Showing papers on "Randomized controlled trial published in 1987"

Equipoise and the ethics of clinical research.

Abstract: The ethics of clinical research requires equipoise--a state of genuine uncertainty on the part of the clinical investigator regarding the comparative therapeutic merits of each arm in a trial. Should the investigator discover that one treatment is of superior therapeutic merit, he or she is ethically obliged to offer that treatment. The current understanding of this requirement, which entails that the investigator have no "treatment preference" throughout the course of the trial, presents nearly insuperable obstacles to the ethical commencement or completion of a controlled trial and may also contribute to the termination of trials because of the failure to enroll enough patients. I suggest an alternative concept of equipoise, which would be based on present or imminent controversy in the clinical community over the preferred treatment. According to this concept of "clinical equipoise," the requirement is satisfied if there is genuine uncertainty within the expert medical community--not necessarily on the part of the individual investigator--about the preferred treatment.

Preliminary Results of a Double-Blind, Randomized, Placebo-Controlled Trial of Cyclosporine in Myasthenia Gravis

Abstract: We randomly assigned 20 patients with progressively worsening generalized myasthenia gravis of recent onset whose illness was not controlled by anticholinesterase therapy to treatment with either cyclosporine (6 mg per kilogram of body weight per day) or placebo. Patients who had been treated with thymectomy, steroids, or other immunosuppressive agents were excluded. The duration of treatment was 12 months. Disease activity was assessed by quantified strength testing and by measurements of antihuman acetylcholine-receptor antibody. Patients were assessed at 6 months and 12 months, or at the following early end points: drug failure (doubling of creatinine), treatment failure (respiratory or swallowing difficulty), or protocol violation (stopping medication for more than five days). At six months, patients in the cyclosporine group had had significantly more objective improvement in strength; one early end point had been reached (drug failure; no treatment failures). In the placebo group, three early end points had been reached (all treatment failures). The decline in titers of acetylcholine-receptor antibody was larger in the treated group, although the difference was not statistically significant. At the end of the study (after 12 months of treatment or arrival at an earlier end point), improvement in strength and reduction in titers of anti-receptor antibody continued to be greater in the cyclosporine group. Nephrotoxicity occurred in three patients receiving cyclosporine but was nonprogressive with a reduction in dosage and reversible with discontinuation of the drug. These results are preliminary and need confirmation, but we conclude that cyclosporine is probably an effective therapy in some patients with myasthenia gravis.

A double-blind controlled trial of high dose methylprednisolone in patients with multiple sclerosis: 1. Clinical effects.

Abstract: A randomised double-blind, placebo-controlled trial of high-dose, pulsed intravenous methylprednisolone was carried out in 50 individuals with multiple sclerosis; 22 patients were in acute relapse and 28 had chronic progressive disease. After a baseline assessment using the Kurtzke functional and expanded disability status scales each patient was randomly allocated to intravenous treatment with methylprednisolone (500 mg) or a saline placebo administered as a single daily dose for 5 days. Clinical assessments were repeated at 1 and 4 weeks after starting treatment. The results from all 50 patients showed a highly significant effect in favour of methylprednisolone treatment (p less than 0.001). In patients with relapse, there was a significant decrease in clinical disability scores at 1 and 4 weeks in the methylprednisolone treated group compared with controls (p less than 0.05 for each comparison). In the chronic progressive group, disability scores at 4 weeks only were significantly lower after treatment with methylprednisolone (p less than 0.01), mainly attributable to improvement in pyramidal function.

Nutritional Therapy for High Blood Pressure: Final Report of a Four-Year Randomized Controlled Trial— The Hypertension Control Program

Abstract: A four-year trial assessed whether less severe hypertensives could discontinue antihypertensive drug therapy, using nutritional means to control blood pressure. Randomization was to three groups: group 1—discontinue drug therapy and reduce overweight, excess salt, and alcohol; group 2—discontinue drug therapy, with no nutritional program; or group 3—continue drug therapy, with no nutritional program. In groups 1 and 2 patients resumed drug therapy if pressure rose to hypertensive levels. Loss of at least 4.5 kg (10+ lb) was maintained by 30% of group 1, with a group mean loss of 1.8 kg (4 lb); sodium intake fell 36% and modest alcohol intake reduction was reported. At four years, 39% in group 1 remained normotensive without drug therapy, compared with 5% in group 2. Study findings demonstrated that nutritional therapy may substitute for drugs in a sizable proportion of hypertensives or, if drugs are still needed, can lessen some unwanted biochemical effects of drug treatment. ( JAMA 1987;257:1484-1491)

Randomized, controlled trial of diabetic patient education: improved knowledge without improved metabolic status.

Abstract: We randomized 749 insulin-treated patients on the rolls of the Mount Sinai Medical Center Diabetes Clinic in a controlled trial of diabetic patient education; 345 agreed to participate, of whom 165 were assigned to the education group and 180 to the control group. Cognitive scores increased from 5.3 +/- 1.6 to 5.8 +/- 1.6 in the education group, but there was no change in the control group, whose score was 5.3 +/- 1.7 before and after the intervention (P = .0073). HbA1c fell from 6.8 +/- 2.1 to 6.1 +/- 2.0% in the education group and from 6.6 +/- 2.0 to 6.3 +/- 2.0% in the control group, an insignificant difference (P = .1995). The fasting blood glucose decreased from 223 +/- 94 to 179 +/- 73 mg/dl in the education group and from 199 +/- 81 to 185 +/- 76 mg/dl in the controls (P = .1983). Triglycerides, high- and low-density lipoprotein cholesterol, and insulin dosage also failed to show significant variation among groups. The foot-lesion score showed similar progression in the education and control groups. Neither diastolic nor systolic blood pressure showed significantly greater change in the education or the control group, with falls noted, particularly in diastolic pressures, in both patient groups. Differences between the groups were not significant for sick days, hospitalizations, emergency room visits, or outpatient visits. The sample sizes of the study and control populations were sufficiently large to detect a difference in means between the education and control groups in the HbA1c, the primary outcome variable, of greater than 1.0%, with alpha = .05 and a power of .95. Thus, our study suggests that patient education may not be an efficacious therapeutic intervention in most adults with insulin-treated diabetes mellitus.

Meta‐analysis of clinical trials as a scientific discipline. I: Control of bias and comparison with large co‐operative trials

Abstract: Meta-analysis is an important method of bridging the gap between undersized randomized control trials and the treatment of patients. However, as in any retrospective study, the opportunities for bias to distort the results are widespread. Attempts must be made to introduce the controls found in prospective studies by blinding the selection of papers and extraction of data and making blinded duplicate determinations. Informal and personalized methods of obtaining data are probably more liable to error and bias than employing only published data. Publication bias is a serious problem requiring further research. There also need to be more comparisons of meta-analysed small studies with large co-operative trials.

Effects of psychological therapy on pain behavior of rheumatoid arthritis patients. Treatment outcome and six-month followup.

Abstract: A randomized clinical trial was performed to evaluate a psychological treatment intervention and a social support program, compared with a control program in which no adjunct treatment was rendered, and their effects upon pain behavior, affect, and disease activity of 53 patients with rheumatoid arthritis. The psychological intervention produced significant reductions in patients' pain behavior and disease activity at posttreatment. Significant reductions were also observed in trait anxiety at posttreatment and 6-month followup. Relaxation training may have been the most important component of the psychological intervention. The social support program produced a significant reduction in trait anxiety only at posttreatment. This is the first well-controlled study to demonstrate reduced pain behavior, disease activity, and trait anxiety following psychological treatment.

Computerized Display of Past Test Results: Effect on Outpatient Testing

Abstract: STUDY OBJECTIVE To determine the effect of displaying previous results of diagnostic tests on the ordering of selected outpatient tests. DESIGN Sixteen-week controlled trial with a 13-week pre-intervention and 8-week post-intervention observation periods. Patients were randomly assigned to intervention or control groups so that each physician was his or her own control. Only scheduled visits were included. Randomization occurred before the pre-intervention observation period. SETTING Academic primary care general medicine clinic affiliated with an urban general hospital. SUBJECTS Pre-intervention period: 111 physicians (97 internal medicine residents, 14 faculty internists), 4683 patients, 5942 scheduled visits. INTERVENTION period: same 111 physicians, 5946 patients, 8148 visits. Post-intervention period: 76 physicians (62 residents, 14 faculty), 2571 patients, 2858 scheduled visits. INTERVENTION With an order for one of eight selected diagnostic tests through microcomputer workstations, a window was opened on the screen and previous test results were displayed along with the time interval between the first and last result. Tests were ordered for control patients into the same workstations without previous results displayed. MEASUREMENTS AND MAIN RESULTS Previous results of one or more study tests were available for display for 96% of scheduled patients. Significantly lower results (p less than 0.05 by paired t-test) for the selected tests were found for intervention patient visits than for control visits: charges per visit (mean +/- SE) for intervention patients $12.17 +/- 0.62, compared with $13.99 +/- 0.77 for controls, a 13.0% difference; tests per visit were 0.51 +/- 0.03, compared with 0.56 +/- 0.03, an 8.5% difference. The number of study tests ordered decreased significantly for intervention patients (16.8%) and for controls (10.9%). During the post-intervention period, ordering of study tests increased for both groups, but the increase from the intervention period was not significant. CONCLUSIONS Presenting physicians with previous test results reduced the ordering of those tests. The actual effect may have been greater than 13%, because there were reductions in study tests ordered for both intervention and control patients during the intervention period when compared with the pre-intervention period, and both tended to rise after the intervention, or display, was turned off.

Interim analyses in randomized clinical trials: ramifications and guidelines for practitioners.

Abstract: Recent developments in group sequential methods have had a great impact on the design and analysis of randomized clinical trials The consequences for both planned and unplanned interim analyses are discussed using several real trials as illustrations Guidelines for the conduct of interim analysis are given, including tables of nominal significance levels and required sample sizes for several group sequential plans Areas in need of further theoretical advance include multiple endpoints, estimation of treatment differences, stratification, and design of multiple-armed trials

Lovastatin (mevinolin) in the treatment of heterozygous familial hypercholesterolemia. A multicenter study.

Abstract: Study Objective:To evaluate the efficacy and tolerability of lovastatin under controlled conditions in heterozygous familial hypercholesterolemia. Design:Randomized, double-blind, placebo-...

Avoidance of large biases and large random errors in the assessment of moderate treatment effects: The need for systematic overviews

Abstract: In order to avoid selective biases and to minimize random errors, inference about the effects of treatment on serious endpoints needs to be based not on one, or a few, of the available trial results, but on a systematic overview of the totality of the evidence from all the relevant unconfounded randomized trials. But, only where coverage of all, or nearly all, randomized patients in all relevant trials (or a reasonably unbiased sample of such trials) can be assured, is a systematic overview of trials reasonably trustworthy, for then any selective biases are likely to be small in comparison with any moderate effects of treatment. Checks for the existence of such biases can best be conducted if reasonably detailed data are available from each trial. Future trials should take into account the results of any relevant overviews in their design, and should plan to obtain sufficient numbers of events to contribute substantially to such overviews. In many cases, this implies the need for randomized trials that are much larger than is currently standard.

Was the international randomized trial of extracranial-intracranial arterial bypass representative of the population at risk?

Abstract: The international, multicenter, randomized trial of extracranial–intracranial arterial anastomoses (EC–IC bypass)1 , 2 has been applauded and cited as a standard for future studies of this type.3 T...

How Does the Team Approach to Outpatient Geriatric Evaluation Compare with Traditional Care: A Report of a Randomized Controlled Trial

Abstract: Although team-oriented geriatric assessment clinics are growing throughout the country, little documentation exists regarding their clinical efficacy, cost-effectiveness, or impact on patient functioning and well-being. This report describes a randomized controlled clinical trial to evaluate the effectiveness of a team-oriented geriatric assessment approach compared to traditional care. One hundred-seventeen subjects 65 years of age and over, meeting eligibility criteria to target frail older persons with changing medical and social needs, were randomly assigned to receive a comprehensive geriatric assessment by a multidisciplinary team (treatment) or by one of a panel of community internists who were reimbursed according to their usual and customary fee (controls). Extensive analysis of baseline information failed to identify any significant differences between groups. Over the 1-year follow-up period, treatment participants experienced 26 hospital admissions and used 670 hospital days compared with 23 admissions and 1113 days for controls (a 39.8% difference). Annual hospital costs averaged $4297 for treatment subjects and $7018 for controls. Overall institutional costs including hospital and nursing home care revealed an average saving of $2189 per person for treatment subjects compared with controls, a 25% reduction. A small proportion of subjects accounted for this difference. No significant differences were noted in patient or caregiver satisfaction with the evaluation process, functional ability, or health status. These findings suggest that team-oriented outpatient geriatric assessment provides a promising way to deliver high-quality, satisfying care to older persons without increasing (and possibly decreasing) health care costs.

Brain-stem tumors in childhood: a prospective randomized trial of irradiation with and without adjuvant CCNU, VCR, and prednisone. A report of the Childrens Cancer Study Group.

Abstract: Seventy-four children with a brain-stem tumor diagnosed between 1977 and 1980 were entered into a prospective study in which exploration and assessment for resection were optional, radiation treatment using standard methods was required, and randomization occurred with regard to the use of adjuvant chemotherapy (1-(2-chloroethyl)-1-nitrosourea, vincristine, and prednisone) or no further treatment. The overall 5-year survival rate was 20% and was not improved by the adjuvant chemotherapy program. An increased risk of infection was associated with the adjuvant therapy.

Canadian multicenter randomized trial comparing sequential and alternating administration of two non-cross-resistant chemotherapy combinations in patients with limited small-cell carcinoma of the lung.

Abstract: In order to assess the effect of scheduling of chemotherapy on the outcome of patients with limited small-cell lung cancer (SCLC), the Clinical Trials Group of the National Cancer Institute of Canada carried out a randomized trial comparing the alternation of cyclophosphamide, Adriamycin (Adria Laboratories, Columbus, OH; doxorubicin) and vincristine (CAV) with etoposide (VP-16) and cisplatin for six cycles to the administration of these two combinations in a sequential fashion (three cycles of CAV followed by three of VP-16/cisplatin). Three hundred eligible patients were enrolled on the trial from September 1981 to October 1984. All responding patients were also treated after completion of chemotherapy with thoracic irradiation in randomly allocated doses of 2,000 and 3,750 cGy. The complete response (CR) rate to chemotherapy was slightly, but not significantly, higher on the alternating arm (52% v 44%, P = .20). However, there was no difference in disease-free or overall survival on the alternating and sequential arms, respectively (47.3 weeks v 45.1 weeks, P = .26; 61.7 weeks v 59.5 weeks, P = .56). Data on the effect of radiotherapy dose on survival are not yet mature, but it does not appear the results of this portion of the trial will alter the interpretation of the chemotherapy comparison. Patient characteristics favorably influencing survival were female sex, good performance status, younger age, and absence of supraclavicular node involvement. Two interpretations of these and other results in SCLC are suggested: (1) the difference between the schedules used is too small for the predictions of the Goldie-Coldman model to be realized in a trial of this size, or (2) VP-16/cisplatin is actually a superior regimen and any schedule that exposes patients to these drugs early in treatment will produce improved results.

Adjunctive imipramine in the treatment of postpsychotic depression. A controlled trial.

Abstract: • The efficacy of adjunctive imipramine hydrochloride treatment for syndromally defined postpsychotic depression was assessed in a six-week, double-blind, placebo-controlled study. All patients had been diagnosed as having schizophrenia or schizoaffective disorder, all were receiving stable doses of fluphenazine decanoate, and all had received benztropine mesylate in an attempt to rule out neuroleptic-induced akinesia. Patients randomized to imipramine therapy fared significantly better in terms of their global improvement and in terms of individual symptoms that are components of the depression syndrome. There were no significant differences in outcome psychosis ratings or side effects. This study indicates the existence of an identifiable syndrome of secondary depression in this patient group that is likely to respond favorably to treatment with adjunctive imipramine.

5-Aminosalicylic acid in the treatment of Crohn's disease. A 16-week double-blind, placebo-controlled, multicentre study with Pentasa.

Abstract: The response to 5-aminosalicylic acid (5-ASA) in mild and moderately active Crohn's disease localized in the small bowel was studied in a randomized, double-blind, placebo-controlled trial in four centres. Sixty-seven patients were included, of whom 30 were treated with 1500 mg slow-release 5-ASA/day (Pentasa) for a scheduled period of 16 weeks. In the 5-ASA group 40% of the patients improved, versus 30% of the placebo-treated group ('intent to treat' basis; p greater than 0.1). Four of the patients treated with 5-ASA left the study owing to disease deterioration, versus 10 of the placebo-treated patients (p greater than 0.2). Seventeen patients were secondarily excluded, and the remaining 50 patients (23 receiving 5-ASA) were reevaluated in greater detail. No statistically significant differences in outcome were shown. Three patients (one given 5-ASA) were withdrawn from the study because of presumed side effects, but no serious adverse reactions were recorded. The present results indicate that 5-ASA, at least in the dosage used, is not superior to placebo. Nevertheless, trends towards a beneficial effect in Crohn's disease in the small bowel justify further clinical trials with a larger dosage of 5-ASA.

The benefits of group occupational therapy for patients with Parkinson's disease.

Abstract: The medical treatment of idiopathic Parkinson's disease has improved the quality of life and increased survival of patients with Parkinson's disease. However, as the illness progresses, impairments in daily living activities occur. A clinical trial for a group rehabilitation program was initiated to maintain the functional status of these patients. The research protocol consisted of a pretreatment evaluation, random assignment to experimental or control groups, and posttreatment evaluations after therapy, at 6 months and at 1 year. The results showed that the subjects of the treated experimental group maintained their functional status after 1 year, demonstrated a significant decrease of bradykinesia, and perceived a significant improvement in their psychological well-being. This study confirms the value of an occupational therapy group approach and its benefits to the functional independence, to the improvement of physical and motor symptoms, and to the quality of life of persons with Parkinson's disease.