Developing innovative drugs takes time, with an average of 9.1 years between the first-in-human trial and regulatory approval.[1] Early-stage trials average even longer at nearly a decade, so many companies do not consider their marketing and sales strategies. Recently, however, early-phase protocols have been collecting patient-reported outcomes (PROs) not only to get regulatory approval but to demonstrate value to public and private payers.
A Shift Toward Healthcare Value in the US
Over the past decade, US healthcare policy has shifted incrementally from service-based payment to value-driven reimbursement. With value-based care, the quality of care is evaluated along with its cost. PROs and other clinical outcome assessments (COAs) are used to measure the impact of care, and reimbursement is dependent on meeting specific COA or PRO thresholds.
It all started in 2010. With the passage of the Patient Protection and Affordable Care Act, value-based care models were introduced.[2] This was followed by the Protecting Access to Medicare Act (PAMA) and the Medicare Access and CHIP Reauthorization Act (MACRA) in 2014 and 2015, respectively. Together, they expanded value-based care opportunities and the measurement of outcomes, and today, PROs are still a key part of the Meaningful Measures Framework intended to guide improved care quality for all Medicare and Medicaid patients.[3]
However, Medicare and Medicaid are not the only entities impacted by the policy shift to value-based reimbursement. With the passage of the 21st Century Cures Act in 2016, the Food and Drug Administration (FDA) must report on the use of patient experience data in regulatory decision-making.[4]
“The FDA increasingly looks to patients to understand how patients describe their health status because patients are the experts in living with their disease or condition,” explains Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence.[5]
“Input from patients or their caregivers about what is important can then be used to select or develop tools to measure what matters most to patients. COAs may capture outcomes that are important to patients, such as how they feel or function or how long they survive. They play a central role in ensuring that what matters to patients is factored into regulatory decision-making.”
As a result, the FDA has provided additional guidance on the use of real-world evidence (RWE), including PROs, and now expects greater inclusion of patient experience data in new drug applications (NDAs) and biologics license applications (BLAs). Recently the FDA reported that 82 percent of NDAs and BLAs for new molecular entities (NMEs) include a Patient Experience Data Table and 30 percent of approved product labeling for those NDAs and BLAs include patient experience data.[6]
Beyond incorporating PROs more fully into the regulatory process, the FDA has also provided guidance on sharing healthcare economic information about drugs and devices to payers in advance of regulatory approval.[7] In response to public and private insurers’ need to understand, estimate, and plan for future expenses, the FDA now permits sponsors to share healthcare economic information (HCEI) with payers while clinical trials are in progress.
US Private Payers Incorporating PROs into Coverage Decisions
HCEI can be shared about “medical products that are not yet approved/cleared by FDA for any use and about unapproved uses of approved/cleared medical products.”[7] The FDA has also provided specific guidance on how COAs, including PROs, can be incorporated into the HCEI provided to payers. “HCEI analyses may be derived from studies involving the approved indication of a drug that assess COAs (e.g., PROs such as work productivity, basic activities of daily living) or other health outcome measures (e.g., quality-adjusted life years [QALY]) when they are evaluated using valid and reliable measures (as determined by experts who are familiar with evaluating the merits of a particular COA or other health outcome measure).”[7]
Knowing that payers sometimes, for cost planning purposes, need to make coverage and reimbursement decisions far in advance of FDA decision dates, the FDA’s guidance facilitates the information sharing necessary for payers to evaluate the value of future therapies.
With the shift in US health policy and legislation, Medicare and Medicaid have been mandated to increase the adoption of value-based care and to use PROs to evaluate care quality. New value-based care models, such as the Centers for Medicare and Medicaid Innovation’s oncology program, have been revamped to include PROs.[8]
As is common in the US, private insurers, including self-insured employers, have followed and adopted aspects of these governmental programs. Private payers are using PROs as they create value-based contracts, determine local-level coverage, identify quality improvement targets, and identify the impact of healthcare technology utilization.[9] Many high-cost procedures, including those requiring medical devices, now require PRO submission as part of the reimbursement pre-authorization process.[10]
PRO and Quality-Adjusted Life Years
More importantly, for many sponsors, insurers are increasingly using PROs as they evaluate therapies to be included in their formularies. Premera Blue Cross, a plan serving more than 2 million patients in the Pacific Northwest, published demonstrated savings using a value-based formulary approach.[11] HCSC, a plan serving more than 16 million patients in 5 midwestern states, reconfigured its pharmacy and therapeutics (P&T) evaluation process to include PROs after the FDA’s guidance on providing HCEI.[12] And, they aren’t alone. CVS’s pharmacy benefit management (PBM) division, with its 65 million patients, allows self-employed insurers to exclude high-cost but low-value drugs, including those valued at more than $100,000 per QALY from their formularies.[13]
In a recent survey of payers about the use of PROs during oncology P&T reviews, 47 percent suggested that not including PROs from oncology clinical trials would influence their decision on formulary inclusion.[14]
When considering formulary inclusion, 78 percent of the surveyed payers believe that PRO evidence would enhance their evaluation of the safety of oncology therapies. More than half (51%) of the surveyed payers see PROs as assisting in how value-based agreements are measured and 34 percent of them want PRO evidence when comparing two similar oncology therapies.
As more payers embrace value-based formularies, they are turning to external, objective sources for economic benefit analyses that incorporate PRO data and calculate cost per QALY.[13] Multiple organizations in the US provide frameworks to assess value and economic benefit, including the Institute for Clinical and Economic Review (ICER), the American Society of Clinical Oncology, the National Comprehensive Cancer Network, and the Innovation and Value Initiative.
In a survey of 99 payers, 59 percent acknowledged using these value analyses.[15] Payers reported citing the analyses as source evidence for making P&T recommendations, validating their own economic analyses, assisting in determining product availability, and developing criteria for prior authorization. Whether from ICER or other sources, these analyses have become increasingly important in payer and PBM coverage and utilization determinations.[16]
A recent survey of payers conducted by the contract research organization, ICON, found that 50 percent of the interviewees expect their use of QALY data in coverage decisions to expand in the future.[17] As one pharmacy benefits manager surveyed stated, “ICER’s whole premise is cost-effectiveness, and a QALY is a data element that resides in that category. We anticipate that we’ll be going there and are approaching using QALYs in our decision-making.[17]
Non-US Payer Use of PRO Evidence for Reimbursement
Although the move toward value-based care has been more recently adopted in the US, other countries have more than a decade of experience using HCEI and PRO data to evaluate healthcare therapies. The National Institute for Health and Care Excellence (NICE) in the UK, the Pharmaceutical Benefits Advisory Committee (PBAC) in Australia, the Canadian Agency for Drugs and Technologies in Health (CADTH), and other health technology assessment (HTA) organizations regularly provide reports that make reimbursement recommendations.[15] Often these recommendations are based, in part, on an estimate of the incremental cost per quality-adjusted life year (QALY) gained from the adoption of the new medicine, as compared with current care. This is one of the most common approaches followed in Europe to assess the value of healthcare technology.[15]
When interviewed and surveyed, payers worldwide recognize high-quality PRO data as a key component of their decision-making process and anticipate the growing importance of PRO data in the future.[18] For some countries and regulatory bodies, the importance of PRO data includes expanded collection and use of real-world data (RWD) and real-world evidence (RWE). In the UK, the Medicines & Healthcare products Regulatory Agency (MHRA) recently issued two guideline documents focusing on the use of RWD to support regulatory decisions. The European Medicines Agency (EMA) currently uses RWE for safety monitoring and recently announced that the use of RWE will be established across its spectrum of regulatory use cases by 2025.[19]
Why Collecting PRO Data in Early Phase Trials Matters
As insurers worldwide continue to incorporate HCEI and value-based analyses into their coverage decisions, they will expect PRO data to support their processes. For sponsors, incorporating the collection of PRO data into early-phase studies may improve reimbursement for the following three reasons.
- First, payers often make decisions about therapy coverage and reimbursement well in advance of FDA approval of the therapy.[15] Under the FDA guidance on sharing HCEI with payers, sponsors have the opportunity to share PRO data collected during clinical trials and to help inform payers’ P&T decision-making.
- Second, payers are unlikely to reconsider a product due to new PRO data generated post-launch once a coverage decision has already been made.[17] While post-marketing PRO data may be required for regulatory reasons, that data will not be evaluated by payers’ P&T committees.
- Third, current trends, such as drug price transparency legislation and inflation, will result in greater scrutiny of a therapy’s value, including the impact of the therapy on patient lives. When selecting PROs, consideration should be given to those that can be incorporated into potential value-based pricing structures that link the purchase price to patient outcomes.[16]
The PRO measures that are most useful during formulary decision-making are those that are collected via validated survey instruments, rather than novel ones.[17] P&T committees appreciate that validated PRO surveys have been peer-reviewed and published; they also appreciate the ability to compare PRO data collected using a common instrument. At the same time, payers prefer PRO data that can be evaluated objectively. PROs that are linked to reduced utilization of healthcare services, such as fewer emergency room visits, or to improve patient functioning, such as activities of daily living measures, provide insurers with a more concrete perspective on a therapy’s value.
How Medrio Can Support Early Phase PRO Collection
For sponsors that want to collect PROs during early phase studies, Medrio offers assistance that goes beyond supplying an electronic PRO (ePRO) tool.
- Protocol review – Medrio’s subject matter experts will review the intended PRO survey instruments in a sponsor’s protocol through the lens of payer reimbursement and suggest opportunities to optimize PRO.
- Selection of PRO collection methodology – Medrio’s staff will review the PRO collection requirements and provide a cost and quality comparison between paper-based and electronic collection of PRO data.
- ePRO deployment – Medrio will support the full implementation of ePRO data collection, from licensing PRO survey instruments to translating surveys into additional languages to training sites on deploying ePRO with patients.
- Adherence monitoring – Medrio’s ePRO system includes text or email reminders to patients to encourage survey completion. In addition, standard reports provide insight into patient adherence to ePRO surveys and pinpoint patients who require site intervention.
- Rapid results – Since Medrio’s ePRO is fully integrated into the EDC, ePRO results are immediately available for review by a sponsor.
Experience the difference having the right ePRO partner can make in your clinical trials. Request a demonstration or schedule time to talk with a Medrio ePRO expert to learn why what makes Medrio different is what makes our ePRO a good fit for you.
[1] Brown, D. G., Wobst, H. J., Kapoor, A., Kenna, L. A., & Southall, N. (2021, November 10). Clinical Development Times for innovative drugs. Nature News. Retrieved January 18, 2023.
[2] CMS. (n.d.). CMS’ value-based programs. CMS. Retrieved January 18, 2023.
[3] Maruszczyk, K., Aiyegbusi, O. L., Torlinska, B., Collis, P., Keeley, T., & Calvert, M. J. (2022, June 2). Systematic review of guidance for the collection and use of patient-reported outcomes in real-world evidence generation to support regulation, reimbursement and Health Policy. Journal of Patient-reported outcomes. SpringerOpen. Retrieved January 18, 2023.
[4] McNeil, C. (2020, July 10). The 21st Century Cures Act: A look back, a look ahead. The ASCO Post. Retrieved January 18, 2023.
[5] Commissioner, O. of the. (2022, September 6). Patient-reported outcomes and other clinical outcome assessments. U.S. Food and Drug Administration. Retrieved January 18, 2023.
[6] Eastern Research Group. (2021, June 12).Assessment of the use of patient experience data in regulatory decision. FDA. Retrieved January 18, 2023.
[7] US Food and Drug Administration. (2018). Drug and device manufacturer communications with payors, formulary committees, and similar entities—questions and answers: guidance for industry and review staff. FDA. Retrieved January 18, 2023.
[8] Cohen, D., Ault, D. O., & Marcus, R. B. (2022, August 23). Enhancing cancer care: New cmmi model invites physician practices, payers to reconsider traditional reimbursement for oncology services. Ropes & Gray. Retrieved January 18, 2023.
[9] Mesana, L., de Gennes, C. D., & Syed, I. A. (2019, May 1). CP4 Payer Perspectives on Patient-Reported Outcomes Measures for Reimbursement Decision-Making in the United States. Value in Health Journal. Retrieved January 18, 2023.
[10] Florida Orthopaedic Institute. (n.d.). Proms (patient-reported outcome measures). Florida Ortho. Retrieved January 18, 2023.
[11] Yeung, K., Basu, A., Hansen, R. N., Watkins, J. B., & Sullivan, S. D. (2017, February). Impact of a value-based formulary on medication utilization, health services utilization, and expenditures. PubMed Central. Retrieved January 18, 2023.
[12] Labson, M. S., Savidge, P., & Weaver, J. (2019, October 17). Payor Guidance Follow Up: Execution and Real World Challenges. Food and Drug Law Institute. Retrieved January 18, 2023.
[13] Dubois, R. W. (2018, September 17). CVS to restrict patient access using cost-effectiveness. Health Affairs Blog. Retrieved January 18, 2023.
[14] Oderda, G., Brixner, D., Biskupiak, J., Burgoyne, D., Arondekar, B., Deal, L. S., Quek, R. G., & Niyazov, A. (2022). Payer perceptions on the use of patient-reported outcomes in oncology decision making. Journal of managed care & specialty pharmacy, 28(2), 188–195. Retrieved January 18, 2023.
[15] Lising, A., Drummond, M., Barry, M., & Augustovski, F. (2017, March). Payers’ Use of Independent Reports in Decision Making – Will There Be an ICER Effect? IPSOR. Retrieved January 19, 2023.
[16] Castle, G. (Ed.). (2020, August). Pricing & Reimbursement 2020. Covington & Burlington LLP . Retrieved January 19, 2023.
[17] ICON (Ed.). (2020). Will US payers give more consideration to PRO data when making their coverage and formulary decisions? ICON plc. Retrieved January 19, 2023.
[18] Brogan, A. P., DeMuro, C., Barrett, A. M., D’Alessio, D., Bal, V., & Hogue, S. L. (2017). Payer Perspectives on Patient-Reported Outcomes in Health Care Decision Making: Oncology Examples. Journal of managed care & specialty pharmacy, 23(2), 125–134.
[19] Maruszczyk, K., Aiyegbusi, O.L., Torlinska, B. et al. (2022). Systematic review of guidance for the collection and use of patient-reported outcomes in real-world evidence generation to support regulation, reimbursement and health policy. J Patient Rep Outcomes 6, 57 (2022).
