A longitudinal study of the Friedreich Ataxia Impact Scale

https://doi.org/10.1016/j.jns.2015.03.024Get rights and content

Highlights

  • The Friedreich Ataxia Impact Scale (FAIS) is a patient reported outcome measure developed for FRDA.

  • The relationship between the FAIS and clinical characteristics of FRDA was assessed.

  • The responsiveness of the FAIS to change over one and two years was determined.

  • The FAIS is a valuable tool for measuring health status in FRDA.

  • The FAIS has limited responsiveness and its use in intervention studies is uncertain.

Abstract

Background

Quality of life in Friedreich ataxia (FRDA) has been explored using various generic health status measurement tools, most commonly the Short Form Health Survey Version 2 (SF-36v2). The tool did not address many specific issues related to disease impact in people with FRDA. The Friedreich Ataxia Impact Scale (FAIS) was developed to examine clinically relevant areas in FRDA. The aims of the current study were to assess the relationship between the FAIS and clinical characteristics of FRDA, as well as to determine the responsiveness of the FAIS to change over one and two years.

Methods

One hundred and four individuals with FRDA, homozygous for the GAA expansion in intron 1 of FXN, completed the FAIS at baseline. Seventy individuals completed the FAIS again 12 months later and 49 completed the FAIS at 24 months. Clinical parameters and neurologic scales (Friedreich Ataxia Rating Scale (FARS)) were also recorded.

Results

The total FARS score, onset age and disease duration correlated significantly with FAIS subscales measuring symptoms and physical functioning. The physical and mental summary measures of the SF-36 V2 also correlated well with the FAIS subscales. Speech was the only subscale that demonstrated significant change over one and two years.

Conclusions

The FAIS provides valuable insight into the perspective of individuals with FRDA on their health status, and is an important measure of morbidity. It has, however, limited responsiveness to change and its use in intervention studies is questionable.

Introduction

Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder that affects approximately 1 in 29,000 individuals [1]. It is characterised by progressive ataxia, scoliosis and cardiomyopathy [2]. The age of onset is typically within the first two decades of life, and individuals are wheelchair-bound approximately ten to fifteen years after disease onset [3].

The progression of FRDA can be assessed using neurological rating scales including the Friedreich Ataxia Rating Scale (FARS), the International Cooperative Ataxia Rating Scale (ICARS) and the Scale for the Assessment and Rating of Ataxia (SARA) [4], [5], [6], [7]. These measurement tools provide objective information on the clinical status of individuals with FRDA but are limited as they do not encompass the perspectives of affected individuals with regards to the impact of disease on their health and well-being [5].

Patient reported outcomes (PROs) are valuable because they capture aspects of the disease that clinician administered measures are unable to. Additionally, the US Food and Drug Administration has decreed PROs be included in all therapeutic trials [8].

PROs can be classified as either generic or disease specific. Generic PROs can be used in specific clinical conditions or the general population. The most widely used PRO is the Medical Outcomes Study 36-item Short Form Health Survey (SF-36) [9], [10], [11]. Version 2 of the SF-36 was developed to reduce the floor and ceiling effects observed in the first version [12]. The main disadvantage of generic tools is that they do not take into account concerns that are specific to the condition of interest, and potentially provide an inaccurate reflection of an individual's perspective of their health status [11]. Disease-specific PROs, on the other hand, are designed to address issues unique to the condition being studied [11].

The health impact of FRDA has previously been studied using various generic health status measurement tools, including both versions of the SF-36 [13], [14], [15], as well as the self-reported Barthel Index (BI), the Generic Health Questionnaire (GHQ-12), EuroQoL (EQ-5D) [13], the PedsQL 4.0 Generic Core Module and the Multidimensional Fatigue Scale [16]. Limitations of these generic health measurement tools include significant ceiling and floor effects [13], [14], particularly in both versions of the SF-36, and poor responsiveness to change [13] which may indicate decreased sensitivity of the tool in identifying significant areas of health affected by FRDA.

The limitations of using generic PROs to measure health impact in FRDA supported the development of a FRDA-specific tool. As a result, the Friedreich Ataxia Impact Scale (FAIS) was developed. The FAIS aims to assess the health impact of FRDA on affected individuals [17] and is currently the only published FRDA-specific PRO. The FAIS comprises 126 items grouped into eight independent subscales, measuring three areas identified as being clinically important to individuals with FRDA: 1) symptoms, 2) physical functioning, and 3) psychological and social impact. Symptoms encompass speech and body movement. Physical functioning includes upper limb function, lower limb function and complex tasks. Psychological and social impact comprises mood, self-perception and isolation [17].

All items on the FAIS initially offered five-point responses (not at all bothered, a little bothered, moderately bothered, quite a bit bothered and extremely bothered). However participants were unable to distinguish between the five options provided. Post hoc analyses were conducted and response options were firstly reduced from five to four (not at all bothered, a little bothered, moderately bothered, and extremely bothered). Further analysis resulted in the decrease of response options to three (not at all bothered, moderately bothered, and extremely bothered). The final tool resulted in six subscales with three response options (body movement, speech, upper limb functioning, complex tasks, self-perception, and isolation) and two subscales with four response options (lower limb functioning and mood) [17]. The FAIS was designed to be used together with current clinician-administered rating scales to capture the true health impact of FRDA [18], [19]. It was constructed using Rasch methodology, and is psychometrically robust [17].

The aims of this study were to assess the relationship between the FAIS and clinical characteristics of FRDA, and to determine the responsiveness of the FAIS to change over one and two years. We hypothesized that the FAIS would correlate with disease characteristics of FRDA and summary scores of the SF-36 V2, and that the FAIS would be able to capture the impact of FRDA on health over time.

Section snippets

Participants

Individuals aged 18 years and older and homozygous for a GAA expansion in intron 1 of FXN were recruited from the Friedreich Ataxia Clinic at Monash Medical Centre in Victoria, Australia. Participants were invited to participate at the time of their annual clinic appointment and received the FAIS via the post prior to their clinic appointment. This enabled participants to complete the FAIS in their own time without time pressures. Participants were encouraged to return completed forms at their

Results

One hundred and four individuals completed the FAIS at baseline. Of these, 70 completed the questionnaire again approximately 12 months later (Year 1), with 49 completing the questionnaire at 24 months (Year 2). Demographic characteristics of the study participants at all three time points are shown in Table 1. The mean age of participants at baseline was 33.6 ± 12.1 (mean ± SD) years and slightly greater than half was male (51.9%). The mean age of disease onset was 15.5 ± 7.5 years and mean disease

Discussion

This study examined the FAIS, a PRO designed to specifically address the impact of disease on individuals with FRDA. The relationship between the health impact as measured by FAIS subscales and FRDA clinical characteristics were assessed, as well as the responsiveness of the FAIS over 12 and 24 months.

As expected, most of the FAIS subscales relating to symptoms and physical functioning (speech, upper limb functioning, complex tasks and lower limb functioning) correlated significantly with the

Conflict of interest

The authors report no conflicts of interest in relation to this work.

Acknowledgements

The authors thank the participants for their involvement in this study and Dr Jeremy Hobart for the provision of the FAIS prior to its publication. Funding was from the Friedreich Ataxia Research Association (Australasia) and the Friedreich Ataxia Research Alliance (USA). EMY is supported by a National Health and Medical Research Council (NHMRC) Early Career Fellowship (1073323) and LAC is supported by a National Health Medical Research Council (NHMRC) Early Career Fellowship (1037002). MBD

References (26)

  • U.S. Department of Health and Human Services FDA Center for Drug Evaluation and Research

    Guidance for industry: patient-reported outcome measures: use in medical product development to support labeling claims: draft guidance

    Health Qual Life Outcomes

    (2006)
  • J. Ware et al.

    SF-36 Health Survey manual and interpretation guide

    (1993)
  • M.B. Delatycki

    Evaluating the progression of Friedreich ataxia and its treatment

    J Neurol

    (2009)
  • Cited by (0)

    View full text