Advancing Decentralized Trials in Oncology
Regulators are increasingly supporting decentralized clinical trials (DCTs) and digitally enabled trial solutions. In this blog post, Ilse-Maria Nolan, senior director of regulatory affairs, and Francis Jones, senior director of DCT strategy and innovation within our PPD® Digital group, discuss emerging regulatory support for these efforts and consider regulatory requirements for decentralized oncology trials.
Benefits of Decentralized Clinical Trials
Oncology represents the largest research area globally, with 6.5% annual growth in the number of oncology drugs from 2000 to 2020 compared to 3.6% for all other non-oncology drugs in development.1 At the same time, oncology trials face a myriad of challenges compared to non-oncology trials, including additional patient enrollment and retention challenges, complex trial designs, larger data collection activity, longer durations, higher volumes of protocol deviations and more substantial amendments.
There are also persistent disparities in cancer prevalence and morbidity across ethnic groups and, therefore, a need for greater patient diversity in oncology trials. Application of decentralized clinical trials (DCTs) and digital solutions in the oncology space could be particularly beneficial in addressing these challenges. Yet, there still appears to be hesitancy across the industry in utilizing digital and decentralized elements for oncology trials.
Increasing Regulatory Acceptance of DCT
The COVID-19 pandemic has significantly accelerated the adoption of DCTs, an area that has long been championed by the PPD™ clinical research business of Thermo Fisher Scientific. Use of DCTs and digitally enabled solutions offer many benefits over traditional trial models. These include reduced burden on patients and sites, the potential for greater patient diversity, increased patient engagement and improved patient-centricity, as well as time and cost savings from accelerated recruitment and enhanced patient retention in trials. This is an exciting and fast-moving area, undergoing significant and rapid development and gaining increasing acceptance of DCTs by stakeholders, including regulators, as we look to the future.
Regulators and industry associations had taken steps toward digitization prior to the pandemic, as we’ve discussed in several previous Regulatory Insights blog posts. Now, with the positive experience gained with this trial model over the past year, demonstrating that patient safety and data integrity can be maintained through appropriate leverage of digital solutions, the use of DCTs is seen as one of the silver linings to aid in patient-centricity and has been cemented as part of the “new norm” of the post-COVID era.
Our regulatory intelligence team routinely collates, evaluates and disseminates regulatory guidance relating to DCTs to our study teams and clients to support business decisions. We capture and review this information in our in-house, proprietary regulatory intelligence platform, PPD® RegView. We are seeing increasing regulatory acceptance and innovation for DCT solutions, not only during the pandemic but beyond, and welcome such advances. Examples of common DCT solutions and increasing levels of regulatory acceptance (comparing situation in March 2021 vs. June 2021) across 72 countries are shown in Figure 1 (source PPD® RegView).
In March 2020, the U.S. Food and Drug Administration (FDA) published guidance for management of trials during the COVID-19 pandemic. This contained considerations and suggestions relating to the use of, inter alia, televisits and other digitally-enabled strategies supporting trial continuity. This guidance was followed by updates from various other regulatory agencies pivoting on this topic.
Recent Examples Of The FDA’s Guidance On DCT’s
- February 2021, the European Medicines Agency (EMA) issued updated “Guidance on the Management of Clinical Trials during the COVID-19 pandemic,” version 4. A key change from the previous version was the broadening of rSDV acceptance for certain trials. Following this, many European regulators updated national guidance, e.g., February/March 2021 – Germany, Austria, Netherlands, Hungary, Greece, Czech Republic, Sweden, Serbia; April 2021 – Ireland, Slovak Republic, Slovenia; and May 2021 – Denmark and Bosnia-Herzegovina. Others, such as France, Poland, Bulgaria, Cyprus and Portugal, advised the EMA guidance should be followed.
- March 2021, the Swedish Medical Products Agency provided an update on its “patient centric, decentralized and virtual clinical trials” project that aims to establish guidelines for conducting DCTs in Sweden.
- April 2021, the FDA asked sponsors to discriminate between “remote” and “trial site” assessments in oncology trial data sets to allow for comparison and ultimately the advancement of DCTs in the post-COVID era (more on this below).
- May 2021, for the first time, the Danish Medicines Agency launched a new guidance on the implementation of decentralized elements in clinical trials, indicating this guidance will be updated regularly based on learnings and remain in force beyond the pandemic.
Advancing Decentralized Oncology Clinical Trials
In June 2021, a search of GlobalData’s recently launched “decentralized/virtual trial” database revealed only approximately 5% of the 4,576 trials utilizing DCT strategies are oncology studies. Various reasons may explain the apparent lower uptake of DCTs for oncology programs, such as the complex trial design, type of investigational product, and need for invasive tests and scans, etc. Also, the uncertainty surrounding the effect of remote assessments on data quality and outcomes may be key. However, as discussed in a recent Oncology Imperatives podcast, many of these hurdles can be overcome through an appropriate and well-designed digital strategy taking into account regulatory and operational concerns.
DCTs and Oncology: FDA and COVID Modifications Experience
In an April 2021 publication, an FDA working group highlighted the current opportunity to evaluate the effect of remote assessments on trial data to advance DCTs in oncology and proposed that New Drug Application/Biologics License Application applicants provide various datasets to help FDA understand the remote modifications to trials. Full details are available on the FDA website.
Embracing DCTs in the Post-COVID Era
During the pandemic, rapid advances have been made and significant experience gained in terms of understanding appropriate application of flexible trial solutions. We have continued to collaborate with leading digital service providers, as well as regulators and sponsors, to provide a best-in-class service and delivery model across therapeutic areas.
We are confident that use of decentralized clinical trial solutions can be particularly impactful to oncology trials by providing potential solutions for enrollment problems, increasing patient diversity, reducing on-site visits, decreasing overall time and costs, and importantly, placing patients and patient needs at the center of the trial. We continue to monitor efforts and developments in this area to enable us to support stakeholders exploring the potential of digital solutions to accelerate timelines and increase participation and accessibility to oncology trials in the post COVID-19 era.
