clinic
A cancer diagnosis is a life-changing experience. Survival and remission are, of course, the highest priority for most, but they are only part of the equation when treating cancer. Quality of life (QoL) – as perceived by the patient – is also important; and for some, QoL can even be the most important factor. It can also be a critical prognostic factor: people reporting clinically significant fatigue have poorer survival and experience more adverse events than those who don’t report that condition.
For companies developing oncology therapies and interventions, the impact a new product has on QoL can also be a key differentiator when healthcare providers and patients are comparing treatment options.
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The challenge then lies in reliably, accurately, and consistently measuring QoL to help establish a new product’s value in the clinical setting. Hearing first-hand from patients is essential. Regulators and experts consider patient-reported outcomes (PROs) as the gold standard when assessing a patient’s subjective treatment experience. PROs may, for example, measure life-impacting disease symptoms, functional debilities, and symptomatic adverse events. PROs complement physician-reported outcomes and may even improve accuracy: evidence suggests that clinicians may at times underreport patient’s symptoms.
The value of PROs in clinical development
PROs provide useful feedback about a product’s safety and tolerability — even during the earlier stages of the clinical trial development process. For example, while serious and severe side effects might be captured by standard clinical trial safety monitoring, subjective elements such as a person’s ability to perform daily activities, or general tolerability, could be better assessed by patients themselves via self-report measures. Additionally, regulators often take a more conservative approach when reviewing a product’s application if PRO data is not available to complement clinician’s observations.
PROs can also motivate patients to stay in a trial, improving their engagement. It is also thought that this is due to people’s altruistic desire to advance therapeutic research and help others. Research shows that PROs can even increase QoL and survival.
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Payers care about PROs too
In a 2021 survey of US payers, almost half (47.1%) suggested that formulary review would be influenced by a lack of PRO evidence from oncology clinical trials. Most payers (78.2%) indicated that PRO evidence provides useful context about the safety of oncology therapies. Importantly, approximately one-third of US payers (34.3%) cited the value of PRO evidence when comparing similar therapies, and 51.5% felt PRO evidence informed value-based agreements.
Considerations for PRO data collection
Patients want to report their symptoms as part of a clinical trial but collecting PRO data comes with certain challenges. For example, if PROs are administered at the site when the patient is exhausted from treatment or travel, or a patient has strong emotional reactions to a clinical trial setting (e.g., anxiety or comfort), their self-reported PRO symptoms may be skewed.
Other factors can also create data variability and lead to quality issues, such as the administration schedule of the drug and its delivery (e.g., intravenous or oral). Both can have a significant impact on the timing of symptomatic adverse effects, and without carefully calibrated PRO assessment frequency, clinical trialists may miss important patient symptomatology.
Electronic PROs (ePROs) can address issues associated with in-clinic or infrequent assessments
Done well, electronic PROs (ePROs) can strike the right balance between collecting a thorough picture of the patient’s symptoms, experiences, and quality of life, and not overburdening patients. At-home ePROs offer a great deal of flexibility and convenience, allowing for more frequent assessment of symptoms (e.g., weekly). Unsurprisingly, patients prefer and recommend ePROs in oncology clinical trials.
Due to their electronic format, ePRO technology offers several benefits to clinical trial sponsors as well, including improved data quality, reductions in missing data, more efficient data collection, and near real-time data monitoring.
Delivering what the FDA & EMA are requesting from trial sponsors
While regulatory agencies recommend including PROs in oncology clinical trials, recent studies indicate that PRO information is limited in oncology drug labels. This shortcoming is an issue that affects patients and industry alike.
Consequently, it’s critical to involve experts capable of evaluating the product both strategically from a commercial perspective as well as from the point of view of the patient to address both needs. Let’s consider an example with a phase II clinical study in which 42% of the people receiving a new drug candidate for multiple myeloma experience the side effect of impaired vision. Impaired vision is a serious adverse event – one that could undermine the viability and value of the drug as a mainstream treatment option. But context is king. Planned thoughtfully, the Phase III trial designers could include the PRO-CTCAE (Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events measurement system), which asks patients about not only the presence of the symptom, but the severity, frequency, and interference with daily activities. Although the drug may impair vision, the duration may only be short-term and not significantly impact patient quality of life or their overall functionality — making an ostensibly serious adverse event far less worrisome. Unobtrusive and well-timed ePRO survey questions could establish the transient nature of this issue, measure it accurately, and give clear guidance to future patients on what they can expect.
Conclusion
ePROs can be the key to product differentiation for sponsors seeking to highlight their product’s ease of administration, tolerability, or compatibility in combination with other components of a treatment regimen. ePROs offer sponsors an opportunity to streamline and inform their studies, reduce patient burdens, and at the same time provide an effective way to meet FDA and EMA regulators’ expectations for oncologic clinical trials. ePROs can ensure that patients’ interests are core to the clinic research endeavor while providing critical commercial utility.
Dr. Kelly Dumais is a scientist with over 13 years of experience in behavioral and life science research. She has expertise in the implementation of electronic clinical outcome assessments (eCOA) and the development and validation of patient reported outcomes (PROs) to support labeling claims. She is currently a Principal Scientific Advisor at Clario, a global data and technology company that helps to minimize risk in clinical trials. She consults on best practices for questionnaire design and eCOA design/use to drive data integrity and patient engagement and develops custom site rater training and participant training for improving accuracy in COA reporting and improving inter-and intra-rater reliability.
