In the lead up to International Clinical Trials Day on May 20, I have been thinking a lot about what the trial of the future will look like. The healthcare industry has become increasingly patient-centric in recent years, and clinical trials are no exception. There is a steady demand in the industry for more patient-centered trial designs, and patient reported outcomes (PRO) to demonstrate the efficacy and real-world impact of treatments. As a result of these trends, I believe the most successful trials in the future will be those that start by focusing on the patient’s experience of the disease or condition and building out from there.

One of the key components of trials in the future will be understanding the patient’s experience with a disease, and then inserting the appropriate PROs. The Food and Drug Administration (FDA) defines a PRO as “any report of the status of a patient’s health condition that comes directly from the patient, without interpretation… by a clinician or anyone else.”  How can the patient experience and PROs help us in clinical trial development, execution and result interpretation?

·       Prior to the trial, the patient experience can be captured be listening to patients, and understanding what PROs to build into a study design that is feasible from the patient’s perspective.
·       During the trial, carefully selected PROs will reflect the patient’s experience in the context of a specific treatment.
·       After the trial, PRO data from well-defined PROs will provide clear insights into the treatment benefit.

FDA and the European Medicines Agency (EMA) have issued several guidance documents on the use of PROs, including FDA’s formal guidance regarding how PRO instruments will be used to support label claims, and EMA’s reflection paper on the Regulatory Guidance for the Use of Health-Related Quality of Life (HRQL) Measures in the Evaluation of Medicinal Products.

Don’t talk, listen
With the increasing emphasis on gathering PROs as part of the clinical trials, it is important for researchers to understand how to best collect this data and to engage patients in the individual clinical trial experience. Far too often, we, clinical researchers, make assumptions about the patient data that should be collected without getting the patient’s perspective or considering what outcomes will be most meaningful to them. In order to address this, we can’t just mine online databases and draw our own conclusions. We have real conversations with patients — actually, we need to listen to our patients’ concerns about their disease and treatment goals. We can then take this input and use it to design truly patient-centered trials.  Initiating this listening exercise increases the value of any PROs included in trials and provides much-needed perspective on the patient experience, ensuring that endpoints and label claims result in a differentiated message of value that resonates with patients, payers, providers and regulators.

Specifically, let’s consider oncology trials where researchers have historically focused on tumor shrinkage and overall survival rates as the key measures of value. While this makes complete sense, given that we are often dealing with aggressive, fatal oncologic diseases, overall survival is no longer a differentiating characteristic of many new treatments.  In the context of two products that have similar overall survival, what selection should a patient or their provider make?  In such a context, we have much to gain from understanding the patient experience on these two products, typically measured using PROs. This is quickly becoming a key component of new evaluations of oncology products.

We recently completed a study of prostate cancer patients that shows “lack of decline” is an extremely important measure of value. Because survival rates with this cancer vary considerably, a lack of progression of the disease can materially lessen anxiety about the disease. Although this may appear to be a subtle difference to us as clinical researchers, maintenance of functioning and quality of life is incredibly meaningful for these patients. By engaging men with prostate cancer in a listening exercise, we are able to were able to identify this outcome — lack of progression — as a differentiator and to tie it to endpoints in the trial. 

We have also found that regulators, payers and health technology assessment bodies are equally excited about data that ties clinical outcomes (i.e., tumor shrinkage) to meaningful lack of decline because it brings clarity to the benefits that patients are receiving. 

PROs, reflecting the patient experience, will always play an important role in clinical trials. The researchers who take the time to collect this data and to really listen to what patients want from a treatment are going to generate the most value from these trials. Regulators, payers, providers and patients all want to understand the real world benefits of the treatments they support. Creating a patient centered trial that is built upon a foundation of patient experience, measured with PROs, is the best way to make that happen.

---

Dr. Paty is an acknowledged leader in the effective strategies and practices of capturing patient perspective data for use in the clinical development and commercial success of new medical products. He has published extensively in the areas of Patient Reported Outcomes (PRO) and electronic PRO (ePRO), as well as on the regulatory guidance for development and implementation of ePRO.  He has worked closely with the international industry and regulatory agencies on ePRO best practices.  His work is well-referenced in a wide variety of peer-reviewed journals and in numerous conferences and events, where he has presented his findings on the scientific, clinical, and regulatory implications of Clinical Outcome Assessment (COA) data collection in clinical trials.