April 7, 2021 PAO-04-21-CL-02
Since that time, oncology clinical trials have seen a resurgence with new digital modalities that have enabled sites, patients, and sponsors to embrace remote treatment paradigms.
Fortunately, before the pandemic, PPD had already been investing in the decentralized trial (DCT) space, creating the necessary infrastructure to keep trials active throughout 2020 and beyond. Looking ahead and building on recent experience, the clearest path to enable and optimize oncology trials is to continue the implementation of DCTs. Decentralizing trials presents the potential to streamline trial conduct, enhance recruitment, strengthen data integrity, increase patient diversity, and reduce the burden on patients and site staff.
The clinical trials industry has a commitment to drive the best and simplest trial designs possible. One solution for making trials more appealing to patients and encouraging their ongoing participation is to deploy a hybrid or decentralized model that combines some aspects of traditional, site-based trials with remote or virtual solutions.
Conventional wisdom might suggest that oncology studies cannot be conducted remotely, owing to the complex evaluations that must be routinely performed on-site. In fact, recent experience applying a number of digital solutions in clinical trials across a variety of complex indications suggests otherwise. Decentralized clinical trials (DCTs) have the potential to improve oncology protocols by reconfiguring how and where assessments are done.
Low levels of patient participation are the greatest challenge to successful clinical trials, a longstanding challenge exacerbated by the COVID-19 pandemic. Just 3-5% of adults with cancer enroll in clinical trials,2 although the participation rate is higher at large academic centers. One reason is a general lack of awareness that clinical trials present a potential treatment option. Another is the inability of many patients and their families to commit to regular site visits — whether because of competing work or family obligations, lack of transportation or simply because they are too frail to navigate the logistics of participation. DCTs expand the drug developer’s reach and allow for more equal access to participation in clinical trials by eliminating the requirement for frequent, in-person site visits that can impose recurring travel burdens for participants to large research institutions. This reduction in site visits not only improves the patient journey, but can make participation a viable option for patients across wide geographic areas, including those who live in remote locations that lack easy access to academic medical centers.
The broader participation challenges in clinical trials are particularly acute among minority groups, which can result in underrepresentation. Although they comprise over 13% of the U.S. population, African Americans made up less than 5% of the clinical trial subjects in trials for 24 oncology drugs approved by the U.S. FDA between 2015 and 2018, including trials targeting cancers that disproportionately affect African Americans.3 One factor in this lower participation rate may be the finding that patients in National Institutes of Health (NIH)-sponsored oncology trials traveled nearly 40 miles on average to study sites, creating a significant burden to patients and caregivers that may be most acutely felt by minority and low-income patients. Removing this clear barrier to participation may result in better minority representation in oncology DCTs going forward.
It is essential to increase awareness about the value and the opportunities presented by clinical studies and to make it easier for patients to participate. At the same time, there are challenges facing investigators and institutions that must also be addressed, particularly with regard to the resources needed to expand access to clinical trial participation to more patients.
DCTs create an opportunity to leverage extended network solutions within countries. Local facilities that do not conventionally run clinical trials can be utilized, with advanced and improving digital technologies enabling data from these remote sites to be linked to the central site or hub. Taking it a step further, it is possible to envision conducting DCTs at less traditional trial sites in more remote locations globally if the necessary assay technologies can be provided in a mobile format.
DCTs expand the drug developer’s reach and allow for more equal access to participation in clinical trials by eliminating the requirement for frequent, in-person site visits that can impose recurring travel burdens for participants to large research institutions. This reduction in site visits not only improves the patient journey, but can make participation a viable option for patients across wide geographic areas.
Oncology IMP types vary across approximately 2,300 clinical trials currently underway. One question that consistently arises during study design is how to enable decentralized oncology trials in which the protocol requires that the IMP be administered via infusion or intravenously to patients.
In many cases, it depends on the IMP and safety profile. Protocols do not always require clinical sites to administer IMP at every visit. When the goal is reducing travel to sites, home visits with a skilled home health care service can be incorporated to administer some intravenous drugs, obviating the necessity for some in-person site visits and improving the patient journey.
One of the shortcomings in translating clinical data into therapeutically relevant results occurs when the trial population may be younger than the population that requires treatment with these therapies. This circumstance sometimes happens because of the challenges in recruitment and enrollment of frailer, elderly patients. Consequently, post-approval, clinical trials may not provide physicians with the most specific, relevant data to inform the treatment of their older patients. Reducing barriers to participation for special populations, such as the elderly, is another potential benefit of decentralization that may ultimately result in delivery of more reliable data and product information.
Long-term follow-up studies in oncology, involving the tracking of disease progression and survival status, can be required for a decade or more after clinical treatment. Currently, disease progression may be assessed by regular imaging and testing, while survival status can be determined via phone calls.
From a patient, caregiver and site perspective, a 10-year follow-up requirement to monitor disease progression can be a significant commitment. Trial sponsors understand this and share a strong motivation to minimize the burden for sites and patients during the follow-up period. A DCT approach is ideal for data collection because patients can incorporate televisits for follow-up with their local oncologist versus travel to more distant facilities. This reduction in travel increases the likelihood of collecting important follow-up data by removing undue burdens to long-term follow-up participation for clinical trial participants.
Overall, telemedicine and other digital approaches can increase patient engagement during the long follow-up period without creating further complexities for stakeholders. With available technology, it is easier to maintain contact with patients by sending upcoming patient-reported outcome reminders, further ensuring timely data collection. Information also can be shared with the patient about the status of the study drug or treatment, as well as how many patients have benefited, which may encourage continued participation. A well-thought-out digital strategy can make a significant impact in reducing the number of patients lost in the long-term follow-up stage.
As you consider implementing DCT solutions to keep studies running and reduce the burden on patients, PPD can provide practical experience and partner with you to bring innovative technologies and patient-centric approaches to your oncology development program.
As you consider implementing DCT solutions to keep studies running and reduce the burden on patients, PPD can provide practical experience and partner with you to bring innovative technologies and patient-centric approaches to your oncology development program. With PPD, you’ll have the experience of a CRO that has conducted more than 575 oncology and hematology clinical studies over the past five years, ranging from early-phase through post-approval and across an extensive array of indications, including solid tumors, hematologic malignancies, cancer-related pain and supportive care.
In tandem, PPD is leading the acceleration of decentralized trials, applying and adding to its extensive operational expertise in reaching more geographically and socioeconomically dispersed patient populations in need of improved treatment options. To directly mitigate lockdowns and uncertainty produced by the COVID-19 pandemic, PPD has focused on alleviating the need for patients to make frequent clinic visits by leveraging DCT technologies and continuing to evaluate protocols from a more patient-centric perspective. This approach has become incorporated into PPD’s ethos when evaluating strategy and execution for all projects, including oncology studies.
PPD® Digital, our dedicated decentralized trial (DCT) unit, frequently operates in the oncology space, whether to introduce DCT solutions for ongoing trials that encounter challenges due to COVID-19 ramifications or to propose innovative strategies and trial designs for upcoming clinical development. This work is done in coordination with PPD’s well-established oncology therapeutic unit, as well as Evidera, PPD’s business unit that provides integrated scientific expertise and global operational capabilities to generate the evidence customers need to maximize market access and the commercial
potential of their products. Of particular relevance to oncology is our epidemiologists who add significant value to long-term follow-up studies, working with physicians to design studies that collect data that will be meaningful for both patients and study sponsors.
Our customers benefit from the advanced DCT infrastructure PPD had proactively built long before the pandemic necessitated it. We understand that the pandemic has put DCTs at the top of sponsors’ minds as they re-evaluate their drug development pipelines and strategy. Our longstanding commitment to DCTs before the pandemic has enabled us to deploy solutions quickly following the emergence of the SARS-CoV-2 virus and implement remote designs that have allowed ongoing studies to continue without disruption to data collection or, ultimately, research timelines. Our early investments in the DCT space provide pre-existing capabilities and experience running these types of studies as well as a unique depth of talent, where our established partnerships offer a competitive edge for clinical programs.
Carlisle, Benjamin Gregory. “Clinical trials stopped by Covid-19.” The Grey Literature. 2020.
Transforming Clinical Research in the United States: Challenges and Opportunities: Workshop Summary. Institute of Medicine (US) Forum on Drug Discovery, Development, and Translation. Washington (DC): National Academies Press (US). 2010.
Terry, Mark. “Pushing for More Ethnic and Racial Diversity in Clinical Trials.” BioSpace. 12 Jun. 2020.
Borno, Hala T. et al. “At What Cost to Clinical Trial Enrollment? A Retrospective Study of Patient Travel Burden in Cancer Clinical Trials.” Oncologist. 24: 1242–1249 (2018).
Mariah Baltezegar is a senior leader within the peri- and post-approval studies (PPAS) group, responsible for the performance, growth and development of virtual trial approaches and associated integrated solu- tions. She has worked in various clinical research capacities for the past 20 years, including a proven 17-year history in operations and business procurement. Baltezegar also has 13 years of experience working in various capacities in the complex space of rare disease development. Baltezegar completed her Master of Business Administration at the University of North Carolina, Wilmington, and holds a bachelor’s degree in psychology with a minor in statistics from Winona State University.