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Quality of life

What endpoints are

meaningful to patients’ QoL?

This article looks at the most often used functional endpoints in PAH, and which are assessed as being meaningful to patients’ daily quality of life

Gabor Kovacs MD Medical University of Graz, Austria; Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria

In clinical studies, but also during routine evaluation of our patients, simplifications are necessary in order to be able to provide clear messages or to make clinical decisions. We use objective haemodynamic parameters, measures of exercise capacity or variables of the right ventricular function as endpoints. We have to recognise, however, that for our patients their quality of life (QoL) and their future prospects, and not a statistically significant change in these parameters, usually represent the most decisive factors. Therefore it is of great importance that we take a look at the most often used functional endpoints in pulmonary arterial hypertension (PAH) and that we assess what is meaningful to our patients’ daily QoL.

Endpoints in PAH studies – how they developed

Much progress has been made since the first PAH trials in the 1990s. Generally the consensus is that primary endpoints must be clinically relevant, sensitive to treatment effects, measurable and interpretable.1

In addition, with PAH 16

being an orphan disease with a potentially rapid deterioration, treatment effects need to be observed within a relatively short time (three to six months) in a relatively small group of patients (medium-sized cohort). These considerations led to the use of the six-minute walk test (6MWT), which is simple, reproducible and cheap, and

“The consensus is that primary endpoints must be clinically relevant, sensitive to treatment effects, measurable and interpretable”

showed a prognostic relevance in PAH.2 It

has also been accepted by the regulatory agencies. In addition, the 6MWT has become one of the most important clinical examinations and is performed routinely in PAH patients in order to assess their exercise capacity during follow-up and to guide therapeutic decisions. From the beginning, of course, the drawbacks and limitations of the 6MWT were obvious. There are significant subjective and objective confounders, including musculoskeletal and psychological factors or the well-known ceiling-effect.3

In addition, a significant

change in a clinical study and a clinically relevant change for the patient may not

necessarily be the same. This question has been addressed in recent analyses and it was estimated that the minimally important difference may lie at 33–42 metres.4–6

This change indicated a

statistically significant reduction in clinical events, so we may resume that such a change in the six-minute walk distance is meaningful for the patients.

Cardiopulmonary exercise testing Cardiopulmonary exercise testing (CPET) represents another method to assess exercise capacity, which was introduced as an endpoint in PAH studies. CPET is widely used in medicine and plays an important role in the evaluation of

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