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Patient-reported outcomes (PROs) must be included in cardiovascular clinical trials using the best available tools, according to leading cardiologists and industry representatives in the Cardiovascular Round Table, an independent forum established by the European Society of Cardiology (ESC). All ESC guideline committees will now consider PROs when making recommendations.
The CRT’s views are published today in the European Heart Journal.
“PROs inform about important (non-survival) aspects of life that are important to patients. They are needed for health technology assessments and reimbursement decisions. But until now PROs have not been routinely evaluated in cardiovascular clinical trials,” noted lead author Stefan D. Anker, M.D., PhD, from the Charité Hospital at the Medical University of Berlin, Germany. “Our paper outlines the value of including PROs in clinical trials and how to make their assessment scientifically rigorous. The ESC Board has now committed to ensuring that PROs are considered by all ESC guideline task forces.”
PROs include symptoms, health-related quality of life (HRQoL), and adherence to therapy. PRO data can be used to inform routine clinical care, particularly when weighing up the risks and benefits of alternative therapies. The data can also support a label claim that a therapy improves symptoms, functional ability or HRQoL, and can support reimbursement decisions, which may consider the effect of a therapy on well-being, functional status or productivity, in addition to the primary clinical endpoint.
“Integrating PRO data into comprehensive efficacy evaluations will ultimately improve the quality of care for patients across the spectrum of cardiovascular disease,” stated the authors, adding that PRO measures should be assessed in “at least a subset of patients enrolled in cardiovascular mega-trials.”
Trialists who use PROs must ensure they apply the same scientific rigor as they do with other endpoints, and the PRO hypothesis should be stated in the protocol, along with a clear statement of the key PRO that will be analyzed, they advised. PRO data should be recorded by the patient whenever possible, and statistical power should be allocated to the PRO endpoint if it is a primary, co-primary, or key secondary endpoint.
According to Anker, “PROs are subject to patient and physician bias and therefore designing studies so that they are bias free is important. Double-blind studies are the key to achieving this.”
Study procedures should be in place to minimise missing data and reasons for missing data should be captured. As the authors point out, “a treatment that prolongs life may perform worse on PRO outcomes than a treatment without a survival benefit because the patients survive to report PROs but still experience disease progression that results in recurrent events or multiple hospitalizations”.
Interpretation of PRO data in cardiovascular clinical trials remains challenging because there is no consensus in many cases on what constitutes a clinically meaningful change, explained the authors.
“Further research efforts are needed to resolve this major issue,” they noted. “Until a common approach to such analyses has been adopted, we suggest that the analysis plan for PROs should be discussed with regulatory agencies and with stakeholders (patients, PRO experts) early in the trial planning process.”
Read the full release here.