Psychometric properties of the Patient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire

Abstract

ObjectiveTo assess the psychometric properties of the Patient Reported Outcomes, Burdens and Experiences (PROBE) questionnaire.MethodsThis study was a cross-sectional, multinational study. Participants were enrolled if they were more than 10 years old and people with haemophilia A or B or people without a bleeding disorder. Participants were invited through non-governmental patient organisations in 21 countries between 01/27/2016 and 02/23/2017. The following psychometric properties: missing data, floor and ceiling effects, exploratory factor analysis and internal consistency reliability were examined. A PROBE Score was derived and assessed for its convergent and known groups validity.ResultsThe study analysed the data on 916 participants with median age of 37.0 (IQR 27.0 to 48.0) years, 74.8% male. In the domain assessing patient-reported outcomes (PROs), more than 15% of participants presented a ceiling effect for all items but two, and a floor effect for one item. Factor analysis identified three factors explaining the majority of the variance. Cronbach’s alpha coefficient indicated good internal consistency reliability (0.84). PROBE items showed moderate to strong correlations with corresponding EuroQol five dimension 5-level instrument (EQ-5D-5L) domains. The PROBE Score has a strong correlation (r=0.67) with EQ-5D-5L utility index score. The PROBE Score has a known groups validity among various groups.ConclusionsThe results of this study suggest that PROBE is a valid questionnaire for evaluating PROs in people with haemophilia as well as control population. The known-group property of PROBE will allow its use in future clinical trials, longitudinal studies, health technology assessment studies, routine clinical care or registries. Additional studies are needed to test responsiveness and sensitivity to change.Trial registration numberNCT02439710; Results.

How to discuss gene therapy for haemophilia? A patient and physician perspective

“…Gene therapy with a factor expression in the normal range would free PWH from their mental burden and may lead to a real reduction in the levels of anxiety and depression . With greater levels of protection, the frequency of bleeds should decrease even in the presence of higher levels of physical activity.…”

“…Gene therapy with a factor expression in the normal range would free PWH from their mental burden and may lead to a real reduction in the levels of anxiety and depression. 36 With greater levels of protection, the frequency of bleeds should decrease even in the presence of higher levels of physical activity. Freedom to carry out normal everyday activities, taken for granted by those without haemophilia, such as walking, running, cycling, swimming and potentially riskier sports participation would all become more attainable.…”

“…In terms of the physician perspective, setting patient expectations, both for clinical trials and ultimately for gene therapy as an approved treatment option for haemophilia, will be important, as some PWH will not qualify for treatment. The standard inclusion/exclusion criteria employed in clinical trials to date have limited participation to adult patients with severe or moderately severe haemophilia, 33,36,37 with exposure to factor treatment for defined periods of time study also excluded patients who were HIV positive. 37 To date, all trials have also excluded patients with pre-existing antibodies to the AAV serotype specific to each of the investigational products; however, at least one phase 3 trial for haemophilia B [NCT03569891] has lifted that exclusion criterion due to lack of evidence for associated reduced efficacy or immune responses due to pre-existing low-titre neutralising antibodies to AAV5.…”

Hemophilia trials in the twenty‐first century: Defining patient important outcomes

“…Validation studies for the PROBE questionnaire have been completed. The questionnaire was assessed for face validity, relevance, clarity and completeness; test‐retest reliability (reproducibility) confirmed; a core analytic framework (psychometric properties) established; and cross‐cultural validation demonstrated, and is now being incorporated into clinical trials ( https://clinicaltrials.gov/ct2/show/NCT03370913; https://clinicaltrials.gov/ct2/show/NCT03392974; https://clinicaltrials.gov/ct2/show/NCT03615053).…”

Exploring regional variations in the cross‐cultural, international implementation of the Patient Reported Outcomes Burdens and Experience (PROBE) study

“…According to the results of the study, most participants completed the questionnaire within 15 minutes. Psychometric properties of the PROBE questionnaire were evaluated in people with haemophilia (PWH) A or B and participants without bleeding disorders . This study showed that the PROBE questionnaire had a good internal consistency (Cronbach's alpha coefficient of 0.84) and a convergent validity comparable to EuroQol five‐dimensional five‐level instrument (EQ‐5D‐5L) items.…”