Spontaneous ambulatory activity as a quantifiable outcome measure for rheumatoid arthritis

D. J. Walker, E. Kidd, P. S. Heslop and C. Chandler1

Musculoskeletal Unit, Freeman Hospital, Newcastle-upon-Tyne NE7 7DN and
1 University of Northumbria at Newcastle, Newcastle-upon-Tyne, UK

Correspondence to: D. J. Walker, Musculoskeletal Unit, Freeman Hospital, Newcastle-upon-Tyne NE7 7DN, UK.


    Abstract
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Objective. To validate the objective monitoring of ambulatory activity as an outcome measure for rheumatoid arthritis (RA).

Methods. We have compared ambulatory activity to a range of currently favoured outcome measures, ranging from subjective opinions to X-ray damage, in a population of 93 RA sufferers.

Results. Correlations were stronger with measures of joint damage and disability, and less strong with measures of disease activity. Sensitivity to change was good. Three different interventions were compared for the quantity of the response, and the results agree with clinical experience, with steroid injection of the knee and use of non-steroidal anti-inflammatory drugs (NSAIDs) having a similar response and the provision of surgical shoes producing a more modest increase in ambulation.

Conclusion. The measurement of ambulatory activity has validity for RA assessment. It provides different but related data to the currently used measures. It is objective, relevant, quantifiable and of unlimited scale. It could be used to quantify interventions aimed at increasing ambulation, in carefully constructed studies.

KEY WORDS: Rheumatoid arthritis, Outcome, Ambulatory activity, Quantification


    Introduction
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Quantifiable outcome measures for disabling diseases such as rheumatoid arthritis (RA) are necessary if we are to compare the benefits of different interventions. This is becoming ever more important when the expenditure of financial resources has to be justified and the best way of spending money identified. Different interventions will have different costs and different benefits. Quantifying the benefit of an intervention is, therefore, important.

Current methods that are used to assess interventions vary from subjective assessments, such as patient and physician opinion, through joint counts and structured questionnaires, to objective tests such as X-rays, which have a subjective element in their interpretation. There are also measures of disease activity such as acute-phase reactants [e.g. erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)] and joint tenderness (e.g. Ritchie index) and subjective assessments of pain [e.g. visual analogue scale (VAS)]. These methods produce results that are ordinal, but not interval. A result that is numerically twice another is not necessarily twice as bad, or good. There are also floor and ceiling effects. As such, they are not sufficient to quantify any change.

Spontaneous ambulatory activity can now be measured using the Numact monitor [1]. Initial studies validated the results against observation and showed that more disabled people were less active. Early studies have shown it to be applicable in arthritic patients [2] and to be sensitive to change of condition [3], and to be a valid assessment of osteoarthritis (OA) of the knee [4]. The measure is objective and relevant to the patient's normal circumstances. The data produced are interval in that 100 steps are twice as many as 50, and so quantification is possible. The relationship between ambulatory activity and disability needed to be defined for RA. RA remains the most disabling common form of inflammatory arthritis and many interventions are recommended for it. We sought to test the validity of monitoring spontaneous ambulatory activity as an assessment of RA, and to explore the possibility of quantifying changes.

Face validity: it is logical that a physically disabled person will be less physically active than a non-physically disabled person. It is likely that the activity will vary with the severity of the disability and the state of the disease. It is equally logical that if the physical disability is reduced, as with effective treatment, then the person will be, on average, more active. Monitoring ambulatory activity will sample this activity and has face validity.


    Methods
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
The population for this study was 93 patients attending hospital with RA satisfying ACR criteria [5]. In order to recruit a range of severity of RA, patients were recruited for a variety of reasons: from early disease (n=8) to trials of anti-inflammatories (n=29) to commencing second-line drugs (n=21), pre-steroid joint injection (n=12), pre-total knee replacement (n=11), pre-surgical shoes (n=8) and pre-steroid therapy (n=4). The local ethics committee approved all intervention studies.

The subjective and questionnaire data were collected on these subjects at the same time as the 24 h activity recordings were performed. X-rays of hands, feet or knees were graded if they had been taken within 2 yr of the recording.

Spontaneous ambulatory activity was recorded using the Numact monitor. This logs posture (sit, stand, lie) and counts the number and vigour of steps using a system of position sensors and an accelerometer with sensors placed on the chest and the thigh, as shown in Fig. 1Go. The data are logged in real time over 24 h periods. This has been validated against observation and the reliability defined [1]. It has been well tolerated by subjects with <1% declining retest. The summary result used in this study was the total ambulatory energy expenditure (numberxamplitude of step) over 24 h.



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FIG. 1.  Ambulatory activity monitor.

 
Subjective data on the patient's condition were collected on five-point scales of patients' and physicians' opinions.

Pain was sampled with a VAS.

The duration of morning stiffness and the Ritchie index [6] were recorded as measures of disease activity.

Questionnaire data on disability were collected using the Health Assessment Questionnaire (HAQ) [7]. This was the full 24 item HAQ with use of an assisting device scoring 2. Lower limb HAQ used the items on: Rising; Walking; Hygiene and Activities.

One person graded X-rays of hands, feet and knees by comparison with the standard films of Larsen [8]. Hand X-rays were graded for the four finger MCP and PIP joints, and for the wrist and carpus, all on five-point scales, and the total score for both hands was used as a measure of overall disease erosiveness (maximum score=100). The feet were scored for the five MTP joints for the worst foot as a factor that limits mobility (maximum score=25) and combined as a measure of the overall disease (maximum score=50). The knee X-rays were graded on a five-point scale and the worst score used as the factor most likely to limit ambulatory activity (maximum score=5).

Statistical analysis
Correlations between ambulatory activity and other outcome measures, i.e. HAQ, morning stiffness, VAS, Ritchie index, patient's and physician's opinion were tested using Spearman rho (ordinal data with non-parametric distribution).

Effect size (mean change/S.D. of pre-intervention results) with 95% CI were calculated for two of the intervention studies: pre- to post-steroid injection of knee and pre- to post-treatment with anti-inflammatory drugs.


    Results
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Construct validity
Construct validity has been tested by comparison with several currently favoured measures.Correlations between ambulatory activity and subjective assessments of the patient's and physician's opinion gave r values of 0.19 (n=81, P=not significant) and 0.22 (n=82, P<0.05), respectively.

Ambulatory activity and VAS for pain did not correlate (r=-0.17, n=71).

Correlation between activity and measures of disease activity was similarly not significant [morning stiffness r=-0.06 (n=82) and Ritchie index r=-0.08 (n=60)].

Stronger correlation was shown with the HAQ with an r value of -0.47 (n=89, P<0.0001) (Fig. 2Go).



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FIG. 2.  Scatterplot of HAQ scores and Numact energy (ampsxno. of steps).

 
Correlations between ambulatory activity and the different Larsen X-rays scores are shown in Table 1Go. Correlations were highly significant for all X-rays with r values between -0.42 and -0.55. They were similar whether the joints scored were marking for severe disease (hands and feet) or directly involved in ambulation (knees and feet).


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TABLE 1.  Correlations of X-ray grades with ambulatory activity
 
Change in ambulatory activity vs change in other measures
For 41 subjects, there were two sets of data, collected on different occasions. Change in ambulatory activity was correlated with change in the other available measures. Correlation coefficients were lower than for the individual measures. The significant correlations were for lower limb HAQ (r=0.22), physician's opinion (r=0.23) and patient's opinion (r=0.21); for all, P<0.05. The patient and the physician judged the change in condition in the same direction as the monitor.

Discriminant validity
Figure 3Go shows the activity (mean and 95% CI) for the population, split according to the reason they were recruited. As can be seen, there are some significant differences according to the reason for inclusion and these are in the expected direction. Patients awaiting knee replacement were significantly less active than those who were simply being given a steroid injection, who were less active than those recruited to a study of anti-inflammatories. It was possible to discriminate between some of these populations on the grounds of activity and ambulatory activity therefore has some discriminant validity. Subjects with early disease were very variable in their activity.



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FIG. 3.  Discriminant validity. Ambulatory activity (mean with 95% CI) for the different populations studied.

 
Sensitivity to change
The summary results of the intervention studies are shown in Fig. 4Go. Effect size was calculated for ambulatory activity for the intervention studies of non-steroidal anti-inflammatory drug (NSAID) and steroid knee injection, and compared to other measures. The results are shown in Table 2Go. For the NSAID study, the sensitivity to change of ambulatory activity was similar to Ritchie index and duration of morning stiffness. For the knee injection study, it proved to be more sensitive to change. Clearly, in this situation where only one tender joint has been treated, the Ritchie index was insensitive.



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FIG. 4.  Percentage change in ambulatory activity (mean with 95% CI) for three intervention studies.

 

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TABLE 2.  Effect size calculated for two interventions (NSAID Arthrotec 50 b.d./triamcinolone 20 mg)
 
Quantification
The main advantage of a quantifiable intervention is to compare the benefits of different interventions. Provided that a main objective of the intervention was to increase mobility, then ambulatory activity can be used in this way. Within the study population were three intervention studies aimed at such an outcome. These were a placebo-controlled study of an NSAID (Arthrotec 50 b.d., previously reported [3]), an observational study of steroid injection (20 mg triamcinolone) of the knee and an observational study of the provision of surgical shoes (Fig. 4Go). The percentage increase in activity was used as the most relevant measure of improvement. For the NSAID, the improvement averaged 50% at 2 weeks (n=8). For the knee injection study, the increase in activity averaged 65% at 1 week (n=12). For the provision of surgical shoes, the increase averaged 10% once the patient was comfortable in the shoes (n=6).

With this information from larger carefully constructed studies that included the duration of effect and the cost of intervention, it should be possible to produce figures for the cost effectiveness of different interventions.


    Discussion
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
The ideal outcome measure for RA would be objective, reliable, relevant to the patient's daily life, sensitive to change and easy to use. It would have an unlimited and interval scale. The monitoring of ambulatory activity has some of these features.

We have broadly followed the method of Tugwell and Boers [9] testing for: face, construct and discriminant validities. These validities are shown for the monitoring of ambulatory activity. The construct validity with patient and and physician opinions in OA knee was similar [4]. There was surprisingly little concurrence between the activity of the disease and the activity of the patient. It would be expected that during a `flare' of the arthritis, the patient would be less active. This study was not directly aimed at testing this and it requires a more detailed study looking at different measures of disease activity, such as the ESR, in a longitudinal study.

The relationship between activity and pain is interesting. A patient who is in greater pain is likely to be less active (a negative relationship). Conversely, a patient who has arthritis and is physically active may have pain because of this physical activity (a positive relationship). A mixture of these two influences may account for the lack of correlation in this study. A study of the relationship between pain and activity through the day would be interesting. This is possible with the Numact monitor, which has the facility for analogue scale input.

There was a strong relationship between the HAQ and activity. This was expected as many questions on the HAQ relate to lower limb function. The relationship to individual sections of the HAQ has been explored elsewhere [10]. There was strong correlation between activity and the X-ray damage, and it did not make much difference whether the X-ray was of a lower limb joint or not. Indeed, the strongest correlation was with hand X-rays. The more destructive the arthritis, the less active the patient. Overall ambulatory activity relates more to disability and damage than to disease activity and pain.

The correlations of change in activity and change in the other measures are low. They are better with specific lower limb HAQ than the full HAQ. They broadly go in the same direction as the patients' and physicians' opinions. X-rays are not sufficiently sensitive to change to be tested.

Discriminant validity was shown by the demonstration that different populations at different phases of the disease could be discriminated on the basis of their activity. Sensitivity to change was also good and to have an objective test showing similar or better sensitivity to change than subjective data or questionnaires is particularly valuable.

The other objective of the study was to see whether activity could quantify changes in condition. As a measure of activity, the data are interval in nature. This is in contrast to the currently used measures, usually questionnaires, which produce ordinal data (i.e. they rank disability in order), but the scale is not even (moving a certain score along the scale at one point is not the same as moving the same distance at another point). How interval the data on activity are in relation to disability is difficult to measure directly without a `gold standard' to compare it to. It is, therefore, necessary to make a judgement based on the spread of the data, the sensitivity to change and the validity of the measure. On all these counts, the measurement of ambulatory activity looks promising. If an objective of a treatment is to increase ambulatory activity, then this sort of monitoring can be used to quantify the response. The preliminary data presented here would suggest that giving an anti-inflammatory tablet, or injecting a knee with steroid, produces a similar magnitude of benefit, and that providing surgical shoes produces a more modest benefit. This is in keeping with clinical experience. With good quantification of response, it becomes possible to do much better cost–benefit analysis for interventions. Studies looking at patients where there is a choice of interventions and comparing the cost–benefit of each would be very interesting.

Spontaneous activity will relate to many influences. Our concept of what contributes to activity is shown in Fig. 5Go. People will do what they need or wish to do, provided that they are able. However, a non-physically disabled person may be able to do all that they need to, but there will always be some wish that their physical ability could not fulfil (e.g. playing for England) (Fig. 5AGo). A physically disabled person will have less ability and more unmet wish and need (Fig. 5BGo). The demonstration of concurrence between activity and other measures of physical disability indicates that ability was a major factor determining activity in this population. In testing interventions, studies will usually be cross-over in design. In this situation, wish and need will be controlled for, and it will be ability that is being tested.



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FIG. 5.  The relationship between factors affecting ambulatory activity.

 
The Numact monitor has the advantage over other accelerometer-based devices in that the use of position sensors allows the activity to be more clearly related to ambulation. The accelerometer is only sampled when the subject is standing, so that passive movement in the sitting position, such as travelling in a car, is not included.

Monitoring ambulatory activity therefore has some of the attributes of the ideal outcome measure. It is objective and relevant, and has no limitations of scale. It produces data that are interval in nature and offers the promise of quantifying improvement.


    Acknowledgments
 
We are grateful to Searle UK for their support of this project through sponsored pharmaceutical studies.


    References
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

  1.  Walker DJ, Heslop PS, Plummer CJ, Essex T, Chandler C. A continuous patient activity monitor: validation and relation to disability. J Physiol Meas 1997;18:49–59.
  2.  Walker DJ, Heslop P, Wright D, Cleary R, Essex T, Chandler C. 24 hr activity in rheumatiod arthritis: comparison with HAQ. Br J Rheumatol 1996;35(supp1.):233.
  3.  Walker DJ, Heslop PS, Chandler C. Ambulatory activity as an objective and quantifiable measure of non-steroidal therapy. J Rheumatol 1998;25:768–70.[ISI][Medline]
  4.  Walker DJ, Heslop PS, Kay LJ, Chandler C. Spontaneous ambulatory activity as a quantifiable outcome measure for osteoarthritis of the knee. Br J Rheumatol 1998;37:969–71.[ISI][Medline]
  5.  Levin RW, Park J, Ostrov B, Reginato A et al. Clinical assessment of the 1987 American College of Rheumatology criteria for rheumatoid arthritis. Scand J Rheumatol 1996;25:277–81.[ISI][Medline]
  6.  Ritchie DM, Boyle JA, McInnes JM et al. Clinical studies with an articular index for the assessment of joint tenderness in patients with rheumatoid arthritis. Q J Med 1968;37:393–406.[Medline]
  7.  Fries JF, Spitz PW, Young DY. The dimensions of health outcomes: the Health Assessment Questionnaire, disability and pain scales. J Rheumatol 1982;9:789–93.[ISI][Medline]
  8.  Larsen A, Dale K, Eek M. Radiographic evaluation of rheumatoid arthritis and related conditions by standard reference films. Acta Radiol Diagn 1977;18:481.[ISI]
  9.  Tugwell P, Boers M. OMERACT conference on outcome measures in rheumatoid arthritis clinical trials: conclusion. J Rheumatol 1993;20:590.[ISI]
  10. Hayes J, Heslop PS, Cleary R, Chandler C, Walker DJ. A comparison of spontaneous ambulatory activity with various aspects of the HAQ in RA. Br J Rheumatol 1998;37(Suppl. 1):131.[ISI][Medline]
Submitted 11 February 1999; revised version accepted 6 July 1999.



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