Health-related quality of life measurement in asthma and chronic obstructive pulmonary disease: review of the 2009-2014 literature

A description of the literature about respiratory, non-biological medicinal products,
developed in the past few years, has allowed to highlight that the PRO measurement
has been often included in the studies’ protocols. This is in line with the recognition
by regulatory authorities, payers and pharmaceutical companies that measurement of
the patient experience with the drug is increasingly important. In all the measurements
observed, the subjective data was considered a secondary endpoint. This is consistent
with the endpoint hierarchy established by EMA and the FDA which sees the physiological
effect produced by the study drug as a priority, and relegates the PRO to a secondary
endpoint.

The choice of tools to be used meets the specifications of the reference documents.
AQLQ is used with the patients with asthma, whereas the SGRQ is used with the patients
with COPD. Both tools have been well documented since their initial development, and
are validated and available in many languages 8], 9]. In all the studies, the time frame for the administration of the questionnaires
is specified. In the shorter studies, the measurements are reported at the baseline
and at the end of the study. In longer studies, there can be interim measurements.
It should be noted that the short duration of a study (in particular in the COPD case)
is planned to allow for functional measurements, but it could not capture the impact
that the drug has on the health, as perceived by the patient. For instance, Kerwin
reports, in the conclusions of his study, that a duration above 12 weeks could have
allowed the patients treated with aclidinium 400 ?g to reach the Minimal Clinical
Important Difference (MCID) in a significantly greater percentage compared with the
patients receiving placebo 10]. A further aspect for consideration is the use of the placebo treatment arm. These
patients may receive rescue treatment, and often the variation in the SGRQ score obtained
with these patients is important, as is the percentage of responder patients (those
who reach the MCID). Another aspect noted in some studies was that the improvement
reported with the SGRQ was in contrast with the bronchodilator effect. For example,
Jones et al point out this aspect in the placebo arm of their study where the spirometry
values decline, but the patients report a better respiratory state of health 11].

The measurements are always accompanied by information on their statistical significance.
With reference to this point, we noted that more COPD than asthma studies reported
a statistical significance. In other words, it seems that COPD drugs are significantly
more effective than asthma drugs. Furthermore, it is to consider that a number of
COPD studies foresaw the analysis versus a placebo arm, and the number of patients
could be excessive for the HRQoL measurement. With reference to the clinical significance,
asthma patients have a higher percentage of patients who experienced a clinically
important change than COPD patients (despite the lower number of measurements). We
can speculate that asthma patients perceive better the changes given by drugs than
COPD patients. On the other hand, asthmatics are generally younger than COPD patients,
and suffer less from other diseases (comorbidities). However, the subjective nature
of the measurements should lead to some considerations on the significance of the
effects produced by the treatment. Usually, the variations in the scores obtained
from the questionnaires on HRQoL are assessed on an effect-size basis, since a change
produced by a treatment may be statistically significant (possibly because the number
of patients calculated for the main endpoint is high), but it may not be perceived
as clinically significant by the patients. In general, effect-size indexes have been
developed for the exact purpose to avoid making incorrect inferences, due also to
high sample sizes. In other words, since the above indicated indexes seek to square
the results net of the effects of the sample (number of subjects), they should not
be affected by this data. The effect-size indexes allow for an evaluation of the amplitude
of an effect in each research design, but there always remains the difficulty of choosing
the most appropriate index and interpreting the results. Perhaps the latter is the
reason why measurement results are usually reported without comments. In some cases,
PRO measurement data are included in the discussion, but in many other cases, they
are only briefly mentioned.

Undoubtedly, the PRO adds knowledge to the drug. Within the respiratory area, there
are many medicinal products available which have demonstrated their efficacy in intervening
on the two main characteristics that define asthma and COPD, i.e. bronchoconstriction
and chronic inflammation. However, only some of them provide information about the
outcomes of treatment which may be important to patients. This data could represent
a discriminatory factor in the choice of the medicinal products to be included into
a formulary. In fact, a medicinal product that is perceived as useful by the patient
could have more probability to be taken (good adherence to treatment) and this would
maximise the financial investment of the third party payer. Among the cited studies,
one has used the Onset of Effect Questionnaire (OEQ) to measure the preference of
the patient with asthma of a certain bronchodilator versus another bronchodilator
in the same pharmacological category, but slower in manifesting its effects 10]. The fact that this questionnaire was not used in other studies may mean that it
is not important to measure this parameter, or that the questionnaire was used in
that study just to reiterate that one of the drugs was faster in manifesting its effects.

Some studies, not included in this analysis because they were published before 2009,
measured the preferences of the patients regarding the inhaler used. Dalby et al cite
these experiences in one article that discusses the development of an inhaler 12]. This measurement can be useful also if the intent is to provide the patient with
a treatment, that, on average, he/she will consider satisfactory and therefore, presumably,
be more willing to adopt.

To conclude, the subjective measurements, initially reserved for patients with very
serious diseases and a limited life expectancy, have become more commonly used even
with patients suffering from chronic diseases. The fact that patients with asthma
and COPD can have a longer life expectancy makes the quality of those years left to
live very important. It is therefore desirable that the PRO measurements be increasingly
used and become part of the daily routine of clinical practice. In this perspective,
tools such as the SGRQs might be considered labour-intensive requiring too long for
their completion and interpretation. To this end, some other easier and simpler tools
could be proposed for development.