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The intra-articular injection of hydrocortisone acetate is commonly used in the treatment of osteoarthritis, although its action in this disease has received less careful study than in rheumatoid arthritis. In 1955 a less soluble ester, hydrocortisone tertiary-butylacetate (TBA) was developed for intraarticular therapy with the claim that its effects were more pronounced and of longer duration (Hollander, Brown, Jessar, Udell, Smukler, and Bowie, 1955 The fortnightly assessments comprised the following measurements:Walking time over 75 yards; Range ofjoint movement and limitation of extension determined by a goniometer; Tenderness (graded 0 = none, 1 = slight, 2 = definite, 3 = wincing, 4 = withdrawal and/or exclamation); Pain (graded 0 = none, 1 = slight on walking, 2 = marked on walking, 3 = mild at rest, 4 = severe at rest).Radiographs of the knees were obtained before and after the trial. ResultsThree patients failed to complete the trial; two defaulted after the second course of injections, and one developed an unrelated disease after the third injection of the second course. This resulted in five knees not receiving a course ofplacebo injections.The specific data (walking time, etc.) derived from the first assessment in each treatment period were compared with the same measurements made at the four assessments in the succeeding 8-week rest period. Changes in walking time and joint movement were estimated as a percentage of the pretreatment measurements; changes in limitation of extension were calculated as a percentage of maximal joint range (145°). Although pain and tenderness were graded at each assessment, because this parameter is entirely subjective, differences were calculated on the basis of improvement and no improvement. In this way the effect of treatment, both immediate and sustained, was calculated for each knee for each of the three treatments. The mean change for each of the three groups (hydrocortisone, TBA, and placebo) between pre-treatment assessments and each of the four post-treatment assessments was analysed by conventional statistical methods.

Since the publication in this Journal of a description of the effects of placebos in rheumatoid conditions (Traut and Passerelli, 1957), there has been a growing literature on the subject of placebo responses, but little has appeared in print regarding such effects in arthritis.During a recent intra-articular injection trial in which two steroid preparations and a placebo were compared, it became apparent that responses to the latter were frequent and well marked. It was decided, therefore, to make a parallel study of the whole question of placebo responses as these occurred during the trial.The results of injection of the two steroids have already been reported; one paper dealt with the effects on rheumatoid arthritics (Chandler, Wright, and Hartfall, 1958) and the other with the effects on osteo-arthritics (Wright, Chandler, Morison, and Hartfall, 1960).The present paper is concerned chiefly with a detailed examination of the responses to the placebo injections in the same trial. It also reports the results of a subsequent dummy tablet trial on the same group of patients. Finally, some of the implications of these findings as they apply to clinical trials are discussed.Material 49 patients were included in the original trial, and of these, 10 dropped out for various reasons during the 18 months that the trial was in progress. The remaining 39 patients from whom results were complete, comprised 34 females and 5 males; 21 were osteo-arthritics, and the remaining eighteen rheumatoid arthritics, the knees being involved in every case. The age range was 29 to 76 years (mean 58 6). The two steroids used were hydrocortisone acetate, and hydrocortisone tertiary butyl acetate. The placebo consisted of the inert aqueous vehicle. Design of Injection TrialEvery patient received three courses of injections into the affected knee, each course comprising four injections with an interval of 2 weeks between injections. There was a resting period of 2 months between courses, and the order in which courses were given was arranged so that every patient eventually received a course of each steroid and a course of the placebo.Assessments for local pain and tenderness, range of joint movement, and walking time, were carried out at each visit. After careful consideration it was felt that walking-times would give the most useful single objective measurement by which clinical improvement or deterioration could be assessed. Patients were asked to walk a distance of 75 yards as quickly as possible while being timed by a stopwatch. The value taken was the mean of the four walking times which were measured fortnightly during the 2-month resting period following each complete injection course. These values were then expressed as percentages of the original walking time.Alterations of less than ±10 per cent. were classified as "unchanged", while decreases or increases of more than 10 per cent. were classified as "improvement" or "deterioration" respectively. Throughout this article the values of these walking times are referred to as "find...

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