Importance of clinical worsening criteria vary, survey finds

Patients, caregivers place different values on the parameters used in clinical trials

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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A doctor listens to a patient who is making a point.

People with pulmonary arterial hypertension (PAH) and their caregivers place different value on the parameters used to evaluate clinical worsening in trials, according to the findings of a survey in Canada.

Patients attributed significant importance to lacking clinical improvement, needing long-term oxygen therapy, and any decrease in health-related quality of life, “supporting the fact that PAH affects many aspects of patients’ lives and contributes to physical, financial, social and emotional burden,” the investigators wrote.

Caregivers placed greater importance on reducing hospitalizations than did patients.

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The study, “Patients’ perceptions on clinical trials outcomes in pulmonary arterial hypertension therapy,” was published in the journal Thorax.

Clinical worsening, the deterioration of a patient’s clinical status, is often used as a main goal in clinical trials of PAH to evaluate the effectiveness of a new treatment.

However, how patients and caregivers value several of the parameters used as part of clinical worsening remains largely unknown. Taking this into consideration is deemed vital to “ensure that trials assess outcomes and interventions relevant to patients’ priorities,” the team wrote.

Survey in Canada

With this in mind, researchers conducted a survey among PAH patients and caregivers recruited at two patient associations, Fondation HTAPQ and PHA Canada, and medical caregivers from 15 PAH centers in Canada.

The investigators included 23 specific parameters used to evaluate clinical worsening in PAH clinical trials, identified as part of a systematic review. Regarding the impact on general well-being, each parameter was evaluated as critical — meaning that patients “would almost prefer to die rather than experiencing it,” — major, mild-to-moderate, or minor (no impact on well-being).

In total, there were 335 participants, 257 PAH patients and 78 caregivers. Most respondents were women (76.7% among patients and 62.8% among caregivers) and white (82.9% of patients and 80.8% caregivers). Most patients were 50 or older, had a high school or higher degree diploma, and lived in large cities.

Idiopathic (no known cause) or hereditary PAH accounted for 39% of cases, and about half of the patients (49%) had slight-to-moderate functional limitations despite diverse therapies.

Overall, patients viewed most outcomes as of major and mild-to-moderate importance. Preventing death was considered critical by the majority of patients. Preventing hospitalization, adding an oral therapy, changes in the dosing of epoprostenol (sold as Veletri and Flolan), and a decrease of 5-15% in the six-minute walk distance test of exercise capacity, were deemed mostly of mild-to-moderate importance.

Among patients, the importance given to several components varied according to their characteristics, such as age and World Health Organization functional classification.

Hospitalization is caregivers’ concern

Caregivers also placed higher value in the prevention of hospitalization, the start of a prostacyclin analogue (which include Flolan and Veletri), and persistent functional decline when compared to patients. However, the overall agreement among caregivers was low.

The need for an atrial septostomy, a procedure to reduce pressure in the right side of the heart, also was considered as of major importance by non-medical caregivers. In addition, needing a lung or heart-lung transplant was deemed of major importance by the overall group of caregivers.

In sum, these findings suggest that the value of parameters used as clinical worsening outcomes in PAH clinical trials is “highly heterogeneous, likely varying between patients with PAH and their caregivers and according to patients’ characteristics,” the researchers wrote.

“To ensure that researchers identify interventions and outcomes of greatest value to those affected by PAH, it is essential to involve a diversity of patients throughout the research process as participants and as key stakeholders,” they concluded.

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