files/dct_recommendations_final.pdf
- https://www.socra.org/blog/the-value-of-centralized-monitoring/
- https://www.fda.gov/regulatory-information/search-fda-guidance-documents/oversight-clinical-investigations-risk-based-approach-monitoring
