In this study, we intended to capture participant’s experience with having AS. Many were young adults (the youngest was 26 years old) or had lived very active lives (the oldest was a 76-year old competitive triathlete) prior to disease onset. Fatigue and pain were often experienced at extreme levels, and the symptoms affected all areas of participants’ lives: mobility, work, career aspirations, social activities, relationships, and emotional well-being. Although participants typically mentioned chronic, and sometimes excruciating, pain when first asked about their experience of AS, when probed about fatigue, they responded with 'Oh yes, very much so’ and 'Oh, I’m always exhausted’. One participant suggested that one possible explanation for not reporting fatigue spontaneously could be the 'normalization’ of the phenomenon by themselves (i.e., feeling fatigued becomes customary) or others (i.e., 'everybody gets tired’), and hence participants’ omission to report this. Fatigue severity was reported to be highly variable from day-to-day as well as throughout the day, with the evening often cited as the time of worst fatigue severity. Participants mentioned a number of factors influencing fatigue severity, including pain, sleep disturbances (that may be related to pain), exercise or activity, and feeling depressed.
Results from the concept elicitation interviews also indicated that all participants clearly understood the term 'fatigue’ and some of them used it spontaneously when describing their condition. It is possible that individuals with AS quickly learn the term because it is used by doctors and other patients when discussing the condition. While participants also used other terms and phrases to describe fatigue, such as tiredness, feeling worn out, exhausted, needing to rest, slowed down, etc., the term 'fatigue’ resonated with participants and was considered clear and appropriate for describing how AS makes them feel.
In summary, the concept elicitation interviews confirmed that fatigue was a key symptom of AS. All participants reported experiencing fatigue at some point during their illness, with all but one participant currently experiencing fatigue. Along with pain, fatigue was considered a bothersome symptom of AS, with one participant reporting that fatigue was the most bothersome symptom.
Although there have been a large number of scales developed with the intent of measuring fatigue , the WF-NRS has a number of characteristics that distinguish it from the alternatives. First, the WF-NRS was developed based on qualitative input (concept elicitation interviews and cognitive debriefing of the BFI) from an AS population ensuring the assessment of an important and relevant aspect of fatigue severity. This type of patient input is a key aspect for establishing content validity as the fatigue experience may differ across patient populations and scales developed for one condition may not be appropriate for use in another. Many of the existing fatigue scales were developed in patient populations other than AS, such as those with cancer [10, 14, 15], chronic fatigue syndrome[16–18], multiple sclerosis [19–21], rheumatoid arthritis , or general medical patients [23, 24]. To the best of our knowledge, content validity in AS has not been established for most of these instruments. Second, the WF-NRS is a single-item, unidimensional instrument inquiring about the worst level of fatigue in a 24 hour period as a measure of fatigue severity, which the interviews revealed to be relevant and understandable in patients with AS. Having respondents answer queries based on their worst experience is consistent with recommendations from PRO development guidelines for using appropriate methods and techniques to enhance the validity and reliability of self-reported data . In contrast, the other measures listed above are all multiple-item tools that assess fatigue as either a unidimensional [10, 14, 16, 19] or a multidimensional [15, 17, 18, 20–24] construct. The brevity of the WF-NRS may make it particularly suitable for use in clinical trials with a patient population that suffers from fatigue, especially if the trial subjects will be expected to complete a battery of other assessment instruments. Finally, the 24-hour recall period appears to be short enough that patients will not have difficulties in accurately completing the instrument. The study participants suggested that fatigue severity was periodic and therefore other recall periods, such as “at the present time”, may not capture clinical peaks. Additionally, capturing the worst level of fatigue in a short timeframe does not require the patient to average his or her symptom severity over time. Patient responses that rely on memory based on long periods of time, or require the responder to average their response, may introduce recall bias . Moreover, incorporating the WF-NRS in a daily diary may help ensure that day-to-day variability in worst fatigue could be readily captured and addresses participants’ concerns that just one assessment may not accurately characterize their fatigue severity. The addition of a clinical outcome assessment tool to capture cognitive impairment should also be considered as participant comments suggest a mental component of fatigue presenting as a consequence of AS.
A limitation of the study may be that the small sample size allowed participant’s input to be obtained from only three clinical sites, although they were located in separate regions of the country. However, the intention of sampling for qualitative research for the development of a patient-reported outcome measure is not to obtain a representative sample of the epidemiologic profile of the patient population but rather to ensure an enriched diversity in patient and disease characteristics, and the distribution of variables indicated a diverse sample with respect to sociodemographic characteristics was obtained. Also, the recruited participants did not include AS patients with a mild level of severity. While the results of this initial qualitative study of fatigue in AS patients were promising, further quantitative research is indicated. In particular, additional research with the WF-NRS is required in order to assess its test-retest reliability; to examine its concurrent, discriminative, and construct validity; and to determine its sensitivity to change. Additionally, the translatability of the WF-NRS into other languages and cultures would also need to be examined before using the instrument in global clinical trials. Nonetheless, the interviews completed with patients with AS in the present study led to the development of the WF-NRS and ensured that the content was relevant to the AS population and the clarity, interpretation (as intended per judgement of the study team), response scale, and recall period were all appropriate.