Defining patient goals for therapy in peripheral artery disease: A need for collaborative science

Commentary on Reed et al. Quantifying patients’ preferences on tradeoffs between mortality risk and reduced need for target vessel revascularization for claudication. Vasc Med 2024; 29: 675-683. ¹

In their recent publication in Vascular Medicine, Reed and colleagues posed trade-offs between length versus quality of life in patients with peripheral artery disease (PAD) requiring lower-extremity revascularization (LER) with a medical device. ¹ Their research was prompted by a 2019 warning issued by the United States Food and Drug Administration (FDA) concerning a possible increased mortality risk from paclitaxel-coated device use during LER for symptomatic PAD. ² Although robust evidence has demonstrated a reduction in clinically driven target vessel LER with drug-coated device use, ³ a meta-analysis in 2018 reported a significantly higher mortality risk in patients treated with these devices. ⁴ Prompted by these findings, the FDA issued a letter warning of harm and recommended that providers discuss the risks and benefits of available treatment options with patients. ² However, providers were left without guidance or tools to help them discuss these new and uncertain findings with patients. Subsequent research has not substantiated an increase in mortality risk with drug-coated device use, but this controversy highlights the important question of mortality versus quality of life trade-off for patients when evaluating medical devices.

Using a discrete choice experiment (DCE) methodology, and based on existing scientific evidence, Reed et al. quantified—from a patient perspective—an acceptable benefit-risk trade-off for drug-coated device use. DCEs are one of the accepted methodologies recommended by the FDA when evaluating patient preferences, with the intent to inform device approval. ⁵ Uniquely and importantly, the study was supported by a contract from the FDA, and FDA staff also served as co-authors, thus demonstrating an impressive and successful public–private partnership to clarify patient preferences for regulatory decision making. In addition, the FDA has led in promoting the use of patient preference information (PPI) to inform medical device decision making. In September 2024, the agency provided draft guidance for public comments on the use of PPI throughout the product life cycle, which are due at the end of this year. ⁶ Details on methodologies to determine patient goals and preferences are provided, including an overview of DCEs designed to detail the trade-offs that patients are willing to make.

Though the question of length versus quality of life has been examined in other medical fields, particularly oncology, ⁷ this trade-off has not been examined in the US PAD population. PAD increases both morbidity and mortality ³ and is associated with worse health-related quality of life (HRQoL). ⁸ This is at least partly explained by worse functional status, given the evidence that patients with PAD who can walk a greater distance have improved HRQoL compared to their more impaired counterparts. ⁹ The two most effective management strategies to improve walking function in patients are: (1) supervised exercise therapy (SET; a class 1 recommendation), and (2) LER (a class 2a indication). ³ Despite a class 1 recommendation, SET remains grossly underutilized in the US, with implementation barriers at multiple levels. ¹⁰ LER results in immediate walking improvement and has been demonstrated to be effective and durable, ¹¹ but increases the risk of major adverse limb events, including the need for further LER procedures. ³ To better understand the quality of life benefits of these strategies, validated PAD-specific patient-reported outcome measures (PROMs) have been utilized in the research setting. ¹² These include the Walking Impairment Questionnaire (WIQ), the Vascular Quality of Life Questionnaire (VascuQoL-25), and the PAD Quality of Life Questionnaire (PAD-QoL). Unfortunately, these instruments have not become part of standard clinical practice. ¹²

The study by Reed et al. targeted patients with PAD and claudication, some of whom had a history of LER. It is important to note that patients with chronic limb-threatening ischemia, who are at higher risk of mortality and major adverse limb events, were not included. A total of 272 US participants completed the survey and were older (mean age 69 years), primarily men (67%), and non-Hispanic White (91%). Of the respondents, ~40% chose the device alternative with the lower 5-year mortality risk in all or most of the scenarios, However, most of the participants indicated that they would accept a higher mortality risk for a more durable LER outcome, with an acceptable increase in 5-year mortality of 4–5%. This finding is consistent with recent research demonstrating that the most important treatment goal (in 31% of the 281-patient cohort) was improvement in quality of life. ¹³

In addition to understanding patients’ goals of care, true healthcare-shared decision-making requires proven decision aids and effective patient-facing education materials. A recently published Cochrane review including 209 studies with more than 100,000 participants provided extensive evidence that validated decision aids improve patient knowledge, increase the congruence of the final decision with patients’ values, and improve patient perceptions of risk. ¹⁴ There is an increasing focus on real-world use of decision aids in vascular disease, with the Centers for Medicare & Medicaid Services (CMS) requiring their use in carotid revascularization, ¹⁵ although validated tools are still needed. ¹⁶ A promising PAD decision aid has been developed and tested in patients and clinicians, but has yet to be validated. ¹⁷

Reed et al.’s work is a model for future collaborative efforts including patients, clinicians, researchers, regulatory partners, and industry to further define patient preferences and goals of care. Although focused on quality versus length of life in the symptomatic PAD population, studies examining this question in other disease processes are needed. The FDA has demonstrated a genuine commitment in supporting and promoting the use of DCEs and PPIs, and its partnership will be crucial in driving patient-centered care forward. As a relatively new field, research efforts will need to be iterative as evidence evolves. In the meantime, healthcare systems and clinicians should work together to improve utilization of validated decision aids and structured conversations using the most current evidence to improve patient-centered care.