What does ‘active disease’ mean? patient and parent perceptions of disease activity in the systemic arthritis form of juvenile idiopathic arthritis (SO-JIA)

M. Batthish1, R. Schneider1, A. V. Ramanan1, C. Achonu1, N. L. Young2–4, and B. M. Feldman1,3,5

1 Department of Pediatrics, Division of Rheumatology, The Hospital for Sick Children, 2 Department of Pediatrics, The Hospital for Sick Children, 3 Department of Health Policy Management and Evaluation, University of Toronto, 4 Graduate Department of Rehabilitation Science, University of Toronto and 5 Department of Public Health Sciences, University of Toronto, Toronto, Ontario, Canada.

Correspondence to: B. M. Feldman, Division of Rheumatology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada. E-mail: Brian.Feldman{at}sickkids.ca


    Abstract
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Objective. The systemic onset form of juvenile idiopathic arthritis (SO-JIA) is a very serious chronic illness of childhood. At present, there is no specific tool to measure disease activity for SO-JIA. Our long-term goal is to develop a disease activity measure for SO-JIA using a consensus (Delphi) approach. In preparation for the development of this measure, we interviewed both patients and their parents. We sought to elicit specific items reflecting their perceptions of active disease that may be considered for inclusion in a disease activity measure for SO-JIA.

Methods. SO-JIA patients followed at The Hospital for Sick Children and their parents were chosen by purposive sampling. A trained research coordinator interviewed all participants using open-ended questions to elicit aspects of disease activity (defined as reversible manifestations of disease) of relevance to families. A list of these aspects was then generated and organized by categories to allow item reduction.

Results. Fourteen patients (eight females) with a mean age of 11.8 yr (mean disease duration 5.2 yr) and their parents were interviewed. A total of 292 items were generated, with an average of 11 items generated per interview. Arthralgia, ambulation difficulties, rash, decreased energy level and fever were the most common items mentioned by patients and their parents. Mood disturbances, decreased activity levels, arthritis severity and decreased school attendance were also common items identified as relevant aspects of disease activity.

Conclusion. This study has allowed us to include patient and parent perspectives in preparation for developing a disease activity measure for SO-JIA. The resulting items will be added to future physician surveys in the further development and validation of a disease activity measure for SO-JIA.

KEY WORDS: Systemic arthritis, Juvenile idiopathic arthritis, Disease activity measures, Patient interviews


    Introduction
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. The systemic onset form (SO-JIA), known as ‘systemic arthritis’ under the ILAR (International League of Associations for Rheumatology) classification scheme, constitutes 10–20% of all juvenile arthritis and is found equally in males and females [1]. The mean age at onset is 4–6 yr, but it can occur at any age during childhood. The clinical features of SO-JIA differ from those of other forms of JIA and include high spiking fevers, characteristic rash, myalgias, generalized lymphadenopathy, hepatosplenomegaly and pericarditis in addition to arthritis. Patients with SO-JIA may follow a monocyclic course with complete remission within 2–3 yr of disease onset, a polycyclic course characterized by recurrent episodes of systemic disease activity, or a course of persistent polyarthritis [2, 3]. The course of SO-JIA is therefore variable and can involve many organ systems, and disease activity changes with time (over periods of a few hours to weeks) and with treatment.

There are more deaths amongst patients with SO-JIA than in any other subtype of JIA. At one point the mortality rate was estimated to be as high as 10–14% in comparison with the 0.5–2% seen in other forms of JIA [4] (although current mortality estimates are lower). In addition to an increased mortality rate, the morbidity seen in SO-JIA is higher. Due to its variable course, increased morbidity and risk of mortality, the measurement of disease activity in SO-JIA is essential. By developing a validated measure of disease activity, the ability to measure the impact of this disease and to determine its response to therapeutic interventions would be greatly improved.

It is necessary to identify the measurable components of disease activity as a precursor to developing a measure of disease activity. The first step was the development of an operational definition of disease activity that could be used to generate items of relevance to patients and their parents. We defined disease activity as reversible manifestations of the disease.

Disease activity measures have been developed for other rheumatic diseases, such as systemic lupus erythematosus [5, 6] and juvenile dermatomyositis [7]. A set of disease activity measures has been developed for the other forms of JIA. However, this core set has only been designed to measure the activity of joint disease and not the activity of the systemic disease characteristic of SO-JIA [8]. Therefore measures of disease activity used in other forms of JIA do not capture important aspects of disease activity in SO-JIA. Currently there are no measures of disease activity available for SO-JIA. A tool to measure disease activity would be very useful in clinical trials to systematically assess the response to therapeutic interventions and to follow the progress of patients with SO-JIA in the clinic.

This study is part of a larger project, in which our long-term goal is to develop and validate an outcome measure for SO-JIA using well-established methods. We have previously surveyed physicians involved in the treatment of SO-JIA to determine which features of the disease must be measured to determine disease activity [9].

When developing a new tool, it is advantageous to have both parents and patients involved in the generation of the items used to measure activity because they have unique perspectives [10]. Several groups who have developed tools to measure physical function in JIA and other paediatric musculoskeletal conditions have included the contribution of patients and parents [10–14]. Our aim in this study was to elicit specific items from patients with SO-JIA and their parents that would be useful in developing a disease activity measure for SO-JIA, in concert with the items previously generated from physicians.


    Methods
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Patient selection
The study received approval from the Hospital for Sick Children Research Ethics Board. All patients and parents completed informed consent or assent forms (according to the Declaration of Helsinki) as appropriate. Fourteen SO-JIA patients followed at the Hospital for Sick Children and their parents were chosen by purposive sampling. Sampling was designed so that there was a mix of age, sex and disease severity that covered the spectrum seen in our clinic. Children less than age 6 were not included as we felt the interview process would be too complex for younger children. Disease severity was determined, before the interviews, by the treating physician on a three-point scale. All types of problems associated with SO-JIA were represented (mild vs severe, active vs inactive, disabled vs non-disabled). Variability in the sample was confirmed by assessment of physical disability using the Child Health Assessment Questionnaire (CHAQ). The CHAQ is a disease-specific, self or parent report, measure of physical disability for children with JIA; the CHAQ scores children on a scale from 0 (no disability) to 3 (very severe disability) [15].

Interview process
Interviews were scheduled along with routine hospital appointments to minimize inconvenience for the families. Children older than 6 yr were interviewed separately. A single, non-physician interviewer, who was not known to the patients beforehand, was trained specifically for this study. Each semistructured interview lasted approximately 30 min and was audio-recorded. The interview followed a prepared script; it consisted of open-ended questions to elicit items (signs and symptoms, etc.) that the families felt were indicative of disease activity. Questions for patients and their parents exactly paralleled each other and differed only in wording. Patient and parent interviews have been shown to be reliable in previous similar studies [10, 12, 16, 17].

Content analysis
All interviews were transcribed verbatim. The transcripts were analysed for items indicative of disease activity, defined as reversible manifestations of disease. A list of items was then generated. The list was organized by categories to allow item reduction.


    Results
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Fourteen patients with SO-JIA and their parents consented to the study. Patient data is shown in Table 1. Participating patients ranged from 6–18 yr in age and had a broad range of both disease severity and disability as measured by the CHAQ (Fig. 1). The distribution of CHAQ scores suggested that our sample was highly representative of our clinic population for disability. Disease duration varied from 0.3 to 11.6 yr (mean 5.2 yr). In total there were 25 interviews; 14 patients (eight females and six males) and 11 parents (10 mothers and one father) participated.


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TABLE 1. Patient characteristics

 


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FIG. 1. Histogram of CHAQ scores of the interviewed patients. The horizontal axis shows that CHAQ scores (from 0, representing no disability, to 3, representing very severe disability). The vertical axis shows the number of patients studied. n = 13. (One subject had a missing CHAQ score.)

 
Interview process
Each interview lasted approximately 20 min; however, the time spent with younger patients was shorter than that spent with older patients and parents (15–45 min).

Content analysis
A total of 292 items were generated in this study. On average, 11 items were generated per interview. The items could be grouped into categories that reflected very similar concepts. Parents and children generated similar items for the most part. The most frequently mentioned disease activity categories are shown in Table 2. Of all items that were elicited by the patient and parent interviews, items describing arthralgia (e.g. ‘joint pain’, ‘sore joints’) were the most frequently mentioned. Other items referring to ambulation and rash were also commonly mentioned.


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TABLE 2. Disease activity categories identified by patients and parents (n = 25)

 
The list of disease activity items generated through the patient and parent interviews correlated well with the list previously obtained through the physician surveys [9]. However, there were several items elicited by both patients and parents that were not mentioned by physicians. These included: ‘looked deathly’, ‘insecure/low confidence level’, ‘glassy eyes’ and ‘decreased ability to write’. Many parents made references to changes in mood or personality that coincided with worsening disease activity. One parent used the term ‘delirious’ to describe their child's state when disease activity seemed to be worsening.


    Discussion
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
This study is part of our project in which we plan to develop an outcome measure for SO-JIA. We had previously surveyed physicians to determine which features of the disease they felt should be measured to determine disease activity [9]. Our current study has elicited disease activity items from patients’ and parents’ perspectives. Item categories such as arthralgia, difficulty in ambulation, rash and energy level were found to be important aspects of disease activity, and were also important according to physicians [9]. In addition, several items, such as confidence and ability to write—items not mentioned by physicians—have given us a further perspective into what patients and parents believe to be important as disease activity measures.

Disease activity measures have been developed for several rheumatic diseases, such as systemic lupus erythematosus [5, 6] and juvenile dermatomyositis [7]. A set of disease response measures has been developed for the other forms of JIA, with the exception of SO-JIA. In general, outcome measures have been elicited from physicians and other experts. In this study, we chose to interview SO-JIA patients and their parents because we believe that they are in the best position to point out items that might not occur to health-care workers but that may be important indicators of disease activity.

One of the limitations of our study is the generalizability of the population. The participants involved in this research were chosen by purposive sampling from a paediatric tertiary care hospital in Canada. The sample represented a wide range of ages, disease severity and disability levels, but only one participant was under the age of 7 yr and a small sample size was recruited. It is possible that more disease activity items would have been elicited if we had had a larger sample. However, it is unlikely that any new items generated by additional interviews would have been common or key concerns. Thus, additional items would have been unlikely to be retained through future item reduction phases. It is also possible, given the fact that most of the parent respondents were mothers, that we did not elicit additional items that fathers may find important.

An additional potential limitation is that parents and children may not have been able to correctly attribute symptoms and signs to disease activity. It is possible, for example, that concerns regarding appetite and gastrointestinal symptoms may be due to medication toxicity rather than active SO-JIA. This must be kept in mind as the final outcome tool is being developed.

The interview method chosen for this study was found to be a useful tool in eliciting aspects of disease activity from patients with systemic arthritis and from their parents. Several other methods would have allowed us to elicit such items. Self-reported questionnaires have been used in a number of studies measuring outcome, disability and function in patients with juvenile arthritis and other related musculoskeletal disorders [11, 13, 14, 18, 19]. A self-reported questionnaire implies that items of potential value to investigators are already listed. In our study, we wanted to elicit items from parents and patients. Although a questionnaire would have been quicker to apply and perhaps have allowed us to study a larger number of subjects, the depth of the responses would not have been as great, and therefore item generation may have been limited.

Recently, the focus group method was used in a study assessing psycho-educational interventions in JIA patients and their parents [20]. The advantage of focus groups is that participants are given the opportunity to raise issues that they themselves find important rather than issues deemed important by researchers. The limitation of the focus group is that certain participants may feel uncomfortable discussing sensitive issues with others.

Interview is the method that we used to elicit data from patients and their parents. Interviews can be performed either one-on-one or in a family context. The family interview has been shown to be effective in assessing family-level coping among families with JIA [16]. Having more than one family member present during the interview allows a discussion to be led and also provides information from multiple perspectives [16]. As with the focus group, however, sensitive issues may be avoided due to the presence of other members of the family during the interview. The one-on-one interview allows a rapport between the interviewer and the participant to be established. Sensitive issues may no longer be avoided. Furthermore, it has been shown that children with chronic diseases who are as young as 5 yr of age are competent reporters of disability [18]. Finally, interviewing patients separate from their parents might reveal certain items that may not have been elicited if the parent was present.

This study has allowed us to add patients’ and parents’ perspectives to the design of a disease activity measure for SO-JIA. The items elicited will be included in the list obtained from the physician's surveys [9]. The resulting categories will be added to future physician surveys in the further development and validation of a disease activity measure for SO-JIA.


    Acknowledgments
 
B.M.F. is supported by a Canada Research Chair. This study was funded in part by an unrestricted grant from Pfizer Inc.

The authors have declared no conflicts of interest.


    References
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

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Submitted 26 September 2004; revised version accepted 4 February 2005.