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At least 37 records · Page 2Linked to original sources
PubMed1999

Mechanisms of death in the CABG Patch trial: a randomized trial of implantable cardiac defibrillator prophylaxis in patients at high risk of death after coronary artery bypass graft surgery.

BACKGROUND: The CABG Patch trial compared prophylactic implantable cardiac-defibrillator (ICD) implantation with no antiarrhythmic therapy in coronary bypass surgery patients who had a left ventricular ejection fraction <0.36 and an abnormal signal-averaged ECG. There were 102 deaths among the 446 ICD group patients and 96 deaths among the 454 control group patients, a hazard ratio of 1.07 (P=0.63). The mechanisms of death were classified, and hypotheses were tested about the effects of ICD therapy on arrhythmic and nonarrhythmic cardiac deaths in the CABG Patch Trial and the Multicenter Automatic Defibrillator Implantation Trial (MADIT). METHODS AND RESULTS: The 198 deaths in the trial were reviewed by an independent Events Committee and classified by the method of Hinkle and Thaler. Only 54 deaths (27%) occurred out of hospital; 145 deaths (73%) were witnessed. Seventy-nine (82%) of the 96 deaths in the control group and 76 (75%) of the 102 deaths in the ICD group were due to cardiac causes. Cumulative arrhythmic mortality at 42 months was 6.9% in the control group and 4.0% in the ICD group (P=0. 057). Cumulative nonarrhythmic cardiac mortality at 42 months was 12. 4% in the control group and 13.0% in the ICD group (P=0.275). Death due to pump failure was significantly associated with death >1 hour from the onset of symptoms, dyspnea within 7 days of death, and overt heart failure within 7 days of death. CONCLUSIONS: In the CABG Patch Trial, ICD therapy reduced arrhythmic death 45% without significant effect on nonarrhythmic deaths. Because 71% of the deaths were nonarrhythmic, total mortality was not significantly reduced.

Anti-Arrhythmia Agents↗
PubMed2005

Improving accrual of older persons to cancer treatment trials: a randomized trial comparing an educational intervention with standard information: CALGB 360001.

PURPOSE: To design and test a geriatric educational intervention to improve accrual of cancer patients age 65 years and older to cooperative group-sponsored treatment trials. METHODS: Main member institutions of the Cancer and Leukemia Group B (CALGB) and its affiliates were randomly assigned to receive standard information (n = 73) or educational intervention (n = 53). Standard information included CALGB Web site access and periodic notification about existing trials. The geriatric educational intervention included standard information plus: (1) an educational seminar; (2) educational materials; (3) a list of available protocols for use on charts; (4) a monthly e-mail and mail reminders for 1 year; and (5) a case discussion seminar. The main outcome was percentage of accrual of older persons to phase II and III treatment protocols after study initiation compared with baseline. RESULTS: There were 3,032 patients entered onto trials in the baseline year, and 2,160 and 1,239 during the 2 years postintervention, respectively. Overall percentage of accrual of older patients was 37% at baseline, and 33% and 31% during the first and second years after intervention. There was no improvement in accrual in the intervention versus control arm: 36% v 32% in the first year and 31% v 31% in the second year. CONCLUSION: Accrual of older patients was not increased by this intervention. Reasons for lack of effect include low intervention intensity, high baseline accrual rates, and closure of several high-accruing protocols during the study. More intense and multifaceted approaches will be needed to change physician (and patient) behavior and to increase accrual of older persons to clinical trials.

Age Factors↗
PubMed2002

Learning by doing: teaching critical appraisal of randomized trials by performing an in-class randomized trial.

OBJECTIVE: Our medical students often encounter difficulty because many have trouble appreciating the relative merits and limitations of clinical research design. In order to remedy these deficits, we developed a novel in-class simulated randomized trial in which students were blinded to their treatment assignment. Specifically, our goals for the session were to demonstrate the importance of randomization of subject populations, to define and use basic terminology such as relative risk reduction along with absolute risk reduction, and to demonstrate the strengths and pitfalls of analysis of subsets of subjects. DESCRIPTION: We proposed the study of a hypothetical new drug, "Flunkimmune," which was claimed to prevent students from failing tests. Students received a random assignment to either the "Flunkimmune" or the placebo group. Students then received an opaque plastic egg appropriate for their randomization. We had prepared the eggs a-priori to each contain a piece of candy, and some to contain a blue dot. The flavor of the candy signified whether a particular student was in the treatment or control group. After all students had received their eggs, we "unblinded" the study by having the students open their eggs and learn to which treatment they had received. We then used an audience response system to construct a demographics table commonly known as Table 1 for the randomized trial-based characteristics of the students' choosing (e.g., "drinks Diet cola," "over six feet tall," "birth weight under seven pounds"). We asked the class to critique their own Table 1 and to comment on the adequacy of the randomization. Students were then informed that the presence of the blue dot signified a "failing" grade on a hypothetical exam to test the efficacy of "Flunkimmune." The eggs had been loaded so that the treatment group had a relative risk reduction of failure rates of 50% compared with the control group and an absolute risk reduction of 20%. This result prompted a debate among students about the relative merits of absolute or relative risk reduction in reporting the results of the study. Students also performed subgroup analyses by determining the failure rates for treatment and control students seated in particular aisles of the lecture hall. This enhanced discussion about the processes of bias and confounding inherent in subgroup analyses. DISCUSSION: This experiential teaching method allowed students to participate directly in a simulated randomized controlled trial, thereby facilitating understanding of this type of study. Students reported that the experience was enjoyable and stimulated active engagement with critical appraisal of randomized trials. Students' subsequent homework assignments, in which they were asked to critically appraise a randomized trial, demonstrated a depth of understanding not previously encountered at this level. We plan to develop and rigorously evaluate additional experiential activities that expose students to the role of the research investigator.

Education, Medical, Undergraduate↗
PubMed2002

Sample size re-estimation in cluster randomization trials.

Cluster randomization trials in which families are the unit of allocation are commonly adopted for the evaluation of disease prevention interventions. Sample size estimation for cluster randomization trials depends on parameters that quantify the variability within and between clusters and the variability in cluster size. Accurate advance estimates of these nuisance parameters may be difficult to obtain and misspecification may lead to an underpowered study. Since families are typically recruited over time, we propose using a portion of the data to estimate the nuisance parameters and to re-estimate sample size based on the estimates. This extends the standard internal pilot study methods to the setting of cluster randomization trials. The effect of this design on the power, significance level and sample size is analysed via simulation and is shown to provide a flexible and practical approach to cluster randomization trials.

Cluster Analysis↗
PubMed2001

Statistical methods for the meta-analysis of cluster randomization trials.

Cluster randomization trials have become a very attractive research strategy, particularly for the evaluation of health service interventions. The need to conduct meta-analyses of such trials is also becoming more common. However, as with cluster randomization trials in general, such analyses raise special methodologic challenges. In this paper, we discuss and illustrate several statistical approaches that might be applied to a meta-analysis of cluster randomization trials, each of which has a binary endpoint. Statistical methods for constructing inferences for a summary intervention odds ratio include those based on Mantel-Haenszel procedures, the ratio estimator approach, Woolf procedures and generalized estimating equations using robust variance estimation. The advantages and disadvantages of each method are discussed in the context of an example.

Cluster Analysis↗
PubMedDate not supplied

Promotion of Breastfeeding Intervention Trial (PROBIT): a randomized trial in the Republic of Belarus.

CONTEXT: Current evidence that breastfeeding is beneficial for infant and child health is based exclusively on observational studies. Potential sources of bias in such studies have led to doubts about the magnitude of these health benefits in industrialized countries. OBJECTIVE: To assess the effects of breastfeeding promotion on breastfeeding duration and exclusivity and gastrointestinal and respiratory infection and atopic eczema among infants. DESIGN: The Promotion of Breastfeeding Intervention Trial (PROBIT), a cluster-randomized trial conducted June 1996-December 1997 with a 1-year follow-up. SETTING: Thirty-one maternity hospitals and polyclinics in the Republic of Belarus. PARTICIPANTS: A total of 17 046 mother-infant pairs consisting of full-term singleton infants weighing at least 2500 g and their healthy mothers who intended to breastfeed, 16491 (96.7%) of which completed the entire 12 months of follow-up. INTERVENTIONS: Sites were randomly assigned to receive an experimental intervention (n = 16) modeled on the Baby-Friendly Hospital Initiative of the World Health Organization and United Nations Children's Fund, which emphasizes health care worker assistance with initiating and maintaining breastfeeding and lactation and postnatal breastfeeding support, or a control intervention (n = 15) of continuing usual infant feeding practices and policies. MAIN OUTCOME MEASURES: Duration of any breastfeeding, prevalence of predominant and exclusive breastfeeding at 3 and 6 months of life and occurrence of 1 or more episodes of gastrointestinal tract infection, 2 or more episodes of respiratory tract infection, and atopic eczema during the first 12 months of life, compared between the intervention and control groups. RESULTS: Infants from the intervention sites were significantly more likely than control infants to be breastfed to any degree at 12 months (19.7% vs 11.4%; adjusted odds ratio [OR], 0.47; 95% confidence interval [CI], 0.32-0.69), were more likely to be exclusively breastfed at 3 months (43.3% vs 6.4%; P<.001) and at 6 months (7.9% vs 0.6%; P =.01), and had a significant reduction in the risk of 1 or more gastrointestinal tract infections (9.1% vs 13.2%; adjusted OR, 0.60; 95% CI, 0.40-0.91) and of atopic eczema (3.3% vs 6.3%; adjusted OR, 0.54; 95% CI, 0.31-0.95), but no significant reduction in respiratory tract infection (intervention group, 39.2%; control group, 39.4%; adjusted OR, 0.87; 95% CI, 0.59-1.28). CONCLUSIONS: Our experimental intervention increased the duration and degree (exclusivity) of breastfeeding and decreased the risk of gastrointestinal tract infection and atopic eczema in the first year of life. These results provide a solid scientific underpinning for future interventions to promote breastfeeding.

Adult↗
PubMed2003

International Collaborative Ovarian Neoplasm trial 1: a randomized trial of adjuvant chemotherapy in women with early-stage ovarian cancer.

BACKGROUND: The question of whether platinum-based adjuvant chemotherapy can improve outcomes in patients with early-stage epithelial ovarian cancer is an important one. We carried out a multicenter, open randomized trial to determine whether adjuvant chemotherapy would improve overall survival and prolong recurrence-free survival in women with early-stage epithelial ovarian cancer. METHODS: Between August 1991 and January 2000, 477 patients in 84 centers in five countries were randomly assigned to receive either adjuvant chemotherapy immediately following surgery (n = 241) or no adjuvant chemotherapy until clinically indicated (n = 236). Kaplan-Meier curves of overall survival and recurrence-free survival were compared using the Mantel-Cox version of the log-rank test. All statistical tests were two-sided. RESULTS: Women who received adjuvant chemotherapy had better overall survival than women who did not (hazard ratio [HR] of 0.66, 95% confidence interval [CI] = 0.45 to 0.97; P =.03). These results translate into 5-year survival figures of 70% for women who did not receive adjuvant chemotherapy and 79% for women who did receive adjuvant chemotherapy, a difference of 9% (95% CI = 1% to 15%). Adjuvant chemotherapy also improved recurrence-free survival (HR = 0.65; 95% CI = 0.46 to 0.91; P =.01). These results translate into 5-year recurrence-free survival figures of 62% for women who did not receive adjuvant chemotherapy and 73% for women who did receive adjuvant chemotherapy, a difference of 11% (95% CI = 3% to 18%). CONCLUSION: These results suggest that platinum-based adjuvant chemotherapy improves survival and delays recurrence in patients with early-stage ovarian cancer.

Aged↗
PubMed2006

Surgical vs nonoperative treatment for lumbar disk herniation: the Spine Patient Outcomes Research Trial (SPORT): a randomized trial.

CONTEXT: Lumbar diskectomy is the most common surgical procedure performed for back and leg symptoms in US patients, but the efficacy of the procedure relative to nonoperative care remains controversial. OBJECTIVE: To assess the efficacy of surgery for lumbar intervertebral disk herniation. DESIGN, SETTING, AND PATIENTS: The Spine Patient Outcomes Research Trial, a randomized clinical trial enrolling patients between March 2000 and November 2004 from 13 multidisciplinary spine clinics in 11 US states. Patients were 501 surgical candidates (mean age, 42 years; 42% women) with imaging-confirmed lumbar intervertebral disk herniation and persistent signs and symptoms of radiculopathy for at least 6 weeks. INTERVENTIONS: Standard open diskectomy vs nonoperative treatment individualized to the patient. MAIN OUTCOME MEASURES: Primary outcomes were changes from baseline for the Medical Outcomes Study 36-item Short-Form Health Survey bodily pain and physical function scales and the modified Oswestry Disability Index (American Academy of Orthopaedic Surgeons MODEMS version) at 6 weeks, 3 months, 6 months, and 1 and 2 years from enrollment. Secondary outcomes included sciatica severity as measured by the Sciatica Bothersomeness Index, satisfaction with symptoms, self-reported improvement, and employment status. RESULTS: Adherence to assigned treatment was limited: 50% of patients assigned to surgery received surgery within 3 months of enrollment, while 30% of those assigned to nonoperative treatment received surgery in the same period. Intent-to-treat analyses demonstrated substantial improvements for all primary and secondary outcomes in both treatment groups. Between-group differences in improvements were consistently in favor of surgery for all periods but were small and not statistically significant for the primary outcomes. CONCLUSIONS: Patients in both the surgery and the nonoperative treatment groups improved substantially over a 2-year period. Because of the large numbers of patients who crossed over in both directions, conclusions about the superiority or equivalence of the treatments are not warranted based on the intent-to-treat analysis. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000410.

Adult↗
PubMed1981

Clinical trials:randomization before consent.

Conventional blind randomized trials involve obtaining consent for treatment prior to randomization into control or treatment groups. When the trial is of necessity an open one, obtaining consent to treatment and then assigning the patient to a control group may lead to undesirable consequences. When consent is required prior to randomization, inability to obtain it diminishes both control and treatment numbers. Obtaining consent after randomization enhances the power of the study since refusal affects only treatment numbers thus making more efficient use of patient material. We propose to analyze the outcome of patients allocated to treatment, but refusing experimental therapy, as a separate group. Comparison of this group with the control population will permit validation of the efficacy of the randomization process and allow testing of the hypothesis that refusers of consent react the same as the control population. If no difference occurs we propose that the refuser and control groups be combined and compared with those patients who receive experimental treatment.

Clinical Trials as Topic↗
PubMedDate not supplied

Implications of overviews of randomized trials.

Many randomized trials are of insufficient sample size to detect with adequate power the small to moderate effects that are most likely to occur. As a result, a single such trial can produce a null finding that is, in fact, uninformative, but none the less is misinterpreted as demonstrating no effect. An overview considers all available trials and can increase the statistical power to detect an effect if present. Thus overviews can provide perhaps the most precise estimate of the magnitude of a treatment effect based on existing data. This may have implications for the formulation of public policy but certainly should influence the conduct and planning of randomized trials. Public policy may be influenced in circumstances where further trials are unlikely to be conducted. Overviews can also provide guidance as to whether changes in protocols of ongoing studies are recommended as a result of new evidence. Perhaps most importantly, overviews can provide information about whether additional trials are warranted, and, if so, the sample size that would be required to answer the research question definitively.

Clinical Trials as Topic↗
PubMed2001

Impact of randomized trials on the application of endoscopic techniques for inguinal hernia repair in The Netherlands.

BACKGROUND: One year after publication of a Dutch prospective trial randomizing patients with inguinal hernias to either endoscopic or open repair, a questionnaire was sent to all Dutch surgeons to evaluate the impact of this trial on the application of endoscopic inguinal hernia repair in the Netherlands. METHODS: All 780 registered Dutch surgeons were surveyed. The performance of endoscopic inguinal hernia repair, the technique and the indications, the involvement of surgical residents, the motives for use of conventional techniques, and the type of open repair were documented. RESULTS: The response rate was 100%. Endoscopic inguinal hernia repair was performed by 16% of Dutch surgeons. For 81% of the surgeons, the total extraperitoneal approach was the preferred endoscopic technique. Primary inguinal hernias were approached endoscopically by only 54% of these surgeons, and recurrent hernias by 92%. The technique of choice for open repair of primary hernias was the Shouldice repair. The predominant repair for recurrent inguinal hernias was the Lichtenstein technique. CONCLUSIONS: Although randomized clinical trials have provided evidence that the endoscopic approach to inguinal hernias is preferable, only 1 of 6 Dutch surgeons has adopted endoscopic inguinal hernia repair. Improvement in training of both surgical residents and surgeons and increasing awareness among medical doctors and patients about the benefits of endoscopic inguinal hernia repair are necessary to enhance the acceptance of this valuable technique for inguinal hernia repair.

Evidence-Based Medicine↗
PubMed2005

Gated SPECT evaluation of outcome after abciximab-supported primary infarct artery stenting for acute myocardial infarction: the scintigraphic data of the abciximab and carbostent evaluation (ACE) randomized trial.

UNLABELLED: We used gated SPECT to evaluate the impact of abciximab on the efficacy of myocardial reperfusion in patients with acute myocardial infarction undergoing infarct-related artery stenting. METHODS: The Abciximab and Carbostent Evaluation (ACE) trial randomized 400 infarct patients to stenting alone or stenting plus abciximab. One-month (99m)Tc-sestamibi gated SPECT was planned in a subgroup of consecutive patients to evaluate infarct size, infarct severity, left ventricular volumes, and ejection fraction. RESULTS: The final study population included 182 patients (99 randomized to abciximab and 83 to stenting alone). Gated SPECT revealed smaller infarcts in the abciximab group than in the stenting-alone group (14.3% +/- 11.7% vs. 18.1% +/- 13%, P < 0.02), and lower infarct severity (minimum-to-maximum count ratio = 0.47 +/- 0.17 vs. 0.41 +/- 0.15, P < 0.02), resulting in a smaller left ventricular end-diastolic volume index (57.8 +/- 20.0 vs. 64.6 +/- 20.8 mL/m(2), P = 0.03) and left ventricular end-systolic volume index (31.7 +/- 17.4 vs. 37.5 +/- 18.6 mL/m(2), P = 0.05) in the abciximab group. One-month left ventricular ejection fraction was significantly higher in patients randomized to abciximab (47.4% +/- 11.3% vs. 43.9% +/- 11.7%, P = 0.05). CONCLUSION: The use of abciximab therapy as an adjunct to infarct-related artery stenting leads to a reduction in infarct size and severity, resulting in smaller 1-mo left ventricular volumes and better left ventricular function. Gated SPECT appears to be an ideal tool for outcome assessment in infarct patients undergoing different treatment strategies.

Abciximab↗
PubMed2000

Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study: a randomized trial of the effect of vitamins E and C on 3-year progression of carotid atherosclerosis.

OBJECTIVES: To study the efficacy of vitamin E and C supplementation on the progression of carotid atherosclerosis, hypothesizing an enhanced preventive effect in men and in smokers and synergism between vitamins. DESIGN AND SUBJECTS: Double-masked two-by-two factorial trial, randomization in four strata (by gender and smoking status) to receive twice daily either 91 mg (136 IU) of d-alpha-tocopherol, 250 mg of slow-release vitamin C, a combination of these or placebo for three years. A randomized sample of 520 smoking and nonsmoking men and postmenopausal women aged 45-69 years with serum cholesterol >/= 5.0 mmol L-1 were studied. SETTING: The population of the city of Kuopio in Eastern Finland. INTERVENTION: Twice daily either a special formulation of 91 mg of d-alpha-tocopherol, 250 mg of slow-release vitamin C, a combination of these (CellaVie(R)) or placebo for three years. MEASUREMENTS: Atherosclerotic progression, defined as the linear regression slope of ultrasonographically assessed common carotid artery mean intima-media thickness (IMT), was calculated over semi-annual assessments. RESULTS: The average increase of the mean IMT was 0.020 mm year-1 amongst men randomized to placebo and 0.018 mm year-1 in vitamin E, 0.017 mm year-1 in vitamin C and 0.011 mm year-1 in the vitamin combination group (P = 0.008 for E + C vs. placebo). The respective means in women were 0.016, 0.015, 0.017 and 0.016 mm year-1. The proportion of men with progression was reduced by 74% (95% CI 36-89%, P = 0.003) by supplementation with the formulation containing both vitamins, as compared with placebo. CONCLUSIONS: Our study shows that a combined supplementation with reasonable doses of both vitamin E and slow-release vitamin C can retard the progression of common carotid atherosclerosis in men. This may imply benefits with regard to other atherosclerosis-based events.

Aged↗
PubMed2001

Final results of a randomized trial comparing the NIR stent to the Palmaz-Schatz stent for narrowings in native coronary arteries.

The NIR stent is a novel second generation tubular stent that was designed to overcome some of the limitations of the earlier Palmaz-Schatz (PS) stent design. The NIR Vascular Advanced North American (NIRVANA) trial randomized 849 patients with single coronary lesions to treatment with the NIR stent or the PS stent. The study was an "equivalency" trial, designed to demonstrate that the NIR stent was not inferior to (i.e., equivalent or better than) the PS stent, for the primary end point of target vessel failure (defined as death, myocardial infarction, or target vessel revascularization) by 9 months. Successful stent delivery was achieved in 100% versus 98.8%, respectively, with a slightly lower postprocedural diameter stenosis (7% vs. 9%, p = 0.04) after NIR and PS stent placement, respectively. Major adverse cardiac events (death, myocardial infarction, repeat target lesion revascularization) were not different at 30 days (4.3% vs. 4.4%). The primary end point of target vessel failure at 9 months was seen in 16.0% of NIR versus 17.2% of PS patients, with the NIR proving to be equal or superior to the PS stent (p <0.001 by test for equivalency). Angiographic restudy in 71% of a prespecified cohort showed no significant difference in restenosis (19.3% vs 22.4%). Thus, the NIR stent showed excellent deliverability with slightly better acute angiographic results and equivalent or better 9-month target vessel failure rate when compared with the PS stent.

Aged↗
PubMed1989

Evaluating triphasic oral contraceptives: the rationale for a randomized trial.

The randomized clinical trial is one of the major achievements of our times. Randomized trials set the standard for scientific rigor. They are medicine's closest approximation to the controlled experiments of the laboratory scientist. These studies prevent selection bias and minimize ascertainment bias. In addition, they are statistically efficient. There have been few randomized clinical trials comparing the metabolic effects and adverse drug experiences of low-dose oral contraceptives. Previous studies conducted with oral contraceptives containing higher doses of estrogen (equivalent to greater than 50 micrograms of ethinyl estradiol) may not be relevant today when low-dose preparations are more widely used. For this reason a randomized trial was conducted to compare three multiphasic oral contraceptives marketed in the United States.

Contraceptives, Oral↗
PubMed1999

Single-agent versus combination chemotherapy in advanced non-small cell lung cancer: a meta-analysis and the Cancer and Leukemia Group B randomized trial.

Several randomized trials have compared single-agent chemotherapy with combination chemotherapy in advanced non-small cell lung cancer. In general, response rates were higher with combination regimens, but their impact on survival is unclear. We conducted a meta-analysis of 25 trials involving a total of 5,156 patients with advanced non-small cell lung cancer randomized to a single-agent arm versus a combination arm. The results showed that combination chemotherapy produced a nearly twofold increase in response rate and a modestly improved 1-year survival rate compared with single-agent chemotherapy. However, toxicity was significantly increased, with a 3.6-fold increase in treatment-related mortality. In a subset analysis of trials using either a platinum analog or vinorelbine as single agents and as a component of the combination regimen, the difference was no longer statistically significant, suggesting that more active single agents provide similar survival with less toxicity than combination regimens. Based on these results, the Cancer and Leukemia Group B initiated a large randomized trial comparing paclitaxel with paclitaxel + carboplatin in stage IIIB-IV non-small cell lung cancer patients. The trial will be able to detect a 30% difference in survival. An extensive quality of life analysis and a resource utilization comparison will allow estimation of the incremental cost per quality of life-year gained. This trial will be the first in the United States to prospectively collect and analyze such data in a multidisciplinary approach.

Antineoplastic Agents↗