ePRO Use and Technology Design in Oncology Development
By Mark Maietta, President, YPrime
The goal of modern drug development is to remove the burdens and barriers inherent to clinical trial participation. The pace of innovation in digital technology and growing interest in decentralized clinical trial (DCT) models has accelerated home-based participation and/or a reduction in clinic visits and has had transformative effects on the design and execution of oncology clinical trials.
Given the requirements of drug administration for specific drugs in oncology clinical trial protocols (i.e., infusion, radiation, etc.), completely virtual trials are not likely soon, but a DCT model may include advanced telemedicine, home health visits, and/or visits to local labs, and may incorporate key technology-based elements to reduce the need for frequent site visits and provide more convenience for the patient and caregiver. Electronic clinical outcome assessments (eCOA) and emerging connected technologies are effectively bridging the gap between traditional models and the future of oncology drug development that promises more choice, flexibility, and convenience for patients.
However, integrating patient-reported outcomes (PROs) into oncology clinical trials can be challenging. Ari Gnanasakthy, an industry-recognized expert on patient-centered outcomes, noted, “For most diseases, patients may experience only the symptoms of their disease. In oncology, however, symptoms and impacts can be a result of cancer treatment [as] well as the disease itself. The impact of the treatment is often immediate and sometimes cumulative, which is why data collection should be targeted and based on the cancer type and the specific treatment regimen.” In addition, researchers should consider strategies that minimize patient burden and missing data at the design stage for PRO integration and eCOA technology.
Technology implementation and clinical protocol considerations should begin in parallel. This rarely happens as protocols are typically written well before software vendors are engaged, arguably without much thought into how technology will fit into the clinical workflow and patients’ daily lives in a trial setting. However, as clinical research transitions to a paperless environment, it is essential for protocol development to incorporate a stepwise understanding and workflow of how eClinical technologies intersect with the patient visit and routine data collection. What’s more, ePRO/eCOA is just one of many technologies employed at the site and patient level, which makes technology alignment in the research setting even more important.
As oncology studies often run longer than those involving other therapeutic areas, study burden and patient adherence considerations go hand in hand. “Given the high attrition rate often seen in cancer studies and because most of the events that need to be captured happen early in treatment, current recommendations focus on frequent assessments during the early cycles of cancer treatment,” said Gnanasakthy.
Illustrating how this technique works when paired with a focus on the most important questions, Gnanasakthy explained, “In lung cancer, you may want to know about coughing, breathing difficulty and chest pain, so ask questions focused on these areas every 10 days for the first three months of the study, and perhaps less frequently until the end of a few more cycles. Recognizing that physical, emotional, and social functioning as well as quality of life change slowly in a cancer setting, it makes sense to ask questions related to these concepts less frequently. This will have a positive impact on data quality as well as on the study and patient burden.”
Assessment timing is an important consideration to ensure contemporaneous data capture. Traditional assessment schedules may not be appropriate to capture the impact of treatment using today’s new therapies because treatment cycle lengths and safety issues are different. Real-time administration and quick clinical action lead to better patient outcomes. Data collection should be designed to capture symptomatic adverse events as and when they happen to fully characterize treatment benefit, and technology should be flexible enough to support this need.
Creative approaches to PRO data collection are needed to minimize missing data. Flexibility with data capture is key when designing eCOA software for oncology studies. For example, eCOA software solutions allow proxy data entry by the caregiver or site staff. In this case, data are stamped with records indicating proxy entry, allowing biostatisticians to address the proxy entries at the analysis level. Completion of observer-reported outcomes versions of PRO instruments, if appropriate, are another mechanism with which the site or caregiver may record relevant data when sickness or fatigue prevents patients from completing assessments. Other specialized features help contextualize missing data for site-based data collection. Fields for explanations of missing data provide the ability to conduct sensitivity analysis, while also allowing participants to continue through the study even if they have missed a previous visit.
Key eCOA software design decisions need to be finalized during protocol development. For example, a traditional visit schedule typically features fixed durations between visits that are projected out to specific dates (plus or minus a day or two) over the course of a trial. Key protocol considerations for oncology trials include the avoidance of rigid visit schedules. It’s all too common for a patient to miss a scheduled visit due to sickness, and it may be a few weeks before he or she is able to return. In this scenario, a rigid visit schedule can inadvertently lock a patient out of ePRO assessments. For oncology studies, consider a flexible visit schedule that mandates assessment completion only in a specific order and not tied to a specific calendar date or elapsed number of days, provided this flexibility doesn’t interfere with per-protocol PRO assessment timing relative to time of dose. The same logic applies to compliance reporting and alerts. One missed visit can throw off an entire schedule if it’s not designed to adapt to flexible visit dates.
Another component of incorporating flexibility in eCOA software is the ability to extend the visit window, which allows the patient to return and complete a visit on a different date. A visit reactivation feature in an eCOA platform is an extremely useful option for oncology studies. A patient may come to a site for a PRO assessment but is then unable to complete the visit and may need to come back to the clinic. In this case, as well as in the previous example, limiting the flexibility will help avoid capturing PRO data outside the desired window relative to the time of dose.
Effective user-experience (UX) processes will map out the path the user expects and consider every step of data acquisition from the perspective of the end user and validate the effort through user testing. Effective user-interface (UI) processes look at the visual design and consider how users will interact with it. eCOA UX and UI will negatively impact compliance if these two critical elements are not thoughtfully considered. It is important to test these applications with actual patients to ensure the application is fit for purpose. For example, look at the buttons and the information flow. Will a patient have to navigate through more screens than necessary? Will it take less time if there are more questions on a page with a different layout? While these recommendations appear straightforward, multiple stakeholders inform and drive eCOA design decisions, and the focus can easily shift away from user-centric principles.
As patient-focused drug development takes shape in oncology and user-centric technology integration in clinical research settings continues to advance, there are many opportunities to improve ePRO implementation in clinical trials. More work is needed to develop, test, and operationalize eCOA patient engagement features that can be implemented in our current site-based trial context and facilitate the transition to the decentralized models that are so needed in the oncology space.
Long term, the push for more industry-wide transparency and data-sharing offers transformative value to patients. Publicly available and easily accessible PRO data across every domain—from physical function and symptoms to patient preferences for education, support, treatment, and outcomes—will enable deeper understanding of holistic patient experiences within each disease area and help facilitate more personalized care. In the short term, more coordination across global regulators, patient advocacy groups, sponsors, and the research community will increase the rigor and usefulness of patient-generated data to better define outcome measures that are meaningful to patients.
- Gnanasakthy et al. A Review of Patient-Reported Outcomes Labeling for Oncology Drugs Approved by the FDA and the EMA (2012-2016). Value in Health. 2019, 22 (203-209) Available at https://doi.org/10.1016/j. jval.2018.09.2842