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Quantitative measures for assessing rheumatoid arthritis in clinical trials and clinical care

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Abstract

There is no single ‘gold standard’ quantitative measure to assess and monitor the clinical status in patients with rheumatoid arthritis (RA). Therefore, a variety of measures have been used in clinical research and clinical care, including laboratory tests, radiographic scores, formal joint counts, physical measures of functional status, global measures and patient self-report questionnaires. These measures may address disease activity, joint damage, both activity and damage, or long-term outcomes. Measures of disease activity, such as joint swelling, are reversible and are emphasized in clinical trials. However, activity measures may be improved over 5 years while measures of damage, such as radiographic score, indicate disease progression. Two quantitative indices which are widely used in clinical trials are the (1) American College of Rheumatology (ACR) Core Data Set, which includes swollen joint count, tender joint count, physician assessment of global status, acute-phase reactant–erythrocyte sedimentation rate or C-reactive protein, functional status, pain, patient estimate of global status, a radiograph in studies over 1 year or longer, and (2) the disease activity score(DAs), which includes a swollen joint count, tender joint count, acute-phase reactant, and patient assessment of global status. Randomized controlled clinical trials provide the optimal method to evaluate new therapies, by comparing a therapy with a placebo or another therapy without selecting patients for specific therapies. However, randomized trials in chronic diseases have important limitations, including a relatively short observation period, patient selection for inclusion and exclusion criteria, inflexible dosage schedules, influence of the design on results despite a control group, emphasis on group data while ignoring individual variation in treatment responses, non-standardized interpretation of adverse effects, and others. Therefore, clinical trials in RA must be supplemented by long-term observational studies to assess results of therapy in regard to long-term outcomes such as work disability, joint replacement surgery and premature mortality. The most simple and effective method of collecting important long-term data from patients in routine clinical care is through patient self-report questionnaires.

Section snippets

Quantitative measures of activity and damage used to assess rheumatoid arthritis

Quantitative measures used to assess patient status in RA include laboratory tests, radiographic scores, formal joint counts, physical measures of functional status, global measures and patient self-report questionnaires (Table 1). These measures may be classified as measures of disease activity, measures of damage to joints and other organs, measures which assess both activity and damage, and long-term outcomes.1

Measures of disease activity, such as joint swelling, are consequences of a

Joint counts

The joint count has been described in many formats. The Glossary Committee of the American Rheumatism Association (ARA) presented a joint count involving 80 joints, each of which was analysed for five variables: swelling, tenderness, pain on motion, limited motion and deformity.19 Swelling was not assessed in the shoulder and hip, in which it is difficult to assess. High correlations were found between tenderness and pain on motion, as well as between deformity and limited motion20, which has

Indices for assessing clinical status and responses to therapy

The classical four-point global scales for assessing functional status and radiographic findings were published in 1949 by Steinbrocker et al.29 These indices are still used today but they are not sufficiently sensitive to changes in clinical status to assess responses to therapy (Table 5).

An early, more detailed, index was ‘a therapeutic scorecard in rheumatoid arthritis’81 (Table 6), which included joint tenderness, joint swelling, joint limited motion, functional status, pain, haemoglobin,

Limitations of randomized clinical trials

The randomized controlled clinical trial is certainly the ‘gold standard’ for evaluating any new therapy89, but is most effective in acute diseases over short periods. In chronic diseases over long periods, important limitations emerge (Table 7); these limitations have been described in reports by several observers89., 90., 91., 92., 93., 94., 95., 96., 97., 98., 99., 100., 101., 102., 103., 104., 105., 106. as well as in our own commentaries.107., 108., 109., 110., 111., 112., 113. Although

Intrinsic limitations of clinical trials

The above pragmatic limitations are potentially surmountable if there were sufficient resources and time to conduct clinical trials, but certain limitations are intrinsic to the method (Table 7).

A rationale for monitoring clinical status in routine clinical care using self-report questionnaires

The limitations of clinical trials, and the strong likelihood that most patients with rheumatic diseases will not be included in clinical trials, indicate that additional approaches are required to obtain optimal information concerning results of clinical care in RA, including the use of new biological agents. As noted above, the question of whether long-term low-dose methotrexate, corticosteroids or new biological agents can change severe long-term outcomes cannot be answered through

A method for collecting data in clinical care using self-report questionnaires

In the clinic of the senior clinical author, a questionnaire has been completed by every patient at every visit135 over the last 20 years. When the patient registers for a visit, he or she is asked by the receptionist to complete a questionnaire mounted on a clipboard, along with a soft pencil or felt-tip pen, while waiting to see the physician. The questionnaire must be distributed in a cheerful and caring manner, so that patients recognize it as an important component of their medical care—to

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