Showing papers on "Randomized controlled trial published in 1984"

Clinical Trials: A Practical Approach

Abstract: Introduction: The Rationale of Clinical Trials. The Historical Development of Clinical Trials. Organization and Planning. The Justificaton for Randomized Controlled Trials. Methods of Randomization. Blinding and Placebos. Ethical Issues. Crossover Trials. The Size of a Clinical Trial. Monitoring Trial Progress. Forms and Data Management. Protocol Deviations. Basic Principles of Statistical Analysis. Further Aspects of Data Analysis. Publication and Interpretation of Findings. References. Index.

Psychosocial influences on mortality after myocardial infarction.

Abstract: Psychosocial interviews with 2320 male survivors of acute myocardial infarction, participants in the beta-Blocker Heart Attack Trial, permitted the definition of two variables strongly associated with an increased three-year mortality risk. With other important prognostic factors controlled for, the patients classified as being socially isolated and having a high degree of life stress had more than four times the risk of death of the men with low levels of both stress and isolation. An inverse association of education with mortality in this population reflected the gradient in the prevalence of the defined psychosocial characteristics. High levels of stress and social isolation were most prevalent among the least-educated men and least prevalent among the best-educated. The increase in risk associated with stress and social isolation applied both to total deaths and to sudden cardiac deaths and was noted among men with both high and low levels of ventricular ectopy during hospitalization for the acute infarction.

The effects of high-dose corticosteroids in patients with septic shock. A prospective, controlled study.

Abstract: To determine whether corticosteroids are efficacious in severe septic shock, we conducted a prospective study of 59 patients randomly assigned to a methylprednisolone, dexamethasone, or control group. Patients were treated 17.5 +/- 5.4 hours (mean +/- S.E.M.) after the onset of shock, and 55 patients required vasopressor agents. Early in the hospital course, reversal of shock was more likely in patients who received corticosteroids than in those who did not. Four (19 per cent) of 21 methylprednisolone-treated, 7 (32 per cent) of 22 dexamethasone-treated, and none of 16 control patients had reversal of shock 24 hours after drug administration (corticosteroid groups vs. control group, P less than 0.05). Patients treated with corticosteroids within four hours after the onset of shock had a higher incidence of shock reversal (P less than 0.05). At 133 hours after drug administration, 17 (40 per cent) of 43 corticosteroid-treated patients had died, and 11 (69 per cent) of 16 control patients had died (P less than 0.05). However, these differences in reversal of shock and survival disappeared later in the course. Overall, 16 (76 per cent) of 21 patients receiving methylprednisolone, 17 (77 per cent) of 22 patients receiving dexamethasone, and 11 (69 per cent) of 16 controls in the hospital died. We conclude that corticosteroids do not improve the overall survival of patients with severe, late septic shock but may be helpful early in the course and in certain subgroups of patients.

Reminders to physicians from an introspective computer medical record. A two-year randomized trial.

Abstract: We developed a computer-stored medical record system containing a limited set of the total clinical data base--primarily diagnostic studies and treatments. This system responds to its own content according to physician-authored reminder rules. To determine the effect of the reminder messages generated by 1490 rules on physician behavior, we randomly assigned practitioners in a general medicine clinic to study or control groups. The computer found indications for six different actions per patient in 12 467 patients during a 2-year study: 61 study group residents who received computer reminders responded to 49% of these indications; 54 control group residents, to only 29% (p less than 0.0001). Preventive care (occult blood testing, mammographic screening, weight reduction diets, influenza and pneumococcal vaccines) was affected. The intentions of the study group to use a given action for an indication predicted their response to the indications (p less than 0.03, r2 = 0.33). The intentions of the control residents did not.

A Controlled Trial of the Effect of a Prepaid Group Practice on Use of Services

Abstract: Does a prepaid group practice deliver less care than the fee-for-service system when both serve comparable populations with comparable benefits? To answer this question, we randomly assigned a group of 1580 persons to receive care free of charge from either a fee-for-service physician of their choice (431 persons) or the Group Health Cooperative of Puget Sound (1149 persons). In addition, 733 prior enrollees of the Cooperative were studied as a control group. The rate of hospital admissions in both groups at the Cooperative was about 40 per cent less than in the fee-for-service group (P less than 0.01), although ambulatory-visit rates were similar. The calculated expenditure rate for all services was about 25 per cent less in the two Cooperative groups (P less than 0.01 for the experimental group, P less than 0.05 for the control group). The number of preventive visits was higher in the prepaid groups, but this difference does not explain the reduced hospitalization. The similarity of use between the two prepaid groups suggests that the mix of health risks at the Cooperative was similar to that in the fee-for-service system. The lower rate of use that we observed, along with comparable reductions found in non-controlled studies by others, suggests that the style of medicine at prepaid group practices is markedly less "hospital-intensive" and, consequently, less expensive.

A Clinical Trial of Change in Maternal Smoking and Its Effect on Birth Weight

Abstract: These clinical trial results are the first, to our knowledge, from a prospective, randomized, and controlled experiment demonstrating that a reduction of smoking during pregnancy improves the birth weight of the infant. Nine hundred thirty-five pregnant smokers were randomly assigned to treatment and control groups; the former received smoking intervention. At the eighth month of pregnancy, differences between the two groups in salivary thiocyanate level and reported smoking were statistically significant. For single, live births, the treatment group infants had a mean birth weight that was 92 g heavier and were 0.6 cm greater in length than the control group infants. The decrement in weight related to smoking cannot be fully explained by gestational age. The findings suggest that some fetal growth retardation can be overcome by the provision of antismoking assistance to pregnant women. (JAMA1984;251:911-915)

Elemental diet as primary treatment of acute Crohn's disease: a controlled trial.

Abstract: Acute exacerbations of Crohn's disease are usually treated with prednisolone or potentially more toxic immunosuppressive drugs or by surgery. In pilot studies replacing the normal diet by a protein free elemental diet also induced remission. A controlled trial was therefore conducted in which 21 patients acutely ill with exacerbations of Crohn's disease were randomised to receive either prednisolone 0.75 mg/kg/day or an elemental diet (Vivonex) for four weeks. Assessment at four and 12 weeks showed that the patients treated with the elemental diet had improved as much as and by some criteria more than the steroid treated group. Elemental diet is a safe and effective treatment for acute Crohn's disease.

Physicians' Reasons for Not Entering Eligible Patients in a Randomized Clinical Trial of Surgery for Breast Cancer

Abstract: We studied the reasons surgical principal investigators chose not to enter patients in a large, multicenter trial sponsored by a cooperative group. In 1976 the National Surgical Adjuvant Project for Breast and Bowel Cancers (NSABP) initiated a clinical trial to compare segmental mastectomy and postoperative radiation, or segmental mastectomy alone, with total mastectomy. Because the low rates of accrual were threatening to close the trial prematurely, we mailed a questionnaire to the 94 NSABP principal investigators, asking why they were not entering eligible patients in the trial. A response rate of 97 per cent was achieved. Physicians who did not enter all eligible patients offered the following explanations: (1) concern that the doctor–patient relationship would be affected by a randomized clinical trial (73 per cent), (2) difficulty with informed consent (38 per cent), (3) dislike of open discussions involving uncertainty (22 per cent), (4) perceived conflict between the roles of scientist an...

Continuity of Outpatient Medical Care in Elderly Men: A Randomized Trial

Abstract: P6 an outpatient repeatedly sees the same practitioner, is his care influenced? This double-blind randomized trial examines the effects of outpatient health care provider continuity on the process and outcome of the medical care for 776 men aged 55 years and older. Participants were randomized to two different groups of provider care: provider discontinuity and provider continuity. The outcome of the continuity group was significantly different from that of the discontinuity group. During an 18-month period, patients who had been randomized to the continuity group had fewer emergent admissions (20% v 39%) and a shorter average length of stay (15.5 v 25.5 days). These patients also perceived that the providers were more knowledgeable, thorough, and interested in patient education. We conclude that continuity of outpatient provider care for men aged 55 years and older results in more patient satisfaction, shorter hospitalizations, and fewer emergent hospital admissions.

Myocardial infarction and mortality in the coronary artery surgery study (CASS) randomized trial.

Abstract: The long-term benefit of coronary bypass surgery in terms of longevity and prevention of major ischemic events in patients who have mild angina is not well defined. The randomized Coronary Artery Surgery Study (CASS) was designed to evaluate this issue; it consists of 780 patients who were considered operable and who had mild stable angina pectoris or who were free of angina after infarction. As a result of the randomization process there were no significant differences in base-line variables between patients randomly assigned to medical and to surgical therapy. The likelihood of death in the five-year period after randomization was only 8 per cent in the medical cohort, as compared with 5 per cent in the surgical cohort (not significant). The likelihood of nonfatal Q-wave myocardial infarction was 11 and 14 per cent, respectively (not significant). The five-year probability of remaining alive and free of infarction was 82 per cent in the patients assigned to medical therapy and 83 per cent in th...

Effect of warfarin anticoagulation on survival in carcinoma of the lung, colon, head and neck, and prostate. Final report of VA Cooperative Study #75.

Abstract: VA Cooperative Study #75 was established to test in a controlled, randomized trial the hypothesis that warfarin anticoagulation would favorably affect the course of certain types of malignancy. No differences in survival were observed between warfarin-treated and control groups for advanced non-small cell lung, colorectal, head and neck and prostate cancers. However, warfarin therapy was associated with a significant prolongation in the time to first evidence of disease progression (P = 0.016) and a significant improvement in survival (P = 0.018) for patients with small cell carcinoma of the lung, including the subgroup of patients with disseminated disease at the time of randomization (P = 0.013). A trend toward improved survival with warfarin treatment was observed for the few patients admitted to this study with non-small cell lung cancer who had minimal disease at randomization. These results suggest that warfarin, as a single anticoagulant agent, may favorably modify the course of some, but not all, types of human malignancy, among which is small cell carcinoma of the lung. Further trials of warfarin may be indicated in patients with limited disease who have cell types that failed to respond when advanced disease was present.

Consequences of assessment and intervention among elderly people: a three year randomised controlled trial.

Abstract: Over three years 285 randomly selected subjects aged 75 years or more and living in a suburb of Copenhagen were visited every three months in their own homes (the intervention group) to assess whether scheduled medically and socially preventive intervention would influence the number of admissions to hospitals or nursing homes, the number of contacts with general practice, or mortality. A randomly selected group of 287 people of the same age and sex were visited during the final three months of the study (the control group). Two hundred and nineteen admissions to hospitals (4884 bed days) were registered for the intervention group compared with 271 (6442 bed days) for the control group. Especially during the second half of the study, a significant reduction in the number of admissions to hospitals was seen in the intervention group. Twenty people in the intervention group and 29 in the control group moved into nursing homes (p greater than 0.05). The corresponding numbers of deaths were 56 and 75 (p less than 0.05). No difference was seen in the number of contacts with general practice. Significantly fewer emergency medical calls, however, were registered for the intervention group. Subjects in the intervention group benefited from the regular visits and the increased distribution of aids and modifications to their homes to which these led. The regular visits probably also produced an important increase in confidence.

A Critical Appraisal of the Efficacy of Continuing Medical Education

Abstract: To determine the efficacy of continuing medical education (CME), we collected 248 original articles describing studies of CME interventions. These articles were reviewed for applicability and scientific credibility by applying preset methodological criteria. Thirteen percent of articles described randomized trials, but only 7% of all articles and 20% of randomized trials assessed the impact of CME on patient outcomes. Seven articles met all our criteria and were reviewed in detail. These studies provide convincing evidence that CME can improve physician behaviors. However, only three of these methodologically sound studies assessed patient outcomes and only one demonstrated any improvement in outcomes. ( JAMA 1984;251:61-64)

Randomized, Double‐Blind, Placebo Controlled Trial of Low‐Dose Pulse Methotrexate in Psoriatic Arthritis

Abstract: Thirty-seven patients with psoriatic arthritis were entered into a 12-week prospective, controlled, double-blind multicenter trial comparing placebo and oral pulse methotrexate therapy. Methotrexate was given in a dose of 2.5-5.0 mg every 12 hours in 3 consecutive doses per week. A stable background medication program with nonsteroidal antiinflammatory drugs was allowed. Methotrexate was superior to placebo only in physician assessment of arthritis activity and in improvement of the amount of skin surface area with psoriasis. A small but statistically significant rise of serum total bilirubin occurred in the methotrexate-treated patients. No patients were withdrawn from the study for adverse drug effects.

An efficacy trial of doxycycline chemoprophylaxis against leptospirosis.

Abstract: Because leptospirosis has been an important cause of morbidity in U.S. soldiers training in the Republic of Panama, we conducted a randomized, double-blind, placebo-controlled field trial during the fall of 1982 to determine whether doxycycline was an effective chemoprophylactic agent against this infection. Doxycycline (200 mg) or placebo was administered orally on a weekly basis and at the completion of training to 940 volunteers from two U.S. Army units deployed in Panama for approximately three weeks of jungle training. Twenty cases of leptospirosis occurred in the placebo group (an attack rate of 4.2 per cent), as compared with only one case in the doxycycline group (attack rate, 0.2 per cent, P less than 0.001), yielding an efficacy of 95.0 per cent. This study demonstrated the value of doxycycline as a prophylactic drug against leptospirosis.

Cognitive therapy for major depressive disorder in primary care.

Abstract: Cognitive therapy for depression is a psychological treatment designed to train patients to identify and correct the negative depressive thinking which, it has been hypothesised, contributes to the maintenance of depression. General practice patients meeting Research Diagnostic Criteria for primary major depressive disorder were randomly allocated either to continue with the treatment they would normally receive (which in the majority of cases included antidepressant medication) or to receive, in addition, sessions of cognitive therapy. At completion of treatment, patients receiving cognitive therapy were significantly less depressed than the comparison group, both on blind ratings of symptom severity made by psychiatric assessors and on a self-report measure of severity of depression. At three-month follow-up cognitive therapy patients no longer differed from patients receiving treatment-as-usual, but this was mainly as a result of continuing improvement in the comparison group.

A randomized trial of A.C.T. (asthma care training) for kids.

Abstract: A randomized control trial of a curriculum, A.C.T. (Asthma Care Training) for Kids, was conducted. Seventy-six children between the ages of 8 and 12 years, whose asthma required treatment with medications at least 25% of the days per month, were randomly assigned to control and experimental groups. The control group received 4 1/2 hours of lecture presentations on asthma and its management. The experimental groups (consisting of four to seven children and their parents) received five 1-hour sessions comprising "the treatment." Children and their parents were interviewed before the sessions and 3, 6, and 12 months after the completion of the experimental treatment. Use of emergency rooms and hospitals was determined by reviewing the records of these patients (all members of the Los Angeles Kaiser Permanente health care system) for the period of 1 year before and 1 year after the treatment. Results include (1) equivalent increases in knowledge and changes in beliefs in both groups, (2) significant changes in the self-reported compliance behaviors of the experimental group only, and (3) significant reductions in emergency room visits and days of hospitalization among those receiving the experimental treatment, compared with the control group. These changes represent an estimated savings of approximately $180 per child per year for those in the experimental group.

Short-Term and Long-Term Survival in Patients with Alcoholic Hepatitis Treated with Oxandrolone and Prednisolone

Abstract: A cooperative study was conducted to determine the efficacy of 30 days of treatment with either a glucocorticosteroid (prednisolone) or an anabolic steroid (oxandrolone) in moderate or severe alcoholic hepatitis. One hundred thirty-two patients with moderate disease and 131 with severe disease were randomly assigned to one of three treatments: prednisolone, oxandrolone, or placebo. During the 30 days, mortality in the groups receiving steroid therapy was not significantly different from mortality in the placebo group. Thirteen per cent of the moderately ill patients and 29 per cent of the severely ill patients died. Although neither steroid improved short-term survival, oxandrolone therapy was associated with a beneficial effect on long-term survival. This was especially true in patients with moderate disease: among those who survived for one or two months after the start of treatment the conditional six-month death rate was 3.5 per cent after oxandrolone and 19 to 20 per cent after placebo (P = 0.02). No consistent long-term effect was associated with prednisolone therapy.

Identification of True Drug Response to Antidepressants: Use of Pattern Analysis

Abstract: The purpose of this study was to develop a method for differentiating specific ("true") and nonspecific antidepressant drug response for the individual patient. Patterns of clinical response, based on weekly global ratings of clinical status, were generated for each of 185 patients participating in six-week placebo-controlled drug trials. We hypothesized and found that substantially more patients receiving active than placebo medication displayed treatment response patterns characterized both by two-week or greater delay in onset of initial improvement and nonfluctuating persistence of improvement once achieved. Identification of a distinctive pattern of clinical response to an active drug has both research and clinical applications. Pattern analysis may contribute to understanding the nature of drug mechanisms of action, may clarify some ambiguous treatment study outcomes, and in the individual case, may facilitate clinical management.

Duration of antidepressant drug treatment. What is an adequate trial

Abstract: • Data from three six-week placebo-controlled randomized antidepressant trials were pooled to test the hypothesis that a four-week trial is insufficient to reach a determination of drug failure in depressed patients. We compared global clinical ratings at weekly intervals for patients receiving drug and patients receiving placebo and calculated the proportion of patients whose clinical status changed over time. We predicted, and found, that a significant proportion of patients who showed no clear-cut response at four weeks would show much improvement at six weeks in drug but not placebo conditions. Baseline Research Diagnostic Criteria diagnosis, baseline illness severity, and drug dose adjustments after four weeks did not predict either late clinical improvement or relapse between four and six weeks. Additional placebo-controlled studies are needed to replicate our findings concerning the advantage of extending trials to five or six weeks in samples of patients of various depressive subtypes.

Final results of a randomized trial on the treatment of rectal cancer with preoperative radiotherapy alone or in combination with 5-fluorouracil, followed by radical surgery. Trial of the European Organization on Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group.

Abstract: To improve surgical results of potentially operable rectal cancer, the European Organization on Research and Treatment of Cancer conducted a two‐arm randomized clinical trial to compare the efficiency of preoperative administration of radiotherapy, with or without 5‐fluorouracil before radical surgery. Two hundred forty‐seven eligible patients were admitted from November 1972 through April 1976. The overall survival observed in the group treated with preoperative radiotherapy appears to be better than in the group of patients where preoperative combined modality was administered. Five‐year survival is 59% versus 46% with a marginal statistical significance of P = 0.06. Although the combined modality arm had a higher incidence of side effects and postoperative deaths, it had a greater effect than the radiotherapyalone arm in controlling the disease process, mainly distant metastases to the liver with a result bordering on statistical significance (P = 0.07). The incidence of nonmalignant and intercurrent deaths were higher in the combined modality group, whereas deaths due to malignancy were higher in the radiotherapyalone group. Observing more stringent selection in disease and patients' criteria, side effects and intercurrent deaths can be effectively reduced with further improvement in adjuvant therapy results. Copyright © 1984 American Cancer Society