Patient-reported outcomes (PROs) have the potential to enhance drug development, regulatory decisions, and shared decision making, and the benefits of using PROs are broadly agreed upon, but there are a variety of challenges facing stakeholders.
Traditionally, clinical end points such as progression-free survival and adverse events have served as clinically meaningful outcomes when guiding clinical and regulatory decision making. However, the US healthcare system continues to see a shift toward patient-centered care, where perspectives from patients and their caregivers play a more important role in these decisions. The hope is that patient-reported outcomes (PROs) will be integrated into clinical trial designs and, subsequently, help guide care and coverage decisions.
But despite the excitement behind these types of measures, integration has been slow, and PROs may not be considered in the beginning steps of the development process. There is also variability in PRO measure use and a lack of standard practice, preventing more widespread use of the measures.
“While there is a push to include PRO measures as end points in phase 3 clinical trials for drug approval, integration has been slow,” Somali Burgess, PhD, senior director, Xcenda, told The American Journal of Managed Care® (AJMC®).
Also commenting on the role of PROs in the drug development process, Theresa Mullin, PhD, associate director for strategic initiatives for the Center for Drug Evaluation and Research at the FDA, wrote in an email to AJMC®, “In the past, these types of outcomes measures have played an important role, but a more limited role and may not be considered until late in the drug development program. In addition, it was not uncommon for PRO measures to be developed with very little input or involvement of patients living with the disease of interest.”
PROs have the potential to enhance drug development, regulatory decisions, and shared decision making, and the benefits of using PROs are broadly agreed upon, but there are a variety of challenges facing stakeholders, explained Burgess. These include:
In recent years, organizations nationwide have put forward tools and efforts to try and mitigate these challenges and facilitate widespread implementation of PRO measures. Last October, the Academy of Managed Care Pharmacy convened a forum1 of key stakeholders representing patients, payers, providers, government agencies, and pharmaceutical companies to discuss and identify solutions to the current challenges and barriers impeding further use of PROs.
In February, a study published in JAMA2 offered recommendations for factors that should be accounted for in clinical trial protocols in which PROs are a primary or key secondary outcome. The review identified 16 PRO-specific items relating to trial rationale, eligibility criteria, PRO instrument selection and measurement properties, and data collection plans.
Despite efforts like these, major barriers still exist, most notably the absence of consistent standards and guidance documents for measuring and utilizing PROs. “For this information to be collected in a more consistent and reliable way, stakeholders need clear guidance on the methods to use and access to information on what measures have already used and accepted,” explained Mullin.
Seeking to fill this gap and incorporate PROs early in the development process, the FDA is creating a dialogue among stakeholders to identify appropriate measures and standards. Noting the agency's broad look at patient experiences, Millen explained that the FDA takes into acocunt various patient perspectives, rather than PROs alone.
“When considering a measurement approach, sponsors and others are encouraged to consider the type of clinical outcome assessment (COA) measure that might be most appropriate,” she said. These COAs can be obtained from a clinician, patient, or a nonclinician observer, or through a performance-based assessment, and include 4 types: PROs, clinical-reported outcome measures, observer-reported outcomes, and performance outcomes.
Today, the agency finished up a 2-day workshop of various stakeholders to address a series of 4 methodological patient-focused drug development documents3 that the agency is developing to provide guidance, in a stepwise fashion, for how stakeholders can collect and submit patient experiences and other relevant information from patients and caregivers. The goal is to facilitate the enhancement and use of systematic approaches to use collected patient and caregiver input to better inform both product development and regulatory decision making.
During the workshop, stakeholders weighed in on methods to identify what’s important to patients in regard to burden of disease, burden of treatment, and the benefits and risks in management of the patient’s disease; best practices for collecting information on what aspects of the disease symptoms, impact, and other issues are important to patients; measuring these symptoms, impacts, and other issues in a meaningful way; and selecting, developing, or modifying fit-for-purpose COAs to measure the patient experience in clinical trials.
Additionally, this summer, the FDA issued a Request for Information4 to inform planned future work to promote the development of publicly available standard core sets of COA measures for specific disease indications. These core sets would include measures, tools, and end points to assess a minimum list of impacts that matter most to patients and are likely to demonstrate change related to disease burden, treatment burden, and if applicable, physical function.
1. AMCP Partnership Forum: improving quality, value, and outcomes with patient-reported outcomes [published March 2018]. J Manag Care Spec Pharm. doi: 10.18553/jmcp.2018.17491.
2. Calvert M, Kyte D, Maercieca-Bebber, R, et al. Guidelines for inclusion of patient-reported outcomes in clinical trial protocols [published February 6, 2018]. JAMA. doi: 10.1001/jama.2017.21903.
3. FDA patient-focused drug development guidance series for enhancing the incorporation of the patient’s voice in medical product development and regulatory decision making. FDA website. www.fda.gov/drugs/developmentapprovalprocess/ucm610279.htm. Published June 29, 2018. Accessed October 15, 2018.
4. FDA standard core clinical outcome assessments and endpoints. National Institutes of Health website. grants.nih.gov/grants/guide/notice-files/NOT-FD-18-014.html. Published July 31, 2018. Accessed October 15, 2018.