Toward an understanding of patient outcome measurement.
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Biomedical subjects
Publications and source records attributed to J F Fries.
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As part of the approval process, new drugs are first studied in controlled clinical trials with carefully selected patients. After gaining approval, however, these drugs are often used in the general community under widely different circumstances. This report explores the effects of such differences on the frequency and severity of side effects using the nonsteroidal anti-inflammatory drugs as a prototype. A review of clinical trials is compared with the accumulated experience at the Stanford and Phoenix Arthritis Centers. Statistical analysis of patient records was accomplished using the American Rheumatism Association Medical Information System Computer Data-Base System. To overcome potential biases in different methods of detecting side effects, a questionnaire was mailed directly to 390 patients, including subjects who were and were not participants in formal drug studies. Agreement between experiment and experience was generally quite good. However, a tendency for severe side effects to occur more frequently in community use than would be predicted from clinical trials was noted.
Outcome assessment attempts to measure the long-term impacts of illness in order to select management strategies and public policies which minimize these impacts. Disability is an important dimension of outcome, particularly in conditions such as rheumatoid arthritis, but cannot be considered apart from other dimensions such as mortality, pain, iatrogenic problems, and economic impact since decisions frequently involve comparing positive effects in one dimension with negative effects in another. Modern techniques of survey research have yielded self-administered patient questionnaire instruments which are more reliable and more valid than traditional endpoints in rheumatic disease assessment and more relevant to the desires of the patient. These new techniques should be widely used in clinical investigation and in clinical practice.
The nature of the international health burden, its changes, its problems, and even its solutions over the next quarter century are surprisingly apparent at this time and are more positive than often supposed. The average period of lessened physical status is likely to shorten, and the need for and cost of hospitalization in the later life of the individual is likely to decrease. The period of infirm physical status will become increasingly compressed between the increasing age at onset of infirmity and the genetically determined lifespan of the individual. Illness at the end of life will come relatively suddenly, be multi-factorial in cause, will be highly resistant to further medical intervention, and will be characterized by increasing inevitability. Implications for retirement age, availability of useful work for older individuals, and programmes designed to stimulate rather than support are discussed.
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When a community-derived population of 840 rheumatoid arthritis patients was used to test the American Rheumatism Association's 11 diagnostic criteria for rheumatoid arthritis, these criteria divided patients into 3 reasonably distinct classifications (probable, definite, and classic). The severity of disease increased in direct proportion to the number of positive criteria. Three criteria involve invasive procedures that are rarely performed; they are unnecessary for effective use of the other 8 criteria. Although 256 possible combinations of these 8 criteria exist, the criteria function principally to classify patients into only 7 major clinical syndromes, each of which corresponds to a major clinical presentation. By identifying the logical interrelationships between criteria in this report, we have confirmed their applicability and provided insight into the manner by which criteria classify patients.
A retrospective study of factors influencing survival in 1,103 patients with systemic lupus erythematosus (SLE) was carried out at 9 university centers diverse in geographic, socioeconomic, and racial characteristics. The mortality and disease characteristics of the patients at study entry varied widely among centers. The survival rates from the time patients with a diagnosis of SLE were first evaluated at the participating center was 90% at 1 year, 77% at 5 years, and 71% at 10 years. Patients with a serum creatinine greater than 3 mg/dl at study entry had the lowest survival rates: 48%, 29%, and 12% at 1, 5, and 10 years, respectively. Survival rate also correlated independently with the entry hematocrit, degree of proteinuria, number of preliminary American Rheumatism Association criteria for SLE satisfied, and source of funding of medical care. When data were corrected for socioeconomic status, race/ethnic origin did not significantly influence survival. Survival rates varied widely at different participating institutions, generally due to differences in disease severity. Place of treatment was independently associated with survival only in the second year after study entry. Disease duration before study entry did not account for the differences in disease severity.
Causes of death were examined for 1,103 systemic lupus erythematosus patients who were followed from 1965 to 1978 at 9 centers that participated in the Lupus Survival Study Group. A total of 222 patients (20%) died. Lupus-related organ system involvement (mainly active nephritis) and infection were the most frequent primary causes of death. Causes of death were similar throughout the followup period. Hemodialysis had little impact on the length of survival for patients with nephritis. Active central nervous system disease and myocardial infarction were infrequent causes of death. There were no deaths from malignancy.
The 1971 preliminary criteria for the classification of systemic lupus erythematosus (SLE) were revised and updated to incorporate new immunologic knowledge and improve disease classification. The 1982 revised criteria include fluorescence antinuclear antibody and antibody to native DNA and Sm antigen. Some criteria involving the same organ systems were aggregated into single criteria. Raynaud's phenomenon and alopecia were not included in the 1982 revised criteria because of low sensitivity and specificity. The new criteria were 96% sensitive and 96% specific when tested with SLE and control patient data gathered from 18 participating clinics. When compared with the 1971 criteria, the 1982 revised criteria showed gains in sensitivity and specificity.
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The relative effectiveness of six nonsteroidal anti-inflammatory agents was studied in 33 patients with rheumatoid arthritis and 32 patients with ankylosing spondylitis in a double-blind, randomized, prospective study employing a six-way multiple crossover design with six-week trials of each agent. In ankylosing spondylitis, naproxen, indomethacin, and fenoprofen calcium were the most effective agents. In rheumatoid arthritis, relatively little mean difference between drugs was found. Most of this difference could be attributed to compliance factors, which favored drugs that required only a small number of pills daily. Despite the small differences in effect, patients had strong preferences. More than 85% of patients were still taking their preferred medication after a mean follow-up period of one year.
The average length of life has risen from 47 to 73 years in this century, but the maximum life span has not increased. Therefore, survival curves have assumed an ever more rectangular form. Eighty per cent of the years of life lost to nontraumatic, premature death have been eliminated, and most premature deaths are now due to the chronic diseases of the later years. Present data allow calculation of the ideal average life span, approximately 85 years. Chronic illness may presumably be postponed by changes in life style, and it has been shown that the physiologic and psychologic markers of aging may be modified. Thus, the average age at first infirmity can be raised, thereby making the morbidity curve more rectangular. Extension of adult vigor far into a fixed life span compresses the period of senescence near the end of life. Health-research strategies to improve the quality of life require careful study of the variability of the phenomena of aging and how they may be modified.
A structure for representation of patient outcome is presented, together with a method for outcome measurement and validation of the technique in rheumatoid arthritis. The paradigm represents outcome by five separate dimensions: death, discomfort, disability, drug (therapeutic) toxicity, and dollar cost. Each dimension represents an outcome directly related to patient welfare. Quantitation of these outcome dimensions may be performed at interview or by patient questionnaire. With standardized, validated questions, similar scores are achieved by both methods. The questionnaire technique is preferred since it is inexpensive and does not require interobserver validation. These techniques appear extremely useful for evaluation of long term outcome of patients with rheumatic diseases.
Rheumatologists and nephrologists were surveyed, by the use of specifically designed case histories, regarding their management of selected aspects of systemic lupus erythematosus (SLE). Treatment was individualized on a case by case basis by the vast majority of respondents. There was agreement on the initial treatment of SLE involving mild arthritis, active nephritis, or central nervous system disease and on steroid tapering practices. There was disagreement about treatment of a "serologic flare" and the management of late-stage nephropathy. Academic centers were more selective and less aggressive than practicing subspecialists. Areas of concordance document current standard treatment practices but sometimes show dissociation between the degree of consensus and the level of available medical knowledge.
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